FA selected

LAXATIVES- B-PM; O-PMLM; S-BS; E-D

OR = (a/c)/(b/d) = ad/bc
RR = a/(a + b) / c/(c + d)
RRR = 1 − RR
AR = a/a+b - c/c+d
AR% = (RR-1 / RR) x 100
ARR = c/c+d - a/a+b
NNT = 1/ARR
NNH = 1/AR
CFR% = (deaths/cases) x 100
Attack rate = People who become ill / Total people exposed
LR+ = sensitivity / 1 – specificity = TP rate / FP rate
LR- = 1-sensitivity / specificity = FN rate / TN rate
PPV = TP/(TP + FP)
Prevalence = TP + FN / (TP + FN + FP + TN)
NPV = TN/(TN + FN)
Sensitivity = TP / (TP + FN) = 1 – FN rate.
Specifcity = TN / (TN + FP) = 1 – FP rate.
Prevalence / 1 – prevalence = Incidence rate × average duration of disease
Variance = (SD)2 . SE = σ/√n. σ = SD; n = sample size.
CI for sample mean = x ± Z(SE) For the 95% CI, Z = 1.96. For the 99% CI, Z = 2.58.
Coeffcient of determination = r2 (r square)
Wall tension = pressure × radius
Wall stress ∝ (pressure × radius)/(2 × wall thickness)
Stroke volume SV = EDV − ESV
Ejection fraction EF = SV/EDV = (EDV − ESV)/EDV
Cardiac output CO = SV × HR.
Fick principle: CO = rate of O2 consumption/(arterial O2 content – venous O2 content)
MAP = CO × total peripheral resistance (TPR).
MAP (at resting HR) = 2/3 DBP + 1/3 SBP = DBP + 1/3 PP.
Volumetric flow rate (Q) = flow velocity (v) × cross-sectional area (A)
Resistance = driving pressure (ΔP)/Q = (8η (viscosity) × length)/πr4
Total resistance of vessels in series: RT = R1 + R2 + R3 . . .
Total resistance of vessels in parallel: 1/RT = 1/R1 + 1/R2 + 1/R3 . . .
Q ∝ r4
R ∝ 1/r4
Jv = net fluid fow = Kf [(Pc − Pi) −σ(πc −πi)]
GLUT1 - P-RBC
GLUT2 - LKG-B
GLUT3 - BP
GLUT4 - AS
GLUT5 - GS
SGLT1/2 - SK
insulin dependent - GLUT4
insulin independent - GLUT1,2,3,5; SGLT1,2 (BRICK-LIPS)
GLUT-2 - bidirectional
GLUT-5 - fructose
GLUT1: RBCs, brain, cornea, placenta.
GLUT2 (bidirectional): B-islet cells, liver, kidney, GI tract.
GLUT3: brain, placenta.
GLUT4: adipose tissue, striated muscle.
GLUT5 (fructose): spermatocytes, GI tract.
SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine.
Signaling pathways of endocrine hormones-
cAMP - FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2- receptor), MSH, PTH, Calcitonin, Histamine (H2-receptor), Glucagon, GHRH. FLAT
ChAMPs CHuGG.
cGMP - BNP, ANP, EDRF (NO). BAD GraMPa. Think vasodilation and diuresis.
IP3 - GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin. GOAT HAG.
Intracellular receptor - Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4,Vitamin D. PET CAT in TV.
Serine/threonine kinase receptor - TGF-B
Receptor tyrosine kinase - IGF-1, FGF, PDGF, EGF, Insulin. MAP kinase pathway. Get Found In the MAP. (Growth factors and insulin).
Nonreceptor tyrosine kinase - G-CSF, Erythropoietin, Thrombopoietin Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH. JAK/STAT
pathway. Think acidophils and cytokines. GET a JAKed PIG.
Hypertension treatment-
Primary (essential) hypertension (CATA) - Thiazide diuretics, ACE inhibitors, angiotensin II receptor blockers (ARBs), dihydropyridine Ca2+ channel
blockers.
Hypertension with heart failure (DABAA) - Diuretics, ACE inhibitors/ARBs, β-blockers (compensated HF), aldosterone antagonists. β- blockers must
be used cautiously in decompensated HF and are contraindicated in cardiogenic shock. In HF, ARBs may be combined with the neprilysin inhibitor
sacubitril.
Hypertension with diabetes mellitus (B-CATA) - ACE inhibitors/ARBs, Ca2+ channel blockers, thiazide diuretics, β-blockers. ACE inhibitors/ARBs
are protective against diabetic nephropathy. β- blockers can mask hypoglycemia symptoms.
Hypertension in asthma (C-CAT) - ARBs, Ca2+ channel blockers, thiazide diuretics, cardioselective β-blockers. Avoid nonselective β- blockers to
prevent β2-receptor–induced bronchoconstriction. Avoid ACE inhibitors to prevent confusion between drug or asthma-related cough.
Hypertension in pregnancy - Nifedipine, methyldopa, labetalol, hydralazine. New moms love hugs.
Live attenuated vaccines (TRAPS BY MIC) - Adenovirus (nonattenuated, given to military recruits), typhoid (Ty21a, oral), polio (Sabin), varicella
(chickenpox), smallpox, BCG, yellow fever, influenza (intranasal), MMR, rotavirus.
Killed or inactivated vaccine (H-TRIP) - Hepatitis A, Typhoid (Vi polysaccharide, intramuscular), Rabies, Influenza, Polio (SalK).
Subunit vaccine (NASHHH) - HBV (antigen = HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP), Neisseria meningitidis (various
strains), Streptococcus pneumoniae, Haemophilus influenzae type b.

Toxoid - Clostridium tetani, Corynebacterium diphtheriae. Psoriasis Rx -

Guselkumab (IL-23),
Ixekizumab (IL-17A),

secukinumab (IL-17A),
Ustekinumab (IL-12/23),
Adalimumab, infiximab (soluble TNF-α).
(gusail abdali infiltrates secular uzbekistan exactly)
Natalizumab, Vedolizumab - α4-integrin. (Natalia and Ved use A4 paper) Adalimumab, infiximab - Soluble TNF-α.
Etanercept - decoy TNF-α receptor.
Eculizumab - Complement protein C5.
Guselkumab - IL-23. (angry beckham)
Ixekizumab, secukinumab - IL-17A. (17 is exactly secular)
Ustekinumab - IL-12/IL-23. (ustaad can bind two)
Denosumab - RANKL.
Emicizumab - Factor IXa and X.
Omalizumab - IgE.
Palivizumab - RSV F protein.
IBD (via) - Adalimumab, infliximab, Vedolizumab.
Alemtuzumab - CD52 (Aalam house no 52)
Bevacizumab - VEGF (inhibits blood vessel formation) (bevas people eat veg) Cetuximab, panitumumab - EGFR (ram setu in pani to bring back eGFr)
Rituximab - CD20 (Ritu house no 20)
Trastuzumab - HER2 (“trust HER”)
(PNC) (Pembrolizumab, nivolumab, cemiplimab - PD-1)

(ADA Laila) (Atezolizumab, durvalumab, avelumab - PD-L1) (Ipilimumab - CTLA-4) (ipill kha aur cut le)
Alectinib - ALK (sounds similar)
(EGF) Erlotinib, Gefitinib, aFatinib - EGFR

(DIN) Imatinib, dasatinib, nilotinib - BCR-ABL (nice din in philadelphia) Ruxolitinib - JAK1/2 (Ruxar and jack got married)
Bortezomib, ixazomib, carfilzomib - Proteasome
(DEV) Vemurafenib, encorafenib, dabrafenib - BRAF (dev removes bra) MEK inhibitors (eg, trametinib) (trams make in india)

Palbociclib - Cyclin-dependent kinase 4/6

Olaparib - Poly(ADP-ribose) polymerase (dec DNA repair)
Na+ CHANNEL BLOCKERS - Carbamazepine Fosphenytoin Lamotrigine Phenytoin Topiramate Valproic acid
SV2A RECEPTOR BLOCKER - Levetiracetam
Ca2+ CHANNEL BLOCKERS - Ethosuximide Gabapentin
GABAA AGONISTS - Benzodiazepines Topiramate Phenobarbital
GABA REUPTAKE INHIBITOR - Tiagabine
GABA TRANSAMINASE INHIBITORS - Valproic acid Vigabatrin
DOPA DECARBOXYLASE INHIBITOR - Carbidopa
COMT INHIBITORS (peripheral) - Entacapone Tolcapone
COMT INHIBITOR (central) - Tolcapone
MAO TYPE B INHIBITORS - Selegiline Rasagiline
DOPAMINE AVAILABILITY - Amantadine
DOPAMINE AGONISTS - Pramipexole (non-ergot), Ropinirole (non-ergot), Bromocriptine (ergot)
(FF = GFR/RPF). RPF can be determined from RBF by multiplying the RBF by (1 – Hct).
RPI = (reticulocyte % × actual Hct)/normal Hct (≈ 45%)
ARPexposed = 100 × [(risk in exposed – risk in unexposed)/risk in exposed]
ARPexposed = 100 × [(RR – 1)/RR], where RR = risk in exposed/risk in unexposed
ARR = control rate – treatment rate
RRR = ARR / control rate
RR = treatment rate / control rate
NNT = 1 / ARR
Volume of distribution Vd = amount of drug in the body/plasma drug concentration
Half-life t1⁄2 = 0.7 × Vd/CL
Drug clearance CL = rate of elimination of drug/plasma drug concentration = Vd × Ke (elimination constant)
Loading dose LD = Cp × Vd/F
Maintenance dose D=Cp ×CL×τ/F
Therapeutic index TI = median toxic dose/median effective dose = TD50/ED50
Relative risk reduction RRR = 1 − RR
Cardiac output CO = rate of O2 consumption/(arterial O2 content − venous O2 content)
CO = stroke volume × heart rate
Reticulocyte production index RPI = reticulocyte % × actual Hct/normal Hct (≈ 45%)
Renal clearance Cx = (UxV)/Px
Glomerular filtration rate Cinulin = GFR = Uinulin × V/Pinulin = Kf [(PGC – PBS) – (πGC – πBS)]
Effective renal plasma flow eRPF = Upah × V/Ppah = Cpah
Renal blood flow RBF = RPF/1 − Hct
Filtration fraction FF = GFR / RPF
Winters formula Pco2 = 1.5 [HCO3–] + 8 ± 2
Anion gap = Na+ − (Cl– + HCO3–). Normal AG = 6-12 mmHg
Physiologic dead space VD = VT × (PaCO2 - PECO2)/PaCO2
Pulmonary vascular resistance PVR = (Ppulm artery – PL atrium) / cardiac output
Alveolar gas equation Pao2 = Pio2 – Paco2/R (R only divides paco2 and not both)
Henderson-Hasselbalch equation (for extracellular pH) pH = 6.1 + log[HCO3−] / 0.03 Pco2
(FF = GFR/RPF). RPF can be determined from RBF by multiplying the RBF by (1 – Hct).
Alveoli —> Collapsing pressure (P) = 2 (surface tension)/radius
Insulin preparations - SE - Hypoglycemia, lipodystrophy, hypersensitivity reactions (rare), weight gain.
Biguanides - Metformin - SE - GI upset, lactic acidosis (use with caution in renal insufficiency), vitamin B12 deficiency. Weight loss (often desired).
TZDs - “-glits” Pioglitazone, rosiglitazone - SE - Weight gain, edema, HF, inc risk of fractures. Delayed onset of action (several weeks). Rosiglitazone:
inc risk of MI, cardiovascular death.

Sulfonylureas (1st gen) - Chlorpropamide, tolbutamide. Sulfonylureas (2nd gen) - Glipizide, glyburide. Meglitinides “-glins” Nateglinide, repaglinide -
SE - Hypoglycemia (inc risk in renal insufficiency), weight gain. Disulfiram-like reaction with first-generation sulfonylureas only (rarely used).
GLP-1 analogs - Exenatide, liraglutide. DPP-4 inhibitors “-glips” Linagliptin, saxagliptin, sitagliptin - SE GLP-1 analogs - Pancreatitis, weight loss, Inc
satiety. SE DPP-4 inh - Respiratory and urinary infections, weight neutral, Inc satiety. (DPP-4 inhibitors - Inhibit DPP-4 enzyme that deactivates GLP-
1.)
SGLT-2 inh - Sodium-glucose co-transporter 2 inhibitors “-glifs” Canagliflozin, dapagliflozin, empagliflozin - SE - Glucosuria (UTIs, vulvovaginal
candidiasis), dehydration (orthostatic hypotension), weight loss. Use with caution in renal insufficiency (dec efficacy with dec GFR).
-glucosidase inhibitors - Acarbose, miglitol - SE - GI upset, bloating. Not recommended in renal insufficiency.
Amylin analogs - Pramlintide - SE - Hypoglycemia. Inc satiety (often desired).
Weight loss (GBS) - Biguanides, GLP-1 analogs, SGLT 2 inhibitors. Weight neutral - DPP-4 inhibitors. Weight gain (MST) - TZDs, sulfonylureas,
meglitinides.
Thionamides - Propylthiouracil, methimazole - ADVERSE EFFECTS Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. PTU use has
been associated with ANCA-positive vasculitis. Methimazole is a possible teratogen (can cause aplasia cutis).
Levothyroxine, liothyronine - ADVERSE EFFECTS Tachycardia, heat intolerance, tremors, arrhythmias.

Erb palsy (“waiter’s tip”) - upper trunk

Klumpke palsy (claw hand / total claw hand) - lower trunk
Wrist drop - posterior cord, radial nerve
Winged scapula - SALT
Deltoid paralysis - axillary nerve
“Saturday night palsy” (wrist drop) - radial nerve, posterior cord
Difficulty flexing elbow, variable C8 sensory loss - musculocutaneous N
Decreased thumb function “hand of benediction” - median nerve
Intrinsic muscles of hand, claw hand (ulnar claw) - ulnar nerve
For both ulnar and median nerve -
loss of flexors with proximal lesion;
loss of extensors with distal lesion.
(ED-PF)
(check distal lesion with extension.
check proximal lesion with flexion.)
Thenar muscles (OAF) - opposition, abduction and flexion of thumb.
Erb palsy (“waiter’s tip”)- DIBs
Iliohypogastric (T12-L1) - IT
Genitofemoral nerve (L1-L2) - cremaster
Lateral femoral cutaneous (L2-L3)
Obturator (L2-L4) - AAA-GOP
Femoral (L2-L4) - SQIP
Sciatic (L4-S3) - BASS
Common (fibular) peroneal (L4-S2) - PPT
(superficial peroneal - PP; deep peroneal - T)
Tibial (L4-S3) - TB-PPF
Superior gluteal (L4-S1) - GGT
Inferior gluteal (L5-S2) - G maximus
Pudendal (S2-S4) - ext sphincters of urethra and anus
Abductors Gluteus medius, gluteus minimus
Adductors Adductor magnus, adductor longus, adductor brevis
Extensors (SSG) Gluteus maximus, semitendinosus, semimembranosus (SSG commandos will extend their support)
Flexors (TRIPS) Iliopsoas, rectus femoris, tensor fascia lata, pectineus, sartorius
Internal rotation (GGT) Gluteus medius, gluteus minimus, tensor fascia latae
External rotation (GOPI) Iliopsoas, gluteus maximus, piriformis, obturator
Osgood-schlatter ds - avulsion of secondary ossification centre of proximal tibial tubercle.
Legg-calve-perthes ds - Idiopathic avascular necrosis of femoral head.
SCFE - Displaced epiphysis relative to femur neck due to axial force on femoral head.
Developmental dysplasia of the hip - Abnormal acetabulum; ortolani and barlow maneuver.
Nursemaid’s elbow - radial head subluxation.
Medial tibial stress syndrome - shin splints.
Iliotibial band syndrome - lateral femoral epicondyle.
De Quervain tenosynovitis - AbPL and EPB tendons; + Finkelstein test - tender radial styloid with stretch of thumb tendons. Unhappy triad (MMA) -
Consists of damage to the ACL, MCL, and medial meniscus (attached to MCL)
Schiller duval bodies - yolk sac tumor
Call-exnar bodies - granulosa cell tumor
Homer-wright rosettes - medulloblastoma, neuroblastoma
Perivascular pseudorosettes - ependymoma
Owl eye inclusions - CMV
Koilocytosis - HPV
Mallory bodies - alcoholic hepatitis
Cowdry A bodies - HSV, VZV, CMV
Clue cells - bacterial vaginosis
Coffee bean sign - volvulus
Target sign on imaging - intussusception
Ewings - onion skin
Giant cell tumor - soap-bubble appearance
Fried egg - dysgerminoma, oligodendroglioma
Lewy bodies(a-synnuclein) - parkinson, LB dementia
Pick bodies - FTD, alzheimers ds
Pseudopalisading - GBM
hurthle cell - hashimotos
Hirano bodies - alzheimers ds
neuroendocrine Kulchitsky cells small cell cancer
orphan annie eye nucleus - papillary thyroid carcinoma
pseudo pelger huet anomaly - neutrophils bilobed nuclei - MDS, CML

Measles - Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia. Yellow fever virus - Councilman bodies
(eosinophilic apoptotic globules) on liver biopsy.
Tay sachs - lysosomes with onion skin
Krabbe ds - globoid cells.

Gaucher ds - Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper). Niemann-Pick disease - foam cells (lipid-laden macrophages)
Hyponatremia - Legionella infection, MDMA use, Cirrhosis.
CO poisoning - bilateral globus pallidus lesions

congenital zika syndrome- ventriculomegaly, subcortical calcifications Kaposi - lymphocytic infiltrate; Bacillary angiomatosis - neutrophilic mucus
plugging, curshman spirals, charcot leyden crystals ASTHMA Myelofibrosis (megakaryocyte proliferation) - tear drop RBCs

parietal cells acidophilic, chief cells basophilic

PAS +ve globules - whippple ds, a1-antitrypsin deficiency
PCP - silver stain
periventricular calcifications - CMV
periventricular plaques - MS
pilocytic astrocytoma - rosenthal fibres
PID - purulent cervical discharge and perihepatitis (fitz hugh curtis syndrome)
vancomycin,echinocandins,opioids flushing - histamine; niacin flushing - prostaglandins
sail shaped - thymus
BL schwannoma at CP angle - NF-2
Burning feet syndrome - vit B5 def
Male child, recurrent infections, no mature B cells Bruton disease (X-linked agammaglobulinemia)
Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of femoral head, bone crises - Gaucher disease (glucocerebrosidase [β-
glucosidase] def
Genital ulcers - Nonpainful, indurated: chancre (1° syphilis, Treponema pallidum);
Painful, with exudate: chancroid (Haemophilus ducreyi)
Pupil accommodates but doesn’t react to light Neurosyphilis (Argyll Robertson pupil)
Smooth, moist, painless, wart-like white lesions on genitals Condylomata lata (2° syphilis)
primary syphilis - chancre
sec syphilis - condylomata lata
neurosyphilis - argyll robertson pupil
HPV - condylomata accuminata
Chorioretinitis, hydrocephalus, intracranial calcifications Congenital toxoplasmosis
Pruritus, serpiginous rash after walking barefoot Hookworm (Ancylostoma spp, Necator americanus)
Child with fever later develops red rash on face that spreads to body Erythema infectiosum/fifth disease (“slapped cheeks” appearance, caused by
parvovirus B19)
Chest pain with ST depressions on ECG - Angina (⊖ troponins) or NSTEMI (⊕ troponins)
Retinal hemorrhages with pale centers Roth spots (bacterial endocarditis)
adrenal insufficiency - chronic - addison; acute - adrenal crisis.
(C-STAT) Short stature, café-au-lait spots, thumb/radial defects, Inc incidence of tumors/leukemia, aplastic anemia - Fanconi anemia Fanconi anemia -
(genetic loss of DNA crosslink repair; often progresses to AML).
Skin hyperpigmentation, orthostatic hypotension, fatigue, weakness, muscle aches, weight loss, GI disturbances - Chronic 1° adrenal insufficiency
(Addison disease), inc ACTH, inc α-MSH Shock, altered mental status, vomiting, abdominal pain, weakness, fatigue - Acute adrenal insufficiency
(adrenal crisis)
Bluish line on gingiva Burton line (lead poisoning)
Painful blue fingers/toes, hemolytic anemia Cold agglutinin disease (autoimmune hemolytic anemia caused by Mycoplasma pneumoniae, infectious
mononucleosis, CLL)
Brachial plexus divisions - RTDCB.
Paget ds of bone - osteitis deformans.
Raynaud phenomenon - w-b-r
Skin patches/plaques, Pautrier microabscesses, atypical T cells Mycosis fungoides (cutaneous T-cell lymphoma) or Sézary syndrome (mycosis
fungoides + malignant T cells in blood)
Bone pain, bone enlargement, arthritis Osteitis deformans (Paget disease of bone, inc osteoblastic and osteoclastic activity)
shuffling gait - parkinsons
gait apraxia - NPH
staggering gait - friedreich ataxia
Common peroneal nerve - foot drop - steppage gait
Parkinsons - shuffling/festinant gait
Duchenne’s muscular dystrophy - waddling gait
SACD - B12 def - wide based gait
Cerebellar lesion - wide based gait
Resting tremor, athetosis, chorea Basal ganglia lesion
Bulbar palsy - weakness of CN 9, 10, 11, 12.
Nephrotic syndrome - hypercholestrolemia
Episodic vertigo, tinnitus, sensorineural hearing loss Ménière disease
Conjugate horizontal gaze palsy, horizontal diplopia Internuclear ophthalmoplegia (damage to MLF; may be unilateral or bilateral)
INO - failue to adduct ipsilateral eye, nystagmus in opposite
Polyuria, renal tubular acidosis type II, growth retardation, electrolyte imbalances, hypophosphatemic rickets Fanconi syndrome (multiple combined
dysfunction of the proximal convoluted tubule) Hereditary nephritis, sensorineural hearing loss, retinopathy, lens dislocation Alport syndrome
(mutation in type IV collagen)
Wilms tumor, macroglossia, organomegaly, hemihyperplasia, omphalocele Beckwith-Wiedemann syndrome (WT2 mutation) (everything is getting
larger)
RTA 1 - distal
RTA 2 - proximal
RTA 4 - hyperkalemic
Hypoxemia, polycythemia, hypercapnia Chronic bronchitis (hypertrophy and hyperplasia of mucous cells, “blue bloater”)
Pink complexion, dyspnea, hyperventilation Emphysema (“pink puffer,” centriacinar [smoking] or panacinar [α1-antitrypsin deficiency])
Thumb sign - epiglotitis
Steeple sign - croup/parainfluenza/acute laryngotracheobronchitis
dec AFP in amniotic fluid/maternal serum - Down syndrome, Edwards syndrome
Dilated cardiomyopathy with apical atrophy Chagas disease (Trypanosoma cruzi)
Takotsubo cardiomyopathy: broken heart syndrome—ventricular apical ballooning likely due to increased sympathetic stimulation.
Eosinophilic intranuclear inclusions with perinuclear halo (cowdry bodies) Cells infected by herpesviruses (eg, HSV, VZV, CMV)
Eosinophilic inclusion bodies in cytoplasm of hippocampal and cerebellar neurons Negri bodies of rabies
Psammoma bodies - Meningiomas, papillary thyroid carcinoma, mesothelioma, papillary serous carcinoma of the endometrium and ovary
Apple-core lesion - left sided CRC
ITP - anti Gp2b/3a abs
lens dislocation - upward and temporal - marfan
downward - homocystinuria
Aortic stenosis - pulsus parvus et tardus (low amplitude pulse with delayed peak)
Cardiac tamponade - electrical alternans
Enlarged thyroid cells with ground-glass nuclei with central clearing “Orphan Annie” eyes nuclei (papillary carcinoma of the thyroid)
“Apple core” lesion on barium enema x-ray Colorectal cancer (usually left-sided)
Eosinophilic cytoplasmic inclusion in liver cell Mallory body (alcoholic liver disease)
Basophilic nuclear remnants in RBCs Howell-Jolly bodies (due to splenectomy or nonfunctional spleen)
Basophilic stippling of RBCs Lead poisoning or sideroblastic anemia
PSC - MPO ANCA/p-ANCA; PBC - AMAs
Lewy bodies - eosinophilic alpha synnuclein cytoplasmic inclusions - parkinsons and LBD
Raised periosteum (creating a “Codman triangle”) Aggressive bone lesion (eg, osteosarcoma, Ewing sarcoma)
Anti-IgG antibodies (rheumatoid factor) Rheumatoid arthritis (systemic inflammation, joint pannus, boutonniere and swan neck deformities)
loop and thiazide diuretics - inc uric acid levels
inc AFP in amniotic fluid/maternal serum - Dating error, anencephaly, spina bifida (open neural tube defects)
Extracellular amyloid deposition in gray matter of brain Senile plaques (Alzheimer disease)
Protein aggregates in neurons from hyperphosphorylation of tau protein Neurofibrillary tangles (Alzheimer disease) and Pick bodies (Pick disease)
Silver-staining spherical aggregation of tau proteins in neurons Pick bodies (frontotemporal dementia: progressive dementia, changes in personality)
Hyperphosphorylated tau- 1. neurofibrillary tangles - alzheimer ds 2. pick bodies - pick ds (fronto-temporal dementia).
Chronic pyelonephritis - thyroid like appearance of kidney.
“Waxy” casts with very low urine flow Chronic end-stage renal disease
“Wire loop” glomerular capillary appearance on light microscopy Diffuse proliferative glomerulonephritis (usually seen with lupus)
Dysplastic squamous cervical cells with “raisinoid” nuclei and hyperchromasia Koilocytes (HPV: predisposes to cervical cancer)
Sheets of uniform “fried egg” cells, inc hCG, inc LDH - Dysgerminoma

Speed of conduction (PAVA): His-Purkinje > Atria > Ventricles > AV node.
Pulsus paradoxus - Seen in constrictive pericarditis, obstructive pulmonary disease (eg, Croup, OSA, Asthma, COPD), cardiac Tamponade (pea
COAT).
Hypertension in pregnancy - Nifedipine, methyldopa, labetalol, hydralazine. New moms love hugs.
Hypertensive emergency - Treat with (CNN-FL) labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside.
Pacemaker rates: SA > AV > bundle of His/ Purkinje/ventricles.
Atherosclerosis (ACPCC) - Abdominal aorta > coronary artery > popliteal artery > carotid artery > circle of Willis.
Interferons Rx CLINICAL USE (HK-CCC-MMR) - Chronic HBV, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma,
malignant melanoma, multiple sclerosis, chronic granulomatous disease.
Acanthocytes (“spur cells”) - (ALE) Liver disease, abetalipoproteinemia, vitamin E defciency.
Echinocytes (“burr cells”) - (EPL) Liver disease, ESRD, pyruvate kinase defciency.
Target cells (HALT) - HbC disease, Asplenia, Liver disease, Thalassemia.
Aluminum hydroxide (Antacid) - Constipation, Hypophosphatemia, Osteodystrophy, Proximal muscle weakness, Seizures (CHOPS)
Nonmegaloblastic macrocytic (CLD)- •Diamond-Blackfan anemia, •Liver disease, •Chronic alcohol overuse.
Antimetabolites (5-MTP-HCC) - Cladribine(Cell cycle nonspecific) Cytarabine 5-fluorouracil Hydroxyurea Methotrexate Pentostatin Thiopurines - S
phase
Cell cycle–independent drugs - (NP-NP-ABD) - Platinum compounds, Alkylating agents: Anthracyclines Busulfan Dactinomycin Nitrogen mustards
Nitrosoureas Procarbazine
Reactive arthritis - (YES-SCC) - Shigella, Campylobacter, E coli, Salmonella, Chlamydia, Yersinia.
Giemsa - RCT-BPH - Chlamydia, Rickettsia, Trypanosomes, Borrelia, Helicobacter pylori, Plasmodium
dont gram stain well - MALT-CRUMBLE - Treponema, Leptospira Mycobacteria Mycoplasma, Ureaplasma Legionella, Rickettsia, Chlamydia,
Bartonella, Anaplasma, Ehrlichia
Encapsulated bacteria - Please SHiNE my SKiS
Aerobes - Nocardia, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Bordetella pertussis
Anaerobes - Clostridium, Bacteroides, Fusobacterium, and Actinomyces israelii.
Facultative anaerobes - Streptococci, staphylococci, and enteric gram ⊖ bacteria.
Obligate intracellular - RCC - Rickettsia, Chlamydia, Coxiella
Thayer-Martin agar - CNTV - Selectively favors growth of Neisseria by inhibiting growth of gram organisms with vancomycin, gram organisms except
Neisseria with trimethoprim and colistin, and fungi with nystatin
Catalase-positive organisms - BB CHESS PLAN - Nocardia, Staphylococci, Serratia, Candida, Listeria, E coli, Burkholderia cepacia, Pseudomonas,
Aspergillus, Helicobacter pylori, Bordetella pertussis.
LYSOGENIC PHAGE - (ABCD’S): Group A strep erythrogenic toxin, Botulinum toxin, Cholera toxin, Diphtheria toxin, Shiga toxin.
Bacteria that inc cAMP (CAPE) include Cholera, Anthracis, Pertussis, Ecoli.
Urease ⊕ Pee CHUNKSS. Proteus, Cryptococcus, H pylori, Ureaplasma, Nocardia, Klebsiella, S epidermidis, S saprophyticus.
Heat-stable toxins - staphylococcal enterotoxin and E coli heatstable toxin.
H. influenzae type b - Epiglottitis (“thumb sign” on lateral neck x-ray)
Croup - parainfluenza; “seal-like” barking cough and inspiratory stridor. Steeple sign on x-ray.
Bordetella pertusis - inspiratory “whoop” (“whooping cough”), posttussive vomiting.
In order of decreasing severity (less toxin produced) - DFBS : S dysenteriae, S fexneri, S boydii, S sonnei
Secondary syphilis - condylomata lata
HPV - condylomata accuminata
Multiple sclerosis, GCA - Marcus-Gunn pupil (RAPD)
Tertiary syphilis - Argyll-Robertson pupil
Syphilis - Argyll Robertson pupil (constricts with accommodation but is not reactive to light).
Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin).
Cestode/tapeworm Rx - (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole).
All are linear except papilloma-, polyoma-, and hepadnaviruses (circular). - PPH
⊕ stranded RNA viruses: (retrovirus) (togavirus) (flavivirus) (coronavirus) (hepevirus) (calicivirus) (picornavirus) - RCT-FHPC
Naked (nonenveloped) viruses include - DNA viruses - papillomavirus, adenovirus, parvovirus, polyomavirus (PAPP); RNA viruses - calicivirus,
picornavirus, reovirus, and hepevirus. (happy rhio khalici naked pic)
Enveloped DNA viruses - (herpesvirus, hepadnavirus, poxvirus) - HHP
CIRCULAR RNA - ARENAVIRUS, BUNYAVIRUS, DELTA VIRUS. - ABD
SEGMENTED VIRUSES - Bunyaviruses (3 segments), Orthomyxoviruses (infuenza viruses) (8 segments), Arenaviruses (2 segments), and Reoviruses
(10-12 segments). BORA
Reovirus - RC Coltivirus —Colorado tick fever. Rotavirus—cause of fatal diarrhea in children.
Picornavirus (PERCH) - Poliovirus—polio-Salk/Sabin vaccines—IPV/OPV. Echovirus—aseptic meningitis. Rhinovirus —“common cold”.
Coxsackievirus—aseptic meningitis; herpangina (mouth blisters, fever); hand, foot, and mouth disease; myocarditis; pericarditis. HAV—acute viral
hepatitis.
Flaviviruses - HYD-SWZ (flavors of hyd and swz) - HCV; Yellow fever; Dengue; St. Louis encephalitis; West Nile virus —meningoencephalitis,
flaccid paralysis; Zika virus.
Togaviruses - Toga CREW—Chikungunya virus (co-infection with dengue virus can occur), Rubella, Eastern and Western equine encephalitis.
Retroviruses - HTLV—T-cell leukemia; HIV—AIDS.
Coronaviruses - “Common cold,” SARS, MERS, COVID-19.
Orthomyxoviruses - Influenza virus
Paramyxoviruses - PaRaMyxovirus: Parainfluenza—croup, RSV—bronchiolitis in babies, Measles, Mumps.
Rhabdoviruses - Rabies.
Filoviruses - Ebola/Marburg hemorrhagic fever—often fatal.
Arenaviruses - LL - LCMV—lymphocytic choriomeningitis virus; Lassa fever encephalitis— spread by rodents.
Bunyaviruses - HSCC (HSBCc) - California encephalitis, Sandfly/Rift Valley fevers, Crimean-Congo hemorrhagic fever, Hantavirus—hemorrhagic
fever, pneumonia.
Delta virus - HDV

Measles - Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia. CD4+ cell count <
500/mm3 - ECHH
CD4+ cell count < 200/mm3 - JPHH
CD4+ cell count < 100/mm3 - CBCT-MECCA

EBV - CNS lymphoma—ring enhancing, may be solitary (vs Toxoplasma). Toxoplasma gondii - Brain abscesses - Multiple ring-enhancing lesions on
MRI.

Measles and rubella - rash beginning at head and moving down; Chickenpox - rash begins on trunk; spreads to face and extremities. RMSF - centripetal
rash
Typhus - centrifugal rash

vaginal pH - >4.5 - trichomonas vaginalis and gardnerella vaginalis; <4.5 - candida. AD - FAN-FAN-HHH-MMM-LTV
AR - COPS-GF-WASH-KTM
XLR - BLOW-DOG-HHF

Mammary gland (“blue domed”) cyst Fibrocystic change of the breast

Bronchial asthma - charcot-leyden crystals, curschmann spirals
Rectangular, crystal-like, cytoplasmic inclusions in Leydig cells - Reinke crystals (Leydig cell tumor)
KEY ASSOCIATIONS
Bacterial meningitis (> 6 months old) S pneumoniae
Bacterial meningitis (newborns and kids) Group B streptococcus/E coli/Listeria monocytogenes (newborns)
Helminth infection (US) Enterobius vermicularis
Osteomyelitis S aureus (most common overall) 180
Osteomyelitis in sickle cell disease Salmonella 180
Osteomyelitis with IV drug use S aureus, Pseudomonas, Candida
Vitamin deficiency (USA) Folate (pregnant women are at high risk; body stores only 3- to 4-month supply; prevents neural tube defects)
Sexually transmitted disease C trachomatis (usually coinfected with N gonorrhoeae)
Nosocomial pneumonia S aureus, Pseudomonas, Klebsiella, Acinetobacter
Metastases to bone Prostate, breast > kidney, thyroid, lung (painful bones kill the lungs)
Metastases to brain Lung > breast > melanoma, colon, kidney (lots of brain mets can kill)
Metastases to liver Colon >> stomach > pancreas>lungs (cancer sometimes penetrates liver)
Constrictive pericarditis - TB (developing world); idiopathic, viral illness (developed world)
Ejection click Aortic stenosis 300
Mid-systolic click - MVP
Opening snap Mitral stenosis 300
Heart murmur, congenital Mitral valve prolapse 300
Chronic arrhythmia Atrial fibrillation (associated with high risk of emboli)
Congenital cardiac anomaly VSD
Aortic aneurysm, thoracic Marfan syndrome (idiopathic cystic medial degeneration) 310
Aortic aneurysm, abdominal Atherosclerosis, smoking is major risk factor 310
Aortic aneurysm, ascending or arch 3° syphilis (syphilitic aortitis), vasa vasorum destruction
Sites of atherosclerosis (ACPCC) - Abdominal aorta > coronary artery > popliteal artery > carotid artery > COW
Heart valve in bacterial endocarditis - Mitral > aortic (rheumatic fever), tricuspid (IV drug abuse)
Endocarditis presentation associated with bacterium S aureus (acute, IVDA, tricuspid valve), viridans streptococci (subacute, dental procedure), S
bovis (colon cancer), culture negative (Coxiella, Bartonella, HACEK)
Cardiac 1° tumor (kids) Rhabdomyoma, often seen in tuberous sclerosis 324
Cardiac tumor (adults) Metastasis, myxoma (90% in left atrium; “ball valve”)
Congenital adrenal hyperplasia, hypotension 21-hydroxylase deficiency
Hypopituitarism Pituitary adenoma (usually benign tumor)
Congenital hypothyroidism (cretinism) Thyroid dysgenesis/dyshormonogenesis, iodine deficiency
Thyroid cancer Papillary carcinoma (childhood irradiation) 351
Hypoparathyroidism Accidental excision during thyroidectomy
Tumor of the adrenal medulla (kids) Neuroblastoma (malignant) 358
Tumor of the adrenal medulla (adults) Pheochromocytoma (usually benign)
Esophageal cancer Squamous cell carcinoma (worldwide); adenocarcinoma (US)
Chronic atrophic gastritis (autoimmune) Predisposition to gastric carcinoma (can also cause pernicious anemia)
Congenital conjugated hyperbilirubinemia (black liver) Dubin-Johnson syndrome (inability of hepatocytes to secrete conjugated bilirubin into bile)
Hereditary harmless jaundice Gilbert syndrome (benign congenital unconjugated hyperbilirubinemia)
Pancreatitis (acute) Gallstones, alcohol 407
Pancreatitis (chronic) Alcohol (adults), cystic fibrosis (kids)
Autosplenectomy (fibrosis and shrinkage) Sickle cell disease (hemoglobin S)
Hereditary bleeding disorder von Willebrand disease 437
Hereditary thrombophilia Factor V Leiden
Malignancy associated with noninfectious fever Hodgkin lymphoma
Type of Hodgkin lymphoma Nodular sclerosis
Type of non-Hodgkin lymphoma Diffuse large B-cell lymphoma
1° bone tumor (adults) Multiple myeloma
Age ranges for patient with ALL/CLL/AML/CML ALL: child, CLL: adult > 60, AML: adult ∼ 65, CML: 442 adult 45–85
Malignancy (kids) Leukemia, brain tumors
Death in CML Blast crisis
Death in SLE Lupus nephropathy
Tumor of infancy Strawberry hemangioma (grows rapidly and regresses spontaneously by childhood)
Herald patch Pityriasis rosea
Atrophy of the mammillary bodies Wernicke encephalopathy (thiamine deficiency causing ataxia, ophthalmoplegia, and confusion)
Demyelinating disease in young women Multiple sclerosis
Dementia Alzheimer disease, multiple infarcts (vascular dementia)
Brain tumor (adults) Supratentorial: metastasis, astrocytoma (including glioblastoma multiforme), meningioma, schwannoma
Pituitary tumor Prolactinoma, somatotropic adenoma 545
Brain tumor (children) Infratentorial: medulloblastoma (cerebellum) or 546 supratentorial: craniopharyngioma
Glomerulonephritis (adults) Berger disease (IgA nephropathy) 620
Nephrotic syndrome (adults) Membranous nephropathy 621
Nephrotic syndrome (children) Minimal change disease
Neuron migration failure Kallmann syndrome (hypogonadotropic hypogonadism and anosmia)
Ovarian tumor (benign, bilateral) Serous cystadenoma

Ovarian tumor (malignant) Serous carcinoma

Tumor in women Leiomyoma (estrogen dependent, not precancerous)
Gynecologic malignancy Endometrial carcinoma (most common in US); cervical carcinoma (most common worldwide)
Breast mass Fibrocystic change, carcinoma (in postmenopausal women)
Breast tumor (benign, young woman) Fibroadenoma
Breast cancer Invasive ductal carcinoma
Testicular tumor Seminoma (malignant, radiosensitive), inc placental ALP
Obstruction of male urinary tract BPH
SIADH Small cell carcinoma of the lung
Cyclosporine - Toxicity - Nephrotoxicity, neurotoxicity, hypertension, hyperlipidemia, gingival hyperplasia, hirsutism. Both calcineurin inhibitors are
highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Tacrolimus (FK506) - Toxicity - Similar to cyclosporine, inc risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism. Both calcineurin
inhibitors are highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Sirolimus (Rapamycin) - Toxicity - “Pansirtopenia” (pancytopenia), insulin resistance, hyperlipidemia; not nephrotoxic.
Basiliximab - Toxicity - Edema, hypertension, tremor.
Azathioprine - TOXICITY - Pancytopenia, pancreatitis. 6-MP degraded by xanthine oxidase; toxicity inc by allopurinol. Pronounce “azathiopurine”
Mycophenolate Mofetil - TOXICITY - GI upset, pancytopenia, hypertension, hyperglycemia. Less nephrotoxic and neurotoxic. Associated with
invasive CMV infection.
Glucocorticoids - TOXICITY - Cushing syndrome, osteoporosis, hyperglycemia, diabetes, amenorrhea, adrenocortical atrophy, peptic ulcers,
psychosis, cataracts, avascular necrosis (femoral head). Rubella rash - starts on face and spreads centrifugally to involve trunk and extremities.
Measles - maculopapular rash that starts at the head/neck and spreads downward.
Roseola - diffuse macular rash (starts on trunk then spreads to extremities).
Chickenpox - Vesicular rash begins on trunk; spreads to face and extremities with lesions of different stages.
RMSF - centripetal rash
Typhus - centrifugal rash

Antimicrobial therapy -
FOLIC ACID SYNTHESIS AND REDUCTION (DNA methylation) - Sulfonamides - Sulfamethoxazole Sulfisoxazole Sulfadiazine, Trimethoprim
MEMBRANE INTEGRITY - Daptomycin (gram ⊕) Polymyxins (gram ⊖)
Cell wall synthesis -
PEPTIDOGLYCAN SYNTHESIS - Glycopeptides - Vancomycin Bacitracin
PEPTIDOGLYCAN CROSS-LINKING - Penicillinase-sensitive penicillins - Penicillin G, V Ampicillin Amoxicillin Penicillinase-resistant penicillins
- Oxacillin Nafcillin Dicloxacillin
Antipseudomonal - Ticarcillin Piperacillin
Cephalosporins (I-V) - 1st—Cefazolin, etc 2nd—Cefoxitin, etc 3rd—Ceftriaxone, etc 4th—Cefepime 5th—Ceftaroline
Carbapenems - Imipenem Meropenem Ertapenem Doripenem
Monobactams - Aztreonam
PROTEIN SYNTHESIS - 50S SUBUNIT - Chloramphenicol Clindamycin Linezolid Macrolides (- Azithromycin Clarithromycin Erythromycin)
Streptogramins (-Quinupristin Dalfopristin)
30S SUBUNIT - Aminoglycosides (-Gentamicin Neomycin Amikacin Tobramycin Streptomycin) Tetracyclines (-Tetracycline Doxycycline
Minocycline) Glycylcycline (Tigecycline)
DNA INTEGRITY (via free radicals) - Metronidazole
mRNA SYNTHESIS (RNA polymerase) - Rifampin
Gyrase - Fluoroquinolones (Ciprofloxacin Levofloxacin, etc) Quinolone (Nalidixic acid)
Protein synthesis inhibitors - Aminoglycosides (30S), Linezolid (50S)
Tetracyclines (30S) - A-site tRNA binding Chloramphenicol (50S) - Peptidyl transferase Macrolides and clindamycin (50S) - Translocation
Sulfonamides, dapsone - inhibit Dihydropteroate synthase
Trimethoprim, pyrimethamine - inhibit Dihydrofolate reductase
Antimycobacterial therapy-
MYCOLIC ACID SYNTHESIS - Isoniazid
ARABINOGALACTAN SYNTHESIS (arabinosyl transferase) - Ethambutol
mRNA SYNTHESIS (DNA-dependent RNA polymerase) - Rifabutin Rifampin
INTRACELLULAR (unclear mechanism) - Pyrazinamide
Antifungal therapy-
LANOSTEROL SYNTHESIS - Terbinafine
ERGOSTEROL SYNTHESIS - Azoles - Clotrimazole Fluconazole Isavuconazole Itraconazole Ketoconazole Miconazole Voriconazole

CELL WALL SYNTHESIS - Echinocandins - Anidulafungin Caspofungin Micafungin CELL MEMBRANE INTEGRITY - Polyenes -Amphotericin B,
Nystatin
NUCLEIC ACID SYNTHESIS - Flucytosine
HIV antiviral therapy-

ENTRY - PENETRATION - Enfuvirtide; ATTACHMENT - Maraviroc

INTEGRASE - Dolutegravir Elvitegravir Raltegravir Bictegravir
PROTEASE - Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Ritonavir Saquinavir
REVERSE TRANSCRIPTASE - NRTIs - Abacavir (ABC) Emtricitabine (FTC) Lamivudine (3TC) Tenofovir (TDF) Zidovudine (ZDV, formerly
AZT); NNRTIs - Delavirdine Efavirenz Nevirapine
OTHER ANTIVIRALS-
NUCLEIC ACID SYNTHESIS -
Guanosine analogs - Acyclovir, etc (HSV, VZV), Ganciclovir (CMV)
Viral DNA polymerase inhibitors - Cidofovir Foscarnet - (HSV(acyclovir resistant) and CMV)
Guanine nucleotide synthesis - Ribavirin (RSV, HCV)
Adenosine analog - Remdesivir (SARS-CoV-2)
Endonuclease inhibitor - Baloxavir (influenza virus)
RELEASE OF PROGENY VIRUS-
Neuraminidase inhibitors - Oseltamivir Zanamivir - Influenza A, B.

REPRODUCTIVE PHARMACOLOGY
Gonadotropin-releasing hormone analogs - ADVERSE EFFECTS Hypogonadism, dec libido, erectile dysfunction, nausea, vomiting.
Degarelix MECHANISM GnRH antagonist. ADVERSE EFFECTS Hot fashes, liver toxicity.
Estrogens - Ethinyl estradiol, DES, mestranol. ADVERSE EFFECTS inc risk of endometrial cancer (when given without progesterone), bleeding in
postmenopausal patients, clear cell adenocarcinoma of vagina in females exposed to DES in utero, inc risk of thrombi. Contraindications—ER ⊕ breast
cancer, history of DVTs, tobacco use in females > 35 years old.
Selective estrogen receptor modulators-
Clomiphene - May cause hot fashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.
Tamoxifen - Hot fashes, inc risk of thromboembolic events (especially with tobacco smoking), and endometrial cancer. Used to treat and prevent
recurrence of ER/PR breast cancer and to prevent gynecomastia in patients undergoing prostate cancer therapy.
Raloxifene - hot fashes, inc risk of thromboembolic events (especially with tobacco smoking), but no increased risk of endometrial cancer (vs
tamoxifen, so you can “relax”); used primarily to treat osteoporosis.

Hormone replacement therapy - Unopposed estrogen replacement therapy inc risk of endometrial cancer, progesterone/progestin is added. Possible
increased cardiovascular risk.
Combined contraception - Adverse effects: breakthrough menstrual bleeding, breast tenderness, VTE, hepatic adenomas. Contraindications: people >
35 years old who smoke tobacco (inc risk of cardiovascular events), patients with inc risk of cardiovascular disease (including history of venous
thromboembolism, coronary artery disease, stroke), migraine (especially with aura), breast cancer, liver disease.
Copper intrauterine device ADVERSE EFFECTS Heavier or longer menses, dysmenorrhea. Insertion contraindicated in active PID (IUD may impede
PID resolution).
Danazol - ADVERSE EFFECTS Weight gain, edema, acne, hirsutism, masculinization, dec HDL levels, hepatotoxicity, idiopathic intracranial
hypertension.
Testosterone, methyltestosterone - ADVERSE EFFECTS Masculinization in females; dec intratesticular testosterone in males by inhibiting release of
LH (via negative feedback) > gonadal atrophy. Premature closure of epiphyseal plates. inc LDL, dec HDL.
Antiandrogens-
Abiraterone - 17 -hydroxylase/17,20-lyase inhibitor (dec steroid synthesis) - Prostate cancer. ADVERSE EFFECTS - Hypertension, hypokalemia (inc
mineralocorticoids)
Finasteride - 5 -reductase inhibitor (dec conversion of testosterone to DHT) - BPH, male-pattern baldness. ADVERSE EFFECTS - Gynecomastia,
sexual dysfunction.
Flutamide, bicalutamide - Nonsteroidal competitive inhibitors at androgen receptor (dec steroid binding) - Prostate cancer. ADVERSE EFFECTS -
Gynecomastia, sexual dysfunction.
Ketoconazole - 17 -hydroxylase/17,20-lyase inhibitor - Prostate cancer. ADVERSE EFFECTS - Gynecomastia.
Spironolactone - Androgen receptor and 17 -hydroxylase/17,20-lyase inhibitor - PCOS. ADVERSE EFFECTS - Amenorrhea.

Perfusion limited—O2 (normal health), CO2 , N2O. Gas equilibrates early along the length of the capillary. Exchange can be inc only if blood flow inc.
Diffusion limited—O2 (emphysema, fbrosis, exercise), CO. Gas does not equilibrate by the time blood reaches the end of the capillary. O2 diffuses
slowly, while CO2 diffuses very rapidly across the alveolar membrane. Disease states that lead to diffusion limitation (eg, pulmonary fibrosis) are more
likely to cause early hypoxia than hypercapnia.
Normal A-a gradient - High altitude (dec barometric pressure), Hypoventilation (eg, opioid use, obesity hypoventilation syndrome). Inc A-a gradient -
V̇/Q̇ mismatch, Diffusion limitation (eg, fibrosis), Right-to-left shunt.
R = respiratory quotient = CO2 produced/ O2 consumed
A-a gradient = Pao2 – Pao2 . Normal A-a gradient estimated as (age/4) + 4 (eg, for a person <40 years old, gradient should be <14).
Diffusion: V̇ gas = A × Dk × (P1 – P2)/Δx
Pulmonary vascular resistance
PVR = (Ppulm artery – PL atrium)/Q
Remember: ΔP = Q × R, so R = ΔP / Q
R = 8ηl/πr4
Alveolar gas equation:
PAo2 = PIo2 – (Paco2/R) ≈ 150 mm Hga – (Paco2/0.8)
Oxygen-hemoglobin dissociation curve - ODC has sigmoidal shape due to positive cooperativity (ie, tetrameric Hb molecule can bind 4 O2 molecules
and has higher affnity for each subsequent O2 molecule bound). Myoglobin is monomeric and thus does not show positive cooperativity; curve lacks
sigmoidal appearance.
Shifting ODC to the right > dec Hb affnity for O2 (facilitates unloading of O2 to tissue) > inc P50 (higher Po2 required to maintain 50% saturation). In
peripheral tissue, inc H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect).
Shifting ODC to the left > dec O2 unloading > renal hypoxia > inc EPO synthesis > compensatory erythrocytosis.
Fetal Hb (2a and 2y subunits) has higher affnity for O2 than adult Hb (due to dec affnity for 2,3-BPG) > dissociation curve is shifted left, driving
diffusion of O2 across the placenta from pregnant patient to fetus.
Left shift (dec O2 unloading to tissue) - Left = lower - Dec H+ (inc pH, base), dec PCO2 , dec 2,3–BPG, dec Temperature, inc CO, inc MetHb, inc
HbF.
Right shift (inc O2 unloading to tissues) - ACE BATs right handed - Inc H+ (dec pH, Acid), inc PCO2 , Exercise, inc 2,3–BPG, High Altitude, inc
Temperature.
Oxygen content of blood = O2 content = (1.34 x Hb x Sao2 ) + (0.003 x Pao2).
O2 delivery to tissues = cardiac output x O2 content of blood.

Respiratory system changes in the elderly - Aging is associated with progressive dec in lung function. TLC remains the same. INCREASED-
Lung compliance (loss of elastic recoil)
RV

V̇/Q̇ mismatch
A-a gradient
DECREASED-
Chest wall compliance (inc chest wall stiffness) FVC and FEV1

Respiratory muscle strength (can impair cough) Ventilatory response to hypoxia/hypercapnia

Elastic recoil - Tendency for lungs to collapse inward and chest wall to spring outward. At FRC, airway and alveolar pressures equal atmospheric
pressure (called zero), and intrapleural pressure is negative (preventing atelectasis). The inward pull of the lung is balanced by the outward pull of the
chest wall. System pressure is atmospheric. Pulmonary vascular resistance (PVR) is at a minimum. Inc compliance = lung easier to flll (eg,
emphysema, aging)
Dec compliance = lung harder to flll (eg, pulmonary fibrosis, pneumonia, ARDS, pulmonary edema).

Hysteresis - Lung infation follows a different pressurevolume curve than lung deflation due to need to overcome surface tension forces in inflation.
Determination of physiologic dead space- VD = VT x (Paco2 – Peco2)/Paco2
Minute ventilation = VE = VT x RR
Alveolar ventilation = VA = (VT - VD) x RR

Lung zones:
V ̇ /Q ̇ at apex of lung = 3 (wasted ventilation)
V ̇ /Q ̇ at base of lung = 0.6 (wasted perfusion)
Both ventilation and perfusion are greater at the base of the lung than at the apex of the lung. With exercise (inc cardiac output), there is vasodilation of
apical capillaries > V̇/Q̇ ratio approaches 1. V̇/Q̇ = 0 = “oirway” obstruction (shunt). In shunt, 100% O2 does not improve Pao2 (eg, foreign body
aspiration).
V̇/Q̇ = infinity = blood flow obstruction (physiologic dead space). Assuming < 100% dead space, 100% O2 improves Pao2 (eg, pulmonary embolus).
Zone 1 = PA>Pa>Pv = decV/dec dec Q > inc V/Q = V̇/Q̇ at apex of lung = 3 (wasted ventilation)
Zone 2 = Pa > PA > Pv = V/Q ~ 1
Zone3=Pa>Pv>PA=incV/incincQ>decV/Q=V̇/Q̇ atbaseoflung=0.6(wastedperfusion)
Response to exercise-
Inc CO2 production.
Inc O2 consumption.
Right shift of ODC.
Inc ventilation to meet O2 demand and remove excess CO2 .
V ̇ /Q ̇ ratio from apex to base becomes more uniform.
Inc pulmonary blood flow due to inc cardiac output.
Dec pH during strenuous exercise (2° to lactic acidosis).
No change in Pao2 and Paco2 , but inc in venous CO2 content and dec in venous O2 content.
Response to high altitude -
Dec atmospheric oxygen (PiO2) > dec Pao2 > inc ventilation > dec Paco2 > respiratory alkalosis > altitude sickness (headaches, nausea, fatigue,
lightheadedness, sleep disturbance). Chronic inc in ventilation. Inc erythropoietin > inc Hct and Hb (due to chronic hypoxia). Inc 2,3-BPG (binds to Hb
> rightward shift of ODC dissociation curve > inc O2 release).
Cellular changes (inc mitochondria).

Inc renal excretion of HCO3 to compensate for respiratory alkalosis (can augment with acetazolamide). Chronic hypoxic pulmonary vasoconstriction >
inc pulmonary vascular resistance > pulmonary hypertension, RVH.

ANTIMETABOLITES- All are S-phase specifc except cladribine, which is cell cycle nonspecifc.

Thiopurines - Azathioprine, 6-mercaptopurine - Purine (thiol) analogs > dec de novo purine synthesis. AZA is converted to 6-MP, which is then
activated by HGPRT. Rx RHEUMATOID ARTHRITIS, IBD, SLE, ALL; STEROID-REFRACTORY DISEASE. PREVENTION OF ORGAN
REJECTION. WEANING FROM STEROIDS. SE - Myelosuppression; GI, liver toxicity. 6-MP is inactivated by xanthine oxidase (inc toxicity with
allopurinol or febuxostat).

Cladribine, pentostatin - Purine analogs > multiple mechanisms (eg, inhibition of ADA, DNA strand breaks). Rx - HAIRY CELL LEUKEMIA. SE -
Myelosuppression.
Cytarabine (arabinofuranosyl cytidine) - Pyrimidine analog > DNA chain termination. Inhibits DNA polymerase. Rx - LEUKEMIAS (AML),
LYMPHOMAS. SE - Myelosuppression.

5-Fluorouracil - Pyrimidine analog bioactivated to 5-FdUMP > thymidylate synthase inhibition > dec dTMP > dec DNA synthesis. Capecitabine is a
prodrug. Rx - COLON CANCER, PANCREATIC CANCER, ACTINIC KERATOSIS, BASAL CELL CARCINOMA (TOPICAL). Effects enhanced
with the addition of leucovorin. SE - Myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome).

Hydroxyurea - Inhibits ribonucleotide reductase > dec DNA synthesis. Rx - MYELOPROLIFERATIVE DISORDERS (eg, CML, polycythemia vera),
SICKLE CELL DISEASE (inc HbF). SE - Severe myelosuppression, megaloblastic anemia.

Methotrexate - Folic acid analog that competitively inhibits dihydrofolate reductase > dec dTMP > dec DNA synthesis. Rx - CANCERS:
LEUKEMIAS (ALL), LYMPHOMAS, CHORIOCARCINOMA, SARCOMAS. NONNEOPLASTIC: ECTOPIC PREGNANCY, MEDICAL
ABORTION (WITH MISOPROSTOL), RHEUMATOID ARTHRITIS, PSORIASIS, IBD, VASCULITIS. SE - Myelosuppression (reversible with
leucovorin “rescue”), hepatotoxicity, mucositis (eg, mouth ulcers), pulmonary fibrosis, folate deficiency (teratogenic), nephrotoxicity.
Anticancer monoclonal antibodies - Work against extracellular targets to neutralize them or to promote immune system recognition (eg, ADCC by NK
cells).
Alemtuzumab - CD52 - Chronic lymphocytic leukemia (CLL), multiple sclerosis. SE - inc risk of infections and autoimmunity (eg, ITP)
Bevacizumab - VEGF (inhibits blood vessel formation). Rx - Colorectal cancer (CRC), renal cell carcinoma (RCC), non–small cell lung cancer
(NSCLC), angioproliferative retinopathy. SE - Hemorrhage, blood clots, impaired wound healing.
Cetuximab, panitumumab - EGFR - Metastatic CRC (wild-type RAS), head and neck cancer. SE - Rash, elevated LFTs, diarrhea.
Rituximab - CD20. Rx - Non-Hodgkin lymphoma, CLL, rheumatoid arthritis, ITP, TTP, AIHA, multiple sclerosis. SE - inc risk of PML in patients with
JC virus.
Trastuzumab - HER2 (“trust HER”) - Breast cancer, gastric cancer. SE - Dilated cardiomyopathy (often reversible). “Heartceptin”
(Pembrolizumab, nivolumab, cemiplimab - PD-1). (Atezolizumab, durvalumab, avelumab - PD-L1). (Ipilimumab - CTLA-4). Rx - Various tumors (eg,
NSCLC, RCC, melanoma, urothelial carcinoma). SE - inc risk of autoimmunity (eg, dermatitis, enterocolitis, hepatitis, pneumonitis, endocrinopathies).
Bivalirudin, argatroban, dabigatran (BAD) - Directly inhibit thrombin (factor IIa). Rx - Venous thromboembolism, atrial fibrillation. Can be used in
HIT, when heparin is BAD for the patient. SE - Bleeding (reverse dabigatran with idarucizumab). Dabigatran is the only oral agent in class. Do not
require lab monitoring.

Apixaban, edoxaban, rivaroxaban - Directly inhibit factor Xa. Treatment and prophylaxis for DVT and PE; stroke prophylaxis in patients with atrial
fibrillation. SE - Bleeding (reverse with andexanet alfa). Oral agents that do not usually require lab monitoring.

Aspirin - Irreversibly blocks COX > dec TXA2 release. Rx - Acute coronary syndrome; coronary stenting. Dec incidence or recurrence of thrombotic
stroke. SE - Gastric ulcers, tinnitus, allergic reactions, renal injury.

Clopidogrel, prasugrel, ticagrelor, ticlopidine (PTCT) - Block ADP (P2Y12) receptor > dec ADP-induced expression of GpIIb/IIIa. Rx - Same as
aspirin; dual antiplatelet therapy. SE - Neutropenia (ticlopidine); TTP may be seen.

Abciximab, eptifibatide, tirofiban (TEA) - Block GpIIb/IIIa (fibrinogen receptor) on activated platelets. Abciximab is made from monoclonal antibody
Fab fragments. Rx - UNSTABLE ANGINA, PERCUTANEOUS CORONARY INTERVENTION. SE - Bleeding, thrombocytopenia.

Cilostazol, dipyridamole (DC) - Block phosphodiesterase > dec cAMP in platelets. Rx - Intermittent claudication, stroke prevention, CARDIAC
STRESS TESTING, PREVENTION OF CORONARY STENT RESTENOSIS. SE - Nausea, headache, FACIAL FLUSHING, HYPOTENSION,
abdominal pain.

Thrombolytics - Alteplase (tPA), reteplase (rPA), streptokinase, tenecteplase (TNK-tPA). Directly or indirectly aid conversion of plasminogen to
plasmin, which cleaves thrombin and fibrin clots. Inc PT, Inc PTT, no change in platelet count. Rx - Early MI, early ischemic stroke, direct
thrombolysis of severe PE. SE - Bleeding. Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known
bleeding diatheses, or severe hypertension. Nonspecific reversal with antifibrinolytics (eg, aminocaproic acid, tranexamic acid), platelet transfusions,
and factor corrections (eg, cryoprecipitate, FFP, PCC).

Amelioration of adverse effects of chemotherapy-

Amifostine - Free radical scavenger - Nephrotoxicity from platinum compounds
Dexrazoxane - Iron chelator - Cardiotoxicity from anthracyclines
Leucovorin (folinic acid) - Tetrahydrofolate precursor - Myelosuppression from methotrexate (leucovorin “rescue”); also enhances the effects of 5-FU
Mesna - Sulfhydryl compound that binds acrolein (toxic metabolite of cyclophosphamide/ifosfamide) - Hemorrhagic cystitis from cyclophosphamide/
ifosfamide
Rasburicase - Recombinant uricase that catalyzes metabolism of uric acid to allantoin - Tumor lysis syndrome
(Ondansetron, granisetron - 5-HT3 receptor antagonists), (Prochlorperazine, metoclopramide - D2 receptor antagonists) - Acute nausea and vomiting
(usually within 1-2 hr after chemotherapy) Aprepitant, fosaprepitant - NK1 receptor antagonists - Delayed nausea and vomiting (>24 hr after
chemotherapy)
Filgrastim, sargramostim - Recombinant G(M)-CSF - Neutropenia
Epoetin alfa - Recombinant erythropoietin - Anemia
Heparin - Activates antithrombin, which dec action primarily of factors IIa (thrombin) and Xa. Short half-life. Immediate anticoagulation for
pulmonary embolism (PE), acute coronary syndrome, MI, deep venous thrombosis (DVT). Used during pregnancy (does not cross placenta). Monitor
PTT. SE - Bleeding (reverse with protamine sulfate), heparin-induced thrombocytopenia (HIT), osteoporosis (with long-term use), drug-drug
interactions. HIT type 1—mild (platelets >100,000/mm3), transient, nonimmunologic drop in platelet count that typically occurs within the first 2 days
of heparin administration. Not clinically significant. HIT type 2—development of IgG antibodies against heparin-bound platelet factor 4 (PF4) that
typically occurs 5–10 days after heparin administration. Antibody-heparin-PF4 complex binds and activates platelets > removal by splenic
macrophages and thrombosis > dec dec platelet count. Highest risk with unfractionated heparin. Low-molecular- weight heparins (eg, enoxaparin,
dalteparin) act mainly on factor Xa. Fondaparinux acts only on factor Xa. Have better bioavailability and 2–4× longer half life than unfractionated
heparin; can be administered subcutaneously and without lab monitoring. LMWHs undergo renal clearance (vs hepatic clearance of unfractionated
heparin) and must be used with caution in patients with renal insufficiency. Not easily reversible.

Warfarin - Inhibits vitamin K epoxide reductase by competing with vitamin K > inhibition of vitamin K– dependent γ-carboxylation of clotting factors
II, VII, IX, and X and proteins C and S. Metabolism affected by polymorphisms in the gene for vitamin K epoxide reductase complex (VKORC1). In
laboratory assay, has effect on extrinsic pathway and inc PT. Long half-life. Rx Chronic anticoagulation (eg, venous thromboembolism prophylaxis and
prevention of stroke in atrial fibrillation). Not used in pregnant patients (because warfarin, unlike heparin, crosses placenta). Monitor PT/INR. SE -
Bleeding, teratogenic effects, skin/tissue necrosis, drug-drug interactions (metabolized by cytochrome P-450 [CYP2C9]). Initial risk of
hypercoagulation: protein C has shorter half-life than factors II and X. Existing protein C depletes before existing factors II and X deplete, and before
warfarin can reduce factors II and X production > hypercoagulation. Skin/tissue necrosis within first few days of large doses believed to be due to small
vessel microthrombosis. Heparin “bridging”: heparin frequently used when starting warfarin. Heparin’s activation of antithrombin enables
anticoagulation during initial, transient hypercoagulable state caused by warfarin. Initial heparin therapy reduces risk of recurrent venous
thromboembolism and skin/ tissue necrosis. For reversal of warfarin, give vitamin K. For rapid reversal, give FFP or PCC.

Epilepsy therapy -
Benzodiazepines - SE - Sedation, tolerance, dependence, respiratory depression.

Carbamazepine - SE - Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis (cleft lip/palate, spina bifida),
induction of cytochrome P-450, SIADH, SJS. Ethosuximide - SIDE EFFECTS - EFGHIJ—Ethosuximide causes Fatigue, GI distress, Headache,
Itching (and urticaria), SJS.
Gabapentin - SE - Sedation, ataxia. Also used for peripheral neuropathy, postherpetic neuralgia.
Lamotrigine and vigabatrin - black-box warning.

Lamotrigine - SE - SJS (must be titrated slowly), hemophagocytic lymphohistiocytosis (black box warning).
Levetiracetam - SE - Neuropsychiatric symptoms (eg, personality change), fatigue, drowsiness, headache.
Phenobarbital - SE - Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression. 1st line in neonates
(“phenobabytal”).
Phenytoin, fosphenytoin - SE - PPHENYTOIN: cytochrome P-450 induction, Pseudolymphoma, Hirsutism, Enlarged gums, Nystagmus, Yellow-brown
skin, Teratogenicity (fetal hydantoin syndrome), Osteopenia, Inhibited folate absorption, Neuropathy. Rare: SJS, DRESS syndrome, drug-induced
lupus. Toxicity leads to diplopia, ataxia, sedation.
Topiramate - SE - Sedation, slow cognition, kidney stones, skinny (weight loss), sight threatened (glaucoma), speech (word- finding) difficulties,
Topiramate (blurred vision/diplopia, haloes).
Valproic acid - SE - VALPPROaTTE: Vomiting, Alopecia, Liver damage (hepatotoxic), Pancreatitis, P-450 inhibition, Rash, Obesity (weight gain),
Tremor, Teratogenesis (neural tube defects). Epigastric pain (GI distress).
Vigabatrin - SE - Permanent visual loss (black box warning). Vision loss with GABA transaminase inhibitor.
Barbiturates - SE - Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by alcohol use); dependence; drug
interactions (induces cytochrome P-450). Overdose treatment is supportive (assist respiration and maintain BP). Contraindicated in porphyria.
BZDs - Dec REM sleep. Most have long half-lives and active metabolites (exceptions [ATOM]: Alprazolam, Triazolam, Oxazepam, and Midazolam
are short acting > higher addictive potential). SE - Dependence, additive CNS depression effects with alcohol and barbiturates (all bind the GABAA
receptor). Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA
benzodiazepine receptor). Can precipitate seizures by causing acute benzodiazepine withdrawal.
Nonbenzodiazepine hypnotics - Examples: Zolpidem, Zaleplon, esZopiclone. SE - Ataxia, headaches, confusion Cause only modest day-after
psychomotor depression and few amnestic effects (vs older sedative-hypnotics). Dec dependency risk and dec sleep cycle disturbance (vs
benzodiazepine hypnotics).
(Orexin - regulates arousal, wakefulness and appetite; defective in narcolepsy)
Suvorexant - Orexin (hypocretin) receptor antagonist. SE - CNS depression (somnolence), headache, abnormal sleep- related activities.
Contraindications: narcolepsy, combination with strong CYP3A4 inhibitors. Not recommended in patients with liver disease. Limited risk of
dependency.
Ramelteon - SE - Dizziness, nausea, fatigue, headache. No known risk of dependency.
Triptans - Sumatriptan. 5-HT1B/1D agonists. SE - Coronary vasospasm (contraindicated in patients with CAD or vasospastic angina), mild paresthesia,
serotonin syndrome (in combination with other 5-HT agonists).
Dopamine agonists - Non-ergot (preferred)—pramipexole, ropinirole; toxicity includes nausea, impulse control disorder (eg, gambling), postural
hypotension, hallucinations, confusion. Ergot— bromocriptine rarely used due to toxicity.
Inc dopamine availability - Amantadine (inc dopamine release and dec dopamine reuptake); toxicity = peripheral edema, livedo reticularis, ataxia.
Carbidopa/Levodopa - SE - Nausea, hallucinations, postural hypotension. With progressive disease, L-DOPA can lead to “on- off” phenomenon with
improved mobility during “on” periods, then impaired motor function during “off” periods when patient responds poorly to L-DOPA or medication
wears off.
Alzheimer ds- 1. Donepezil, rivastigmine, galantamine - AChE inhibitor. 1st-line treatment. Adverse effects: nausea, dizziness, insomnia.
Contraindicated in patients with cardiac conduction abnormalities.
2. Memantine - NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+ ). Used for moderate to advanced dementia. Adverse
effects: dizziness, confusion, hallucinations.
Inhaled anesthetics - Myocardial depression, respiratory depression, postoperative nausea/vomiting, inc cerebral blood flow and ICP, dec cerebral
metabolic demand. SE - Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane, epileptogenic), expansion of trapped
gas in a body cavity (N2O). Malignant hyperthermia—rare, life-threatening condition in which inhaled anesthetics or succinylcholine induce severe
muscle contractions and hyperthermia. Susceptibility is often inherited as autosomal dominant with variable penetrance. Mutations in ryanodine
receptor (RYR1) cause inc Ca2+ release from sarcoplasmic reticulum. Treatment: dantrolene (a ryanodine receptor antagonist).
Thiopental - Dec cerebral blood flow. High lipid solubility. Effect terminated by rapid redistribution into tissue, fat.
Midazolam - May cause severe postoperative respiratory depression, dec BP, anterograde amnesia.
Propofol - May cause respiratory depression, dec BP.
Ketamine - NMDA receptor antagonist. Dissociative anesthesia, Sympathomimetic. Inc cerebral blood flow. Emergence reaction possible with
disorientation, hallucination, vivid dreams.
Local anesthetics - SE - CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, arrhythmias (cocaine),
methemoglobinemia (benzocaine, prilocaine).
Depolarizing neuromuscular blocking drugs - Succinylcholine—Complications include hypercalcemia, hyperkalemia, malignant hyperthermia. Inc risk
of prolonged muscle paralysis in patients with pseudocholinesterase deficiency.
Cyclobenzaprine - Acts within CNS, mainly at the brain stem. Muscle spasticity. Centrally acting. Structurally related to TCAs May cause
anticholinergic side effects, sedation.
Opioid analgesics - Full agonist: morphine, heroin, meperidine (long acting), methadone, codeine (prodrug; activated by CYP2D6), fentanyl. Partial
agonist: buprenorphine. Mixed agonist/antagonist: nalbuphine, pentazocine, butorphanol. Antagonist: naloxone, naltrexone, methylnaltrexone. SE -
Nausea, vomiting, pruritus (histamine release), opiate use disorder, respiratory depression, constipation, sphincter of Oddi spasm, miosis (except
meperidine > mydriasis), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Treat toxicity with
naloxone (competitive opioid receptor antagonist) and prevent relapse with naltrexone once detoxified.
Pentazocine - κ-opioid receptor agonist and μ-opioid receptor weak antagonist or partial agonist. Can cause opioid withdrawal symptoms if patient is
also taking full opioid agonist (due to competition for opioid receptors).
Butorphanol - κ-opioid receptor agonist and μ-opioid receptor partial agonist. Causes less respiratory depression than full opioid agonists. Use with full
opioid agonist can precipitate withdrawal. Not easily reversed with naloxone.
Tramadol - SE - Similar to opioids; decreases seizure threshold; serotonin syndrome.
α-agonists - Mydriasis (α1); do not use in closed-angle glaucoma. Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions,
ocular pruritus.
Prostaglandins - Darkens color of iris (browning), eyelash growth.
Cholinomimetics (M3) - Direct: pilocarpine, carbachol Indirect: physostigmine, echothiophate. Miosis (contraction of pupillary sphincter muscles) and
cyclospasm (contraction of ciliary muscle).

Topoisomerase inhibitors - All cause DNA degradation resulting in cell cycle arrest in S and G2 phases.
Irinotecan, topotecan - Inhibit topoisomerase I “-tecone”. Rx - Colon, ovarian, small cell lung cancer. SE - Severe myelosuppression, diarrhea
Etoposide, teniposide - Inhibit topoisomerase II “-bothside”. Rx - Testicular, small cell lung cancer, leukemia, lymphoma. SE - Myelosuppression,
alopecia
Alkylating agents - All are cell cycle nonspecifc.
Busulfan - Cross-links DNA. Used to ablate patient’s bone marrow before bone marrow transplantation. SE - Severe myelosuppression (in almost all
cases), pulmonary fibrosis, hyperpigmentation. (farmer uses cycle to get mustard seeds but uses car to get urea)
Nitrogen mustards - Cyclophosphamide, ifosfamide - Cross-link DNA. Require bioactivation by liver. Rx - Solid tumors, leukemia, lymphomas,
rheumatic disease (eg, SLE, granulomatosis with polyangiitis). SE - Myelosuppression, SIADH, Fanconi syndrome (ifosfamide), hemorrhagic cystitis
and bladder cancer (prevent with mesna).
Nitrosoureas - Carmustine, lomustine - Cross-link DNA. Require bioactivation. Cross blood-brain barrier > CNS entry. Rx - Brain tumors (including
glioblastoma multiforme). SE - CNS toxicity (convulsions, dizziness, ataxia)
Procarbazine - Mechanism unknown. Weak MAO inhibitor. Rx - Hodgkin lymphoma, brain tumors. SE - Bone marrow suppression, pulmonary
toxicity, leukemia, disulfiram-like reaction.
Platinum compounds - Cisplatin, carboplatin, oxaliplatin. Cross-link DNA. Cell cycle nonspecific. Rx - Solid tumors (eg, testicular, bladder, ovarian,
GI, lung), lymphomas. SE - Nephrotoxicity (eg, Fanconi syndrome; prevent with amifostine), peripheral neuropathy, ototoxicity.
Microtubule inhibitors - All are M-phase specifc.
Taxanes - Docetaxel, paclitaxel - Hyperstabilize polymerized microtubules > prevent mitotic spindle breakdown. (Paclitaxel pakad ke takhta hai) Rx -
Various tumors (eg, ovarian and breast carcinomas). SE - Myelosuppression, neuropathy, hypersensitivity
Vinca alkaloids - Vincristine, vinblastine. Bind β -tubulin and inhibit its polymerization into microtubules > prevent mitotic spindle formation. Rx -
Solid tumors, leukemias, Hodgkin and non-Hodgkin lymphomas. SE - Vincristine (crisps the nerves): neurotoxicity (axonal neuropathy), constipation
(including ileus). Vinblastine (blasts the marrow): myelosuppression.
Bleomycin - Induces free radical formation > breaks in DNA strands. Rx - TESTICULAR CANCER, HODGKIN LYMPHOMA. SE - Pulmonary
fibrosis, skin hyperpigmentation.
Dactinomycin (actinomycin D) - Intercalates into DNA, preventing RNA synthesis. Rx - WILMS TUMOR, EWING SARCOMA,
RHABDOMYOSARCOMA. SE - Myelosuppression.
Anthracyclines - Doxorubicin, daunorubicin - Generate free radicals. Intercalate in DNA > breaks in DNA > dec replication. Inhibit topoisomerase II.
Rx - SOLID TUMORS, LEUKEMIAS, LYMPHOMAS. SE - Dilated cardiomyopathy (often irreversible; prevent with dexrazoxane),
myelosuppression, alopecia.
Alectinib - ALK - Non–small cell lung cancer - Edema, rash, diarrhea.
Erlotinib, gefitinib, afatinib - EGFR - Non–small cell lung cancer - Rash, diarrhea.

Imatinib, dasatinib, nilotinib - BCR-ABL (also other tyrosine kinases [eg, c-KIT]) - CML, ALL, GISTs - Myelosuppression, inc LFTs, edema,
myalgias.
Ruxolitinib - JAK1/2 - Polycythemia vera - Bruises, inc LFTs.
Bortezomib, ixazomib, carfilzomib - Proteasome (induce arrest at G2-M phase > apoptosis) - Multiple myeloma, mantle cell lymphoma - Peripheral
neuropathy, herpes zoster reactivation. Vemurafenib, encorafenib, dabrafenib - BRAF - Rx Melanoma. Often co-administered with MEK inhibitors (eg,
trametinib). - Rash, fatigue, nausea, diarrhea.
Palbociclib - Cyclin-dependent kinase 4/6 (induces arrest at G1-S phase > apoptosis). - Breast cancer - Myelosuppression, pneumonitis.
Olaparib - Poly(ADP-ribose)polymerase (dec DNA repair) - Breast, ovarian, pancreatic, and prostate cancers - Myelosuppression, edema, diarrhea.
Tamoxifen - Selective estrogen receptor modulator with complex mode of action: antagonist in breast tissue, partial agonist in endometrium and bone.
Blocks the binding of estrogen to ER in ER ⊕ cells. Rx - Prevention and treatment of breast cancer, prevention of gynecomastia in patients undergoing
prostate cancer therapy. SE - Hot flashes, inc risk of thromboembolic events (eg, DVT, PE) and endometrial cancer.
Key chemotoxicities-
Cisplatin, Carboplatin - ototoxicity
Cisplatin, Carboplatin - nephrotoxicity
Vincristine - peripheral neuropathy
Bleomycin, Busulfan - pulmonary fibrosis
Doxorubicin, Daunorubicin - cardiotoxicity
Trastuzumab - cardiotoxicity
CYclophosphamide - hemorrhagic cystitis
Nonspecific common toxicities of nearly all cytotoxic chemotherapies include myelosuppression (neutropenia, anemia, thrombocytopenia), GI toxicity
(nausea, vomiting, mucositis), alopecia. Anticoagulation reversal-
Heparin - Protamine sulfate (⊕ charged peptide that binds ⊖ charged heparin)
Warfarin - Vitamin K (slow) +/– FFP or PCC (rapid)
Dabigatran - Idarucizumab - (Monoclonal antibody Fab fragments)
Direct factor Xa inhibitors - Andexanet alfa - Recombinant modified factor Xa (inactive)
Anthrax - Prophylaxis with ciprofoxacin or doxycycline when exposed.
Diphtheria Rx - diphtheria antitoxin +/– erythromycin or penicillin.
Listera - Treatment: ampicillin.
SNAP: Sulfonamides—Nocardia; Actinomyces—Penicillin.
Leprosy - Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
N. gonorrheae - Treatment: ceftriaxone + azithromycin (to cover possible chlamydial coinfection, ceftriaxone-resistant strains). Erythromycin eye
ointment prevents neonatal blindness.
Meningococci - Prophylaxis - Rifampin, ciprofloxacin, or ceftriaxone. Treatment: ceftriaxone or penicillin G.
H. influenzae - Treatment: amoxicillin +/ clavulanate for mucosal infections; ceftriaxone for meningitis; rifampin prophylaxis for close contacts.
Pertussis - Treatment: macrolides; if allergic use TMP-SMX.
Brucella - Treatment: doxycycline + rifampin or streptomycin.
Legionella - Treatment: macrolide or quinolone.
Pseudomonas Treatments: Antipseudomonal penicillins in combination with -lactamase inhibitor (eg, piperacillintazobactam) 3rd- and 4th-generation
cephalosporins (eg, ceftazidime, cefepime) Monobactams Fluoroquinolones Carbapenems (AACCMQ)
Salmonella typhi - treat with ceftriaxone or fuoroquinolone
S. agalactae - GBS - Patients with +ve culture receive intrapartum penicillin/ampicillin prophylaxis.
H. pylori - Most common initial treatment is triple therapy: amoxicillin (metronidazole if penicillin allergy) + clarithromycin + proton pump inhibitor;
antibiotics cure Pylori. Bismuth-based quadruple therapy if concerned about macrolide resistance.
Lyme ds - Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Rx Penicillin G
Congenital syphilis - To prevent, treat patient early in pregnancy, as placental transmission typically occurs after first trimester.
Gardnerella vaginalis - Treatment: metronidazole or clindamycin.
Chlamydia - Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for possible concomitant gonorrhea.
Rickettsial diseases and vector-borne illnesses Treatment: doxycycline.
Mycoplasma pneumoniae - Treatment: macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since Mycoplasma has no cell wall).
Chronic hepatitis B or C - IFN-α (HBV and HCV); ribavirin, simeprevir, sofosbuvir (HCV)
Clostridium difficile - Oral metronidazole; if refractory, oral vancomycin. Refractory cases: repeat regimen or fecal microbiota transplant
Haemophilus influenzae (B) Amoxicillin ± clavulanate (mucosal infections), ceftriaxone (meningitis), rifampin (prophylaxis)
Neisseria gonorrhoeae Ceftriaxone (add azithromycin or doxycycline to cover likely concurrent C trachomatis) Oral erythromycin to treat chlamydial
conjunctivitis in infants also gonococcal eye infection
Neisseria meningitidis Penicillin/ceftriaxone, rifampin/ciprofloxacin/ceftriaxone (prophylaxis)
Legionella pneumophila Macrolides (eg, azithromycin or fluoroquinolones)
Systemic mycosis - Treatment: fluconazole or itraconazole for local infection; amphotericin B for systemic infection.
Tinea (pityriasis) versicolor - Treatment: selenium sulfide, topical and/or oral antifungal medications.
Candida - Treatment: oral fluconazole/topical azoles for vaginal; nystatin, azoles, or, rarely, echinocandins for oral; fluconazole, echinocandins, or
amphotericin B for esophageal or systemic disease. Aspergillus - Treatment: voriconazole/isavuconazole or echinocandins (2nd-line).
Cryptococcus - Treatment: amphotericin B + flucytosine followed by fluconazole for cryptococcal meningitis.
Mucor and Rhizopus spp - Treatment: surgical debridement, amphotericin B or isavuconazole
Pneumocystis jirovecii - Treatment/prophylaxis: TMP-SMX, pentamidine, dapsone (prophylaxis as single agent, or treatment in combination with
TMP), atovaquone. Start prophylaxis when CD4+ cell count drops to < 200 cells/mm3 in people living with HIV.
Sporothrix schenckii - Treatment: itraconazole or potassium iodide (only for cutaneous/lymphocutaneous). Think of a rose gardener who smokes a
cigar and pot.
Giardia lamblia - Rx Metronidazole.
Entamoeba histolytica - Rx Metronidazole; paromomycin or iodoquinol for asymptomatic cyst passers.
Cryptosporidium - Rx Prevention (by filtering city water supplies); nitazoxanide in immunocompetent hosts.
Protozoa—CNS infections-
Toxoplasma gondii - Rx Sulfadiazine + pyrimethamine. Prophylaxis with TMP-SMX when CD4+ cell count < 100 cells/mm3.
Naegleria fowleri - Rx Amphotericin B has been effective for a few survivors.
Trypanosoma brucei - Rx Suramin for bloodborne disease or melarsoprol for CNS penetration.
Protozoa—hematologic infections-
Plasmodium - TREATMENT Chloroquine (for sensitive species); if resistant, use mefloquine or atovaquone/ proguanil. If life-threatening, use
intravenous quinidine or artesunate (test for G6PD deficiency). For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency).
Babesia - Rx Atovaquone + azithromycin.
Visceral infections-
Trypanosoma cruzi - Rx Benznidazole or nifurtimox; cruzing in my Benz, with a fur coat on.
Leishmania spp - Rx Amphotericin B, sodium stibogluconate.
Sexually transmitted infections-
Trichomonas vaginalis -
Rx Metronidazole for patient and partner(s) (prophylaxis; check for STI).
Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin).
Cestode/tapeworm Rx - (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole).
Nematodes (roundworms)

Intestinal-
Enterobius vermicularis (pinworm) - Bendazoles, pyrantel pamoate.
Ascaris lumbricoides (giant roundworm) - Bendazoles.
Strongyloides stercoralis (threadworm) - Ivermectin or bendazoles.
Ancylostoma spp, Necator americanus (hookworms) - Bendazoles or pyrantel pamoate.
Trichinella spiralis - Bendazoles.
Trichuris trichiura (whipworm) - Bendazoles.
Tissue-
Toxocara canis - Visceral larva migrans. Bendazoles.
Onchocerca volvulus - Ivermectin (ivermectin for river blindness).
Loa loa - Diethylcarbamazine.
Wuchereria bancrofti, Brugia malayi - Diethylcarbamazine.
Cestodes (tapeworms)
Taenia solium1 - Praziquantel.
Taenia solium2 - Praziquantel; albendazole for neurocysticercosis.
Diphyllobothrium latum - Praziquantel, niclosamide.
Echinococcus granulosus - Albendazole; surgery for complicated cysts.
Trematodes (flukes)
Schistosoma - Praziquantel.
Clonorchis sinensis - Praziquantel.
Ectoparasites
Sarcoptes scabiei - Treatment: permethrin cream, oral ivermectin, washing/drying all clothing/bedding, treat close contacts.
Pediculus humanus/ Phthirus pubis - Treatment: pyrethroids, malathion, or ivermectin lotion, and nit combing. Children with head lice can be treated at
home without interrupting school attendance. Capacity - MASSIVE - Mental illness, Age, mental Status, Stability, Informed, Values, Expresses
preferences.
Exceptions to informed consent - WIPE it away - Waiver, Legally Incompetent, Therapeutic privilige, emergency.
Exceptions to patient confdentiality - SAVED Suicide/homicide, abuse, protect victim, epilepsy, reportable disease
Situations in which parental consent is usually not required: Sex (contraception, STIs, prenatal care— usually not abortion), Drugs (substance use
disorder treatment), Rock and roll (emergency/trauma)
Goals - Specific, Measurable, Achievable, Relevant, and Time bound (SMART).
Patient-centered interviewing techniques (VR-FAIR / IAR-VRF) - Introduction Agenda Reflection Validation Recapitulation Facilitation
Expressing empathy PEARLS - Partnership Empathy Apology Respect Legitimization Support
Delivering bad news SPIKES - Setting Perception Invitation Knowledge Emotions Strategy

Cholinomimetic agents - Watch for exacerbation of COPD, asthma, and peptic ulcers in susceptible patients. Direct agonists-
Bethanechol - Rx Urinary retention.
Carbachol - Rx Constricts pupil and relieves intraocular pressure in open-angle glaucoma.

Methacholine - Rx Challenge test for diagnosis of asthma.

Pilocarpine - Rx Potent stimulator of sweat, tears, and saliva. Open-angle and closed-angle glaucoma, xerostomia (Sjögren syndrome).
Indirect agonists (anticholinesterases)-
Donepezil, rivastigmine, galantamine - Rx 1st line for Alzheimer disease.
Edrophonium - Rx Historically used to diagnose myasthenia gravis; replaced by anti-AChR Ab (anti-acetylcholine receptor antibody) test.
Neostigmine - Rx Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade
(postoperative).
Pyridostigmine - Used with glycopyrrolate, hyoscyamine, or propantheline to control pyridostigmine side effects. Rx Myasthenia gravis (long acting);
does not penetrate CNS (quaternary amine). Physostigmine - Crosses blood-brain barrier as not charged > CNS (tertiary amine). Rx Antidote for
anticholinergic toxicity; physostigmine “phyxes” atropine overdose.
Anticholinesterase poisoning - Muscarinic effects - Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Sweating,
Salivation. (DUMBBELSS). Reversed by atropine, a competitive inhibitor. Atropine can cross BBB to relieve CNS symptoms. Nicotinic effects -
Neuromuscular blockade (mechanism similar to succinylcholine). Reversed by pralidoxime, regenerates AChE via dephosphorylation if given early.
Pralidoxime (quaternary amine) does not readily cross BBB.
Muscarinic antagonists-
Atropine, homatropine, tropicamide - Eye - Produce mydriasis and cycloplegia
Benztropine, trihexyphenidyl - CNS - Parkinson disease (“park my Benz”). Acute dystonia.
Glycopyrrolate - GI, respiratory - Parenteral: preoperative use to reduce airway secretions Oral: reduces drooling, peptic ulcer.
Hyoscyamine, dicyclomine - GI - Antispasmodics for irritable bowel syndrome
Ipratropium, tiotropium - Respiratory - COPD, asthma. Duration: tiotropium > ipratropium
Solifenacin, Oxybutynin, Flavoxate, Tolterodine - Genitourinary - Reduce bladder spasms and urge urinary incontinence (overactive bladder). Make
bladder SOFT.
Scopolamine - CNS - Motion sickness
Atropine - Blocks muscarinic effects (DUMBBELSS) of anticholinesterases, but not the nicotinic effects. ADVERSE EFFECTS inc body temperature
(due to dec sweating); inc HR; dry mouth; dry, fushed skin; cycloplegia; constipation; disorientation. Can cause acute angle-closure glaucoma in
elderly (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants. Side effects:Hot as a hare Fast as a fiddle
Dry as a bone Red as a beet Blind as a bat Mad as a hatter Full as a flask.
(Anticholinergic) Jimson weed (Datura) > gardener’s pupil (mydriasis due to plant alkaloids).
Sympathomimetics-
Direct sympathomimetics-
Albuterol, salmeterol, terbutaline - Rx Albuterol for acute asthma/COPD. Salmeterol for serial (long-term) asthma/COPD. Terbutaline for acute
bronchospasm in asthma and tocolysis.
Dobutamine - Rx Cardiac stress testing, acute decompensated heart failure (HF) with cardiogenic shock (inotrope).
Dopamine - Rx Unstable bradycardia, shock; inotropic and chronotropic effects at lower doses via β effects; vasoconstriction at high doses via α
effects.
Epinephrine- Rx Anaphylaxis, asthma, shock, open-angle glaucoma; α effects predominate at high doses. Stronger effect at β2-receptor than
norepinephrine.
Fenoldopam- Rx Postoperative hypertension, hypertensive crisis. Vasodilator (coronary, peripheral, renal, and splanchnic). Promotes natriuresis. Can
cause hypotension, tachycardia, fushing, headache.
Isoproterenol Rx Electrophysiologic evaluation of tachyarrhythmias. Can worsen ischemia. Has negligible α effect.
Midodrine (α1) - Rx Autonomic insuffciency and postural hypotension. May exacerbate supine hypertension.
Mirabegron - Rx Urinary urgency or incontinence or overactive bladder.
Norepinephrine Rx Hypotension, septic shock.
Phenylephrine- Rx Hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant), ischemic priapism.
Indirect sympathomimetics-
Amphetamine - Rx Narcolepsy, obesity, ADHD.
Cocaine - Rx Causes mydriasis in eyes with intact sympathetic innervation > used to confirm Horner syndrome.
Ephedrine - Rx Nasal decongestion (pseudoephedrine), urinary incontinence, hypotension.
Sympatholytics (α2-agonists) -
Clonidine, guanfacine - Rx Hypertensive urgency (limited situations), ADHD, Tourette syndrome, symptom control in opioid withdrawal. SE - CNS
depression, bradycardia, hypotension, respiratory depression, miosis, rebound hypertension with abrupt cessation.
α-methyldopa - Rx Hypertension in pregnancy. SE - Direct Coombs ⊕ hemolysis, drug-induced lupus, hyperprolactinemia.
Tizanidine - Relief of spasticity - Hypotension, weakness, xerostomia.
α-blockers-

Nonselective -
Phenoxybenzamine - Irreversible. Rx Pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis. SE - Orthostatic
hypotension, reflex tachycardia.
Phentolamine - Reversible. Rx Given to patients on MAO inhibitors who eat tyramine-containing foods and for severe cocaine-induced hypertension
(2nd line). Also used to treat norepinephrine extravasation. SE - Orthostatic hypotension, reflex tachycardia.
α1 selective (-osin ending) - Prazosin, terazosin, doxazosin, tamsulosin- Urinary symptoms of BPH; PTSD (prazosin); hypertension (except
tamsulosin). SE - 1st-dose orthostatic hypotension, dizziness, headache.
α2 selective - Mirtazapine - Rx Depression. SE - Sedation, inc serum cholesterol, inc appetite.
β-blockers - Angina pectoris, Glaucoma-Rx Timolol, Heart failure (BMC) Rx Bisoprolol, carvedilol, metoprolol (β-blockers curb mortality),
Hypertension, Hyperthyroidism/thyroid storm Rx Propranolol, Hypertrophic cardiomyopathy, Myocardial infarction, Supraventricular tachycardia
(ME) Rx Metoprolol, esmolol, Variceal bleeding (PNC) Rx Nadolol, propranolol, carvedilol. ADVERSE EFFECTS Erectile dysfunction,
cardiovascular (bradycardia, AV block, HF), CNS (seizures, sleep alterations), dyslipidemia (metoprolol), masked hypoglycemia, asthma/COPD
exacerbations. Use of β-blockers for acute cocaine-associated chest pain remains controversial due to unsubstantiated concern for unopposed α-
adrenergic stimulation.
Nonspecifc PDE inhibitor - Theophylline Rx COPD/asthma (rarely used). SE - Cardiotoxicity (eg, tachycardia, arrhythmia), neurotoxicity (eg, seizures,
headache), abdominal pain.
PDE-5 inhibitors - Sildenafl, vardenafl, tadalafl, avanafl - Rx Erectile dysfunction, Pulmonary hypertension, Benign prostatic hyperplasia (tadalafl
only). SE - Facial fushing, headache, dyspepsia, hypotension in patients taking nitrates; “hot and sweaty,” then headache, heartburn, hypotension.
Sildenafl only: cyanopia (blue-tinted vision) via inhibition of PDE-6 (six) in retina.
PDE-4 inhibitor - Rofumilast - Rx Severe COPD. SE - Abdominal pain, weight loss, depression, anxiety, insomnia.
PDE-3 inhibitor - Milrinone - Rx - Acute decompensated HF with cardiogenic shock (inotrope). SE - Tachycardia, ventricular arrhythmias,
hypotension.
“Platelet inhibitors” Cilostazol, Dipyridamole - Rx - Intermittent claudication, Stroke or TIA prevention (with aspirin), Cardiac stress testing
(dipyridamole only, due to coronary vasodilation). Prevention of coronary stent restenosis. SE - Nausea, headache, facial flushing, hypotension,
abdominal pain.
Ingested seafood toxins -
(BMMT) Histamine (scombroid poisoning) - Spoiled dark-meat fish such as tuna, mahi-mahi, mackerel, and bonito. Bacterial histidine decarboxylase
converts histidine to histamine Frequently misdiagnosed as fish allergy. Mimics anaphylaxis: oral burning sensation, facial flushing, erythema, urticaria,
itching; may progress to bronchospasm, angioedema, hypotension. Rx Antihistamines, Albuterol +/– epinephrine.
Tetrodotoxin - Pufferfish - Binds fast voltage-gated Na+ channels in nerve tissue, preventing depolarization. Nausea, diarrhea, paresthesias, weakness,
dizziness, loss of reflexes. Rx Supportive. (BMS) Ciguatoxin - Reef fish such as barracuda, snapper, and moray eel. Opens Na+ channels, causing
depolarization. Nausea, vomiting, diarrhea; perioral numbness; reversal of hot and cold sensations; bradycardia, heart block, hypotension. Rx
Supportive.
Common causes of pneumonia
NEONATES(< 4 WK) - Group B streptococci, E coli
CHILDREN (4 WK–18 YR) - Viruses (RSV), Mycoplasma, C trachomatis (infants–3 yr), C pneumoniae (schoolaged children), S pneumoniae. Runts
May Cough Chunky Sputum.
ADULTS(18–40 YR) - Mycoplasma, C pneumoniae, S pneumoniae, Viruses (eg, influenza)
ADULTS(40–65 YR) - S pneumoniae, H influenzae, Anaerobes, Viruses, Mycoplasma
ELDERLY - S pneumoniae, Influenza virus, Anaerobes, H influenzae, Gram ⊖ rods
Special groups-
Alcohol overuse - Klebsiella, anaerobes usually due to aspiration (eg, Peptostreptococcus, Fusobacterium, Prevotella, Bacteroides)
IV drug use - S pneumoniae, S aureus
Aspiration - Anaerobes
Atypical - Mycoplasma, Chlamydophila, Legionella, viruses (RSV, CMV, influenza, adenovirus)
Cystic fibrosis - Pseudomonas, S aureus, S pneumoniae, Burkholderia cepacia
Immunocompromised - S aureus, enteric gram ⊖ rods, fungi, viruses, P jirovecii (with HIV)
Nosocomial - S aureus, Pseudomonas, other enteric gram ⊖ rods
Postviral - S pneumoniae, S aureus, H influenzae
COPD - S pneumoniae, H influenzae, M catarrhalis, Pseudomonas
Common causes of meningitis
NEWBORN (0–6 MO) - Group B Streptococcus E coli Listeria
CHILDREN (6 MO–6YR) - S pneumoniae N meningitidis H influenzae type b Group B Streptococcus Enteroviruses
6–60 YR - S pneumoniae N meningitidis Enteroviruses HSV
60 YR+ - S pneumoniae N meningitidis H influenzae type b Group B Streptococcus Listeria
Give ceftriaxone and vancomycin empirically (add ampicillin if Listeria is suspected).
Viral causes of meningitis: enteroviruses (especially coxsackievirus), HSV-2 (HSV-1 = encephalitis), HIV, West Nile virus (also causes encephalitis),
VZV. In HIV: Cryptococcus spp.

Age-related changes in pharmacokinetics - It’s how aging bodies are MADE.

Metabolism - dec hepatic mass, dec hepatic blood flow and dec drug metabolism. Liver transaminases remain the same. Phase I metabolism lost first
with aging. Drugs metabolized during phase II (eg, lorazepam, acetaminophen) are safer than drugs metabolized during phase I (eg, diazepam). Thus
therapeutic doses may suffce in elderly.
Absorption - inc gastric pH, dec gastric emptying. Drug absorption influenced via drug-drug/food interactions.
Distribution - inc body fat content (inc Vd for lipophilic drugs, eg, propofol). Dec albumin (dec binding of acidic drugs). Dec total body water (dec Vd
for hydrophilic drugs, eg, digoxin).
Elimination - dec GFR and dec tubular secretion. Inc plasma concentration of renally excreted drugs; thus dec therapeutic doses may suffice in elderly.
Beers criteria (drugs avoided in elderly) - Examples:
a-blockers (inc risk of hypotension)
Anticholinergics, antidepressants, antihistamines, opioids (inc risk of delirium, sedation, falls, constipation, urinary retention)
Benzodiazepines (inc risk of delirium, sedation, falls)
NSAIDs (inc risk of GI bleeding, especially with concomitant anticoagulation)
PPIs (inc risk of C diffcile infection)

Phenylalanine hydroxylase def - classic PKU

BH4/dihydropteridine def - malignant PKU
Median nerve - travels b/w two heads of pronator teres.
Anti-IgE monoclonal therapy - Omalizumab.
Mepolizumab, reslizumab—against IL-5.
Benralizumab—against IL-5 receptor α.
Cirrhosis -
nodules - hepatocytes
fibrosis - stellate cells of ito
unambiguous vs degenerate/redundant
Degenerate/redundant Exceptions: methionine (AUG) and tryptophan (UGG) encoded by only 1 codon.
NHEJ - Defective in ataxia-telangiectasia.
HR - Defective in breast/ovarian cancers with BRCA1 mutation and in Fanconi anemia.
NER - Defective in xeroderma pigmentosum.
BER - Important in repair of spontaneous/toxic deamination.
MMR - Defective in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]).
Nucleotide excision repair - Occurs in G1 phase of cell cycle. Defective in xeroderma pigmentosum.
Base excision repair - Occurs throughout cell cycle. Important in repair of spontaneous/toxic deamination. AP-Endonuclease, which cleaves 5ʹ end.
AP- Lyase cleaves 3ʹ end. Mismatch repair - Occurs predominantly in S phase of cell cycle. Defective in Lynch syndrome (hereditary nonpolyposis
colorectal cancer [HNPCC]).
Helicase deficient in bloom syndrome
CAP - Binds CAP site, induces transcription. CAP site stimulates promoter site.

Repressor protein - binds operator, blocks transcription.

Shine-Dalgarno sequence—ribosomal binding site in prokaryotic mRNA. Enables protein synthesis initiation by aligning the ribosome with the start
codon so that code is read correctly.
In spinal muscular atrophy, snRNP assembly is affected due to dec SMN protein > congenital degeneration of anterior horns of spinal cord > symmetric
weakness (hypotonia, or “foppy baby syndrome”).
RNA polymerase I makes rRNA.
RNA polymerase II makes mRNA (massive), microRNA (miRNA), and small nuclear RNA (snRNA).
RNA polymerase III makes 5S rRNA, tRNA (tiny).
α-amanitin, found in Amanita phalloides (death cap mushrooms), inhibits RNA polymerase II.
Actinomycin D, also called dactinomycin, inhibits RNA polymerase in both prokaryotes and eukaryotes.
Rifamycins (rifampin, rifabutin) inhibit DNA- dependent RNA polymerase in prokaryotes.

RNA polymerase II opens DNA at promoter site. INITIATION

1. eIFs identify 5’ cap
2. 40s + initiator tRNA

3. mRNA + 60s + 40s/tRNA complex. GTP.

ELONGATION
1. Charged tRNA binds A site. EF & GTP.
2. rRNA - peptide bond formation, transfers polypeptide to A site’s amino acid. 3. Moves peptidyl tRNA to P site (translocation).

TERMINATION
eRFs recognise stop codon > release completed polypeptide. GTP.
ATP—tRNA Activation (charging). GTP—tRNA Gripping and Going places (translocation).
Zellweger syndrome—autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes.
Refsum disease—autosomal recessive disorder of α-oxidation > buildup of phytanic acid due to inability to degrade it.
Adrenoleukodystrophy—X-linked recessive disorder of β-oxidation due to mutation in ABCD1 gene.
Free ribosomes—unattached to any membrane; site of synthesis of cytosolic, peroxisomal, and mitochondrial proteins.
N-linked glycosylation occurs in the eNdoplasmic reticulum.
Mucus-secreting goblet cells of small intestine and antibody-secreting plasma cells are rich in RER.
Proteins within organelles (eg, ER, Golgi bodies, lysosomes) are formed in RER.
Golgi - Posttranslational events in O- oligosaccharides include modifying N-oligosaccharides on asparagine, adding O-oligosaccharides on serine and
threonine, and adding mannose-6-phosphate to proteins for lysosomal and other proteins.
GOlgi is distribution center for proteins and lipids from ER to vesicles and plasma membrane
Endosomes are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the
membrane/Golgi for further use.
Smooth endoplasmic reticulum - Location of glucose-6-phosphatase (last step in both glycogenolysis and gluconeogenesis).
Kartagener syndrome - Lab findings: dec nasal nitric oxide (used as screening test).
Microflaments - Muscle contraction, cytokinesis - Actin, microvilli.
Intermediate flaments - Maintain cell structure - Vimentin, desmin, cytokeratin, lamins, glial fbrillary acidic protein (GFAP), neuroflaments.
Microtubules - Movement, cell division - Cilia, fagella, mitotic spindle, axonal traffcking, centrioles.
bortezomib - proteasome inhibitor
Microtubule - Cylindrical outer structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.
Cilia structure - 9 doublet + 2 singlet arrangement of microtubules. Basal body (base of cilium below cell membrane) consists of 9 microtubule triplets
with no central microtubules.
Hydroxyproline is used for lab quantifcation of collagen.
Type 1 - cornea
Type 4 - lens
EDS -
Hypermobility type (joint instability): most common type.
Classical type (joint and skin symptoms): caused by a mutation in type V collagen (eg, COL5A1, COL5A2).
Vascular type (fragile tissues including vessels [eg, aorta], muscles, and organs that are prone to rupture [eg, gravid uterus]): mutations in type III
procollagen (eg, COL3A1).

Changes with aging: dec dermal collagen and elastin, dec synthesis of collagen fibrils; cross-linking remains normal. PCR - 95, 55, 72
Random insertion—constitutive expression.
Targeted insertion— conditional expression.

MicroRNA - Loose nucleotide pairing allows broad targeting of related mRNAs.

Small interfering RNA - Once inside a cell, siRNA requires complete nucleotide pairing, leading to highly specifc mRNA targeting.
Loss of heterozygosity - Retinoblastoma and the “two-hit hypothesis,” Lynch syndrome (HNPCC), Li-Fraumeni syndrome.
Dominant negative mutation - A single mutated p53 tumor suppressor gene results in a protein that is able to bind DNA and block the nonmutated p53
from binding to the promoter.
XLD - fragile X syndrome, Alport syndrome, hypophosphatemic rickets (also called X-linked hypophosphatemia)— phosphate wasting at proximal
tubule rickets-like presentation.
AD - FAN-FAN-HHH-MMM-LTV
AR - COPS-GF-WASH-KTM
XLR - BLOW-DOG-HHF
If parents and relatives do not have the disease, suspect gonadal (or germline) mosaicism.
HeterodIsomy (heterozygous) indicates a meiosis I error. IsodIsomy (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication
of one of a pair of chromosomes, and loss of the other of the original pair.
Heterodisomy is caused by non-segregation in stage I meiosis, and the affected individual inherits two homologous chromosomes from the same
parent; isodisomy is caused by non-segregation in stage II meiosis, and the affected individual inherits two sister chromatids of one homologous
chromosome from one parent.
Prader-willi - paternal deletion, moti choti female.
Angelman - maternal deletion, happy male puppet.
Locus heterogeneity Mutations at different loci can produce a similar phenotype. Albinism, retinitis pigmentosa, familial hypercholesteremia.
Allelic heterogeneity Different mutations in the same locus produce the same phenotype. B-thalassemia.
AR - Unaffected individual with affected sibling has 2/3 probability of being a carrier.
Inc Na+ reabsorption also causes more negative transepithelial potential difference.
DIAGNOSIS - inc Cl concentration in pilocarpine-induced sweat test is diagnostic.
Inc immunoreactive trypsinogen (newborn screening) due to clogging of pancreatic duct.
Fragile X syndrome - Most common inherited cause of intellectual disability (Down syndrome is most common genetic cause, but most cases occur
sporadically).
Fragile X syndrome - Premutation (50-200 repeats) > tremor, ataxia, 1° ovarian insuffciency. Full mutation (>200 repeats) > postpubertal
macroorchidism (enlarged testes), long face with large jaw, large everted ears, autism, mitral valve prolapse, hypermobile joints.
Common peroneal nerve - foot drop - steppage gait
Parkinsons - shuffling/festinant gait
Duchenne’s - waddling gait
SACD - B12 def - wide based gait
Cerebellar lesion - wide based gait
lumacaftor/tezacaftor - correct misfolding.
ivacaftor - opens Cl- channels.

Down’s syndrome - Most common viable chromosomal disorder and most common cause of genetic intellectual disability. Fragile X syndrome - Most
common inherited cause of intellectual disability.
Rett syndrome - MECP2 on X chromosome.
Charcot marie tooth - Most common type, CMT1A, is caused by PMP22 gene duplication.

aVit A -
Acute toxicity—Pseudotumor cerebri (Inc ICP) (eg, vertigo, blurred vision).
Chronic toxicity—idiopathic intracranial hypertension.
Down’s
1st trimester - β-hCG inc only
2nd trimester - β-hCG and Inhibin A inc only
rest everything is dec irrespective of trimester
Edward’s
everything dec in 1st and 2nd trimester
Patau’s
everything dec in 1st and normal/NA in 2nd trimester
PKD1-16, PKD2-4
TSC1-9, TSC2-16
NF1-17, NF2-22
β-globin 11, α-globin 16
BRCA1-17, BRCA2-13
RB1-13, TP53-17(sum 8)
williams - 7
wilms - 11
wilson - 13
BAD - linoleic acid (omega 6) - arachidonic acid
GOOD - linolenic acid (omega 3) - antihyperlipidemic/cardioprotective
B1 def - Diagnosis made by inc in RBC transketolase activity following vitamin B1 administration.
Niacin - Facial flushing (induced by prostaglandin, not histamine; can avoid by taking aspirin with niacin)
Vancomycin - flushing by histamine release.
(ENDOCRINOLOGY - intermittent PTH release can also stimulate bone formation)
Vit D and K given to breast-fed infants.
Ethanol metabolism inc NADH/ NAD+ ratio in liver, causing: Lactic acidosis, Fasting hypoglycemia, Ketoacidosis, Hepatosteatosis. Malonyl-CoA is
produced during fatty acid synthesis and it inhibits Carnitine acyltransferase I (fatty acid oxidation).
Glycolysis Phosphofructokinase-1 (PFK-1) AMP ⊕, fructose-2,6-bisphosphate ⊕ ATP ⊖, citrate ⊖
Gluconeogenesis Fructose-1,6-bisphosphatase 1 AMP ⊖, fructose-2,6-bisphosphate ⊖
TCA cycle Isocitrate dehydrogenase ADP ⊕ ATP ⊖, NADH ⊖
Glycogenesis Glycogen synthase Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕ Epinephrine ⊖, glucagon ⊖
Glycogenolysis Glycogen phosphorylase Epinephrine ⊕, glucagon ⊕, AMP ⊕ Glucose-6-phosphate ⊖, insulin ⊖, ATP ⊖
HMP shunt Glucose-6-phosphate dehydrogenase (G6PD) NADP+ ⊕ NADPH ⊖
De novo pyrimidine synthesis Carbamoyl phosphate synthetase II (cytoplasm) ATP ⊕, PRPP ⊕ UTP ⊖
De novo purine synthesis Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase AMP ⊖, inosine monophosphate (IMP) ⊖, GMP ⊖ Urea
cycle Carbamoyl phosphate synthetase I (mitochondria) N-acetylglutamate ⊕
Fatty acid synthesis Acetyl-CoA carboxylase (ACC) Insulin ⊕, citrate ⊕ Glucagon ⊖, palmitoyl-CoA ⊖
Fatty acid oxidation Carnitine acyltransferase I Malonyl-CoA ⊖
Ketogenesis HMG-CoA synthase
Cholesterol synthesis HMG-CoA reductase Insulin ⊕, thyroxine ⊕, estrogen ⊕ Glucagon ⊖, cholesterol ⊖
cortisol ⊕ GLYCOGENESIS
UTP ⊖ de novo pyrimidine synthesis
palmitoyl-CoA ⊖ fatty acid synthesis
Malonyl-CoA ⊖ fatty acid oxidation
Palmitoyl-CoA ⊖ fatty acid synthesis (Acetyl-CoA carboxylase (ACC))
Malonyl-CoA ⊖ fatty acid oxidation (Carnitine acyltransferase I)
Glucagon inhibits glycogen synthesis, fatty acid synthesis and cholestrol synthesis
Cholestrol synthesis stimulated by Insulin ⊕, thyroxine ⊕, estrogen ⊕
Palmitoyl-CoA ⊖ fatty acid synthesis (Acetyl-CoA carboxylase (ACC))
Malonyl-CoA ⊖ fatty acid oxidation (Carnitine acyltransferase I)
Glucagon inhibits glycogen synthesis, fatty acid synthesis and cholestrol synthesis
Cholestrol synthesis stimulated by Insulin ⊕, thyroxine ⊕, estrogen ⊕
MA shuttle(heart and liver) - 32 ATP
G3P shuttle(muscle) - 30 ATP
NADPH is used in:
Anabolic processes
Respiratory burst
Cytochrome P-450 system
Glutathione reductase
glucokinase - liver, b-cells
hexokinase - other tissues
glucokinase feedback F6P
hexokinase feedback G6P
Glucokinase deficiency is a cause of maturity onset diabetes of the young (MODY) and gestational diabetes.
Glucokinase is induced by insulin but hexokinase is not.

Oncogenes -
ALK - Receptor tyrosine kinase Lung adenocarcinoma
HER2/neu (ERBB2) - Receptor tyrosine kinase Breast and gastric carcinomas
RET - REceptor Tyrosine kinase MEN 2A and 2B, medullary and papillary thyroid carcinoma, pheochromocytoma
BCR-ABL - Non-receptor tyrosine kinase CML, ALL
JAK2 - Non-receptor tyrosine kinase Myeloproliferative neoplasms
BRAF - Serine/threonine kinase Melanoma, non-Hodgkin lymphoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia c-KIT -
CytoKIne receptor Gastrointestinal stromal tumor (GIST), mastocytosis
c-MYC - Transcription factor Burkitt lymphoma
MYCL1 - Transcription factor Lung cancer
MYCN (N-myc) - Transcription factor Neuroblastoma
KRAS - RAS GTPase Colorectal, lung, pancreatic cancers
BCL-2 - Antiapoptotic molecule (inhibits apoptosis) Follicular and diffuse large B-Cell Lymphomas

Tumor suppressor genes -

APC - Negative regulator of β-catenin/WNT pathway Colorectal cancer (associated with FAP)
BRCA1/BRCA2 - BRCA1/BRCA2 proteins BReast, ovarian, prostate, pancreatic CAncers
CDKN2A - p16, blocks G1 > S phase Many cancers (eg, melanoma, lung)
DCC - DCC—Deleted in Colorecta Cancer Colorectal cancer
SMAD4 (DPC4) - DPC—Deleted in Pancreatic Cancer Pancreatic cancer, colorectal cancer
MEN1 - MENin Multiple Endocrine Neoplasia type 1
NF1 - Neurofbromin (Ras GTPase activating protein) NeuroFibromatosis type 1
NF2 - Merlin (schwannomin) protein NeuroFibromatosis type 2
PTEN - Negative regulator of PI3k/AKT pathway Prostate, breasT, and ENdometrial cancers
RB1 - Inhibits E2F; blocks G1 > S phase Retinoblastoma, osteosarcoma (bone cancer)
TP53 - p53, activates p21, blocks G1 > S phase Most cancers, Li-Fraumeni syndrome (multiple malignancies at early age, aka, SBLA syndrome:
Sarcoma, Breast, Leukemia, Adrenal gland) TSC1 - Hamartin protein Tuberous sclerosis
TSC2 - Tuberin (“2berin”) Tuberous sclerosis
VHL - Inhibits hypoxia-inducible factor 1a von Hippel-Lindau disease
WT1 - Urogenital development transcription factor Wilms Tumor (nephroblastoma)

Carcinogens
Afatoxins (Aspergillus) Stored grains and nuts Liver Hepatocellular carcinoma
Alkylating agents Oncologic chemotherapy Blood Leukemia/lymphoma
Aromatic amines (eg, benzidine, 2-naphthylamine) Textile industry (dyes), tobacco smoke (2-naphthylamine) Bladder Transitional cell carcinoma
Arsenic Herbicides (vineyard workers), metal smelting, wood preservation Liver Lung Skin Hepatic angiosarcoma Lung cancer Squamous cell
carcinoma
Asbestos Old roofing material, shipyard workers Lung Bronchogenic carcinoma > mesothelioma
Tobacco smoke Bladder Cervix Esophagus Kidney Larynx Lung Oropharynx Pancreas Transitional cell carcinoma Squamous cell carcinoma
Squamous cell carcinoma/ adenocarcinoma Renal cell carcinoma Squamous cell carcinoma Squamous cell and small cell carcinoma Oropharyngeal
cancer Pancreatic adenocarcinoma
Ethanol Esophagus Liver Breast Squamous cell carcinoma Hepatocellular carcinoma Breast cancer
Ionizing radiation Thyroid Papillary thyroid carcinoma, leukemias
Nickel, chromium, beryllium, silica Occupational exposure Lung Lung cancer
Nitrosamines Smoked foods Stomach Gastric cancer (intestinal type)
Radon Byproduct of uranium decay, accumulates in basements Lung Lung cancer (2nd leading cause after tobacco smoke)
Vinyl chloride Used to make PVC pipes (plumbers) LiVer Hepatic angiosarcoma

Oncogenic microbes -
EBV Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, 1° CNS lymphoma (in immunocompromised patients) HBV, HCV
Hepatocellular carcinoma
HHV-8 Kaposi sarcoma
HPV (usually types 16, 18) Cervical and penile/anal carcinoma, head and neck cancer
H pylori Gastric adenocarcinoma and MALT lymphoma
HTLV-1 Adult T-cell Leukemia/Lymphoma
Liver fluke (Clonorchis sinensis) Cholangiocarcinoma
Schistosoma haematobium Squamous cell bladder cancer

Serum tumor markers -

Alkaline phosphatase Metastases to bone or liver, Paget disease of bone, seminoma (placental ALP). Exclude hepatic origin by checking LFTs and
GGT levels.
α-fetoprotein Hepatocellular carcinoma, endodermal sinus (yolk sac) tumor, mixed germ cell tumor, ataxia-telangiectasia, neural tube defects.
Normally made by fetus. Transiently elevated in pregnancy. High levels associated with neural tube and abdominal wall defects, low levels associated
with Down syndrome.
hCG Hydatidiform moles and Choriocarcinomas (Gestational trophoblastic disease), testicular cancer, mixed germ cell tumor. Produced by
syncytiotrophoblasts of the placenta. CA15-3/CA27-29 Breast cancer.
CA 19-9 Pancreatic adenocarcinoma.
CA 125 Ovarian cancer.
Calcitonin Medullary thyroid carcinoma (alone and in MEN2A, MEN2B). Calci2nin.
CEA Colorectal and pancreatic cancers. Minor associations: gastric, breast, and medullary thyroid carcinomas. CarcinoEmbryonic Antigen. Very
nonspecifc.
Chromogranin Neuroendocrine tumors.
LDH Testicular germ cell tumors, ovarian dysgerminoma, other cancers. Can be used as an indicator of tumor burden.
Neuron-specifc enolase Neuroendocrine tumors (eg, small cell lung cancer, carcinoid tumor, neuroblastoma).
PSA Prostate cancer. Prostate-Specifc Antigen. Also elevated in BPH and prostatitis. Questionable risk/beneft for screening. Marker for recurrence
after treatment.

Important immunohistochemical stains -

Chromogranin and synaptophysin Neuroendocrine cells Small cell carcinoma of the lung, carcinoid tumor, neuroblastoma
Cytokeratin Epithelial cells Epithelial tumors (eg, squamous cell carcinoma)
Desmin Muscle Muscle tumors (eg, rhabdomyosarcoma)
GFAP NeuroGlia (eg, astrocytes, Schwann cells, oligodendrocytes) Astrocytoma, Glioblastoma
Neuroflament Neurons Neuronal tumors (eg, neuroblastoma)
PSA Prostatic epithelium Prostate cancer
S-100 Neural crest cells Melanoma, schwannoma, Langerhans cell histiocytosis
TRAP Tartrate-resistant acid phosphatase Hairy cell leukemia
Vimentin Mesenchymal tissue (eg, fibroblasts, endothelial cells, macrophages) Mesenchymal tumors (eg, sarcoma), but also many other tumors (eg,
endometrial carcinoma, renal cell carcinoma, meningioma).

PSAMMOMaS bodies are seen in: Papillary carcinoma of thyroid, Somatostatinoma, Adrenals (calcifying fbrous pseudotumor), Meningioma,
Malignant Mesothelioma, Ovarian serous carcinoma, Prolactinoma (Milk), Serous endometrial carcinoma.

Paraneoplastic syndromes
Musculoskeletal and cutaneous-
Dermatomyositis Progressive proximal muscle weakness, Gottron papules, heliotrope rash Adenocarcinomas, especially ovarian
Acanthosis nigricans Hyperpigmented velvety plaques in axilla and neck Gastric adenocarcinoma and other visceral malignancies
Sign of Leser-Trélat Sudden onset of multiple seborrheic keratoses GI adenocarcinomas and other visceral malignancies
Hypertrophic osteoarthropathy Abnormal proliferation of skin and bone at distal extremities > clubbing, arthralgia, joint effusions, periostosis of
tubular bones. Adenocarcinoma of the lung. Endocrine-
Hypercalcemia - PTHrP - SCa2+mous cell carcinomas of lung, head, and neck; renal, bladder, breast, and ovarian carcinomas. Inc 1,25-(OH)2 vitamin
D3 (calcitriol) - Lymphoma.

Cushing syndrome inc ACTH Small cell lung cancer

Hyponatremia (SIADH) inc ADH Small cell lung cancer
Hematologic-
Polycythemia inc Erythropoietin Paraneoplastic rise to High hematocrit levels Pheochromocytoma, renal cell carcinoma, HCC, hemangioblastoma,
leiomyoma Pure red cell aplasia Anemia with low reticulocytes Thymoma

Good syndrome Hypogammaglobulinemia Thymoma

Trousseau syndrome - Migratory superfcial thrombophlebitis Adenocarcinomas, especially pancreatic.
Nonbacterial thrombotic (marantic) endocarditis - Deposition of sterile platelet thrombi on heart valves - Adenocarcinomas, especially pancreatic
Neuromuscular-
Anti-NMDA receptor encephalitis Psychiatric disturbance, memory defcits, seizures, dyskinesias, autonomic instability, language dysfunction Ovarian
teratoma
Opsoclonusmyoclonus ataxia syndrome “Dancing eyes, dancing feet” Neuroblastoma (children), small cell lung cancer (adults)
Paraneoplastic cerebellar degeneration Antibodies against antigens in Purkinje cells Small cell lung cancer (anti-Hu), gynecologic and breast cancers
(anti-Yo), and Hodgkin lymphoma (anti-Tr) Paraneoplastic encephalomyelitis Antibodies against Hu antigens in neurons Small cell lung cancer
Lambert-Eaton myasthenic syndrome Antibodies against presynaptic (P/Q-type) Ca2+ channels at NMJ Small cell lung cancer
Myasthenia gravis Antibodies against postsynaptic ACh receptors at NMJ Thymoma
Posterior cerebral artery - Occipital lobe. Contralateral hemianopia with macular sparing; alexia without agraphia (dominant hemisphere, extending to
splenium of corpus callosum); prosopagnosia (nondominant hemisphere).
Basilar artery (think lower midbrain and upper pons) - Pons, medulla, lower midbrain - Reticular activating system (RAS). Corticospinal and
corticobulbar tracts. Ocular cranial nerve nuclei, paramedian pontine reticular formation. Locked-in syndrome.
Anterior inferior cerebellar artery - Facial nucleus. Vestibular nuclei. Spinothalamic tract, spinal trigeminal nucleus. Sympathetic fbers. Middle and
inferior cerebellar peduncles. Labyrinthine artery. Lateral pontine syndrome.
Posterior inferior cerebellar artery - Nucleus ambiguus (CN IX, X, XI). Vestibular nuclei. Lateral spinothalamic tract, spinal trigeminal nucleus.
Sympathetic fbers. Inferior cerebellar peduncle. Lateral medullary (Wallenberg) syndrome.
Anterior spinal artery - Corticospinal tract. Medial lemniscus. Caudal medulla—hypoglossal nerve (tongue deviates ipsilaterally - pushing effect).
Medial Medullary syndrome— caused by infarct of paramedian branches of ASA and/or vertebral arteries.

If > 12 mEq/L then Inc Anion gap Metabolic acidosis - GOLDMARK: Glycols (ethylene glycol, proplyene glycol) Oxoproline (toxic metabolite of
acetaminophen) L-lactate (lactic acidosis) D-lactate (exogenous lactic acid) Methanol (and other alcohols) Aspirin (late e ect) Renal failure Keytones
(diabetic, alcoholic, starvation).
If 8–12 mEq/L then Normal anion gap - HARDASS Hyperchloremia/hyperalimentation Addison disease Renal tubular acidosis Diarrhea
Acetazolamide Spironolactone Saline infusion
Distal renal tubular acidosis (RTA type 1) - Inability of a-intercalated cells to secrete H+ > no new HCO3 – is generated > metabolic acidosis. URINE
pH > 5.5. SERUM K+ dec.

Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption > inc excretion of HCO3 – in urine > metabolic acidosis. Urine pH
- < 5.5 when plasma HCO3 – below reduced resorption threshold. > 5.5 when filtered HCO3 – exceeds resorptive threshold. SERUM K+ dec.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia > dec NH3 synthesis in PCT > dec NH4 +
excretion. Urine pH - < 5.5 (or variable). SERUM K+ inc.

Distal renal tubular acidosis (RTA type 1) - Inability of a-intercalated cells to secrete H+.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia.
Glomerular diseases-
Nephritic syndrome PGI-AM - Examples Acute poststreptococcal glomerulonephritis Goodpasture syndrome IgA nephropathy (Berger disease) Alport
syndrome Membranoproliferative glomerulonephritis.
Nephrotic syndrome MAD-FM - EXAMPLES May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process): Focal
segmental glomerulosclerosis (1° or 2°) Minimal change disease (1° or 2°) Membranous nephropathy (1° or 2°) Amyloidosis (2°) Diabetic
glomerulonephropathy (2°)
Nephritic-nephrotic syndrome DPGN and MPGN - Diffuse proliferative glomerulonephritis, Membranoproliferative glomerulonephritis.
Tay-Sachs disease - DEFICIENT ENZYME Hexosaminidase A (“TAy-Sax”). ACCUMULATED SUBSTRATE GM2 ganglioside. AR
Fabry disease DEFICIENT ENZYME α-galactosidase A. ACCUMULATED SUBSTRATE Ceramide trihexoside (globotriaosylceramide). XR
Metachromatic leukodystrophy DEFICIENT ENZYME Arylsulfatase A. ACCUMULATED SUBSTRATE Cerebroside sulfate. AR
Krabbe disease DEFICIENT ENZYME Galactocerebrosidase (galactosylceramidase). ACCUMULATED SUBSTRATE Galactocerebroside,
psychosine. AR
Gaucher disease DEFICIENT ENZYME Glucocerebrosidase (β-glucosidase); treat with recombinant glucocerebrosidase. ACCUMULATED
SUBSTRATE Glucocerebroside. AR
Niemann-Pick disease DEFICIENT ENZYME Sphingomyelinase. ACCUMULATED SUBSTRATE Sphingomyelin. AR.
Hurler syndrome - DEFICIENT ENZYME α-l-iduronidase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. AR
Hunter syndrome - DEFICIENT ENZYME Iduronate-2 (two)- sulfatase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. XR.
Brain - Lung > breast > melanoma, colon, kidney (lots of brain metastases can kill)
Liver - Colon >> stomach > pancreas (cancer sometimes penetrates liver)
Bone - Prostate, breast > kidney, thyroid, lung (painful bones kill the lungs)
Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis
P-selectin (released from Weibel- palade bodies) + sialyl lewis
GlyCAM-1/CD34 + L-selectin
Adhesion-
defective in LAD type 1 (dec CD18/LFA-1 integrin subunit)
ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1)
VCAM-1 (CD106) + VLA-4 integrin
Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
PSGN - LM—glomeruli enlarged and hypercellular. IF - (“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition
along GBM and mesangium. EM—subepithelial IC humps.
Type 1 MPGN - subendothelial IC deposits + granular IF. Type 2 MPGN - intramembranous deposits.
DPGN - LM—“wire looping” of capillaries. IF—granular; EM—subendothelial, sometimes subepithelial or intramembranous IgG-based ICs often
with C3 deposition.
Berger ds - LM—mesangial proliferation IF—IgA-based IC deposits in mesangium; EM—mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
Diabetic glomerulonephropathy - LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions).
Minimal change ds - LM—Normal glomeruli (lipid may be seen in PCT cells). IF—⊖. EM—effacement of podocyte foot processes.
FSGS - LM—segmental sclerosis and hyalinosis. IF—often ⊖ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1. EM—EFFACEMENT OF
FOOT PROCESSES SIMILAR TO MINIMAL CHANGE DS. Membranous nephropathy - LM—diffuse capillary and GBM thickening. IF—granular
due to immune complex (IC) deposition. EM—“Spike and dome” appearance of subepithelial deposits. Amyloidosis - LM—Congo red stain shows
apple-green birefringence under polarized light due to amyloid deposition in the mesangium
PSGN - subepithelial IC humps
Membranous nephropathy - EM—“Spike and dome” appearance of subepithelial deposits.
Type 1 MPGN - subendothelial IC deposits + granular IF
Type 2 MPGN - intramembranous deposits
DPGN - MC subendothelial, sometimes subepithelial or intramembranous deposits
Berger ds - mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.

(In proliferative GN (MPGN and DPGN) deposits are subendothelial/intramembranous. In PSGN and membranous nephropathy deposits are
subepithelial.) Filtered load = GFR × Px.
Excretion rate = V × Ux.
Reabsorption rate = filtered – excreted.

Secretion rate = excreted – filtered FeNa = Na+ excreted/Na+ filtered = (V × UNa)/(GFRxPNa) =

(PCr × UNa)/(UCr × PNa)

where GFR = (UCr × V)/PCr.

FeNA = (PCr × UNa)/(UCr × PNa)
Fanconi syndrome - DEFECTS Generalized reabsorption defect in PCT > inc excretion of amino acids, glucose, HCO3 – , and PO4 3–, and all
substances reabsorbed by the PCT.
Bartter syndrome - DEFECTS Reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter).
Gitelman syndrome - DEFECTS Reabsorption defect of NaCl in DCT.
Liddle syndrome - DEFECTS Gain of function mutation > dec Na+ channel degradation > inc Na+ reabsorption in collecting tubules.
Syndrome of Apparent Mineralocorticoid Excess - DEFECTS - Hereditary 11β-HSD deficiency > inc cortisol > inc mineralocorticoid receptor activity.
Fanconi - EFFECTS Metabolic acidosis (proximal RTA), hypokalemia, HYPOPHOSPHATEMIA
(like loops) Bartter - EFFECTS Metabolic alkalosis, hypokalemia, HYPERCALCIURIA.
(like thiazides) Gittelman - EFFECTS Metabolic alkalosis, hypokalemia, HYPOMAGNESEMIA, HYPOCALCIURIA.
Liddle - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
SAME - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
(All have hypokalemia. All have metabolic alkalosis except fanconi syndrome (proximal RTA).)
(First is fanconi, rest are alphabetical)
See diagram on page 611. [TF/P] > 1 = KCU-ICP. [TF/P] < 1 = HAG. [TF/P] = 1 = Na+.
(K+,Cl-,urea,inulin, creatinine,PAH) (HCO3-,amino acids,glucose)
HYPOKALEMIA - Hypo-osmolarity, Alkalosis, β-adrenergic agonist (inc Na+/K+ ATPase), Insulin (inc Na+/K+ ATPase), Insulin shifts K+ into cells.
(BHAI).
HYPERKALEMIA - Digoxin (blocks Na+/K+ ATPase), HyperOsmolarity, Lysis of cells (eg, crush injury, rhabdomyolysis, tumor lysis syndrome),
Acidosis, β-blocker, High blood Sugar (insulin deficiency), Succinylcholine (inc risk in burns/muscle trauma). (Hyperkalemia? DO LAβSS).
Calcium oxalate: hypocitraturia - Radiopaque - Radiopaque - Shaped like envelope or dumbbell. Treatment: thiazides, citrate, low-sodium diet.
Calcium phosphate: inc pH. Xray-Radiopaque, CT-Radiopaque. Wedgeshaped prism. Treatment: low-sodium diet, thiazides.
Ammonium magnesium phosphate (struvite) - inc pH. XRAY - Radiopaque. CT - Radiopaque. Coffin lid. Treatment: eradication of underlying
infection, surgical removal of stone.
Uric acid - dec pH. XRAY - Radiolucent. CT - Visible. Rhomboid or rosettes. Treatment: alkalinization of urine, allopurinol.
Cystine - dec pH. XRAY - Faintly radiopaque. CT - Moderately radiopaque. Hexagonal. Treatment: low sodium diet, alkalinization of urine, chelating
agents (eg, tiopronin, penicillamine) if refractory. Prerenal - URINE OSMOLALITY (mOsm/kg) >500. URINE Na+ (mEq/L) <20. FENa <1%.
SERUM BUN/Cr >20.
Intrinsic - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) >40. FENa >2%. SERUM BUN/Cr <15.
Postrenal - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) Varies. FENa Varies. SERUM BUN/Cr Varies.
Distal renal tubular acidosis (RTA type 1) - Inability of -intercalated cells to secrete H+ > no new HCO3 – is generated > metabolic acidosis. URINE
pH > 5.5. SERUM K+ dec.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption > inc excretion of HCO3 – in urine > metabolic acidosis. Urine pH
- < 5.5 when plasma HCO3 – below reduced resorption threshold. > 5.5 when filtered HCO3 – exceeds resorptive threshold. SERUM K+ dec.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia > dec NH3 synthesis in PCT > dec NH4 +
excretion. Urine pH - < 5.5 (or variable). SERUM K+ inc.
Plasma volume = TBV x (1 – Hct). (TBV=total blood volume).
Renal clearance - Cx = (Ux V)/Px
Cinulin = GFR = Uinulin V/Pinulin = Kf [(PGC – PBS) – ( GC – BS)] (GC = glomerular capillary; BS = Bowman space; BS normally equals zero; Kf
= filtration coefficient).
Inulin clearance = GFR
Creatine clearance approximates GFR (slightly overestimates)
PAH clearance = eRPF (eRPF slightly underestimates true RPF)
eRPF = UPAH x V/PPAH = CPAH.
Renal blood flow (RBF) = RPF/(1 - Hct).
Plasma volume = TBV x (1 – Hct)
RPF = RBF x (1 - Hct)
Cinulin = GFR = Uinulin V/Pinulin
Cpah = eRPF = Upah V/Ppah.
Follicular cyst - Most common ovarian mass in young females.
Ovarian tumors - Most common adnexal mass in females > 55 years old.
Serous cystadenoma - Most common ovarian neoplasm.
Serous carcinoma - Most common malignant ovarian neoplasm.
Mature cystic teratoma (dermoid cyst) - Most common ovarian tumor in young females.
Dysgerminoma - Malignant. Most common in adolescents. Sheets of uniform “fried egg” cells. Tumor markers: inc hCG, inc LDH.
Yolk sac tumor (endodermal sinus tumor) - Schiller-Duval bodies (resemble glomeruli). Tumor marker: inc AFP.
Granulosa cell tumor - Most common malignant sex cord stromal tumor. Call-Exner bodies (granulosa cells arranged haphazardly around collections of
eosinophilic fuid, resembling primordial follicles). Tumor marker: inc inhibin.
Endometrial carcinoma - Most common gynecologic malignancy.
Endometriod type endometrial carcinoma - Early pathogenic events include loss of PTEN or mismatch repair proteins.
Leiomyoma (fibroid) - Most common tumor in females.
VD = VT x (Paco2 – Peco2)/Paco2

VE = VT x RR
VA = (VT - VD) x RR
Oxygen content of blood O2 content = (1.34 x Hb x Sao2 ) + (0.003 x Pao2).
O2 delivery to tissues = cardiac output x O2 content of blood.
Bronchi and proximal bronchiole - columnar, goblet cells and cilia
Terminal and respiratory bronchiole - cuboidal, club cells and cilia
Ciliated epithelium persists up to the respiratory bronchioles.
Cilia are last to disappear. Cilia terminate in respiratory bronchioles.
Lung development - EPCSA - 7, 17 ,25, birth, 8 years
Diffusion: V̇ gas = A × Dk × (P1 – P2)/Δx
Pulmonary vascular resistance
PVR = (Ppulm artery – PL atrium)/Q
Remember: ΔP = Q × R, so R = ΔP / Q
R = 8ηl/πr4
PAo2 = PIo2 – (Paco2/R) ≈ 150 mm Hga – (Paco2/0.8)
Sites of metastases from lung cancer: liver (jaundice, hepatomegaly), adrenals, bone (pathologic fracture), brain. Lung mets - Most often from breast,
colon, prostate, and bladder cancer.

Ethylene glycol/methanol intoxication Fomepizole (alcohol dehydrogenase inhibitor)

Chronic hepatitis B or C IFN-α (HBV and HCV); ribavirin, simeprevir, sofosbuvir (HCV)
Streptococcus bovis Penicillin prophylaxis; evaluation for colon cancer if linked to endocarditis
Clostridium botulinum Human botulinum immunoglobulin
Clostridium tetani Antitoxin and wound debridement
Clostridium difficile Oral metronidazole; if refractory, oral vancomycin. Refractory cases: repeat regimen or fecal microbiota transplant
Haemophilus influenzae (B) Amoxicillin ± clavulanate (mucosal infections), ceftriaxone (meningitis), rifampin (prophylaxis)
Neisseria gonorrhoeae Ceftriaxone (add azithromycin or doxycycline to cover likely concurrent C trachomatis)
Neisseria meningitidis Penicillin/ceftriaxone, rifampin/ciprofloxacin/ceftriaxone (prophylaxis)
Legionella pneumophila Macrolides (eg, azithromycin or fluoroquinolones)
Pseudomonas aeruginosa Piperacillin-tazobactam, cephalosporins, monobactams, fluoroquinolones, carbapenems
Treponema pallidum Penicillin G
Chlamydia trachomatis Azithromycin or doxycycline (+ ceftriaxone for gonorrhea coinfection), oral erythromycin to treat chlamydial conjunctivitis in
infants Candida albicans Topical azoles (vaginitis); nystatin, fluconazole, caspofungin (oral); fluconazole, caspofungin,
amphotericin B (esophageal or systemic)
Cryptococcus neoformans Induction with amphotericin B and flucytosine, maintenance with fluconazole (in AIDS patients)
Sporothrix schenckii Itraconazole, oral potassium iodide 154
Pneumocystis jirovecii TMP-SMX (prophylaxis and treatment in immunosuppressed patients, CD4 < 200/mm3)
Toxoplasma gondii Sulfadiazine + pyrimethamine 156
Malaria Chloroquine, mefloquine, atovaquone/proguanil (for blood schizont), primaquine (for liver hypnozoite)
Trichomonas vaginalis Metronidazole (patient and partner[s]) 158
Streptococcus pyogenes Penicillin prophylaxis 187
Streptococcus pneumoniae Penicillin/cephalosporin (systemic infection, pneumonia), 187, vancomycin (meningitis) 190
Staphylococcus aureus MSSA: nafcillin, oxacillin, dicloxacillin 188, (antistaphylococcal penicillins); MRSA: vancomycin, 190, daptomycin, linezolid,
ceftaroline Enterococci Vancomycin, aminopenicillins/cephalosporins. VRE: 189, daptomycin, linezolid, tigecycline, streptogramins
Rickettsia rickettsii Doxycycline, chloramphenicol 192
Mycobacterium tuberculosis RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) 196
UTI prophylaxis TMP-SMX 198
Influenza Oseltamivir, zanamivir 201
CMV Ganciclovir, foscarnet, cidofovir 202
Patent ductus arteriosus Close with indomethacin; keep open with PGE analogs 291
Stable angina Sublingual nitroglycerin 312
Hypercholesterolemia Statin (first-line) 328
Hypertriglyceridemia Fibrate 328
Arrhythmia in damaged cardiac tissue Class IB antiarrhythmic (lidocaine, mexiletine) 330
Prolactinoma Cabergoline/bromocriptine (dopamine agonists) 338
Diabetes insipidus Desmopressin (central); hydrochlorothiazide, 346 indomethacin, amiloride (nephrogenic)
SIADH Fluid restriction, IV hypertonic saline, conivaptan/ 346 tolvaptan, demeclocycline
Diabetic ketoacidosis/hyperosmolar hyperglycemic state Fluids, insulin, K+ 355
Pheochromocytoma α-antagonists (eg, phenoxybenzamine) 359
Carcinoid syndrome Octreotide, telotristat 361
Diabetes mellitus type 1 Dietary intervention (low carbohydrate) + insulin 362 replacement
Diabetes mellitus type 2 Dietary intervention, oral hypoglycemics, and insulin (if 362 refractory)
Crohn disease Corticosteroids, infliximab, azathioprine 392
Ulcerative colitis 5-ASA preparations (eg, mesalamine), 6-mercaptopurine, 392 infliximab, colectomy
Sickle cell disease Hydroxyurea (inc fetal hemoglobin) 432
Chronic myelogenous leukemia BCR-ABL tyrosine kinase inhibitors (eg, imatinib) 442
Acute promyelocytic leukemia (M3) All-trans retinoic acid, arsenic trioxide 442
Drug of choice for anticoagulation in pregnancy Low-molecular-weight heparin 445
Immediate anticoagulation Heparin 445
Long-term anticoagulation Warfarin, dabigatran, direct factor Xa inhibitors 446
Heparin reversal Protamine sulfate 447
Warfarin reversal Vitamin K (slow) +/– fresh frozen plasma or prothrombin 447 complex concentrate (rapid)
Dabigatran reversal Idarucizumab 447
Direct factor Xa inhibitor reversal Andexanet alfa 447
HER2 ⊕ breast cancer Trastuzumab 452
Hemorrhagic cystitis from cyclophosphamide/ifosfamide Mesna 453
Nephrotoxicity from platinum compounds Amifostine 453
Cardiotoxicity from anthracyclines Dexrazoxane 453
Myelosuppression from methotrexate Leucovorin 453
Osteoporosis Calcium/vitamin D supplementation (prophylaxis); 474 bisphosphonates, PTH analogs, SERMs, calcitonin,denosumab (treatment)
Osteomalacia/rickets Vitamin D supplementation 475
Chronic gout Xanthine oxidase inhibitors (eg, allopurinol, febuxostat); 479 pegloticase; probenecid
Acute gout attack NSAIDs, colchicine, glucocorticoids 479
Buerger disease Smoking cessation 484
Kawasaki disease IVIG, aspirin 484
Temporal arteritis High-dose glucocorticoids 484
Granulomatosis with polyangiitis Cyclophosphamide, glucocorticoids 485
Neural tube defect prevention Prenatal folic acid 505
Migraine Abortive therapies (eg, sumatriptan, NSAIDs); prophylaxis 536 (eg, propranolol, topiramate, anti-CGRP antibodies, amitriptyline)
Multiple sclerosis Disease-modifying therapies (eg, β-interferon, glatiramer, 541 natalizumab); for acute flares, use IV steroids
Tonic-clonic seizures Levetiracetam, phenytoin, valproate, carbamazepine 564
Absence seizures Ethosuximide 564
Trigeminal neuralgia (tic douloureux) Carbamazepine
Malignant hyperthermia Dantrolene
Anorexia Nutrition, psychotherapy, SSRIs
Bulimia nervosa Nutrition rehabilitation, psychotherapy, SSRIs
Alcohol use disorder Disulfiram, acamprosate, naltrexone, supportive care
ADHD Methylphenidate, amphetamines, behavioral therapy, atomoxetine, guanfacine, clonidine
Alcohol withdrawal Long-acting benzodiazepines
Bipolar disorder Mood stabilizers (eg, lithium, valproic acid, carbamazepine), atypical antipsychotics
Depression SSRIs (first-line)
Generalized anxiety disorder SSRIs, SNRIs (first line); buspirone (second line)

Schizophrenia Atypical antipsychotics

Hyperaldosteronism Spironolactone
Benign prostatic hyperplasia α1-antagonists, 5α-reductase inhibitors, PDE-5 inhibitors, TURP
Infertility Leuprolide, GnRH (pulsatile), clomiphene
Breast cancer in postmenopausal woman Aromatase inhibitor (anastrozole)
ER/PR ⊕ breast cancer Tamoxifen
Uterine fibroids Leuprolide, GnRH (continuous)
Medical abortion Mifepristone
Prostate adenocarcinoma Flutamide, GnRH (continuous), degarelix, ketoconazole
Erectile dysfunction Sildenafil
Pulmonary arterial hypertension (idiopathic) Sildenafil, bosentan, epoprostenol, iloprost
Common antibiotic resistance mechanisms
PENICILLINS Beta-lactamase, ESBL , Mutated PBP, Mutated porin protein
VANCOMYCIN Mutated peptidoglycan cell wall, Impaired influx/increased efflux
QUINOLONES Mutated DNA gyrase, Impaired influx/increased efflux
AMINOGLYCOSIDES Aminoglycoside-modifying enzymes , Mutated ribosomal subunit protein , Mutated porin protein
TETRACYCLINES Impaired influx/increased efflux , Inactivated enzyme
RIFAMYCINS Mutated RNA polymerase
ESBL = extended-spectrum beta-lactamase; PBP = penicillin-binding protein.
Mutated porin protein - penicillins, aminoglycosides
Impaired influx/increased efflux - vancomycin, quinolones, tetracyclines
Collagen - Type I Most common (90%)—Bone (made by osteoblasts), Skin, Tendon, dentin, fascia, cornea, late wound repair. Type I: bone, tendone.
Dec production in osteogenesis imperfecta type I. Type II Cartilage (including hyaline), vitreous body, nucleus pulposus. Type II: cartwolage.
Type III Reticulin—skin, blood vessels, uterus, fetal tissue, early wound repair. Type III: defcient in vascular type of EhlersDanlos syndrome (threE D).
Type IV Basement membrane (basal lamina), lens. Type IV: under the foor (basement membrane). Defective in Alport syndrome; targeted by
autoantibodies in Goodpasture syndrome.
Collagen synthesis and structure SHG-EPC
[Link]—translation of collagen chains (preprocollagen)—usually Gly-X-Y (X and Y are proline or lysine). Collagen is 1 ⁄3 glycine; glycine
content of collagen is less variable than that of lysine and proline. [Link] is used for lab quantifcation of collagen. Hydroxylation—
hydroxylation (“hydroxCylation”) of specifc proline and lysine residues. Requires vitamin C; defciency scurvy. [Link]—glycosylation of pro-
-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfde bonds (triple helix of 3 collagen chains). Problems forming
triple helix > osteogenesis imperfecta.
[Link]—exocytosis of procollagen into extracellular space.
[Link] processing—cleavage of disulfde-rich terminal regions of procollagen > insoluble tropocollagen. [Link]-linking—reinforcement of many
staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by copper- containing lysyl oxidase) to make collagen fbrils. Cross-
linking of collagen increases with age. Problems with crosslinking > Menkes disease. Osteogenesis imperfecta - Patients can’t BITE: Bones = multiple
fractures I (eye) = blue sclerae Teeth = dental imperfections Ear = hearing loss.
Menkes disease X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein
ATP7A (Absent copper), vs ATP7B in Wilson disease (copper Buildup). Leads to dec activity of lysyl oxidase (copper is a necessary cofactor) >
defective collagen.
Elastin - Rich in nonhydroxylated proline, glycine, and lysine residues, vs the hydroxylated residues of collagen.
Marfan - FBN1 gene mutation on chromosome 15 (fifteen) results in defective fibrillin-1, a glycoprotein that forms a sheath around elastin and
sequesters TGF-B.
Marfan syndrome INHERITANCE Autosomal dominant INTELLECT Normal VASCULAR COMPLICATIONS Aortic root dilatation LENS
DISLOCATION Upward (Marfan fans out)
Homocystinuria INHERITANCE Autosomal recessive INTELLEC Decreased VASCULAR COMPLICATIONS Thrombosis LENS DISLOCATION
Downward

Km is inversely related to the affnity of the enzyme for its substrate. Vmax is directly proportional to the enzyme concentration.
The closer to 0 on the Y-axis, the higher the Vmax.
The closer to 0 on the X-axis, the higher the Km.

The higher the Km, the lower the affnity.

Competitive inhibitors cross each other, whereas noncompetitive inhibitors do not.
Kompetitive inhibitors increase Km.
Bioavailability F = [AUCoral x DoseIV] / [Doseoral x AUCIV]
CL = rate of elimination of drug/plasma drug concentration = Vd x Ke (elimination constant)
t1/2 = (0.7 x Vd)/CL in first-order elimination
Loading dose = (Cp x Vd)/F
Maintenance dose = (Cp x CL x t)/F
TI = TD50/ED50 = median toxic dose/median effective dose
Gq - (q-tie), HAVe 1 M&M! - H1, α1, V1, M1, M3
Gi - too (2) MAD - M2, α2, D2
Gs - HD-BV - β1, β2, β3, D1, H2, V2
ANS RECEPTORS-
↑ IP3 - alpha-1 - Peripheral vasoconstriction, Urethral constriction, Pupillary dilation
↓ cAMP - alpha-2 - CNS sympatholytic, ↓ INSULIN RELEASE & INTESTINAL MOTILITY
↑ cAMP - beta-1 - ↑ Cardiac contractility & heart rate, ↑ Renin release by JG cells of kidney
↑ cAMP - beta-2 - Peripheral vasodilation, Bronchodilation, inc INSULIN RELEASE
↓ cAMP - M2 - ↓ Cardiac contractility & heart rate
↑ IP3 - M3 - Bronchoconstriction, ↑ INSULIN RELEASE & INTESTINAL MOTILITY, Bladder contraction, Pupillary constriction, Peripheral
vasodilation* (*Via release of nitric oxide). ↑ IP3 - alpha-1, M3
↑ cAMP - beta-1, beta-2
↓ cAMP - alpha-2, M2
M3 - inc INSULIN RELEASE & INTESTINAL MOTILITY
a2 - dec INSULIN RELEASE & INTESTINAL MOTILITY
B2 - inc INSULIN RELEASE
M3 and B2 - inc insulin release.
All 3 inc CO and HR.
Dopamine/epinephrine - inc BP (high dose)
Dobutamine - no effect or dec
Fenoldopam - dec BP
Arsenic (DS) - Dimercaprol, succimer
Mercury (DS) - Dimercaprol, succimer
Copper - “Penny”cillamine (penicillamine), trientine (3 copper pennies)
Lead (PEDS) - Calcium disodium EDTA, dimercaprol, succimer, penicillamine
Inducers - SGPC-CMRN-P
Substrates - The OCPs are Anti-War
Inhibitors - [Link]-RAG
Specifc toxicity treatments-

Acetaminophen - N-acetylcysteine (replenishes glutathione)

AChE inhibitors, organophosphates - Atropine > pralidoxime
Antimuscarinic, anticholinergic agents - Physostigmine (crosses BBB), control hyperthermia
Arsenic - Dimercaprol, succimer
Benzodiazepines - Flumazenil
β-blockers - Atropine, glucagon, saline
Carbon monoxide - 100% O2, hyperbaric O2
Copper - “Penny”cillamine (penicillamine), trientine (3 copper pennies)
Cyanide - Hydroxocobalamin, nitrites + sodium thiosulfate
Dabigatran - Idarucizumab
Digoxin - Digoxin-specifc antibody fragments
Direct factor Xa inhibitors (eg, apixaban) - Andexanet alfa
Heparin - Protamine sulfate
Iron (Fe) - Deferoxamine, deferasirox, deferiprone
Lead - Calcium disodium EDTA, dimercaprol, succimer, penicillamine
Mercury - Dimercaprol, succimer
Methanol, ethylene glycol (antifreeze) - Fomepizole > ethanol, dialysis
Methemoglobin - Methylene blue, vitamin C (reducing agent)
Methotrexate - Leucovorin
Opioids - Naloxone
Salicylates - NaHCO3 (alkalinize urine), dialysis
TCAs - NaHCO3 (stabilizes cardiac cell membrane)
Warfarin - Vitamin K (delayed effect), PCC (prothrombin complex concentrate)/FFP (immediate effect)
LR+ > 10 indicates a highly specifc test, while
LR– < 0.1 indicates a highly sensitive test.
Patient-centered interviewing techniques (VR-FAIR / IAR-VRF)
Introduction Agenda Reflection Validation Recapitulation Facilitation
Expressing empathy PEARLS
Partnership Empathy Apology Respect Legitimization Support
Delivering bad news SPIKES
Setting Perception Invitation Knowledge Emotions Strategy
Limited panel & cheaper - EPO and HMO
Outside network & expensive - POS and PPO
No referral reqd - EPO and PPO
Referral reqd - POS and HMO
(Start with P - outside network and expensive)
(PO-provider organisation - no referral required)
(when u pee outside u get fined for it and its expensive)
RENAL PHARMACOLOGY
Mannitol - ADVERSE EFFECTS Dehydration, hypo- or hypernatremia, pulmonary edema. Contraindicated in anuria, HF.
Acetazolamide - ADVERSE EFFECTS Proximal renal tubular acidosis (type 2 RTA), paresthesias, NH3 toxicity, sulfa allergy, hypokalemia. Promotes
calcium phosphate stone formation (insoluble at high pH). “Acid”azolamide causes acidosis.
Loop diuretics -
Furosemide, bumetanide, torsemide - MECHANISM Sulfonamide loop diuretics. ADVERSE EFFECTS Ototoxicity, Hypokalemia, Hypomagnesemia,
Dehydration, Allergy (sulfa), metabolic Alkalosis, Nephritis (interstitial), Gout. OHH DAANG
Ethacrynic acid - MECHANISM Nonsulfonamide inhibitor of cotransport system (Na+/K+/2Cl ). ADVERSE EFFECTS Similar to furosemide, but
more ototoxic. Loop earrings hurt your ears.
Thiazide diuretics ADVERSE EFFECTS (Hypergluc.) Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia,
hyperuricemia, hypercalcemia. Sulfa allergy.
Potassium-sparing diuretics - ADVERSE EFFECTS Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (eg, gynecomastia,
antiandrogen effects).
Diuretics: electrolyte changes
Urine NaCl - Inc with all diuretics (concentration varies based on potency of diuretic effect). Serum NaCl may decrease as a result.
Urine K+ - Inc especially with loop and thiazide diuretics, excluding K+-sparing diuretics.
Blood pH- Dec (acidemia): carbonic anhydrase inhibitors: HCO3 reabsorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+
secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.
Inc (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms: Volume contraction > inc AT II > inc Na+/H+ exchange in
PCT > inc HCO3 reabsorption (“contraction alkalosis”). K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells.
In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule > alkalosis and “paradoxical aciduria”.
Urine Ca2+ - Inc with loop diuretics: Dec paracellular Ca2+ reabsorption > hypocalcemia. Dec with thiazides: enhanced Ca2+ reabsorption.
Angiotensin-converting enzyme inhibitors - ADVERSE EFFECTS Cough, Angioedema (both due to inc bradykinin; contraindicated in C1 esterase
inhibitor defciency), Teratogen (fetal renal malformations), inc Creatinine (dec GFR), Hyperkalemia, and Hypotension. Used with caution in bilateral
renal artery stenosis because ACE inhibitors will further dec GFR > renal failure. (Captopril’s CATCHH.)
Angiotensin II receptor blockers - ADVERSE EFFECTS Hyperkalemia, dec GFR, hypotension; teratogen.
Aliskiren - ADVERSE EFFECTS Hyperkalemia, dec GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE
inhibitors or ARBs and contraindicated in pregnancy. Response to high altitude -
Dec atmospheric oxygen (PiO2) > dec Pao2 > inc ventilation > dec Paco2 > respiratory alkalosis > altitude sickness (headaches, nausea, fatigue,
lightheadedness, sleep disturbance). Chronic inc in ventilation. Inc erythropoietin > inc Hct and Hb (due to chronic hypoxia). Inc 2,3-BPG (binds to Hb
> rightward shift of ODC dissociation curve > inc O2 release).
Cellular changes (inc mitochondria).
Inc renal excretion of HCO3 to compensate for respiratory alkalosis (can augment with acetazolamide). Chronic hypoxic pulmonary vasoconstriction >
inc pulmonary vascular resistance > pulmonary hypertension, RVH.
Carboxyhemoglobin - CO + Hb
Carbaminohemoglobin - CO2 + Hb
In peripheral tissue, inc H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect). (bahr effect)
In lungs, oxygenation of Hb promotes dissociation of H+ from Hb. This shifts equilibrium toward CO2 formation; therefore, CO2 is released from
RBCs (Haldane effect).
HCO3−/Cl− transporter on RBC membrane allows HCO3− to diffuse out to plasma and Cl− to diffuse into RBC (chloride shift).
In peripheral tissue - (Bohr effect). (bahr effect)
In lungs - (Haldane effect).
V ̇ /Q ̇ at apex of lung = 3 (wasted ventilation)
V ̇ /Q ̇ at base of lung = 0.6 (wasted perfusion)
Epistaxis - Nose bleed. Most commonly occurs in anterior segment of nostril (Kiesselbach plexus). Lifethreatening hemorrhages occur in posterior
segment (sphenopalatine artery, a branch of maxillary artery). Common causes include foreign body, trauma, allergic rhinitis, and nasal angiofbromas
(common in adolescent males). Kiesselbach drives his Lexus with his LEGS: superior Labial artery, anterior and posterior Ethmoidal arteries, Greater
palatine artery, Sphenopalatine artery.
Superior meatus—drains sphenoid, posterior ethmoid;
Middle meatus—drains frontal, maxillary, and anterior ethmoid;
Inferior meatus— drains nasolacrimal duct.

Pneumomediastinum = + Hamman sign (crepitus on cardiac auscultation).

Centriacinar—affects respiratory bronchioles while sparing distal alveoli, associated with tobacco smoking. Frequently in upper lobes (smoke rises up).
Panacinar—affects respiratory bronchioles and alveoli, associated with a-1-antitrypsin defciency. Frequently in lower lobes.
Calretinin and cytokeratin 5/6 + in almost all mesotheliomas, ⊖ in most carcinomas.
ARDS - CAUSES Sepsis (most common), aspiration, pneumonia, trauma, pancreatitis. DIAGNOSIS Diagnosis of exclusion with the following criteria
(ARDS):
Abnormal chest X-ray (bilateral lung opacities) B
Respiratory failure within 1 week of alveolar insult
Decreased Pao2 /Fio2 (ratio < 300, hypoxemia due to inc intrapulmonary shunting and diffusion abnormalities)
Symptoms of respiratory failure are not due to HF/fuid overload
CONSEQUENCES Impaired gas exchange, dec lung compliance; pulmonary hypertension.
MANAGEMENT Treat the underlying cause. Mechanical ventilation: dec tidal volume, inc PEEP (keeps alveoli open during expiration).
Central sleep apnea - Impaired respiratory effort due to CNS injury/toxicity, Congestive HF, opioids. May be associated with Cheyne- Stokes
respirations (oscillations between apnea and hyperpnea). Treatment: positive airway pressure.
Obesity hypoventilation syndrome - Also called Pickwickian syndrome. Obesity (BMI 30 kg/m2 ) > hypoventilation > inc Paco2 during waking hours
(retention); dec Pao2 and inc Paco2 during sleep. Treatment: weight loss, positive airway pressure.
Pulmonary hypertension causes-
Pulmonary arterial hypertension
Left heart disease
Lung diseases or hypoxia
Chronic thromboembolic
Multifactorial
Simple pneumothorax - TRACHEAL DEVIATION None.
Tension pneumothorax - TRACHEAL DEVIATION Away from side of lesion.
Pleural effusion - TRACHEAL DEVIATION None if small. Away from side of lesion if large.
Atelectasis - TRACHEAL DEVIATION Toward side of lesion.
Breath sounds and fremitus are directly proportional.
Breath sounds and fremitus both decreased in effusion, atelectasis and pneumothorax.
Consolidation (lobar pneumonia, pulmonary edema) - BREATH SOUNDS Bronchial breath sounds; late inspiratory crackles, egophony, whispered
pectoriloquy, FREMITUS inc.
Pleural efusion - Based on the Light criteria, fuid is exudate if pleural fuid protein/serum protein > 0.5, pleural fluid LDH/serum LDH > 0.6, or pleural
fluid LDH > 2/3 upper limit of normal serum LDH. (protein > 0.5; LDH > 0.6)
Lobar pneumonia - S pneumoniae (most common), Legionella, Klebsiella.
Bronchopneumonia - S pneumoniae, S aureus, H infuenzae, Klebsiella.
Interstitial (atypical) pneumonia - Mycoplasma, Chlamydophila pneumoniae, Chlamydophila psittaci, Legionella, Coxiella burnetii, viruses (RSV,
CMV, infuenza, adenovirus).
Sites of metastases from lung cancer (LABB) : liver (jaundice, hepatomegaly), adrenals, bone (pathologic fracture), brain.
Lung mets (BPBC) - Most often from breast, colon, prostate, and bladder cancer.
Anti-IgE monoclonal therapy - Omalizumab.
Mepolizumab, reslizumab—against IL-5.
Benralizumab—against IL-5 receptor α.
Caffeine and theophylline are adenosine antagonists.

CNS stimulants - SE - Nervousness, agitation, anxiety, insomnia, anorexia, tachycardia, hypertension, weight loss, tics, bruxism.
Antipsychotics - Typical (1st-generation) antipsychotics—haloperidol, pimozide, trifluoperazine, fluphenazine, thioridazine, chlorpromazine. Atypical
(2nd-generation) antipsychotics—aripiprazole, asenapine, clozapine, olanzapine, quetiapine, iloperidone, paliperidone, risperidone, lurasidone,
ziprasidone. SE - Antihistaminic (sedation), anti- 1-adrenergic (orthostatic hypotension), antimuscarinic (dry mouth, constipation) (anti-HAM). Use
with caution in dementia. Metabolic: weight gain, hyperglycemia, dyslipidemia. Highest risk with clozapine and olanzapine (obesity). Endocrine:
hyperprolactinemia > galactorrhea, oligomenorrhea, gynecomastia. Cardiac: QT prolongation. Neurologic: neuroleptic malignant syndrome.
Ophthalmologic: chlorpromazine— corneal deposits; thioridazine—retinal deposits. Clozapine—agranulocytosis (monitor WBCs clozely), seizures
(dose related), myocarditis. Extrapyramidal symptoms—ADAPT: Hours to days: Acute Dystonia (muscle spasm, stiffness, oculogyric crisis).
Treatment: benztropine, diphenhydramine. Days to months: Akathisia (restlessness). Treatment: B-blockers, benztropine, benzodiazepines.
Parkinsonism (bradykinesia). Treatment: benztropine, amantadine. Months to years: Tardive dyskinesia (chorea, especially orofacial). Treatment:
benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine. NOTES - Lipid soluble > stored in body fat > slow to be removed from
body. Typical antipsychotics have greater affinity for D2 receptor than atypical antipsychotics > inc risk for hyperprolactinemia, extrapyramidal
symptoms, neuroleptic malignant syndrome. High- potency typical antipsychotics: haloperidol, trifluoperazine, pimozide, fluphenazine (Hal tries pie to
fly high)— more neurologic side effects (eg, extrapyramidal symptoms). Low-potency typical antipsychotics: chlorpromazine, thioridazine (cheating
thieves are low)— more antihistaminic, anti- 1-adrenergic, antimuscarinic effects.
Lithium - SE - Tremor, hypothyroidism, hyperthyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis (causes Ebstein anomaly).
Narrow therapeutic window requires close monitoring of serum levels. Almost exclusively excreted by kidneys; most is reabsorbed at PCT via Na+
channels. Thiazides, NSAIDs, and other drugs affecting clearance are implicated in lithium toxicity. *LiTHIUM: Low Thyroid (hypothyroidism) Heart
(Ebstein anomaly) Insipidus (nephrogenic diabetes insipidus) Unwanted Movements (tremor)*
Buspirone - Partial 5-HT1A receptor agonist. Does not cause sedation, addiction, or tolerance. Begins to take effect after 1–2 weeks. Does not interact
with alcohol (vs barbiturates, benzodiazepines).
SSRis - Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram. SE - Fewer than TCAs. Serotonin syndrome, GI distress, SIADH,
sexual dysfunction (anorgasmia, dec libido), mania precipitation if underlying bipolar disorder. It normally takes 4–8 weeks for antidepressants to show
appreciable effect.
SNRIs - Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran. SE - inc BP, stimulant effects, sedation, nausea.
TCAs - Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine. SE - Sedation, a1- blocking effects including
postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3° TCAs (amitriptyline) have more
anticholinergic effects than 2° TCAs (nortriptyline). Can prolong QT interval. Tri- CyCliC’s: Convulsions, Coma, Cardiotoxicity (arrhythmia due to
Na+ channel inhibition); also respiratory depression, hyperpyrexia. Confusion and hallucinations are more common in the elderly due to
anticholinergic side effects (2° amines [eg, nortriptyline] better tolerated). Treatment: NaHCO3 to prevent arrhythmia.
MAO inh - SE - CNS stimulation; hypertensive crisis, most notably with ingestion of tyramine. Contraindicated with SSRIs, TCAs, St. John’s wort,
meperidine, dextromethorphan, pseudoephedrine, linezolid (to avoid precipitating serotonin syndrome). Wait 2 weeks after stopping MAOIs before
starting serotonergic drugs or stopping dietary restrictions.
Bupropion - Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in patients with bulimia and anorexia nervosa. dec risk of sexual
side effects and weight gain compared to other antidepressants.
Mirtazapine - Toxicity: sedation (which may be desirable in depressed patients with insomnia), inc appetite, weight gain (which may be desirable in
underweight patients), dry mouth.
Trazodone - Toxicity: sedation, nausea, priapism, postural hypotension. Think traZZZobone due to sedative and male- specific side effects.
Varenicline - Toxicity: sleep disturbance. Varenicline helps nicotine cravings decline.
Vilazodone - Toxicity: headache, diarrhea, nausea, anticholinergic effects. May cause SEROTONIN SYNDROME if taken with other serotonergic
agents.
Vortioxetine - Toxicity: nausea, sexual dysfunction, sleep disturbances, anticholinergic effects. May cause SEROTONIN SYNDROME if taken with
other serotonergic agents.
Buprenorphine - Sublingual form (partial agonist) used to prevent relapse. Can precipitate withdrawal symptoms when combined with full agonist.
(CASE) Coronary vasospasm - Cocaine, Amphetamines, Sumatriptan, Ergot alkaloids
(VANCEN) Cutaneous flushing - Vancomycin, Adenosine, Niacin, Ca2+ channel blockers, Echinocandins, Nitrates.
(ABCDEF) Torsades de pointes - Agents that prolong QT interval: antiArrhythmics (class IA, III), antiBiotics (eg, macrolides, fluoroquinolones),
anti“C”ychotics (eg, ziprasidone), antiDepressants (eg, TCAs), antiEmetics (eg, ondansetron), antiFungals (eg, fluconazole)
(The people need hard candies) Hyperglycemia - Tacrolimus, protease inhibitors, niacin, HCTZ, corticosteroids.
(ARMM) Hyperprolactinemia - Typical antipsychotics (eg, haloperidol), atypical antipsychotics (eg, risperidone), metoclopramide, methyldopa,
reserpine.

(Can’t Concentrate Serum Sodium) SIADH - Carbamazepine, Cyclophosphamide, SSRIs.

(CCC-MSALA) Diarrhea - Acamprosate, antidiabetic agents (acarbose, metformin, pramlintide), colchicine, cholinesterase inhibitors, lipid-lowering
agents (eg, ezetimibe, orlistat), macrolides (eg,

erythromycin), SSRIs, chemotherapy (eg, irinotecan)

(Liver “HAVAc”) Focal to massive hepatic necrosis - Halothane, Amanita phalloides (death cap mushroom), valproic acid, acetaminophen.
(Drugs Causing A Violent Abdominal Distress) Pancreatitis - Didanosine, corticosteroids, alcohol, valproic acid, azathioprine, diuretics (eg,
furosemide, HCTZ)
(B-PINT) Pill-induced esophagitis - Bisphosphonates, ferrous sulfate, NSAIDs, potassium chloride, tetracyclines.
(Drugs can cause pretty major collapse to granulocytes) Agranulocytosis - Dapsone, clozapine, carbamazepine, propylthiouracil, methimazole,
colchicine, ticlopidine, ganciclovir.

(Can’t make New blood cells properly) Aplastic anemia - Carbamazepine, methimazole, NSAIDs, benzene, chloramphenicol, propylthiouracil. (P
Diddy Coombs) Direct Coombs ⊕ hemolytic anemia - Penicillin, methylDopa, Cephalosporins.
(ABCs) Drug reaction with eosinophilia and systemic symptoms - Allopurinol, antiBiotics, antiConvulsants, sulfa drugs.

(Hemolysis IS D PAIN) Hemolysis in G6PD deficiency - Isoniazid, sulfonamides, dapsone, primaquine, aspirin, ibuprofen, nitrofurantoin. (I have
quickly gotten very low amounts) Thrombocytopenia - Indinavir, heparin, quinidine, ganciclovir, vancomycin, linezolid, abciximab. (MEM-SHIPP)
Drug-induced lupus - Methyldopa, minocycline, hydralazine, isoniazid, phenytoin, sulfa drugs, etanercept, procainamide.

(Fat protects glutes) Fat redistribution - Protease inhibitors, glucocorticoids.

(Can Cause puffy gums.) Gingival hyperplasia - Cyclosporine, Ca2+ channel blockers, phenytoin.
(Painful tophi and feet need care.) Hyperuricemia (gout) Pyrazinamide, thiazides, furosemide, niacin, cyclosporine.
(FIND-CGHS-P) Myopathy - Statins, fibrates, niacin, colchicine, daptomycin, hydroxychloroquine, interferon-α, penicillamine, glucocorticoids.
(SAT For photo) Photosensitivity - Sulfonamides, amiodarone, tetracyclines, 5-FU.
(ASAP) Rash (Stevens-Johnson syndrome) - Anti-epileptic drugs (especially lamotrigine), allopurinol, sulfa drugs, penicillin.
(Cogwheel rigidity of ARM) Parkinson-like syndrome - Antipsychotics, reserpine, metoclopramide.
(VIPPP) Peripheral neuropathy - Isoniazid, phenytoin, platinum agents (eg, cisplatin), paclitaxtel, vincristine
(Always grow head tension) Idiopathic intracranial hypertension - Vitamin A, growth hormones, tetracyclines.
(With seizures, I BITE my tongue) Seizures - Isoniazid, bupropion, imipenem/cilastatin, tramadol, enfurane.
(These horrible drugs irritate very Precious eyes) Visual disturbance - Topiramate (blurred vision/diplopia, haloes), hydroxychloroquine (dec visual
acuity, visual field defects), digoxin (yellow-tinged vision), isoniazid (optic neuritis), vigabatrin (visual field defects), PDE-5 inhibitors (blue-tinged
vision), ethambutol (color vision changes).

(eTITC) Fanconi syndrome - Cisplatin, ifosfamide, expired tetracyclines, tenofovir

(5 P’s) Interstitial nephritis - Diuretics (Pee), NSAIDs (Pain-free), Penicillins and cephalosporins, PPIs, rifamPin, sulfa drugs.
(My nose cannot breathe bad air) Pulmonary fibrosis - Methotrexate, nitrofurantoin, carmustine, bleomycin, busulfan, amiodarone.

(HAAT) Antimuscarinic - Atropine, TCAs, H1-blockers, antipsychotics

(m-SGPC) Disulfram-like reaction - 1st-generation sulfonylureas, procarbazine, certain cephalosporins, griseofulvin, metronidazole.

(CAVAL) Nephrotoxicity/ototoxicity - Loop diuretics, cisplatin, aminoglycosides, amphotericin, vancomycin. Cisplatin toxicity may respond to
amifostine.
(P-FACTsss) Sulfa drugs - Sulfonamide antibiotics, Sulfasalazine, Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonylureas.
Patients with sulfa allergies may develop fever, urinary tract infection, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia,
agranulocytosis, acute interstitial nephritis, and urticaria (hives).
(FRIPS) Hepatitis - Rifampin, isoniazid, pyrazinamide, statins, fibrates.

For patients with speech diffculties, provide extra time for the interview. If their speech is diffcult to understand, consider asking them to write down a
few words or ask them to rephrase their sentence. Repeat what they said to ensure you understood it correctly. For patients with a cognitive impairment,
use concrete, specifc language. Ask simple, direct questions. Eliminate background noise and distractions. Do not assume the patient can read. Adjust
to how the patient understands best (eg, use hand gestures or ask them to demonstrate a task). Ask patients who are deaf or hard of hearing their
preferred mode of communication. Use light touch or waving to get their attention. For patients who prefer to speak and lipread, eliminate background
noise, face the patient, and do not change your mode of speaking.
Visits with a patient who speaks little English should utilize a professionally trained medical interpreter unless the physician is also fuent in the
patient’s preferred language.

Interpretation services may be provided in person, by telephone, or by video call. If the patient prefers to utilize a family member, this should be
recorded in the chart.
Unfavorable prognosis - However, if you believe the patient might seriously harm self or others if informed, you may invoke therapeutic privilege and
withhold the information.
Many states require parental notifcation or consent for minors for an abortion. Unless there are specifc medical risks associated with pregnancy, a
physician should not sway the patient’s decision for, or against, an elective abortion (regardless of patient’s age or fetal condition). Discuss options for
terminating the pregnancy and refer to abortion care, if needed.
A 15-year-old is pregnant and wants to raise the child. Her parents want you to tell her to give the child up for adoption. The patient retains the right to
make decisions regarding her child, even if her parents disagree.
Patient is victim of intimate partner violence. Ask if patient is safe and help devise an emergency plan if there isn’t one. Educate patient on intimate
partner violence resources. Do not necessarily pressure patient to leave a partner or disclose the incident to the authorities (unless required by state
law).
A pharmaceutical company offers you a sponsorship in exchange for advertising its new drug. Reject this offer. Generally, decline gifts and
sponsorships to avoid any confict of interest. The AMA Code of Ethics does make exceptions for gifts directly beneftting patients; special funding for
medical education of students, residents, fellows; grants whose recipients are chosen by independent institutional criteria; and funds that are distributed
without attribution to sponsors.
Mother and 15-year-old daughter are unresponsive following a car accident and are bleeding internally. Father says do not transfuse because they are
Jehovah’s Witnesses. Transfuse daughter, but do not transfuse mother.
Disease prevention
Primary disease prevention Prevent disease before it occurs (eg, HPV vaccination)
Secondary disease prevention Screen early for and manage existing but asymptomatic disease (eg, Pap smear for cervical cancer)
Tertiary disease prevention Treatment to reduce complications from disease that is ongoing or has long-term effects (eg, chemotherapy)
Quaternary disease prevention Quit (avoid) unnecessary medical interventions to minimize incidental harm (eg, imaging studies, optimizing
medications to reduce polypharmacy)
Discounted fee-forservice - (eg, PPOs).
. Medicare is available to patients ≥ 65 years old, < 65 with certain disabilities, and those with end-stage renal disease. Medicaid is joint federal and
state health assistance for people with limited income and/ or resources. MedicarE is for Elderly. MedicaiD is for Disadvantaged.
The 4 parts of Medicare:
Part A: hospital Admissions, including hospice, skilled nursing - IPD
Part B: Basic medical bills (eg, physician fees, diagnostic testing) - OPD
Part C: (parts A + B = Combo) delivered by approved private companies - combined
Part D: prescription Drugs
Hospice - Available to patients on Medicare or Medicaid and in most private insurance plans whose life expectancy is < 6 months.
Quality measurements - SPOB
MEASURE EXAMPLE
Structural Physical equipment, resources, facilities Number of diabetes educators
Process Performance of system as planned Percentage of patients with diabetes whose HbA1c was measured in the past 6 months Outcome Impact on
patients Average HbA1c of patients with diabetes
Balancing Impact on other systems/outcomes Incidence of hypoglycemia among patients who tried an intervention to lower HbA1c
Medical errors - Medical errors should be disclosed to patients, independent of immediate outcome (harmful or not). Active error Occurs at level of
frontline operator (eg, wrong IV pump dose programmed). Immediate impact.
Latent error Occurs in processes indirect from operator but impacts patient care (eg, different types of IV pumps used within same hospital). Accident
waiting to happen.
Never event Adverse event that is identifable, serious, and usually preventable (eg, scalpel retained in a surgical patient’s abdomen). Major error that
should never occur.
Near miss Unplanned event that does not result in harm but has the potential to do so (eg, pharmacist recognizes a medication interaction and cancels
the order). Narrow prevention of harm that exposes dangers.

H1 binds to the nucleosome and to “linker DNA,” thereby stabilizing the chromatin fber.
Phosphate groups give DNA a charge. Lysine and arginine give histones a charge.
DNA and histone synthesis occurs during S phase. Mitochondria have their own DNA, which is circular and does not utilize histones. Methylation
within gene promoter (CpG islands) typically represses (silences) gene transcription. CpG methylation makes DNA mute. Histone methylation mostly
makes DNA mute.

Histone acetylation makes DNA active.

Thyroid hormone receptors alter thyroid hormone synthesis by acetylation. Dysregulated acetylation is implicated in Huntington disease.

Purines (A,G)—2 rings. Pyrimidines (C,U,T)—1 ring.

Deamination reactions: Cytosine > uracil, Adenine > hypoxanthine, Guanine > xanthine, 5-methylcytosine > thymine.
Uracil found in RNA; thymine in DNA. Methylation of uracil makes thymine.
5 end of incoming nucleotide bears the triphosphate (energy source for the bond). -Phosphate is target of 3 hydroxyl attack.
C-G bond (3 H bonds) stronger than A-T bond (2 H bonds). C-G content melting temperature of DNA. “C-G bonds are like Crazy Glue.” Amino acids
necessary for purine synthesis (cats purr until they GAG): Glycine Aspartate Glutamine
6-mercaptopurine (6-MP) and its prodrug azathioprine: inhibit de novo purine synthesis
CPS1 = m1tochondria (urea cycle) CPS2 = cytwosol
Dec ADA > inc dATP > dec ribonucleotide reductase activity > dec DNA precursors in cells > dec lymphocytes. One of the major causes of autosomal
recessive SCID.
Exceptions: methionine (AUG) and tryptophan (UGG) encoded by only 1 codon.
Universal Genetic code is conserved throughout evolution. Exception in humans: mitochondria.

AT-rich sequences (such as TATA box regions) are found in promoters and origins of replication. Helicase - Defcient in Bloom syndrome (BLM gene
mutation).

In eukaryotes: irinotecan/topotecan inhibit topoisomerase (TOP) I, etoposide/teniposide inhibit TOP II. In prokaryotes: fuoroquinolones inhibit TOP II
(DNA gyrase) and TOP IV. DNA polymerase III has 5 > 3 synthesis and proofreads with 3 > 5 exonuclease.

Drugs blocking DNA replication often have a modifed 3 OH, thereby preventing addition of the next nucleotide (“chain termination”).
DNA polymerase I Prokaryotes only. Degrades RNA primer; replaces it with DNA. Same functions as DNA polymerase III, also excises RNA primer
with 5 > 3 exonuclease.
Telomerase Eukaryotes only. A reverse transcriptase (RNAdependent DNA polymerase) that adds DNA (TTAGGG) to 3 ends of chromosomes to avoid
loss of genetic material with every duplication. Often upregulated in cancer, downregulated in aging and progeria.
Base excision repair Base-specifc Glycosylase removes altered base and creates AP site (apurinic/apyrimidinic). One or more nucleotides are removed
by AP-Endonuclease, which cleaves 5 end. APLyase cleaves 3 end. DNA Polymerase- flls the gap and DNA ligase seals it. Occurs throughout cell
cycle.
Transition—purine to purine (eg, A to G) or pyrimidine to pyrimidine (eg, C to T).
Transversion—purine to pyrimidine (eg, A to T) or pyrimidine to purine (eg, C to G).
Frameshift - Examples: Duchenne muscular dystrophy, Tay-Sachs disease.
Spilce site mutations - Examples: rare causes of cancers, dementia, epilepsy, some types of -thalassemia, Gaucher disease, Marfan syndrome.
Lac operon - Mechanism of shift:
Low glucose > inc adenylate cyclase activity > inc generation of cAMP from ATP > activation of catabolite activator protein (CAP) > inc transcription.
High lactose > unbinds repressor protein from repressor/operator site > inc transcription
Promoter Site where RNA polymerase II binds.
The following processes occur in the nucleus:
Capping of 5 end (addition of 7-methylguanosine cap) Polyadenylation of 3 end ( 200 A’s > poly-A tail) Splicing out of introns
mRNA is transported out of nucleus to be translated in cytosol.

mRNA quality control occurs at cytoplasmic processing bodies (P-bodies), which contain exonucleases, decapping enzymes, and microRNAs; mRNAs
may be degraded or stored in P-bodies for future translation.
Prokaryotes 1 RNA polymerase (multisubunit complex) makes all 3 kinds of RNA.

Anti-U1 snRNP antibodies are associated with SLE, mixed connective tissue disease, other rheumatic diseases.
Splicing - Primary transcript combines with small nuclear ribonucleoproteins (snRNPs) and other proteins to form spliceosome. Cleavage at 5 splice
site; lariatshaped (loop) intermediate is generated.
Cleavage at 3 splice site; lariat is released to precisely remove intron and join 2 exons.
Introns are intervening sequences and stay in the nucleus, whereas exons exit and are expressed.
The amino acid is covalently bound to the 3 end of the tRNA.
T-arm: contains the T C (ribothymidine, pseudouridine, cytidine) sequence necessary for tRNAribosome binding. T-arm Tethers tRNA molecule to
ribosome. D-arm: contains Dihydrouridine residues necessary for tRNA recognition by the correct aminoacyltRNA synthetase. D-arm allows Detection
of the tRNA by aminoacyl-tRNA synthetase.
Charging Aminoacyl-tRNA synthetase (uses ATP; 1 unique enzyme per respective amino acid) and binding of charged tRNA to the codon are
responsible for the accuracy of amino acid selection.

A mischarged tRNA reads the usual codon but inserts the wrong amino acid.
mRNA start codons AUG. AUG inAUGurates protein synthesis.
Eukaryotes Codes for methionine, which may be removed before translation is completed. Prokaryotes Codes for N-formylmethionine (fMet). fMet
stimulates neutrophil chemotaxis.
Protein Synthesis occurs from N-terminus to C-terminus.
Elongation factors are targets of bacterial toxins (eg, Diphtheria, Pseudomonas).
Tumor suppressors p53 > p21 induction > CDK inhibition > Rb hypophosphorylation (activation) > G1-S progression inhibition
Growth factors (eg, insulin, PDGF, EPO, EGF) bind tyrosine kinase receptors to transition the cell from G1 to S phase.
RER - N-linked oligosaccharide addition to lysosomal and other proteins.
Smooth endoplasmic reticulum Site of steroid synthesis and detoxifcation of drugs and poisons. Lacks surface ribosomes. Location of glucose-6-
phosphatase (last step in both glycogenolysis and gluconeogenesis).
I-cell disease (inclusion cell disease/mucolipidosis type II)—inherited lysosomal storage disorder (autosomal recessive); defect in N-
acetylglucosaminyl-1-phosphotransferase failure of the Golgi to phosphorylate mannose residues (dec mannose-6-phosphate) on glycoproteins
enzymes secreted extracellularly rather than delivered to lysosomes > lysosomes defcient in digestive enzymes > build-up of cellular debris in
lysosomes (inclusion bodies).
Signal recognition particle (SRP) Abundant, cytosolic ribonucleoprotein that traffcs polypeptide-ribosome complex from the cytosol to the RER.
Absent or dysfunctional SRP > accumulation of protein in cytosol.
“Two (COPII) steps forward (anterograde); one (COPI) step back (retrograde).”
COP - (b/w golgi and ER)
Clathrin - (b/w golgi and plasma membrane)
Zellweger syndrome—autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes. Hypotonia, seizures, hepatomegaly, early
death.
Refsum disease—autosomal recessive disorder of -oxidation buildup of phytanic acid due to inability to degrade it. Scaly skin, ataxia, cataracts/night
blindness, shortening of 4th toe, epiphyseal dysplasia. Treatment: diet, plasmapheresis.
Adrenoleukodystrophy—X-linked recessive disorder of -oxidation due to mutation in ABCD1 gene VLCFA buildup in adrenal glands, white (leuko)
matter of brain, testes. Progressive disease that can lead to adrenal gland crisis, progressive loss of neurologic function, death

Retrograde to microtubule (+ > )—dynein. Anterograde to microtubule ( > +)—kinesin.

Clostridium tetani toxin, herpes simplex virus, poliovirus, and rabies virus use dynein for retrograde transport to the neuronal cell body. Drugs that act
on microtubules (microtubules get constructed very terribly): Mebendazole (antihelminthic)
Griseofulvin (antifungal) Colchicine (antigout)
Vinca alkaloids (anticancer) Taxanes (anticancer)
Negative end near nucleus. Positive end points to periphery.

Drug reactions—cardiovascular
(CASE) Coronary vasospasm - Cocaine, Amphetamines, Sumatriptan, Ergot alkaloids
(VANCEN) Cutaneous flushing - Vancomycin, Adenosine, Niacin, Ca2+ channel blockers, Echinocandins, Nitrates. Red man syndrome—rate-
dependent infusion reaction to vancomycin causing widespread pruritic erythema due to histamine release. Manage with diphenhydramine, slower
infusion rate.
Dilated cardiomyopathy - Alcohol, anthracycline (eg, doxorubicin, daunorubicin; prevent with dexrazoxane), trastuzumab.
(ABCDEF) Torsades de pointes - Agents that prolong QT interval: antiArrhythmics (class IA, III), antiBiotics (eg, macrolides, fluoroquinolones),
anti“C”ychotics (eg, ziprasidone), antiDepressants (eg, TCAs), antiEmetics (eg, ondansetron), antiFungals (eg, fluconazole)

Drug reactions—endocrine/reproductive
Adrenocortical insuffciency - HPA suppression 2° to glucocorticoid withdrawal
Diabetes insipidus - Lithium, demeclocycline
Gynecomastia - Ketoconazole, cimetidine, spironolactone, GnRH analogs/antagonists, androgen receptor inhibitors, 5α-reductase inhibitors
Hot fashes - SERMs (eg, tamoxifen, clomiphene, raloxifene)
(The people need hard candies) Hyperglycemia - Tacrolimus, protease inhibitors, niacin, HCTZ, corticosteroids.
(ARMM) Hyperprolactinemia - Typical antipsychotics (eg, haloperidol), atypical antipsychotics (eg, risperidone), metoclopramide, methyldopa,
reserpine. Presents with hypogonadism (eg, infertility, amenorrhea, erectile dysfunction) and galactorrhea.
Hyperthyroidism - Amiodarone, iodine, lithium
Hypothyroidism - Amiodarone, lithium.
(Can’t Concentrate Serum Sodium) SIADH - Carbamazepine, Cyclophosphamide, SSRIs.
Drug reactions—gastrointestinal
Acute cholestatic hepatitis, jaundice - Macrolides (eg, erythromycin)
(CCC-MSALA) Diarrhea - Acamprosate, antidiabetic agents (acarbose, metformin, pramlintide), colchicine, cholinesterase inhibitors, lipid-lowering
agents (eg, ezetimibe, orlistat), macrolides (eg, erythromycin), SSRIs, chemotherapy (eg, irinotecan)

(Liver “hAvac”) Focal to massive hepatic necrosis - Halothane, Amanita phalloides (death cap mushroom), valproic acid, acetaminophen.
(FRIPS) Hepatitis - Rifampin, isoniazid, pyrazinamide, statins, fibrates.
(Drugs Causing A Violent Abdominal Distress) Pancreatitis - Didanosine, corticosteroids, alcohol, valproic acid, azathioprine, diuretics (eg,
furosemide, HCTZ)
(B-PINT) Pill-induced esophagitis - Bisphosphonates, ferrous sulfate, NSAIDs, potassium chloride, tetracyclines. Usually occurs at anatomic sites of
esophageal narrowing (eg, near level of aortic arch); caustic effect minimized with upright posture and adequate water ingestion.
Pseudomembranous colitis - Ampicillin, cephalosporins, clindamycin, fluoroquinolones, PPIs. Antibiotics predispose to superinfection by resistant C
difficile.
Drug reactions—hematologic
(Drugs can cause pretty major collapse to granulocytes) Agranulocytosis - Dapsone, clozapine, carbamazepine, propylthiouracil, methimazole,
colchicine, ticlopidine, ganciclovir.

(Can’t make New blood cells properly) Aplastic anemia - Carbamazepine, methimazole, NSAIDs, benzene, chloramphenicol, propylthiouracil. (P
Diddy Coombs) Direct Coombs ⊕ hemolytic anemia - Penicillin, methylDopa, Cephalosporins.
(ABCs) Drug reaction with eosinophilia and systemic symptoms - Allopurinol, antiBiotics, antiConvulsants, sulfa drugs.
Gray baby syndrome - Chloramphenicol.

(hemolysis IS D PAIN) Hemolysis in G6PD deficiency - Isoniazid, sulfonamides, dapsone, primaquine, aspirin, ibuprofen, nitrofurantoin.
Megaloblastic anemia - Hydroxyurea, Phenytoin, Methotrexate, Sulfa drugs.
(I have quickly gotten very low amounts) Thrombocytopenia - Indinavir, heparin, quinidine, ganciclovir, vancomycin, linezolid, abciximab.
Thrombotic complications - Combined oral contraceptives, hormone replacement therapy, SERMs, epoetin alfa. (Estrogen-mediated adverse effect)
*DRESS is a delayed hypersensitivity reaction associated with latent herpesvirus reactivation. Latency period (2–8 weeks), then fever, morbilliform
skin rash, multiorgan involvement. Treatment: withdrawal of offending drug, corticosteroids.

Drug reactions—musculoskeletal/skin/connective tissue

(MEM-SHIPP) Drug-induced lupus - Methyldopa, minocycline, hydralazine, isoniazid, phenytoin, sulfa drugs, etanercept, procainamide.

(Fat protects glutes) Fat redistribution - Protease inhibitors, glucocorticoids.

(Can Cause puffy gums.) Gingival hyperplasia - Cyclosporine, Ca2+ channel blockers, phenytoin.
(Painful tophi and feet need care.) Hyperuricemia (gout) Pyrazinamide, thiazides, furosemide, niacin, cyclosporine.
(FIND-CGHS-P) Myopathy - Statins, fibrates, niacin, colchicine, daptomycin, hydroxychloroquine, interferon-α, penicillamine, glucocorticoids.
Osteoporosis - Corticosteroids, depot medroxyprogesterone acetate, GnRH agonists, aromatase inhibitors, anticonvulsants, heparin, PPIs
(SAT For photo) Photosensitivity - Sulfonamides, amiodarone, tetracyclines, 5-FU.
(ASAP) Rash (Stevens-Johnson syndrome) - Anti-epileptic drugs (especially lamotrigine), allopurinol, sulfa drugs, penicillin. (Steven Johnson has
epileptic allergy to sulfa drugs and penicillin) Teeth discoloration - Tetracyclines
Tendon/cartilage damage - Fluoroquinolones
Drug reactions—neurologic
Cinchonism - Quinidine, quinine. Can present with tinnitus, hearing/vision loss, psychosis, and cognitive impairment
(Cogwheel rigidity of ARM) Parkinson-like syndrome - Antipsychotics, reserpine, metoclopramide.
(VIPPP) Peripheral neuropathy - Isoniazid, phenytoin, platinum agents (eg, cisplatin), paclitaxtel, vincristine
(Always grow head tension) Idiopathic intracranial hypertension - Vitamin A, growth hormones, tetracyclines.
(with seizures, I BITE my tongue) Seizures - Isoniazid, bupropion, imipenem/cilastatin, tramadol, enfurane.
Tardive dyskinesia - Antipsychotics, metoclopramide.
(These horrible drugs irritate very Precious eyes) Visual disturbance - Topiramate (blurred vision/diplopia, haloes), hydroxychloroquine ( visual acuity,
visual field defects), digoxin (yellow-tinged vision), isoniazid (optic neuritis), vigabatrin (visual field defects), PDE-5 inhibitors (blue-tinged vision),
ethambutol (color vision changes).
Drug reactions—renal/genitourinary

(eTITC) Fanconi syndrome - Cisplatin, ifosfamide, expired tetracyclines, tenofovir

Hemorrhagic cystitis - Cyclophosphamide, ifosfamide. Prevent by coadministering with mesna
Remember the 5 P’s Interstitial nephritis - Diuretics (Pee), NSAIDs (Pain-free), Penicillins and cephalosporins, PPIs, rifamPin, sulfa drugs. Drug
reactions—respiratory
Dry cough - ACE inhibitors

(My nose cannot breathe bad air) Pulmonary fibrosis - Methotrexate, nitrofurantoin, carmustine, bleomycin, busulfan, amiodarone. Drug reactions—
multiorgan
(HAAT) Antimuscarinic - Atropine, TCAs, H1-blockers, antipsychotics
(m-SGPC) Disulfram-like reaction - 1st-generation sulfonylureas, procarbazine, certain cephalosporins, griseofulvin, metronidazole.

(CAVAL) Nephrotoxicity/ototoxicity - Loop diuretics, cisplatin, aminoglycosides, amphotericin, vancomycin. Cisplatin toxicity may respond to
amifostine.
(P-FACTsss) Sulfa drugs - Sulfonamide antibiotics, Sulfasalazine, Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonylureas.
Patients with sulfa allergies may develop fever, urinary tract infection, Stevens-Johnson syndrome, hemolytic anemia, thrombocytopenia,
agranulocytosis, acute interstitial nephritis, and urticaria (hives).
Acetaminophen - SE - Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts
in liver. N-acetylcysteine is antidote — regenerates glutathione.
Aspirin - SE - Gastric ulceration, tinnitus (CN VIII), allergic reactions (especially in patients with asthma or nasal polyps). Chronic use can lead to
acute kidney injury, interstitial nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Toxic doses cause
respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis. Treatment of overdose: NaHCO3.
Celecoxib - SE - Inc risk of thrombosis, sulfa allergy.
NSAIDS - SE - Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia (prostaglandins vasodilate afferent arteriole),
aplastic anemia.
Leflunomide - SE - Diarrhea, hypertension, hepatotoxicity, teratogenicity.
Teriparatide - SE - Inc risk of osteosarcoma (avoid use in patients with Paget disease of the bone or unexplained elevation of alkaline phosphatase).
Avoid in patients who have had prior cancers or radiation therapy. Transient hypercalcemia.
Bisphosphonates - SE - Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of jaw,
atypical femoral stress fractures.
Probenicid - Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin). Can precipitate uric acid calculi.
NSAIDs - Any NSAID. Use salicylates with caution (may decrease uric acid excretion, particularly at low doses).
Colchicine - GI, neuromyopathic side effects. Can also cause myelosupression, nephrotoxicity.
TNF- inhibitors - Etanercept - SE - Predisposition to infection, including reactivation of latent TB, since TNF is important in granuloma formation and
stabilization. Can also lead to drug-induced lupus.
TNF- inhibitors - Infliximab, adalimumab, certolizumab, golimumab - SE - Predisposition to infection, including reactivation of latent TB, since TNF
is important in granuloma formation and

stabilization. Can also lead to drug-induced lupus.

Calcium channel blockers - ADVERSE EFFECTS Gingival hyperplasia. Dihydropyridine: peripheral edema, fushing, dizziness. Nondihydropyridine:
cardiac depression, AV block, hyperprolactinemia (verapamil), constipation.
Hydralazine - ADVERSE EFFECTS Compensatory tachycardia (contraindicated in angina/CAD), fuid retention, headache, angina, drug-induced
lupus.
Hypertensive emergency - Treat with (CNN-FL) labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside. Nitroprusside - Can cause cyanide
toxicity (releases cyanide). Fenoldopam - Can cause hypotension, tachycardia, fushing, headache, nausea.

Nitrates - ADVERSE EFFECTS Refex tachycardia (treat with -blockers), hypotension, fushing, headache, “Monday disease” in industrial nitrate
exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend —> tachycardia,
dizziness, headache upon reexposure. Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5
inhibitor use.
Ranolazine - ADVERSE EFFECTS Constipation, dizziness, headache, nausea.

Sacubitril - ADVERSE EFFECTS Hypotension, hyperkalemia, cough, dizziness; contraindicated with ACE inhibitors due to angioedema (both drugs
inc bradykinin). HMG-CoA reductase inhibitors - SE - Hepatotoxicity (inc LFTs), myopathy (esp when used with fibrates or niacin).
Bile acid resins - Cholestyramine, colestipol, colesevelam - SE - GI upset, dec absorption of other drugs and fat- soluble vitamins
Ezetimibe - SE - Rare inc LFTs, diarrhea

Fibrates - SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7 -hydroxylase). Niacin - SE - Flushed face
(prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia Hyperuricemia. PCSK9 inhibitors - SE - Myalgias, delirium, dementia,
other neurocognitive effects.
Fish oil and marine omega-3 fatty acids - SE - Nausea, fish-like taste.
Cardiac glycosides Digoxin. ADVERSE EFFECTS Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (think van Glow),
arrhythmias, AV block. Can lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to toxicity: renal failure ( excretion),
hypokalemia (permissive for digoxin binding at K+-binding site on Na+ /K+ ATPase), drugs that displace digoxin from tissue- binding sites, and dec
clearance (eg, verapamil, amiodarone, quinidine). ANTIDOTE Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+.
1A - Quinidine, procainamide, disopyramide. SE - Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF
(disopyramide), thrombocytopenia, torsades de pointes due to inc QT interval.
1B - Lidocaine, phenytoin, mexiletine. SE - CNS stimulation/depression, cardiovascular depression.
1C - Flecainide, propafenone. SE - Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.
Antiarrhythmics— -blockers (class II) - ADVERSE EFFECTS Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV
block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can
exacerbate vasospasm in vasospastic angina. B-blockers (except the nonselective - and - antagonists carvedilol and labetalol) cause unopposed 1-
agonism if given alone for pheochromocytoma or for cocaine toxicity (unsubstantiated). Treat B-blocker overdose with saline, atropine, glucagon.
Antiarrhythmics—potassium channel blockers (class III) - ADVERSE EFFECTS Sotalol —torsades de pointes, excessive blockade. Ibutilide—
torsades de pointes. Amiodarone—pulmonary fbrosis, hepatotoxicity, hypothyroidism or hyperthyroidism (amiodarone is 40% iodine by weight), acts
as hapten (corneal deposits, blue/gray skin deposits resulting in photodermatitis), neurologic effects, constipation, cardiovascular effects (bradycardia,
heart block, HF). Remember to check PFTs, LFTs, and TFTs when using amiodarone. Amiodarone is lipophilic and has class I, II, III, and IV effects.
Antiarrhythmics—calcium channel blockers (class IV) - ADVERSE EFFECTS Constipation, fushing, edema, cardiovascular effects (HF, AV block,
sinus node depression).
Adenosine - Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm.
IVabradine - SE - Luminous phenomena/visual brightness, hypertension, bradycardia.

Insulin preparations - SE - Hypoglycemia, lipodystrophy, hypersensitivity reactions (rare), weight gain.

Biguanides - Metformin - SE - GI upset, lactic acidosis (use with caution in renal insufficiency), vitamin B12 deficiency. Weight loss (often desired).
TZDs - “-glits” Pioglitazone, rosiglitazone - SE - Weight gain, edema, HF, inc risk of fractures. Delayed onset of action (several weeks). Rosiglitazone:
inc risk of MI, cardiovascular death. Sulfonylureas (1st gen) - Chlorpropamide, tolbutamide. Sulfonylureas (2nd gen) - Glipizide, glyburide.
Meglitinides “-glins” Nateglinide, repaglinide - SE - Hypoglycemia (inc risk in renal insufficiency), weight gain. Disulfiram-like reaction with first-
generation sulfonylureas only (rarely used).
GLP-1 analogs - Exenatide, liraglutide. DPP-4 inhibitors “-glips” Linagliptin, saxagliptin, sitagliptin - SE GLP-1 analogs - Pancreatitis, weight loss, Inc
satiety. SE DPP-4 inh - Respiratory and urinary infections, weight neutral, Inc satiety. (DPP-4 inhibitors - Inhibit DPP-4 enzyme that deactivates GLP-
1.)
SGLT-2 inh - Sodium-glucose co-transporter 2 inhibitors “-glifs” Canagliflozin, dapagliflozin, empagliflozin - SE - Glucosuria (UTIs, vulvovaginal
candidiasis), dehydration (orthostatic hypotension), weight loss. Use with caution in renal insufficiency (dec efficacy with dec GFR).
-glucosidase inhibitors - Acarbose, miglitol - SE - GI upset, bloating. Not recommended in renal insufficiency.
Amylin analogs - Pramlintide - SE - Hypoglycemia. Inc satiety (often desired).
Weight loss (GBS) - Biguanides, GLP-1 analogs, SGLT 2 inhibitors. Weight neutral - DPP-4 inhibitors. Weight gain (MST) - TZDs, sulfonylureas,
meglitinides.
Thionamides - Propylthiouracil, methimazole - ADVERSE EFFECTS Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. PTU use has
been associated with ANCA-positive vasculitis. Methimazole is a possible teratogen (can cause aplasia cutis).
Levothyroxine, liothyronine - ADVERSE EFFECTS Tachycardia, heat intolerance, tremors, arrhythmias.
Fludrocortisone - ADVERSE EFFECTS Similar to glucocorticoids; also edema, exacerbation of heart failure, hyperpigmentation
Cinacalcet - ADVERSE EFFECTS Hypocalcemia.
Sevelamer ADVERSE EFFECTS Hypophosphatemia, GI upset.
Cation exchange resins Patiromer, sodium polystyrene sulfonate, zirconium cyclosilicate - ADVERSE EFFECTS Hypokalemia, GI upset.
H2-blockers ADVERSE EFFECTS Cimetidine is a potent inhibitor of cytochrome P- 450 (multiple drug interactions); it also has antiandrogenic effects
(prolactin release, gynecomastia, impotence, dec libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta.
Cimetidine dec renal excretion of creatinine. Other H2 blockers are relatively free of these effects. Proton pump inhibitors ADVERSE EFFECTS inc
risk of C diffcile infection, pneumonia, acute interstitial nephritis. Vitamin B12 malabsorption; dec serum Mg2+ and dec Ca2+ absorption (potentially
leading to increased fracture risk in elderly).
Antacids - Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.
All can cause hypokalemia. Overuse can also cause the following problems:
Aluminum hydroxide - Constipation, Hypophosphatemia, Osteodystrophy, Proximal muscle weakness, Seizures (CHOPS)
Calcium carbonate - Hypercalcemia (milk-alkali syndrome), rebound acid inc. Can chelate and dec effectiveness of other drugs (eg, tetracycline).
Magnesium hydroxide - Diarrhea, hyporefexia, hypotension, cardiac arrest (Mg2+ = Must go 2 the bathroom)
Misoprostol ADVERSE EFFECTS Diarrhea. Contraindicated in patients of childbearing potential (abortifacient).
Octreotide ADVERSE EFFECTS Nausea, cramps, steatorrhea. Inc risk of cholelithiasis due to CCK inhibition.
Sulfasalazine ADVERSE EFFECTS Malaise, nausea, sulfonamide toxicity, reversible oligospermia.
Loperamide ADVERSE EFFECTS Constipation, nausea.
Ondansetron ADVERSE EFFECTS Headache, constipation, QT interval prolongation, serotonin syndrome.
Metoclopramide ADVERSE EFFECTS - Inc parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea. Drug
interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction, Parkinson disease (due to D2-receptor
blockade), dec seizure threshold.
Orlistat ADVERSE EFFECTS Abdominal pain, fatulence, bowel urgency/frequent bowel movements, steatorrhea; dec absorption of fat-soluble
vitamins.
Laxatives - Indicated for constipation or patients on opiates requiring a bowel regimen.
Bulk-forming laxatives - (PM) ADVERSE EFFECTS Bloating.
Osmotic laxatives - (PMLM) ADVERSE EFFECTS Diarrhea, dehydration; may be misused by patients with bulimia nervosa; overuse may cause
metabolic alkalosis.
Stimulants - (BS) ADVERSE EFFECTS Diarrhea, melanosis coli; overuse may cause metabolic alkalosis.
Emollients - Docusate ADVERSE EFFECTS Diarrhea; overuse may cause metabolic alkalosis.
B-PM
O-PMLM
S-BS
E-D
RESPIRATORY PHARMACOLOGY

H1-blockers - ADVERSE EFFECTS Sedation, antimuscarinic, anti- -adrenergic. Second generation - Loratadine, fexofenadine, desloratadine,
cetirizine. Names usually end in “- adine.” Setirizine (cetirizine) is second- generation agent. CLINICAL USE Allergy. ADVERSE EFFECTS Far less
sedating than 1st generation because of dec entry into CNS.
Dextromethorphan - Antitussive (antagonizes NMDA glutamate receptors). May cause serotonin syndrome if combined with other serotonergic agents.
Pseudoephedrine, phenylephrine - ADVERSE EFFECTS Hypertension. Rebound congestion (rhinitis medicamentosa) if used more than 4–6 days.
Associated with tachyphylaxis. Can also cause CNS stimulation/anxiety (pseudoephedrine).

Pulmonary hypertension drugs-

Endothelin receptor antagonists - Hepatotoxic (monitor LFTs). Example: bosentan.
PDE-5 inhibitors - Contraindicated when taking nitroglycerin or other nitrates (due to risk of severe hypotension). Example: sildenafl.
Prostacyclin analogs - Side effects: fushing, jaw pain. Examples: epoprostenol, iloprost.
Asthma drugs -
Inhaled 2-agonists - Albuterol—Can cause tremor, arrhythmia.
Salmeterol, formoterol—Can cause tremor, arrhythmia.
Zileuton—Hepatotoxic.
Methylxanthines - Theophylline— Limited use due to narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by cytochrome P-450.
Blocks actions of adenosine.
Intellectual disabilities and mental illnesses are not exclusion criteria for informed decision-making unless their condition presently impairs their ability
to make healthcare decisions.
Capacity is determined by a physician for a specifc healthcare-related decision (eg, to refuse medical care). Competency is determined by a judge and
usually refers to more global categories of decision making (eg, legally unable to make any healthcare-related decision).
Components (assessing capacity is of MASSIVE importance):
Decision is not a result of Mental illness exacerbation
Patient is 18 years of Age or otherwise legally emancipated
Decision is not a result of altered mental Status (eg, delirium, intoxication) Decision remains Stable over time
Patient is Informed and understands
Decision is consistent with patient’s Values and goals
Patient Expresses preferences
Exceptions to informed consent (WIPE it away):
Waiver—patient explicitly relinquishes the right of informed consent
Legally Incompetent—patient lacks decisionmaking capacity (obtain consent from legal surrogate)
Therapeutic Privilege—withholding information when disclosure would severely harm the patient or undermine informed decision-making capacity
Emergency situation—implied consent may apply
Priority of surrogates: spouse > adult children > parents > siblings > other relatives (the spouse ChiPS in).
Examples of exceptions to patient confdentiality (many are state specifc) include the following (“The physician’s good judgment SAVED the day”):
Patients with Suicidal/homicidal ideation
Abuse (children, elderly, and/or prisoners)
Duty to protect—state-specifc laws that sometimes allow physician to inform or somehow protect potential Victim from harm Patients with Epilepsy
and other impaired automobile drivers Reportable Diseases (eg, STIs, hepatitis, food poisoning); physicians may have a duty to warn public offcials,
who will then notify people at risk. Dangerous communicable diseases, such as TB or Ebola, may require involuntary treatment.
Encapsulated bacteria - Please SHiNE my SKiS
Aerobes - Nocardia, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Bordetella pertussis
Anaerobes - Clostridium, Bacteroides, Fusobacterium, and Actinomyces israelii.
Facultative anaerobes - Streptococci, staphylococci, and enteric gram ⊖ bacteria.
Pneumococcal vaccines: PCV13 (pneumococcal conjugate vaccine), PPSV23 (pneumococcal polysaccharide vaccine with no conjugated protein). H
infuenzae type b (conjugate vaccine). Meningococcal vaccine (conjugate vaccine).
Giemsa - RCT-BPH
dont gram stain well - MALT-CRUMBLE
Gram ⊕ only - Spore, Lipoteichoic acids
Gram ⊖ only - Outer membrane, periplasm, porins, endotoxin
Thayer-Martin agar - CNTV
Encapsulated bacteria - Please SHiNE my SKiS
Aerobes - Nocardia, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Bordetella pertussis
Anaerobes - Clostridium, Bacteroides, Fusobacterium, and Actinomyces israelii.
Facultative anaerobes - Streptococci, staphylococci, and enteric gram ⊖ bacteria.
Obligate intracellular - RCC - Rickettsia, Chlamydia, Coxiella
Thayer-Martin agar - CNTV - Selectively favors growth of Neisseria by inhibiting growth of gram organisms with vancomycin, gram organisms except
Neisseria with trimethoprim and colistin, and fungi with nystatin
Catalase-positive organisms - BB CHESS PLAN - Nocardia, Staphylococci, Serratia, Candida, Listeria, E coli, Burkholderia cepacia, Pseudomonas,
Aspergillus, Helicobacter pylori, Bordetella pertussis.
Protein A - S aureus
M protein - gp A strep
IgA protease - S pneumoniae, H infuenzae type b, and Neisseria (SHiN).
Transposition - Tn1546 with vanA from Enterococcus to S aureus.
Exotoxins - Destroyed rapidly at 60°C (except staphylococcal enterotoxin and E coli heatstable toxin).
Endotoxins - Stable at 100°C for 1 hr.
Hydrogen peroxide and iodine-based agents are also sporicidal
Catalase-positive organisms - BB CHESS PLAN
Spore-forming bacteria - bacillus and clostridium
Exotoxins - Destroyed rapidly at 60°C (except staphylococcal enterotoxin and E coli heatstable toxin).
Endotoxins - Stable at 100°C for 1 hr.
F+ x F- —> No transfer of chromosomal DNA.
Hfr x F- —> few fanking chromosomal genes transferred.
Hfr × F– and Specialized transduction commonality-
Incorporation into bacterial chromosomal DNA
Transduction-
(GP-SE)
Generalized - Packaging error, Lytic phage.
Speciaized - Excision error, Lysogenic phage.
Generalized transduction - GP packaging error; lytic phage;
Bacterial DNA cleaved > parts of DNA packaged in phage capsid > phage infects another bacterium > transfer.
There is NO incorporation of phage DNA into bacterial chromosomal DNA.
Speciaized transduction - SE Excision error; Lysogenic phage;
Viral DNA INCORPORATES into bacterial chromosome > phage DNA is excised with flanking bacterial genes > DNA is packaged into phage capsid
> phage infects another bacterium > transfer LYSOGENIC PHAGE - (ABCD’S): Group A strep erythrogenic toxin, Botulinum toxin, Cholera toxin,
Diphtheria toxin, Shiga toxin.
Bacteria that inc cAMP (CAPE) include Cholera, Anthracis, Pertussis, Ecoli.
Cholera - (inc cAMP) by permanently activating Gs

Bordetella pertussis - inc cAMP by Inactivating inhibitory G subunit (Gi)

Superantigens -
Staphylococcus aureus - Toxic shock syndrome toxin (TSST-1) - Toxic shock syndrome. Streptococcus pyogenes - Erythrogenic exotoxin A - Toxic
shock-like syndrome

Inactivate elongation factor (EF-2) - DIPHTHERIA AND PSEUDOMONAS

Inactivate 60S ribosome by removing adenine from rRNA - shigella and EHEC
Bordetella pertusis - Whooping cough—child coughs on expiration and “whoops” on inspiration; can cause “100-day cough” in adults; associated with
posttussive emesis.
Infant botulism - spores (toxin formed in-vivo)
Adult botulism - preformed toxin
Lyse cell membranes - Clostridium perfringens (alpha toxin), Streptococcus pyogenes (Streptolysin O).
Enterotoxigenic E coli - LA-SG
Endotoxins - Stable at 100°C for 1 hr.
MRSA - Resistance due to altered penicillin-binding proteins (conferred by mecA gene). Some strains release Panton-Valentine leukocidin (PVL),
which kills leukocytes and causes tissue necrosis. Staphylococcus aureus - Gram ⊕, β-hemolytic, catalase ⊕, coagulase ⊕ cocci in clusters
Staphylococcus epidermidis - Gram ⊕, catalase ⊕, coagulase ⊖, urease ⊕ cocci in clusters
Staphylococcus saprophyticus - Gram ⊕, catalase ⊕, coagulase ⊖, urease ⊕ cocci in clusters.
Streptococcus pneumoniae - Gram ⊕, α-hemolytic, lancet-shaped diplococci.
Viridans group streptococci - Gram ⊕, α-hemolytic cocci.
Streptococcus pyogenes (group A streptococci) - β-hemolytic, pyrrolidonyl arylamidase (PYR) ⊕
Streptococcus agalactiae (group B streptococci) - Gram ⊕ cocci, bacitracin resistant, β-hemolytic. Hippurate test ⊕. PYR ⊖.
Enterococci (E faecalis and E faecium) - Catalase ⊖, PYR ⊕
S aureus Enterotoxin is heat stable > not destroyed by cooking
Urease ⊕ Pee CHUNKSS.
Staphylococcus epidermidis - Does not ferment mannitol (vs S aureus)
GAS - PYR+
GBS - Hippurate test ⊕. PYR ⊖. Produces CAMP factor.
Enterococci - are penicillin G resistant and cause UTI, biliary tract infections, and subacute endocarditis (following GI/GU procedures). Catalase ⊖,
PYR ⊕, typically nonhemolytic
Anthrax toxin (an exotoxin consisting of protective antigen, lethal factor, and edema factor). Polypeptide capsule (poly d-glutamate). Colonies -
“medusa head” appearance. Woolsorter’s disease. Staphylococcus aureus - Toxic shock syndrome toxin (TSST-1) - Toxic shock syndrome.
Streptococcus pyogenes - Erythrogenic exotoxin A - Toxic shock-like syndrome
B cereus - (reheated rice syndrome). Emetic type causes nausea and vomiting within 1–5 hours, caused by cereulide, a preformed toxin
Urease ⊕ Pee CHUNKSS.
Heat-stable toxins - staphylococcal enterotoxin and E coli heatstable toxin.
Streptococcus pyogenes (group A streptococci) - Pyogenic - cellulitis, Toxigenic - necrotizing fascitis.
Streptococcus agalactiae (group B streptococci) - Produces CAMP factor, which enlarges the area of hemolysis formed by S aureus.
Heat-stable toxins - staphylococcal enterotoxin and E coli heatstable toxin.

Penicillin G, V - Rx Mostly used for gram ⊕ organisms (S pneumoniae, S pyogenes, Actinomyces). Also used for gram ⊖ cocci (mainly N
meningitidis) and spirochetes (mainly T pallidum). Bactericidal for gram ⊕ cocci, gram ⊕ rods, gram ⊖ cocci, and spirochetes. β-lactamase sensitive.
SE - Hypersensitivity reactions, direct Coombs ⊕ hemolytic anemia, drug-induced interstitial nephritis. RESISTANCE - β-lactamase cleaves the β-
lactam ring. Mutations in PBPs.
Penicillinase-sensitive penicillins - Amoxicillin, ampicillin; Rx Extended-spectrum penicillin—H influenzae, H pylori, E coli, Enterococci, Listeria
monocytogenes, Proteus mirabilis, Salmonella, Shigella. Coverage: ampicillin/amoxicillin HHEELPSS kill enterococci. SE - Hypersensitivity
reactions, rash, pseudomembranous colitis. RESISTANCE - Penicillinase (a type of β-lactamase) cleaves β-lactam ring.

Penicillinase-resistant penicillins - Dicloxacillin, nafcillin, oxacillin. Rx S aureus (except MRSA). “Use naf (nafcillin) for staph.” SE - Hypersensitivity
reactions, interstitial nephritis. RESISTANCE - MRSA has altered penicillin-binding protein target site.
Antipseudomonal penicillins - Piperacillin, ticarcillin. Rx Pseudomonas spp. and gram ⊖ rods. SE - Hypersensitivity reactions.
Cephalosporins - Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma),
MRSA, and Enterococci. 1st generation (cefazolin, cephalexin)—gram ⊕ cocci, Proteus mirabilis, E coli, Klebsiella pneumoniae. Cefazolin used prior
to surgery to prevent S aureus wound infections. 1st generation—⊕ PEcK. 2nd generation (cefaclor, cefoxitin, cefuroxime, cefotetan)—gram ⊕ cocci,
H influenzae, Enterobacter aerogenes, Neisseria spp., Serratia marcescens, Proteus mirabilis, E coli, Klebsiella pneumoniae. 2nd graders wear fake fox
fur to tea parties. 2nd generation—⊕ HENS PEcK. 3rd generation (ceftriaxone, cefotaxime, cefpodoxime, ceftazidime, cefixime)—serious gram ⊖
infections resistant to other β- lactams. Can cross blood-brain barrier. Ceftriaxone—meningitis, gonorrhea, disseminated Lyme disease. Ceftazidime—
Pseudomonas. 4th generation (cefepime)—gram ⊖ organisms, with inc activity against Pseudomonas and gram ⊕ organisms. 5th generation
(ceftaroline)—broad gram ⊕ and gram ⊖ organism coverage; unlike 1st–4th generation cephalosporins, ceftaroline covers MRSA, and Enterococcus
faecalis—does not cover Pseudomonas. SE - Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency.
Low rate of cross- reactivity even in penicillin- allergic patients. Inc nephrotoxicity of aminoglycosides. RESISTANCE - Inactivated by
cephalosporinases (a type of β-lactamase). Structural change in penicillin- binding proteins (transpeptidases).

Carbapenems - Doripenem, imipenem, meropenem, ertapenem. Rx Gram ⊕ cocci, gram ⊖ rods, and anaerobes. Wide spectrum and significant side
effects limit use to life-threatening infections or after other drugs have failed. Meropenem has a dec risk of seizures and is stable to dehydropeptidase I.
SE - GI distress, rash, and CNS toxicity (seizures) at high plasma levels. RESISTANCE - Inactivated by carbapenemases produced by, eg, K
pneumoniae, E coli, E aerogenes.
Aztreonam - Rx Gram ⊖ rods only—no activity against gram ⊕ rods or anaerobes. For penicillin- allergic patients and those with renal insufficiency
who cannot tolerate aminoglycosides. SE - Usually nontoxic; occasional GI upset.

Vancomycin - Rx Gram ⊕ bugs only—for serious, multidrug-resistant organisms, including MRSA, S epidermidis, sensitive Enterococcus species, and
Clostridium difficile (oral route). SE - Well tolerated in general but not trouble free: nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing (red
man syndrome - idiopathic reaction largely preventable by pretreatment with antihistamines), DRESS syndrome. RESISTANCE - Occurs in bacteria
(eg, Enterococcus) via amino acid modification of D-Ala-D-Ala to D-Ala-D-Lac. “If you Lack a D-Ala (dollar), you can’t ride the van (vancomycin).”

Aminoglycosides - Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin. Rx Severe gram ⊖ rod infections. Synergistic with β-lactam
antibiotics. Neomycin for bowel surgery. SE - Nephrotoxicity, neuromuscular blockade (absolute contraindication with myasthenia gravis), ototoxicity
(especially with loop diuretics), teratogenicity. RESISTANCE - Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or
adenylation.
Tetracyclines - Tetracycline, doxycycline, minocycline. Rx Borrelia burgdorferi, M pneumoniae. Drugs’ ability to accumulate intracellularly makes
them very effective against Rickettsia and Chlamydia. Also used to treat acne. Doxycycline effective against community-acquired MRSA. SE - GI
distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. “Teratocylines” are teratogenic; generally avoided in
pregnancy and in children (except doxycycline). RESISTANCE - Dec uptake or inc efflux out of bacterial cells by plasmid-encoded transport pumps.
Tigecycline - Rx Broad-spectrum anaerobic, gram ⊖, and gram ⊕ coverage. Multidrug-resistant organisms (MRSA, VRE) or infections requiring deep
tissue penetration. SE - Nausea, vomiting. Chloramphenicol - Rx Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus
pneumoniae) and rickettsial diseases (eg, Rocky Mountain spotted fever [Rickettsia rickettsii]). Limited use due to toxicity but often still used in
developing countries because of low cost. SE - Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature
infants because they lack liver UDP-glucuronosyltransferase). RESISTANCE - Plasmid- encoded acetyltransferase inactivates the drug.
Clindamycin - Rx Anaerobic infections (eg, Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections.
Also effective against invasive group A streptococcal infection. Treats anaerobic infections above the diaphragm vs metronidazole (anaerobic
infections below diaphragm). SE - Pseudomembranous colitis (C difficile overgrowth), fever, diarrhea.
Linezolid - Rx Gram ⊕ species including MRSA and VRE. SE - Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy,
serotonin syndrome (due to partial MAO inhibition). RESISTANCE - Point mutation of ribosomal RNA.
Macrolides - Rx - Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram ⊕ cocci (streptococcal infections in patients
allergic to penicillin), and B pertussis. SE - MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic
hepatitis, Rash, eOsinophilia. Increases serum concentration of theophylline, oral anticoagulants. Clarithromycin and erythromycin inhibit cytochrome
P-450. RESISTANCE - Methylation of 23S rRNA- binding site prevents binding of drug.
Polymyxins - Colistin (polymyxin E), polymyxin B. Rx Salvage therapy for multidrug-resistant gram ⊖ bacteria (eg, P aeruginosa, E coli, K
pneumoniae). Polymyxin B is a component of a triple

antibiotic ointment used for superficial skin infections. SE - Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory
failure.
Sulfonamides - Rx Gram ⊕, gram ⊖, Nocardia. TMP-SMX for simple UTI. SE - Hypersensitivity reactions, hemolysis if G6PD deficient,
nephrotoxicity (tubulointerstitial nephritis), photosensitivity, Stevens-Johnson syndrome, kernicterus in infants, displace other drugs from albumin (eg,
warfarin). RESISTANCE - Altered enzyme (bacterial dihydropteroate synthase), dec uptake, or inc PABA synthesis.
Dapsone - Rx Leprosy (lepromatous and tuberculoid), Pneumocystis jirovecii prophylaxis, or treatment when used in combination with TMP. SE -
Hemolysis if G6PD deficient, methemoglobinemia, agranulocytosis.
Trimethoprim - Rx Used in combination with sulfonamides (trimethoprim- sulfamethoxazole [TMP- SMX]), causing sequential block of folate
synthesis. Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.
SE - Hyperkalemia (high doses), megaloblastic anemia, leukopenia, granulocytopenia, which may be avoided with coadministration of leucovorin
(folinic acid). TMP Treats Marrow Poorly.
Fluoroquinolones - Rx Gram ⊖ rods of urinary and GI tracts (including Pseudomonas), some gram ⊕ organisms, otitis externa. SE - GI upset,
superinfections, skin rashes, headache, dizziness. Less commonly, can cause leg cramps and myalgias. Contraindicated during pregnancy or
breastfeeding and in children < 18 years old due to possible damage to cartilage. Some may prolong QT interval. May cause tendonitis or tendon
rupture in people > 60 years old and in patients taking prednisone. Ciprofloxacin inhibits cytochrome P-450. Fluoroquinolones hurt attachments to your
bones. RESISTANCE - Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
Daptomycin - Rx S aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE. Not used for pneumonia (avidly binds to and is
inactivated by surfactant). “Dapto-myo-skin” is used for skin infections but can cause myopathy. SE - Myopathy, rhabdomyolysis.
Metronidazole - Rx Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C difficile). Can be used in place of
amoxicillin in H pylori “triple therapy” in case of penicillin allergy. GET GAP on the Metro with metronidazole! Treats anaerobic infection below the
diaphragm vs clindamycin (anaerobic infections above diaphragm). SE - Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with
alcohol; headache, metallic taste.
Antimycobacterial therapy - M tuberculosis - Prophylaxis Isoniazid - Rx Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE for treatment)
M avium–intracellulare - Prophylaxis Azithromycin, rifabutin - Rx Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.
M leprae - Prophylaxis N/A - Rx Long-term treatment with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.
Rifamycins - Rx Mycobacterium tuberculosis; delay resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and
chemoprophylaxis in contacts of children with H influenzae type b. SE - Minor hepatotoxicity and drug interactions (inc cytochrome P-450); orange
body fluids (nonhazardous side effect). Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation.
Resistance - Mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to resistance. Rifampin’s 4 R’s: RNA polymerase
inhibitor; Ramps up microsomal cytochrome P-450; Red/orange body fluids; Rapid resistance if used alone. Rifampin ramps up cytochrome P-450, but
rifabutin does not.
Isoniazid - Rx Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB. Also used as monotherapy for latent TB. Different
INH half-lives in fast vs slow acetylators. SE - Hepatotoxicity, cytochrome P-450 inhibition, drug-induced SLE, anion gap metabolic acidosis, vitamin
B6 deficiency (peripheral neuropathy, sideroblastic anemia), seizures (in high doses, refractory to benzodiazepines). Administer with pyridoxine (B6).
INH Injures Neurons and Hepatocytes. Resistance - Mutations leading to underexpression of KatG.
Pyrazinamide - Rx Mycobacterium tuberculosis. SE - Hyperuricemia, hepatotoxicity.
Ethambutol - Rx Mycobacterium tuberculosis. SE - Optic neuropathy (red-green color blindness, usually reversible). Pronounce “eyethambutol.”
Streptomycin - Rx Mycobacterium tuberculosis (2nd line). SE - Tinnitus, vertigo, ataxia, nephrotoxicity.
Antimicrobial prophylaxis-
Exposure to meningococcal infection - Ceftriaxone, ciprofoxacin, or rifampin
High risk for endocarditis and undergoing surgical or dental procedures - Amoxicillin
History of recurrent UTIs - TMP-SMX
Malaria prophylaxis for travelers - Atovaquone-proguanil, mefoquine, doxycycline, primaquine, or chloroquine (for areas with sensitive species)
Pregnant patients carrying group B strep - Intrapartum penicillin G or ampicillin
Prevention of gonococcal conjunctivitis in newborn - Erythromycin ointment on eyes
Prevention of postsurgical infection due to S aureus - Cefazolin; vancomycin if ⊕ for MRSA
Prophylaxis of strep pharyngitis in child with prior rheumatic fever - Benzathine penicillin G or oral penicillin V
Prophylaxis in HIV infection/AIDS -
CD4 < 200 cells/mm3 - PROPHYLAXIS TMP-SMX - Pneumocystis pneumonia.
CD4 < 100 cells/mm3 - PROPHYLAXIS TMP-SMX - Pneumocystis pneumonia and toxoplasmosis
Treatment of highly resistant bacteria - MRSA: vancomycin, daptomycin, linezolid, tigecycline, ceftaroline, doxycycline.
VRE: daptomycin, linezolid, tigecycline, and streptogramins (quinupristin, dalfopristin).
Multidrug-resistant P aeruginosa, multidrug-resistant Acinetobacter baumannii: polymyxins B and E (colistin).
Amphotericin B - CLINICAL USE Serious, systemic mycoses. Cryptococcus (amphotericin B +/– flucytosine for cryptococcal meningitis),
Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for coccidioidal meningitis. Supplement K+ and Mg2+ because of altered renal
tubule permeability. ADVERSE EFFECTS Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis
(“amphoterrible”).Hydration dec nephrotoxicity. Liposomal amphotericin dec toxicity.
Nystatin - Rx “Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.
Flucytosine - CLINICAL USE Systemic fungal infections (especially meningitis caused by Cryptococcus) in combination with amphotericin B.
ADVERSE EFFECTS Bone marrow suppression.
Azoles - CLINICAL USE Local and less serious systemic mycoses. Fluconazole for chronic suppression of cryptococcal meningitis in people living
with HIV and candidal infections of all types. Itraconazole may be used for Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii.
Clotrimazole and miconazole for topical fungal infections. Voriconazole for Aspergillus and some Candida. Isavuconazole for serious Aspergillus and
Mucor infections. ADVERSE EFFECTS Testosterone synthesis inhibition (gynecomastia, especially with ketoconazole), liver dysfunction (inhibits
cytochrome P-450).
Terbinafne - CLINICAL USE Dermatophytoses (especially onychomycosis— fungal infection of fnger or toe nails). ADVERSE EFFECTS GI upset,
headaches, hepatotoxicity, taste disturbance. Echinocandins - Anidulafungin, caspofungin, micafungin. CLINICAL USE Invasive aspergillosis,
Candida. ADVERSE EFFECTS GI upset, fushing (by histamine release).
Griseofulvin - CLINICAL USE Oral treatment of superfcial infections; inhibits growth of dermatophytes (tinea, ringworm). ADVERSE EFFECTS
Teratogenic, carcinogenic, confusion, headaches, disulfram-like reaction, inc cytochrome P-450 and warfarin metabolism.
Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin).
Cestode/tapeworm Rx - (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole).
Antiprotozoal therapy Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (T cruzi), sodium stibogluconate
(leishmaniasis).
Anti-mite/louse therapy - Permethrin, malathion (acetylcholinesterase inhibitor), topical or oral ivermectin. Used to treat scabies (Sarcoptes scabiei)
and lice (Pediculus and Pthirus).
Chloroquine - CLINICAL USE Treatment of plasmodial species other than P falciparum (frequency of resistance in P falciparum is too high).
Resistance due to membrane pump that dec intracellular concentration of drug. Treat P falciparum with artemether/lumefantrine or
atovaquone/proguanil. For life-threatening malaria, use quinidine in US (quinine elsewhere) or artesunate. ADVERSE EFFECTS Retinopathy; pruritus
(especially in dark-skinned individuals).
Antihelminthic therapy - Pyrantel pamoate, ivermectin, mebendazole (microtubule inhibitor to treat “bendy worms”), praziquantel (inc Ca2+
permeability, inc vacuolization), diethylcarbamazine. Oseltamivir, zanamivir CLINICAL USE Treatment and prevention of infuenza A and B.
Beginning therapy within 48 hours of symptom onset may shorten duration of illness.
Baloxavir - MECHANISM Inhibits the “cap snatching” endonuclease activity of the infuenza virus RNA polymerase > dec viral replication.
CLINICAL USE Treatment within 48 hours of symptom onset shortens duration of illness.
Remdesivir - MECHANISM Prodrug of an ATP analog. The active metabolite inhibits viral RNA- dependent RNA polymerase and evades
proofreading by viral exoribonuclease (ExoN) > dec viral RNA production. CLINICAL USE Recently approved for treatment of COVID-19 requiring
hospitalization.
Acyclovir, famciclovir, valacyclovir - CLINICAL USE HSV and VZV. Weak activity against EBV. No activity against CMV. Used for HSV-induced
mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in patients who are immunocompromised. No effect on latent forms of HSV
and VZV. Valacyclovir, a prodrug of acyclovir, has better oral bioavailability. For herpes zoster, use famciclovir. ADVERSE EFFECTS Obstructive
crystalline nephropathy and acute kidney injury if not adequately hydrated. MECHANISM OF RESISTANCE Mutated viral thymidine kinase.
Ganciclovir - CLINICAL USE CMV, especially in patients who are immunocompromised. Valganciclovir, a prodrug of ganciclovir, has better oral
bioavailability. ADVERSE EFFECTS Bone marrow suppression (leukopenia, neutropenia, thrombocytopenia), renal toxicity. More toxic to host
enzymes than acyclovir. MECHANISM OF RESISTANCE Mutated viral kinase.
Foscarnet - CLINICAL USE CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSV. ADVERSE EFFECTS
Nephrotoxicity, electrolyte abnormalities (hypo- or hypercalcemia, hypo- or hyperphosphatemia, hypokalemia, hypomagnesemia) can lead to seizures.
MECHANISM OF RESISTANCE Mutated DNA polymerase.
Cidofovir - CLINICAL USE CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half-life. ADVERSE EFFECTS
Nephrotoxicity (coadminister with probenecid and IV saline to dec toxicity).
NRTIs - TOXICITY - Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin), peripheral
neuropathy, lactic acidosis (nucleosides), anemia (ZDV). Abacavir contraindicated if patient has HLA-B*5701 mutation due to inc risk of
hypersensitivity.

NNRTIs - TOXICITY - Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz.
Integrase inhibitors - TOXICITY - inc creatine kinase.
Protease inhibitors - TOXICITY - Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy (Cushing-like syndrome). Rifampin (potent
CYP/UGT inducer) reduces protease inhibitor concentrations; use rifabutin instead.
Hepatitis C therapy - Chronic HCV infection treated with multidrug therapy that targets specifc steps within HCV replication cycle (HCV- encoded
proteins). Examples of drugs are provided.
(LOV) NS5A inhibitors - Ledipasvir, Ombitasvir, Velpatasvir - Inhibits NS5A, a viral phosphoprotein that plays a key role in RNA replication. Exact
mechanism unknown. TOXICITY - Headache, diarrhea. (SD) NS5B inhibitors - Sofosbuvir, Dasabuvir - Inhibits NS5B, an RNA-dependent RNA
polymerase acting as a chain terminator. Prevents viral RNA replication. TOXICITY - Fatigue, headache.
(SG) NS3/4A inhibitors - Grazoprevir, Simeprevir. Inhibits NS3/4A, a viral protease, preventing viral replication. TOXICITY - Grazoprevir: headache,
fatigue. Simeprevir: photosensitivity reactions, rash.
Alternative drugs - Ribavirin Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase. Used as adjunct in cases
refractory to newer medications. TOXICITY - Hemolytic anemia, severe teratogen.

Anti-β2 glycoprotein I - Antiphospholipid syndrome

Anticardiolipin, lupus anticoagulant - SLE, antiphospholipid syndrome
Anti-U1 RNP (ribonucleoprotein) - Mixed connective tissue disease
Anti-Ro/SSA, anti-La/SSB - Sjögren syndrome
Anti-Scl-70 (anti-DNA topoisomerase I) - Scleroderma (diffuse)
Anticentromere - Limited scleroderma (CREST syndrome)
Antisynthetase (eg, anti-Jo-1), anti-SRP, anti-helicase (anti-Mi-2) - Polymyositis, dermatomyositis
Antimitochondrial - 1° biliary cholangitis
Anti-smooth muscle, anti-liver/kidney microsomal-1 -Autoimmune hepatitis
(MPO-ANCA)/perinuclear ANCA (p-ANCA) - Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, ulcerative colitis, 1° sclerosing
cholangitis
Anti-phospholipase A2 receptor - 1° membranous nephropathy
Anti-glutamic acid decarboxylase, islet cell cytoplasmic antibodies - Type 1 diabetes mellitus
Antimitochondrial - 1° biliary cholangitis
(MPO-ANCA)/perinuclear ANCA (p-ANCA) - 1° sclerosing cholangitis
CVID - B cell defect.
X-linked (Bruton) agammaglobulinemia - Defect in BTK, a tyrosine kinase gene > no B-cell maturation. Absent B cells in peripheral blood, dec Ig of
all classes.
Common variable immunodeficiency - Defect in B-cell differentiation. Dec plasma cells, dec immunoglobulins.
Leukocyte adhesion deficiency (type 1) - Defect in LFA-1 integrin (CD18) protein on phagocytes.
Chédiak-Higashi syndrome - PLAIN: Progressive neurodegeneration, Lymphohistiocytosis, Albinism (partial), recurrent pyogenic Infections,
peripheral Neuropathy. Giant granules in granulocytes and platelets. Pancytopenia. Mild coagulation defects.
CGD - Abnormal dihydrorhodamine (flow cytometry) test (dec green fluorescence). Nitroblue tetrazolium dye reduction test (obsolete) fails to turn
blue.
Wiskott-Aldrich syndrome - leukocytes and platelets unable to reorganize actin cytoskeleton > defective antigen presentation. Dec to normal IgG, IgM.
Inc IgE, IgA. Fewer and smaller platelets.
CGD and dec granulocytes produce same effect --> catalase +ve organisms
Fungi/parasites-
dec T CELLS - (PCC) - Candida (local), PCP, Cryptococcus
dec B CELLS - GI giardiasis (no IgA)
dec GRANULOCYTES - (CAM) - Candida (systemic), Aspergillus, Mucor
Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis
P-selectin (released from Weibel- palade bodies) + sialyl lewis
GlyCAM-1/CD34 + L-selectin
Adhesion-
defective in LAD type 1 (dec CD18 integrin subunit)
ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1)
VCAM-1 (CD106) + VLA-4 integrin
Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
Gram ⊕ only - Spore, Lipoteichoic acids
Gram ⊖ only - Outer Gram ⊕ only - Spore, Lipoteichoic acids
Gram ⊖ only - Outer membrane, periplasm, porins, endotoxin, periplasm
Cyclosporine - Toxicity - Nephrotoxicity, neurotoxicity, hypertension, hyperlipidemia, gingival hyperplasia, hirsutism. Both calcineurin inhibitors are
highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Tacrolimus (FK506) - Toxicity - Similar to cyclosporine, inc risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism. Both calcineurin
inhibitors are highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Sirolimus (Rapamycin) - Toxicity - “Pansirtopenia” (pancytopenia), insulin resistance, hyperlipidemia; not nephrotoxic.
Basiliximab - Toxicity - Edema, hypertension, tremor.
Azathioprine - TOXICITY - Pancytopenia. 6-MP degraded by xanthine oxidase; toxicity inc by allopurinol. Pronounce “azathiopurine”
Mycophenolate Mofetil - TOXICITY - GI upset, pancytopenia, hypertension, hyperglycemia. Less nephrotoxic and neurotoxic. Associated with
invasive CMV infection.
Glucocorticoids - TOXICITY - Cushing syndrome, osteoporosis, hyperglycemia, diabetes, amenorrhea, adrenocortical atrophy, peptic ulcers,
psychosis, cataracts, avascular necrosis (femoral head). Natalizumab - Risk of PML in patients with JC virus.
Mycophenolate mofetil - Associated with invasive CMV infection.
Toll-like receptor 7 - Imiquimod - CLINICAL USES Anogenital warts, actinic keratosis.
Interleukin-2 - Aldesleukin - CLINICAL USES Renal cell carcinoma, metastatic melanoma.

IFN-α - CLINICAL USES Chronic hepatitis C (not preferred) and B, renal cell carcinoma IFN-β - CLINICAL USES Multiple sclerosis
IFN-γ - CLINICAL USES Chronic granulomatous disease
Natalizumab, Vedolizumab - α4-integrin.

Vedolizumab - gut-specific anti integrin

Emici sounds like mistletoe and factor 9 is christmas factor. IBD (via) - Adalimumab, infliximab, Vedolizumab.
Crohn ds - Natalizumab
Epoetin alfa (EPO analog),
Filgrastim (G-CSF),
Sargramostim (GM-CSF),
Romiplostim (TPO analog),
eltrombopag - TPO receptor agonist.
Psoriasis -
Guselkumab (IL-23),
Ixekizumab (IL-17A),
secukinumab (IL-17A),

Ustekinumab (IL-12/23),
Adalimumab, infiximab (soluble TNF-α).
(gusail abdali infiltrates secular uzbekistan exactly)
Natalizumab, Vedolizumab - α4-integrin. (Natalia and Ved use A4 paper)
Adalimumab, infiximab - Soluble TNF-α.
Etanercept - decoy TNF-α receptor.
Eculizumab - Complement protein C5.
Guselkumab - IL-23. (angry beckham)
Ixekizumab, secukinumab - IL-17A. (17 is exactly secular)
Ustekinumab - IL-12/IL-23. (ustaad can bind two)
Denosumab - RANKL.
Emicizumab - Factor IXa and X.
Omalizumab - IgE.
Palivizumab - RSV F protein.
ANTIMICROBIAL - ADVERSE EFFECT
Sulfonamides - Kernicterus
Aminoglycosides - Ototoxicity
Fluoroquinolones - Cartilage damage
Clarithromycin - Embryotoxic
Tetracyclines - Discolored teeth, inhibition of bone growth
Ribavirin - Teratogenic
Griseofulvin - Teratogenic
Chloramphenicol - Gray baby syndrome
Anti PD-1 (PNC) (eg, pembrolizumab, nivolumab, cemiplimab)
Anti PD-L1 (ADA) (eg, atezolizumab, durvalumab, avelumab)
Ipilimumab (anti-CTLA-4 antibody).
Anti PD-1 (PNC) (eg, pembrolizumab, nivolumab, cemiplimab)
Anti PD-L1 (ADA) (eg, atezolizumab, durvalumab, avelumab)
Ipilimumab (anti-CTLA-4 antibody).
Brain - Lung > breast > melanoma, colon, kidney (lots of brain metastases can kill)
Liver - Colon >> stomach > pancreas (cancer sometimes penetrates liver)
Bone - Prostate, breast > kidney, thyroid, lung (painful bones kill the lungs)
ALK - Receptor tyrosine kinase
HER2/neu (ERBB2) - Receptor tyrosine kinase
RET - REceptor Tyrosine kinase
BCR-ABL - Non-receptor tyrosine kinase
JAK2 - Non-receptor tyrosine kinase
BRAF - Serine/threonine kinase
c-KIT - CytoKIne receptor
KRAS - RAS GTPase
BCL-2 - Antiapoptotic molecule
Aromatic amines (eg, benzidine, 2-naphthylamine) - Transitional cell carcinoma
Schistosoma haematobium - Squamous cell bladder cancer
Aromatic amines (eg, benzidine, 2-naphthylamine) - Transitional cell carcinoma
Schistosoma haematobium - Squamous cell bladder cancer
Urothelial carcinoma of the bladder - Associated with problems in your Pee SAC: Phenacetin, tobacco Smoking, Aromatic amines (found in dyes),
Cyclophosphamide.
Squamous cell carcinoma of the bladder - Risk factors include 4 S’s: Schistosoma haematobium infection (Middle East), chronic cystitis (“systitis”),
smoking, chronic nephrolithiasis (stones). P-glycoprotein - ATP-dependent effux pump also known as multidrug resistance protein 1 (MDR1).
Classically seen in adrenocortical carcinoma but also expressed by other cancer cells (eg, colon, liver). Used to pump out toxins, including
chemotherapeutic agents (one mechanism of dec responsiveness or resistance to chemotherapy over time).
Paraneoplastic cerebellar degeneration - Antibodies against antigens in Purkinje cells - Small cell lung cancer (anti-Hu), gynecologic and breast cancers
(anti-Yo), and Hodgkin lymphoma (anti-Tr). Paraneoplastic encephalomyelitis - Antibodies against Hu antigens in neurons - Small cell lung cancer.
Anti-NMDA receptor encephalitis - Ovarian teratoma.
Opsoclonus-myoclonus ataxia syndrome - “Dancing eyes, dancing feet” - Neuroblastoma (children), small cell lung cancer (adults).
Pure red cell aplasia Anemia with low reticulocytes Thymoma
Good syndrome Hypogammaglobulinemia Thymoma

Km is inversely related to the affnity of the enzyme for its substrate. Vmax is directly proportional to the enzyme concentration.
The closer to 0 on the Y-axis, the higher the Vmax.
The closer to 0 on the X-axis, the higher the Km.

The higher the Km, the lower the affnity.

Competitive inhibitors cross each other, whereas noncompetitive inhibitors do not.
Kompetitive inhibitors increase Km.
Bioavailability F = [AUCoral x DoseIV] / [Doseoral x AUCIV]
Weak acids - Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to
alkalinize urine.
Weak bases - Examples: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride to acidify urine.
TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channel blocking activity of TCAs, but not for accelerating drug
elimination.
TCA toxicity Rx ammonium chloride and sodium bicarbonate.
Zero-order elimination - Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp dec linearly with
time. Examples of drugs— (PEA) Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations). Capacity-limited elimination. Time of t1/2 dec as
concentration dec.
First-order elimination - Rate of first-order elimination is directly proportional to the drug concentration (ie, constant fraction of drug eliminated per
unit time). Cp dec exponentially with time. Applies to most drugs. Flow-dependent elimination. Time of t1/2 is constant as concentration dec.

In renal or liver disease, maintenance dose dec and loading dose is usually unchanged. Time to steady state depends primarily on t1/2 and is
independent of dose and dosing frequency.

*1 NADH gives 2.5 ATP*

2 pyruvate (per glucose) —> 2 acetyl-CoA gives 2 NADH = 5 ATP
2 acetyl-CoA = 20 ATP (TCA cycle)
2 NADH = 5 ATP
2 ATP
So total = 32 ATP per glucose (MA shuttle)
FBPase-2 active in fasting state, stimulating gluconeogenesis. (F for fasting)
PFK-2 active in fed state, stimulating glycolysis. (P for peth is full)
PFK-2 makes frustose-2,6-BP which stimulates PFK-1 which stimulates glycolysis in fed state PFK-1 and PFK-2 stimulate glycolysis

FBPase-1 and FBPase-2

stimulate gluconeogenesis
Anaerobic glycolysis - (major pathway in RBCs, WBCs, kidney medulla, lens, testes, and cornea).
HMP shunt - Sites: lactating mammary glands, liver, adrenal cortex (sites of fatty acid or steroid synthesis), RBCs.
Essential fructosuria - Hexokinase becomes 1° pathway for converting fructose to fructose-6-phosphate.
Fructose intolerance - Urine dipstick will be -ve (tests for glucose only). Treatment: dec intake of fructose, sucrose (glucose + fructose), and sorbitol
(metabolized to fructose).
Fructose is to Aldolase B as Galactose is to UridylTransferase (FAB GUT).
Liver, ovaries, and seminal vesicles have both enzymes (they lose sorbitol). Lens has primarily Aldose reductase. Retina, Kidneys, and Schwann cells
have only aldose reductase (LARKS).
ETC - DRAACCO
Fructose 2,6-bisphosphate inhibits Fructose-1,6- bisphosphatase 1 (Gluconeogenesis).
Fructose 2,6-bisphosphate stimulates PFK-1 (Glycolysis).
Essential PVT TIM HaLL: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Leucine, Lysine.
Glucogenic (HMV): Methionine, histidine, valine.
Glucogenic/ketogenic (PITT): Isoleucine, phenylalanine, threonine, tryptophan.
Ketogenic: leucine, lysine. The only purely ketogenic amino acids.
Acidic: Aspartic acid, glutamic acid. Negatively charged at body pH.
Basic: Arginine, histidine, lysine. His lys (lies) are basic.
Lactase deficiency - Primary: age-dependent decline after childhood (absence of lactase-persistent allele). Secondary: loss of intestinal brush border
due to gastroenteritis (eg, rotavirus), autoimmune disease. Congenital lactase deficiency: rare, due to defective gene.
Hyperammonimemia - Inc NH3 changes relative amounts of a-ketoglutarate, glutamate, GABA, and glutamine to favor inc glutamine. CNS toxicity
may involve dec GABA, dec a-ketoglutarate, TCA cycle inhibition, and cerebral edema due to glutamine-induced osmotic shifts.
Hyperammoniemia - No megaloblastic anemia (vs orotic aciduria).

In homocystinuria, lens subluxes “down and in” (vs Marfan, “up and fans out”).
Cystinuria detected with urinary sodium cyanide nitroprusside test and proton nuclear magnetic resonance spectroscopy of urine.
Maple syrup urine disease Blocked degradation of branched amino acids (Isoleucine, leucine, valine) due to dec branched-chain a-ketoacid
dehydrogenase (B1).
VOMIT pathway - valine, odd chain fatty acids, methionine, isoleucine, threonine (Fatty acids with odd number of carbons, branched-chain amino
acids).
Organic acidemias - Propionic acidemia - Defciency of propionyl-CoA carboxylase > inc propionyl-CoA, dec methylmalonic acid.
Methylmalonic acidemia - Defciency of methylmalonyl-CoA mutase or vitamin B12.
Treatment: low-protein diet limited in substances that metabolize into propionylCoA: Valine, Odd-chain fatty acids, Methionine, Isoleucine, Threonine
(VOMIT).
Cori disease - normal blood lactate levels. Limit dextrin–like structures accumulate in cytosol. Gluconeogenesis is intact.
Von-gierke - inc blood lactate, inc triglycerides, inc uric acid (Gout). Impaired gluconeogenesis and glycogenolysis.
McArdle - Second-wind phenomenon noted during exercise due to inc muscular blood flow. Characterized by a flat venous lactate curve with normal
rise in ammonia levels during exercise. Blood glucose levels typically unaffected.
Tay sachs - lysosomes with onion skin
Krabbe ds - globoid cells.
Gaucher ds - Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper).
Niemann-Pick disease - foam cells (lipid-laden macrophages)
Hurler syndrome - DEFICIENT ENZYME α-l-iduronidase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. AR
Hunter syndrome - DEFICIENT ENZYME Iduronate-2 (two)- sulfatase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. XR.
Tay-Sachs disease - DEFICIENT ENZYME Hexosaminidase A (“TAy-Sax”). ACCUMULATED SUBSTRATE GM2 ganglioside. AR
Fabry disease DEFICIENT ENZYME α-galactosidase A. ACCUMULATED SUBSTRATE Ceramide trihexoside (globotriaosylceramide). XR
Metachromatic leukodystrophy DEFICIENT ENZYME Arylsulfatase A. ACCUMULATED SUBSTRATE Cerebroside sulfate. AR
Krabbe disease DEFICIENT ENZYME Galactocerebrosidase (galactosylceramidase). ACCUMULATED SUBSTRATE Galactocerebroside,
psychosine. AR
Gaucher disease DEFICIENT ENZYME Glucocerebrosidase (β-glucosidase); treat with recombinant glucocerebrosidase. ACCUMULATED
SUBSTRATE Glucocerebroside. AR
Niemann-Pick disease DEFICIENT ENZYME Sphingomyelinase. ACCUMULATED SUBSTRATE Sphingomyelin. AR.
Hurler syndrome - DEFICIENT ENZYME α-l-iduronidase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. AR
Hunter syndrome - DEFICIENT ENZYME Iduronate-2 (two)- sulfatase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. XR.
Systemic 1° carnitine deficiency—no cellular uptake of carnitine > no transport of LCFAs into mitochondria > toxic accumulation of LCFAs (long
chain fatty acids) in the cytosol. Causes weakness, hypotonia, hypoketotic hypoglycemia, dilated cardiomyopathy.
Medium-chain acyl-CoA dehydrogenase deficiency— dec ability to break down fatty acids into acetyl-CoA > accumulation of fatty acyl carnitines in
the blood with hypoketotic hypoglycemia. Causes vomiting, lethargy, seizures, coma, liver dysfunction, hyperammonemia.

Urine test for ketones can detect acetoacetate, but not B-hydroxybutyrate. Hurler syndrome - DEFICIENT ENZYME α-l-iduronidase.
Hunter syndrome - DEFICIENT ENZYME Iduronate-2 (two)- sulfatase.
Major apolipoproteins

E - Mediates remnant uptake (everything except LDL) - Chylomicron Chylomicron remnant VLDL IDL HDL.
A-I - Found only on alphalipoproteins (HDL), activates LCAT - HDL.
C-II - Lipoprotein lipase cofactor that catalyzes cleavage. - Chylomicron VLDL IDL HDL.
B-48 - Mediates chylomicron secretion into lymphatics. Only on particles originating from the intestines - Chylomicron Chylomicron remnant. B-100 -
Binds LDL receptor Only on particles originating from the liver - VLDL IDL LDL.

Abetalipoproteinemia - Autosomal recessive. Mutation in gene that encodes microsomal transfer protein (MTP). Chylomicrons, VLDL, LDL absent.
Defciency in ApoB-48, ApoB-100. Axillary - skin above umblicus
Lymph node-
Medullary cords - lymphocytes and plasma cells

Medullary sinuses - macrophages and reticular cells

Epitrochlear nodes - Hand, forearm - Secondary syphilis
Colon from splenic flexure to upper rectum - inferior mesentric
lower rectum to anal canal (above pectinate line) - internal iliac
anal canal (below pectinate line) - superficial inguinal
skin above umblicus - axillary
skin below umblicus (except popliteal area) - superficial inguinal
Primary lymph node drainage of the
female reproductive system(UWorld)
Uterus - External iliac
Cervix - Internal iliac
Proximal Vagina: internal iliac
Distal Vagina: inguinofemoral
Vulva - Inguinofemoral
Ovaries - Paraaortic
Spleen-
Periarteriolar lymphatic sheath - Contains T cells. Located within white pulp.
Follicle - Contains B cells. Located within white pulp.
Marginal zone - Contains macrophages and specialized B cells. Site where antigen-presenting cells (APCs) capture blood borne antigens for
recognition by lymphocytes. Located between red pulp

and white pulp.

Thymus epithelium is derived from third pharyngeal pouch (endoderm), whereas thymic lymphocytes are of mesodermal origin.

White pulp-
PALS - T cells
Follicles - B cells
Marginal zone - macrophages and specialized B cells

Located between red pulp and white pulp.

Thymoma—neoplasm of thymus. Associated with myasthenia gravis, superior vena cava syndrome, pure red cell aplasia, Good syndrome. Thymus -
Cortex is dense with immature T cells; medulla is pale with mature T cells and Hassall corpuscles containing epithelial reticular cells. B-cells - somatic
hypermutation
T cell has CD40L and CD40 on APC

NK cell - Activity enhanced by IL-2, IL-12, IFN-α, and IFN-β.

Th17- + by TGF-β, IL-1, IL-6; - by IFN-γ, IL-4; secrete IL-17, IL-21, IL-22; induce neutrophils.
Treg (express CD3, CD4, CD25, FOXP3)- + by TGF-β, IL-2; - by IL-6; secrete TGF-β, IL-10, IL-35; (Treg)Prevent autoimmunity (maintain
tolerance).
Th1- + by IFN-γ, IL-12; - by IL-4, IL-10; secrete IFN-γ, IL-2; Activate macrophages and cytotoxic T cells.
Th2- + by IL-2, IL-4; - by IFN-γ; secrete IL-4, IL-5, IL-6, IL-10, IL-13; Activate eosinophils, ↑ IgE.
IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome— genetic defciency of FOXP3 > autoimmunity. Characterized by
enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infants.
Autoimmune polyendocrine syndrome-1 (Chronic mucocutaneous candidiasis, Hypoparathyroidism, Adrenal insuffciency, Recurrent Candida
infections). “Without AIRE, your body will CHAR”. DR3 - G-DASH
DR4 - RAD

NK cell - Activity enhanced by IL-2, IL-12, IFN-α, and IFN-β.

IgG - Associated with warm autoimmune hemolytic anemia
IgM - Associated with cold autoimmune hemolytic anemia
The CH50 test is used to screen for activation of the classical complement pathway. antibody diversity (antigen independent)

antibody specifcity (antigen dependent)

Fab - idiotype
Fc - isotype
Generation of antibody diversity (antigen independent)-
1. Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes
2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) 3. Random combination of heavy
chains with light chains

Generation of antibody specifcity (antigen dependent)-

4. Somatic hypermutation and affnity maturation (variable region)
5. Isotype switching (constant region).
C5a—neutrophil chemotaxis
C3b—opsonization.
C3a, C4a, C5a—anaphylaxis.
C5a—neutrophil chemotaxis.
C5b-9 (MAC)—cytolysis.
Complement inhibitors—decay-accelerating factor (DAF, aka CD55) and C1 esterase inhibitor help prevent complement activation on self cells (eg,
RBCs).
C3b binds to lipopolysaccharides on bacteria.
C3b also helps clear immune complexes.
IL-1 - osteoclast-activating factor.
IL-8 - chemotactic factor for neutrophils
Interferon-γ - Induces IgG isotype switching in B cells
Interleukin-13 - Promotes IgE production by B cells. Induces alternative macrophage activation.
Catalase ⊕ species (eg, S aureus, Aspergillus)
Oxidative burst also leads to K+ infux, which releases lysosomal enzymes. Lactoferrin is a protein found in secretory fuids and neutrophils that inhibits
microbial growth via iron chelation.
B cell/APCs - B7
T cells - CD28
Regulatory T cells - CD4, CD25.
Macrophages - CD14, CD40, CCR5
NK cells - CD16 (binds Fc of IgG), CD56.
Hematopoietic stem cells - CD34.
Anergy - State during which a cell cannot become activated by exposure to its antigen. T and B cells become anergic when exposed to their antigen
without costimulatory signal (signal 2). Another mechanism of self-tolerance.
After exposure to tetanus toxin, HBV, varicella, rabies virus, botulinum toxin, or diphtheria toxin, unvaccinated patients are given preformed antibodies
(passive)
Combined passive and active immunizations can be given for hepatitis B or rabies exposure
Live attenuated vaccines (TRAPS BY MIC) - Adenovirus (nonattenuated, given to military recruits), typhoid (Ty21a, oral), polio (Sabin), varicella
(chickenpox), smallpox, BCG, yellow fever, influenza (intranasal), MMR, rotavirus.
Killed or inactivated vaccine (H-TRIP) - Hepatitis A, Typhoid (Vi polysaccharide, intramuscular), Rabies, Influenza, Polio (SalK).
Subunit vaccine (NASHHH) - HBV (antigen = HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP), Neisseria meningitidis (various
strains), Streptococcus pneumoniae, Haemophilus influenzae type b.
Toxoid - Clostridium tetani, Corynebacterium diphtheriae.

MMR and varicella vaccines can be given to people living with HIV without evidence of immunity if CD4 cell count ≥ 200 cells/mm3.
TRALI - DONOR BLOOD - Donor antileukocyte IgG. HOST BLOOD - Host neutrophils.
Transfusion-related acute lung injury - Two-hit mechanism: 1. Neutrophils are sequestered and primed in pulmonary vasculature due to recipient risk
factors. 2. Neutrophils are activated by a product (eg, antileukocyte antibodies) in the transfused blood and release inflammatory mediators > inc
capillary permeability > pulmonary edema. DONOR BLOOD - Donor antileukocyte IgG. HOST BLOOD - Host neutrophils.
Hyper-IgM syndrome - Most commonly due to defective CD40L on Th cells. Opportunistic infection with Pneumocystis, Cryptosporidium, CMV.
Wiskott-Aldrich syndrome - leukocytes and platelets unable to reorganize actin cytoskeleton > defective antigen presentation. Dec to normal IgG, IgM.
Inc IgE, IgA. Fewer and smaller platelets. Selective IgA deficiency - Most common 1° immunodeficiency. Can cause false-negative celiac disease test.
IL-12 receptor deficiency - Most common cause of Mendelian susceptibility to mycobacterial diseases (MSMD).
Hyper-IgE syndrome (Job syndrome) - Deficiency of Th17 cells due to STAT3 mutation > impaired recruitment of neutrophils.
Chronic mucocutaneous candidiasis - T-cell dysfunction.
Severe combined immunodeficiency - Several types including defective IL-2R gamma chain (most common, X-linked recessive); adenosine deaminase
deficiency (autosomal recessive); RAG mutation > VDJ recombination defect. Dec T-cell receptor excision circles (TRECs)
Ataxia-telangiectasia - Defects in ATM gene > failure to detect DNA damage. Inc AFP. Dec IgA, IgG, and IgE.

Internal male genitalia - Seminal vesicle Epididymis Ejaculatory duct Ductus deferens External male genitalia - Penis Scrotum Prostate External female
genitalia - Clitoris Labia Distal vagina

Internal female genitalia - Fallopian tubes Uterus Proximal vagina

Testosterone - Pubic, axillary, and facial hair, inc penis size/length, growth spurt, etc.
Uterine (Müllerian duct) anomalies - dec fertility and risk of complicated pregnancy (eg, spontaneous abortion, prematurity, IUGR, malpresentation).
Contrast with normal uterus. Septate uterus - Incomplete resorption of septum. Common anomaly. Treat with septoplasty. Bicornuate uterus -
Incomplete fusion of Müllerian ducts.
Uterus didelphys - Complete failure of fusion > double uterus, cervix, vagina.
Male/female genital homologs-
Glans penis - Genital tubercle - Glans clitoris
Corpus cavernosum and spongiosum - Genital tubercle - Vestibular bulbs
Bulbourethral glands (of Cowper) - Urogenital sinus - Greater vestibular glands (of Bartholin) Prostate gland - Urogenital sinus - Urethral and
paraurethral glands (of Skene) Ventral shaft of penis (penile urethra) - Urogenital folds - Labia minora
Scrotum - Labioscrotal swelling - Labia majora
Genital tubercle - glans and muscles
Urogenital sinus - glands
Urogenital fold - ventral shaft/labia minora
Labioscrotal swelling - scrotum/labia majora
Hypospadias - Due to failure of urethral folds to fuse. Associated with inguinal hernia, cryptorchidism, chordee. Can be seen in 5α-reductase defciency.
Epispadias - Due to faulty positioning of genital tubercle. Exstrophy of the bladder is associated with epispadias.
Lymphatic drainage -
Ovaries/testes/fundus of uterus > para-aortic lymph nodes.
Body of uterus/cervix/superior part of bladder > external iliac nodes.
Prostate/cervix/corpus cavernosum/proximal vagina > internal iliac nodes.
Distal vagina/vulva/scrotum/distal anus > superfcial inguinal nodes.
Clitoris/glans penis > deep inguinal nodes.
Pathway of sperm during ejaculation— SEVEN UP: Seminiferous tubules Epididymis Vas deferens Ejaculatory ducts (Nothing) Urethra Penis.

Superior bladder wall (dome) injury—direct trauma to full bladder (eg, seatbelt) > abrupt inc intravesical pressure > dome rupture (weakest part) >
intraperitoneal urine accumulation. Peritoneal absorption of urine > inc BUN, inc creatinine.
Anterior bladder wall or neck injury—pelvic fracture > perforation by bony spicules > extraperitoneal urine accumulation (retropubic space).

Anterior urethral injury—perineal straddle injury > disruption of bulbar (spongy) urethra > scrotal hematoma. If Buck fascia is torn, urine escapes into
perineal space.
Posterior urethral injury—pelvic fracture > disruption at bulbomembranous junction (weakest part) > urine leakage into retropubic space and high-
riding prostate.
Physiologic changes in pregnancy - Changes that nurture the developing fetus and prepare the pregnant patient for labor and delivery. Mediated by inc
hormones (eg, estrogen, progesterone) and mechanical effects of gravid uterus.
CARDIOVASCULAR - dec SVR (dec afterload) and inc blood volume (inc preload) > inc SV > inc CO > inc placental perfusion. Inc HR is the major
contributor to inc CO in late pregnancy. Hemodilution > dec oncotic pressure > peripheral edema.
ENDOCRINE - Insulin resistance and hypoglycemia > inc lipolysis and fat utilization (to preserve glucose and amino acids for fetus). Pituitary
enlargement (lactotroph hyperplasia). Inc TBG, inc CBG, inc SHBG.
GASTROINTESTINAL - dec GI motility, dec LES tone, gallbladder stasis; predispose to constipation, GERD, gallstones.
HEMATOLOGIC - Dilutional anemia (inc inc plasma volume, inc RBC mass), hypercoagulable state (to decrease blood loss at delivery). Inc
micronutrient requirements predispose to defciency (eg, iron, folate).
MUSCULOSKELETAL - Lordosis (to realign gravity center), joint laxity (to facilitate fetal descent).
SKIN - Hyperpigmentation (eg, melasma, linea nigra, areola darkening), striae gravidarum (stretch marks), vascular changes (eg, spider angiomas,
palmar erythema, varicosities).
RENAL - Vasodilation > inc renal plasma flow > inc GFR > dec BUN and dec creatinine. Mild glucosuria, proteinuria. Ureter and renal pelvis dilation
(hydroureter and hydronephrosis) predisposes to pyelonephritis.
RESPIRATORY - Respiratory center stimulation > chronic hyperventilation (to increase fetal CO2 elimination).
Stage 1 - Pre-pubertal - No sexual hair, Flat-appearing chest with raised nipple.

Stage 2 - 8 - 11.5 yrs - Pubic hair appears (pubarche), Testicular enlargement, Breast bud forms (thelarche), mound forms.
Stage 3 - 11.5 - 13 yrs - Coarsening of pubic hair, Penis size/length inc, Breast enlarges.
Stage 4 - 13 - 15 yrs - Coarse hair across pubis, sparing thigh; Penis width/glans inc; Breast enlarges, raised areola, mound on mound.
Stage 5 - Usually > 15 years - Coarse hair across pubis and medial thigh; Penis and testis enlarge to adult size; Adult breast contour, areola flattens.

Complete mole-
KARYOTYPE 46,XX (most common); 46,XY
COMPONENTS Most commonly enucleated egg + single sperm (subsequently duplicates paternal DNA). HISTOLOGY Hydropic villi,
circumferential and diffuse trophoblastic proliferation. FETAL PARTS No.
STAINING FOR P57 PROTEIN (paternally imprinted).
UTERINE SIZE — inc
hCG - inc inc inc inc
IMAGING “Honeycombed” uterus or “clusters of grapes” A , “snowstorm” B on ultrasound
RISK OF INVASIVE MOLE 15–20%
RISK OF CHORIOCARCINOMA 2%
Partial mole-
KARYOTYPE 69,XXX; 69,XXY; 69,XYY
COMPONENTS 2 sperm + 1 egg
HISTOLOGY Only some villi are hydropic, focal/minimal trophoblastic proliferation FETAL PARTS Yes (partial = fetal parts)
STAINING FOR P57 PROTEIN (maternally expressed) Partial mole is P57 positive UTERINE SIZE —
hCG - inc
IMAGING - Fetal parts
RISK OF INVASIVE MOLE < 5%
RISK OF CHORIOCARCINOMA Rare
Breast pathology-
Lactiferous duct, Major duct - Intraductal papilloma, Abscess/mastitis, Paget disease
Terminal duct lobular unit - Fibrocystic change, DCIS, LCIS, Ductal carcinoma, Lobular carcinoma Stroma - Fibroadenoma, Phyllodes tumor

Hormone levels in germ cell tumors- SEMINOMA - PALP inc, AFP - , -hCG -/inc
YOLK SAC TUMOR - PALP - , AFP inc inc , -hCG -/inc CHORIOCARCINOMA - PALP - , AFP - , -hCG inc inc TERATOMA - PALP - , AFP -/inc ,
-hCG - EMBRYONAL CARCINOMA - PALP - , AFP -/inc (when mixed), β-hCG inc
Left shift (dec O unloading to tissue) - Left = lower -
Dec H+ (inc pH, base), dec PCO , dec 2,3–BPG, dec Temperature, inc CO, inc MetHb, inc HbF.

Right shift (inc O unloading to tissues) - ACE BATs right handed -

Inc H+ (dec pH, Acid), inc PCO , Exercise, inc 2,3–BPG, High Altitude, inc Temperature.

Flow-volume loops -
Obstructive lung disease RV inc
FRC inc
TLC inc
FEV1 dec dec
FVC dec
FEV1 /FVC - dec (FEV1 decreased more than FVC)
Restrictive lung disease RV dec
FRC dec
TLC dec
FEV1 dec
FVC dec
FEV1 /FVC - Normal or inc (FEV1 decreased proportionately to FVC)
Lobar pneumonia - S pneumoniae (most common), Legionella, Klebsiella.
Bronchopneumonia - S pneumoniae, S aureus, H infuenzae, Klebsiella.
Interstitial (atypical) pneumonia - Mycoplasma, Chlamydophila pneumoniae, Chlamydophila psittaci, Legionella, Coxiella burnetii, viruses (RSV,
CMV, infuenza, adenovirus). Sites of metastases from lung cancer (LABB) : liver (jaundice, hepatomegaly), adrenals, bone (pathologic fracture), brain.
Lung mets (BPBC) - Most often from breast, colon, prostate, and bladder cancer.

Myocardial infarction complications-

Cardiac arrhythmia Occurs within the frst few days after MI. Important cause of death before reaching the hospital and within the frst 24 hours post-
MI.
Postinfarction fbrinous pericarditis 1–3 days: friction rub.
Papillary muscle rupture 2–7 days: posteromedial papillary muscle rupture inc risk due to single blood supply from posterior descending artery. Can
result in severe mitral regurgitation. Interventricular septal rupture 3–5 days: macrophage-mediated degradation > VSD > inc O2 saturation and
pressure in RV.
Ventricular pseudoaneurysm formation 3–14 days: free wall rupture contained by adherent pericardium or scar tissue B ; dec CO, risk of arrhythmia,
embolus from mural thrombus. Ventricular free wall rupture 5–14 days: free wall rupture > cardiac tamponade. LV hypertrophy and previous MI
protect against free wall rupture. Acute form usually leads to sudden death. True ventricular aneurysm 2 weeks to several months: outward bulge with
contraction (“dyskinesia”), associated with fbrosis.
Dressler syndrome Several weeks: autoimmune phenomenon resulting in fbrinous pericarditis.
LV failure and pulmonary edema Can occur 2° to LV infarction, VSD, free wall rupture, papillary muscle rupture with mitral regurgitation.
TeAnthrax - Prophylaxis with ciprofoxacin or doxycycline when exposed. Diphtheria Rx - diphtheria antitoxin +/– erythromycin or penicillin. Listera -
Treatment: ampicillin.
SNAP: Sulfonamides—Nocardia; Actinomyces—Penicillin.

Leprosy - Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
N. gonorrheae - Treatment: ceftriaxone + azithromycin (to cover possible chlamydial coinfection, ceftriaxone-resistant strains). Erythromycin eye
ointment prevents neonatal blindness.
Meningococci - Prophylaxis - Rifampin, ciprofloxacin, or ceftriaxone. Treatment: ceftriaxone or penicillin G.
H. influenzae - Treatment: amoxicillin +/ clavulanate for mucosal infections; ceftriaxone for meningitis; rifampin prophylaxis for close contacts.
Pertussis - Treatment: macrolides; if allergic use TMP-SMX.
Brucella - Treatment: doxycycline + rifampin or streptomycin.
Legionella - Treatment: macrolide or quinolone.
Pseudomonas Treatments: Antipseudomonal penicillins in combination with -lactamase inhibitor (eg, piperacillintazobactam) 3rd- and 4th-generation
cephalosporins (eg, ceftazidime, cefepime) Monobactams Fluoroquinolones Carbapenems (AACCMQ)
Salmonella typhi - treat with ceftriaxone or fuoroquinolone
S. agalactae - GBS - Patients with culture receive intrapartum penicillin/ampicillin prophylaxis.
H. pylori - Most common initial treatment is triple therapy: amoxicillin (metronidazole if penicillin allergy) + clarithromycin + proton pump inhibitor;
antibiotics cure Pylori. Bismuth-based quadruple therapy if concerned about macrolide resistance.
Lyme ds - Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Rx Penicillin G
Congenital syphilis - To prevent, treat patient early in pregnancy, as placental transmission typically occurs after first trimester.
Gardnerella vaginalis - Treatment: metronidazole or clindamycin.
Chlamydia - Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for possible concomitant gonorrhea.
Rickettsial diseases and vector-borne illnesses Treatment: doxycycline.
Mycoplasma pneumoniae - Treatment: macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since Mycoplasma has no cell wall).xt
Systemic mycosis - Treatment: fluconazole or itraconazole for local infection; amphotericin B for systemic infection.
Tinea (pityriasis) versicolor - Treatment: selenium sulfide, topical and/or oral antifungal medications.
Candida - Treatment: oral fluconazole/topical azoles for vaginal; nystatin, azoles, or, rarely, echinocandins for oral; fluconazole, echinocandins, or
amphotericin B for esophageal or systemic disease. Aspergillus - Treatment: voriconazole/isavuconazole or echinocandins (2nd-line).
Cryptococcus - Treatment: amphotericin B + flucytosine followed by fluconazole for cryptococcal meningitis.
Mucor and Rhizopus spp - Treatment: surgical debridement, amphotericin B or isavuconazole
Pneumocystis jirovecii - Treatment/prophylaxis: TMP-SMX, pentamidine, dapsone (prophylaxis as single agent, or treatment in combination with
TMP), atovaquone. Start prophylaxis when CD4+ cell count drops to < 200 cells/mm3 in people living with HIV.
Sporothrix schenckii - Treatment: itraconazole or potassium iodide (only for cutaneous/lymphocutaneous). Think of a rose gardener who smokes a
cigar and pot.
Giardia lamblia - Rx Metronidazole.
Entamoeba histolytica - Rx Metronidazole; paromomycin or iodoquinol for asymptomatic cyst passers.
Cryptosporidium - Rx Prevention (by filtering city water supplies); nitazoxanide in immunocompetent hosts.
Protozoa—CNS infections-
Toxoplasma gondii - Rx Sulfadiazine + pyrimethamine. Prophylaxis with TMP-SMX when CD4+ cell count < 100 cells/mm3.
Naegleria fowleri - Rx Amphotericin B has been effective for a few survivors.
Trypanosoma brucei - Rx Suramin for bloodborne disease or melarsoprol for CNS penetration.
Protozoa—hematologic infections-
Plasmodium - TREATMENT Chloroquine (for sensitive species); if resistant, use mefloquine or atovaquone/ proguanil. If life-threatening, use
intravenous quinidine or artesunate (test for G6PD deficiency). For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency).
Babesia - Rx Atovaquone + azithromycin.
Visceral infections-
Trypanosoma cruzi - Rx Benznidazole or nifurtimox; cruzing in my Benz, with a fur coat on.
Leishmania spp - Rx Amphotericin B, sodium stibogluconate.
Sexually transmitted infections-
Trichomonas vaginalis -
Rx Metronidazole for patient and partner(s) (prophylaxis; check for STI).

Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin). Cestode/tapeworm Rx
- (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole). Nematodes (roundworms)
Intestinal-
Enterobius vermicularis (pinworm) - Bendazoles, pyrantel pamoate.
Ascaris lumbricoides (giant roundworm) - Bendazoles.
Strongyloides stercoralis (threadworm) - Ivermectin or bendazoles.
Ancylostoma spp, Necator americanus (hookworms) - Bendazoles or pyrantel pamoate. Trichinella spiralis - Bendazoles.

Trichuris trichiura (whipworm) - Bendazoles.

Tissue-
Toxocara canis - Visceral larva migrans. Bendazoles.
Onchocerca volvulus - Ivermectin (ivermectin for river blindness). Loa loa - Diethylcarbamazine.

Wuchereria bancrofti, Brugia malayi - Diethylcarbamazine. Cestodes (tapeworms)

Taenia solium1 - Praziquantel.
Taenia solium2 - Praziquantel; albendazole for neurocysticercosis. Diphyllobothrium latum - Praziquantel, niclosamide.

Echinococcus granulosus - Albendazole; surgery for complicated cysts. Trematodes (flukes)

Schistosoma - Praziquantel.
Clonorchis sinensis - Praziquantel.

Ectoparasites
Sarcoptes scabiei - Treatment: permethrin cream, oral ivermectin, washing/drying all clothing/bedding, treat close contacts.
Pediculus humanus/ Phthirus pubis - Treatment: pyrethroids, malathion, or ivermectin lotion, and nit combing. Children with head lice can be treated at
home without interrupting school attendance. Reversible cell injury -
- cellular swelling (earliest morphologic manifestation).
- Myelin figures - (aggregation of peroxidized lipids).
Irreversible cell injury - Amorphous densities/inclusions in mitochondria
DNA laddering (fragments in multiples of 180 bp) is a sensitive indicator of apoptosis.
BAX and BAK are proapoptotic (BAd for survivial),
Bcl-2 and Bcl-xL are antiapoptotic
Extrinsic (death receptor) pathway-
1. Fas (CD95) + FasL or TNF-α + TNF-R
2. CD8+ T-cell - perforin + granzyme-B
Fas-FasL interaction is necessary in thymic medullary negative selection.
Neurons most vulnerable to hypoxic-ischemic insults include Purkinje cells of the cerebellum and pyramidal cells of the hippocampus and neocortex
(zones 3, 5, 6).
Free radicals damage cells via membrane lipid peroxidation, protein modifcation, DNA breakage.
Carbon tetrachloride - centrilobular necrosis
Metastatic calcification - Predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly; inc pH favors Ca2+
deposition). 2° to hypercalcemia or high calcium-phosphate product levels.
Metastatic calcification - Predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly; inc pH favors Ca2+
deposition). 2° to hypercalcemia or high calcium-phosphate product levels.
Amyloidosis -
Congo-red stain - non-polarized light - red/orange; polarized light - apple-green birefringence.
Fever - IL-1 and TNF > inc COX activity in perivascular cells of anterior hypothalamus > inc PGE2 > inc temperature set point.
Hepcidin - dec iron absorption (by degrading ferroportin) and dec iron release (from macrophages).
Hemochromatosis - impaired hepcidinn function.
Inc ESR - pregnancy.
Dec ESR - Sickle cell anemia (altered shape), Polycythemia (inc RBCs “dilute” aggregation factors), HF, Microcytosis, Hypofibrinogenemia.
Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis
P-selectin (released from Weibel- palade bodies) + sialyl lewis
GlyCAM-1/CD34 + L-selectin
Adhesion-
defective in LAD type 1 (dec CD18 integrin subunit)
ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1)
VCAM-1 (CD106) + VLA-4 integrin
Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
Migration - Chemotactic factors: C5a, IL-8, LTB4, kallikrein, platelet-activating factor, N-formylmethionyl peptides.
Rubor and calor - N-BPH
Dolor - BPH
Tumor - LHS
Inflammasome—Cytoplasmic protein complex that recognizes products of dead cells, microbial products, and crystals (eg, uric acid crystals) >
activation of IL-1 and infammatory response. Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis
P-selectin (released from Weibel- palade bodies) + sialyl lewis
GlyCAM-1/CD34 + L-selectin
Adhesion-
defective in LAD type 1 (dec CD18 integrin subunit)
ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1)
VCAM-1 (CD106) + VLA-4 integrin
Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
Outcomes - Resolution and healing - IL-10, TGF-B
Persistent acute inflammation - IL-8
Chronic inflammation - macrophages/APCs > CD4+ Th cells
Abscess
Scarring

Th1 cells secrete IFN-γ > macrophage classical activation (proinfammatory)

Th2 cells secrete IL-4 and IL-13 > macrophage alternative activation (repair and antiinfammatory).
FGF Stimulates angiogenesis
TGF- Angiogenesis, fibrosis
VEGF Stimulates angiogenesis
PDGF Secreted by activated platelets and macrophages. Induces vascular remodelling and smooth muscle cell migration. Stimulates fibroblast growth
for collagen synthesis.
Metalloproteinases Tissue remodeling
EGF Stimulates cell growth via tyrosine kinases (eg, EGFR/ErbB1).
Infammatory (up to 3 days after wound) - Platelets, neutrophils, macrophages. Clot formation, inc vessel permeability and neutrophil migration into
tissue; macrophages clear debris 2 days later. Proliferative (day 3–weeks after wound) - Fibroblasts, myofbroblasts, endothelial cells, keratinocytes,
macrophages. Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound
contraction (mediated by myofbroblasts). Delayed second phase of wound healing in vitamin C and copper defciency.
Remodeling (1 week–6+ months after wound) - Fibroblasts. Type III collagen replaced by type I collagen, inc tensile strength of tissue. Collagenases
(require zinc to function) break down type III collagen. Zinc defciency > delayed wound healing.
Bone metastasis can be: Lytic (eg, thyroid, kidney, non-small cell lung cancer), Blastic (eg, prostate, small cell lung cancer) OR Mixed (eg, breast
cancer).
Four carcinomas route hematogenously: follicular thyroid carcinoma, choriocarcinoma, renal cell carcinoma, and hepatocellular carcinoma.

In order of decreasing severity (less toxin produced) - DFBS : S dysenteriae, S fexneri, S boydii, S sonnei EHEC - Does not ferment sorbitol (vs other
E coli)
vaginal pH
>4.5 - trichomonas vaginalis and gardnerella vaginalis

<4.5 - candida
Secondary syphilis - condylomata lata
HPV - condylomata accuminata
Weil disease (icterohemorrhagic leptospirosis)—severe form with jaundice and azotemia from liver and kidney dysfunction, fever, hemorrhage, and
anemia. Multiple sclerosis, GCA - Marcus-Gunn pupil (RAPD)
Tertiary syphilis - Argyll-Robertson pupil
Syphilis - Argyll Robertson pupil (constricts with accommodation but is not reactive to light).
Staphylococcus epidermidis - Does not ferment mannitol (vs S aureus)

False-Positive results on VDRL with: Pregnancy Viral infection (eg, EBV, hepatitis) Drugs (eg, chlorpromazine, procainamide) Rheumatic fever (rare)
Lupus (anticardiolipin antibody) and Leprosy. Chlamydia trachomatis causes neonatal and follicular adult conjunctivitis, nongonococcal urethritis, PID,
and reactive arthritis.
Secondary syphilis - condylomata lata
HPV - condylomata accuminata

Multiple sclerosis, GCA - Marcus-Gunn pupil (RAPD)

Tertiary syphilis - Argyll-Robertson pupil
Syphilis - Argyll Robertson pupil (constricts with accommodation but is not reactive to light).
RMSF - centripetal rash
Typhus - centrifugal rash
Types D-K - neonatal pneumonia (staccato cough) with eosinophilia, neonatal conjunctivitis (1–2 weeks after birth).

Q fever (coxiella burnetii) is caused by a Quite Complicated Bug because it has no rash or vector and its causative organism can survive outside in its
endospore form. RMSF - centripetal rash
Typhus - centrifugal rash
Rickettsii starts on the wrists, typhus starts on the trunk.

Typhus Endemic (fleas)—R typhi.

Epidemic (human body louse)—R prowazekii
(powerful causes epidemic)
louse - relapsing fever (borrelia recurrentis)
human body louse - epidemic typhus (Rickettsia prowazekii)
(powerful causes epidemic)
fleas - plague, endemic typhus (Rickettsia typhi)
P vivax/ovale—48-hr cycle (tertian). P falciparum—severe; irregular fever patterns;
P malariae—72-hr cycle (quartan).
DIAGNOSIS Blood smear: trophozoite ring form within RBC, schizont containing merozoites; red granules (Schüffner stippling) throughout RBC
cytoplasm seen with P vivax/ovale.
TREATMENT Chloroquine (for sensitive species); if resistant, use mefloquine or atovaquone/ proguanil. If life-threatening, use intravenous quinidine
or artesunate (test for G6PD deficiency). For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency).
Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin).
Cestode/tapeworm Rx - (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole).
Hematuria, squamous cell bladder cancer - Schistosoma haematobium
Portal hypertension - Schistosoma mansoni, Schistosoma japonicum
Body lice can transmit Rickettsia prowazekii (epidemic typhus), Borrelia recurrentis (relapsing fever), Bartonella quintana (trench fever).
(happy rhio khalici naked pic) - naked RNA virus
All are linear except papilloma-, polyoma-, and hepadnaviruses (circular). - PPH
⊕ stranded RNA viruses: (retrovirus) (togavirus) (flavivirus) (coronavirus) (hepevirus) (calicivirus) (picornavirus) - RCT-FHPC
Naked (nonenveloped) viruses include - DNA viruses - papillomavirus, adenovirus, parvovirus, polyomavirus (PAPP); RNA viruses - calicivirus,
picornavirus, reovirus, and hepevirus. (happy rhio khalici naked pic)
Enveloped DNA viruses - (herpesvirus, hepadnavirus, poxvirus) - HHP
CIRCULAR RNA - ARENAVIRUS, BUNYAVIRUS, DELTA VIRUS. - ABD
SEGMENTED VIRUSES - Bunyaviruses (3 segments), Orthomyxoviruses (infuenza viruses) (8 segments), Arenaviruses (2 segments), and Reoviruses
(10-12 segments). - BORA
Purified nucleic acids of most dsDNA viruses (except poxviruses and HBV) and ⊕ strand ssRNA (≈ mRNA) viruses are infectious. Naked nucleic acids
of ⊖ strand ssRNA and dsRNA viruses are not infectious.
DNA viruses - All replicate in the nucleus (except poxvirus). “Pox is out of the box (nucleus).”
RNA viruses - All replicate in the cytoplasm (except retrovirus and influenza virus). “Retro flu is outta cyt (sight).”
Poxvirus - (largest DNA virus)
Parvovirus - (smallest DNA virus)
Calicivirus - norovirus
RECEPTORS-
CMV Integrins (heparan sulfate)
Parvovirus B19 P antigen on RBCs
Rhinovirus ICAM-1 (I CAMe to see the rhino)
Intranuclear eosinophilic Cowdry-A inclusions also seen with HSV-1, HSV-2, VZV.
Human herpesviruses 6 and 7 - Saliva. Roseola infantum (exanthem subitum): high fevers for several days that can cause seizures, followed by diffuse
macular rash (starts on trunk then spreads to extremities); usually seen in children <2 years old. Roseola: fever first, Rosy (rash) later. Self-limited
illness. HHV-7—less common cause of roseola.
Reovirus - RC - Coltivirus —Colorado tick fever. Rotavirus—cause of fatal diarrhea in children.
Picornavirus (PERCH) - Poliovirus—polio-Salk/Sabin vaccines—IPV/OPV. Echovirus—aseptic meningitis. Rhinovirus —“common cold”.
Coxsackievirus—aseptic meningitis; herpangina (mouth blisters,

fever); hand, foot, and mouth disease; myocarditis; pericarditis. HAV—acute viral hepatitis. (PERCH).
Flaviviruses - HYD-SWZ (flavors of hyd and swz) - HCV; Yellow fever; Dengue; St. Louis encephalitis; West Nile virus —meningoencephalitis,
flaccid paralysis; Zika virus. Togaviruses - Toga CREW—Chikungunya virus (co-infection with dengue virus can occur), Rubella, Eastern and Western
equine encephalitis.
Retroviruses - HTLV—T-cell leukemia; HIV—AIDS.
Coronaviruses - “Common cold,” SARS, MERS, COVID-19.
Orthomyxoviruses - Influenza virus
Paramyxoviruses - PaRaMyxovirus: Parainfluenza—croup, RSV—bronchiolitis in babies, Measles, Mumps.
Rhabdoviruses - Rabies.
Filoviruses - Ebola/Marburg hemorrhagic fever—often fatal.
Arenaviruses - LL - LCMV—lymphocytic choriomeningitis virus; Lassa fever encephalitis— spread by rodents.
Bunyaviruses - HSCC (HSBCc) - California encephalitis, Sandfly/Rift Valley fevers, Crimean-Congo hemorrhagic fever, Hantavirus—hemorrhagic
fever, pneumonia.
Delta virus - HDV

All contain surface F (fusion) protein, which causes respiratory epithelial cells to fuse and form multinucleated cells. Palivizumab (monoclonal
antibody against F protein) prevents pneumonia caused by RSV infection in premature infants. Palivizumab for paramyxovirus (RSV) prophylaxis in
preemies.
Croup - Results in a “seal-like” barking cough and inspiratory stridor. Narrowing of upper trachea and subglottis leads to characteristic steeple sign on
x-ray.
Roseola - diffuse macular rash (starts on trunk then spreads to extremities).

Rubella rash - starts on face and spreads centrifugally to involve trunk and extremities.
Measles - maculopapular rash that starts at the head/neck and spreads downward.
Chickenpox - Vesicular rash begins on trunk; spreads to face and extremities with lesions of different stages. RMSF - centripetal rash
Typhus - centrifugal rash

Stroke-
Histologic features
12-24 hrs - Eosinophilic cytoplasm + pyknotic nuclei (red neurons) 24-72 hrs - Necrosis + neutrophils
3-5 days - Macrophages (microglia)
1-2 wks - Reactive gliosis (astrocytes) + vascular proliferation
>2 wks - Glial scar
Hypertensive hemorrhages (Charcot-Bouchard microaneurysm) most often occur in putamen of basal ganglia (lenticulostriate vessels), followed by
thalamus, pons, and cerebellum.
Parinaud syndrome (pinealoma) - vertical gaze palsy
PPRF lesion - horizontal gaze palsy
Alexia without agraphia - reading lost, writing preserved.
Prosopagnosia - inability to recognises faces.
Pons lesion - locked in syndrome.
Parinaud syndrome (pinealoma) - vertical gaze palsy
PPRF lesion - horizontal gaze palsy
Uncal transtentorial herniation - Uncus = medial temporal lobe. Early herniation > ipsilateral blown pupil (unilateral CN III compression), contralateral
hemiparesis. Late herniation > coma, Kernohan phenomenon (misleading contralateral blown pupil and ipsilateral hemiparesis due to contralateral
compression against Kernohan notch).
Brown-Séquard syndrome - Hemisection of spinal cord. Findings:
[Link] loss of all sensation at level of lesion
[Link] LMN signs (eg, faccid paralysis) at level of lesion
[Link] UMN signs below level of lesion (due to corticospinal tract damage)
[Link] loss of proprioception, vibration, and light (2-point discrimination) touch below level of lesion (due to dorsal column damage)
[Link] loss of pain, temperature, and crude (non- discriminative) touch below level of lesion (due to spinothalamic tract damage). If lesion
occurs above T1, patient may present with ipsilateral Horner syndrome due to damage of oculosympathetic pathway.
Common cranial nerve lesions
CN V motor lesion Jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle.
CN X lesion Uvula deviates away from side of lesion. Weak side collapses and uvula points away.
CN XI lesion Weakness turning head to contralateral side of lesion (SCM). Shoulder droop on side of lesion (trapezius). The left SCM contracts to help
turn the head to the right.
CN XII lesion LMN lesion. Tongue deviates toward side of lesion (“lick your wounds”) due to weakened tongue muscles on affected side.
Diagnosing hearing loss-
Weber test - Tuning fork on vertex of skull.
NORMAL - No localization
CONDUCTIVE - Localizes to afected ear, transmission of background noise. SENSORINEURAL - Localizes to unafected ear, transmission of all
sound.
Rinne test Tuning fork in front of ear (air conduction, AC), Tuning fork on mastoid process (bone conduction, BC) NORMAL - AC>BC
CONDUCTIVE - BC>AC
SENSORINEURAL - AC>BC
Central vertigo - Findings: directional or purely VERTICAL nystagmus, skew deviation (VERTICAL misalignment of the eyes), diplopia, dysmetria.
Focal neurologic findings.
Trabecular outflow (90%) - inc with M3 agonist (eg, carbachol, pilocarpine).
Uveoscleral outflow (10%) - inc with prostaglandin agonists (eg latanoprost, bimatoprost).

Iris - Dilator muscle (α1), Sphincter muscle (M3).

Aqueous humour production - dec by B-blockers (eg, timolol), α2-agonists (eg, brimonidine), and carbonic anhydrase inhibitors (eg, acetazolamide).

Miosis - 1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III 2nd neuron: short ciliary nerves to sphincter pupillae muscles

Mydriasis - 1st neuron: hypothalamus to ciliospinal center of Budge (C8–T2)

2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels)
3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers
also innervate smooth muscle of eyelids (minor retractors - superior tarsal muscles) and sweat glands of forehead and face.

Pupillary light reflex - Light in either retina sends a signal via CN II to PRETECTAL nuclei in midbrain that activates bilateral Edinger- Westphal
nuclei; pupils constrict bilaterally (direct and consensual reflex).
Marcus Gunn pupil - Also called relative afferent pupillary defect (RAPD). When the light shines into a normal eye, constriction of the ipsilateral
(direct reflex) and contralateral eye (consensual reflex) is observed. When the light is then swung to the affected eye, both pupils DILATE instead of
constrict due to impaired conduction of light signal along the injured optic nerve. Associated with optic neuritis (eg, multiple sclerosis), optic
neuropathies (eg, giant cell arteritis).

Horner syndrome- Sympathetic denervation of face. Ptosis (slight drooping of eyelid: superior tarsal muscle). Anhidrosis (absence of sweating) and
flushing of affected side of face. Miosis (pupil constriction). Associated with lesions along the sympathetic chain: 1st neuron: pontine hemorrhage,
lateral medullary syndrome, spinal cord lesion above T1 (eg, Brown-Séquard syndrome, late-stage syringomyelia). 2nd neuron: stellate ganglion
compression by Pancoast tumor. 3rd neuron: carotid dissection (painful); anhidrosis is usually absent.
Na+ CHANNEL BLOCKERS - Carbamazepine Fosphenytoin Lamotrigine Phenytoin Topiramate Valproic acid SV2A RECEPTOR BLOCKER -
Levetiracetam

Ca2+ CHANNEL BLOCKERS - Ethosuximide Gabapentin

GABAA AGONISTS - Benzodiazepines Topiramate Phenobarbital GABA REUPTAKE INHIBITOR - Tiagabine GABA TRANSAMINASE
INHIBITORS - Valproic acid Vigabatrin DOPA DECARBOXYLASE INHIBITOR - Carbidopa
COMT INHIBITORS (peripheral) - Entacapone Tolcapone
COMT INHIBITOR (central) - Tolcapone
MAO TYPE B INHIBITORS - Selegiline Rasagiline
DOPAMINE AVAILABILITY - Amantadine
DOPAMINE AGONISTS - Pramipexole (non-ergot), Ropinirole (non-ergot), Bromocriptine (ergot)
P5S3O3; C5R3W; D3F2L2. (SOaP CRoW DLF)
P5S3O3 (INFANT 0–12 mo);
Primitive reflexes (MRPB - 3,4,6,12), Posture, Picks 6, Pincer grasp 10, Points to objects 12.
(Posture—lifts head 1, rolls and sits 6, crawls 8, stands 10, walks 12–18)
Social smile 2, Stranger anxiety 6, Separation anxiety 9.
Orients (voice 4, names/gestures 9), Object permanence 9, Oratory 10.

C5R3W (TODDLER 12–36 mo);

Cruises 12, Climbs stairs 18, Cubes age x 3, Cutlery 20, Kicks ball 24. Recreation 24-36, Rapproachment 24, Realization 36.
Words 200-2, 300-3.

D3F2L2 (PRE-SCHOOL 3–5 yr);

Drive 3, Dexterity 4 (buttons/zippers/grooms self 5), Drawings 4
Freedom 3, Friends 4.
Language (1000 words 3, sentences/prepositions 4), Legends 4.
Diagnostic criteria by symptom duration-
Narcolepsy > 3m
> 1m Selective mutism, Separation anxiety
ADHD, Specific learning, Oppositional defiant > 6m
Tic disorder, Disruptive mood dysregulation > 1y
< 1 m Acute stress
> 1m Panic, Posttraumatic stress disorder
Adjustment < 6m
Phobias, Generalized anxiety disorder > 6m
< 1 m Brief psychotic disorder
Delusional disorder > 1 m
Schizophreniform disorder 1-6 m
Schizophrenia > 6 m
Dysthymic disorder, Cyclothymic disorder > 2y
> 2w Major depressive disorder
> 1 w Manic sx of bipolar disorder
REM sleep - Nightmares. Memory of nightmare present.
N3 - Night terrors, bed-wetting, sleep-walking. No memory of the arousal episode.
Transtheoretical model of change
STAGE - FEATURES - MOTIVATIONAL STRATEGIES
Precontemplation Denies problem and its consequences. Encourage introspection. Use patient’s personal priorities in explaining risks. Affirm your
availability to the patient.
Contemplation Acknowledges problem but is ambivalent or unwilling to change. Discuss pros of changing and cons of maintaining current behavior.
Suggest means to support behavior changes. Preparation/ determination Committed to and planning for behavior change. Encourage initial changes,
promote expectations for positive results, provide resources to assist in planning. Action/willpower Executes a plan and demonstrates a change in
behavior. Assist with strategies for self-effcacy, contingency management, and coping with situations that trigger old behaviors. Maintenance New
behaviors become sustained, integrate into personal identity and lifestyle. Reinforce developing habits. Evaluate and mitigate relapse risk. Praise
progress.
Relapse Regression to prior behavior (does not always occur). Varies based on degree of regression. Encourage return to changes. Provide reassurance
that change remains possible.
Serotonin syndrome - Any drug that inc 5-HT. Psychiatric drugs: MAOIs, SSRIs, SNRIs, TCAs, vilazodone, vortioxetine, buspirone Nonpsychiatric
drugs: tramadol, ondansetron, triptans, linezolid, MDMA, dextromethorphan, meperidine, St. John’s wort.

Serotonin syndrome Rx Cyproheptadine (5-HT2 receptor antagonist). Prevention: avoid simultaneous serotonergic drugs, and allow a washout period
between them. Hypertensive crisis - Rx Phentolamine.
Neuroleptic malignant syndrome - Rx Dantrolene, dopaminergics (eg, bromocriptine, amantadine), benzodiazepines; discontinue causative agent.
Delirium tremens - Rx Longer-acting benzodiazepines.

Acute dystonia - Rx Benztropine or diphenhydramine.

Lithium toxicity - Rx Discontinue lithium, hydrate aggressively with isotonic sodium chloride, consider hemodialysis.
Tricyclic antidepressant toxicity - Rx Supportive treatment, monitor ECG, NaHCO3 (prevents arrhythmia), activated charcoal.
3-36 hrs - Tremors, insomnia, diaphoresis, agitation, GI upset
6-48 hrs - Withdrawal seizures
12-48 hrs - Alcoholic hallucinosis (usually visual)
48-96 hrs - Delirium tremens
PCP - miosis
LSD, MDMA - mydriasis
MDMA - hyponatremia
TCAs, SNRIs, bupropion - inh NE reuptake.
TCAs, SSRIs, SNRIs, trazodone - inh 5-HT reuptake.
Mirtazapine - inh α2 (autoreceptor) adrenergic receptor.
MDD - bupropion;
GAD - buspirone;
buprenorphine - opioid partial agonist
Bupropion - Bupropion - Inhibits NE and DA reuptake. Also used for smoking cessation. Toxicity: stimulant effects (tachycardia, insomnia), headache,
seizures in patients with bulimia and anorexia nervosa. Dec risk of sexual side effects and weight gain compared to other antidepressants.
Buspirone - Partial 5-HT1A receptor agonist. Rx Generalized anxiety disorder. Does not cause sedation, addiction, or tolerance. Begins to take effect
after 1–2 weeks. Does not interact with alcohol (vs barbiturates, benzodiazepines).
Buprenorphine - Sublingual form (partial opioid agonist) used to prevent relapse. Can precipitate withdrawal symptoms when combined with full
agonist.
High-potency vs Low-potency typical antipsychotics:
flu’s hal? > tri pi and get HIGH - haloperidol, trifluoperazine, pimozide, fluphenazine
CH-i-THI is a low-potency mode of - chlorpromazine, thioridazine
Extrapyramidal symptoms—ADAPT:

Hours to days:

Acute Dystonia (muscle spasm, stiffness, oculogyric crisis). Treatment: benztropine, diphenhydramine.

Days to months:
Akathisia (restlessness). Treatment: β-blockers, benztropine, benzodiazepines. Parkinsonism (bradykinesia). Treatment: benztropine, amantadine.

Months to years:
Tardive dyskinesia (chorea, especially orofacial). Treatment: benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine.
Bupropion - Inhibits NE and DA reuptake.
Mirtazapine - a2-antagonist (inc release of NE and 5-HT), potent 5-HT2 and 5-HT3 receptor antagonist, and H1 antagonist.
Trazodone - Primarily blocks 5-HT2, a1-adrenergic, and H1 receptors; also weakly inhibits 5-HT reuptake.
Varenicline - Nicotinic ACh receptor partial agonist.
Vilazodone - Inhibits 5-HT reuptake; 5-HT1A receptor partial agonist.
Vortioxetine - Inhibits 5-HT reuptake; 5-HT1A receptor agonist and 5-HT3 receptor antagonist.
Inulin clearance = GFR
Creatine clearance approximates GFR (slightly overestimates) PAH clearance = eRPF (eRPF slightly underestimates true RPF)
Inc plasma protein concentration - dec GFR, no change in RPF, dec FF (GFR/RPF)
Dec plasma protein concentration - inc GFR, no change in RPF, inc FF (GFR/RPF)
Dehydration - dec GFR, dec dec RPF, inc FF (GFR/RPF)
Plasma volume = TBV x (1 – Hct). (TBV=total blood volume).
Renal clearance - Cx = (Ux V)/Px
Cinulin = GFR = Uinulin V/Pinulin = Kf [(PGC – PBS) – ( GC – BS)] (GC = glomerular capillary; BS = Bowman space; BS normally equals zero; Kf
= filtration coefficient). Inulin clearance = GFR
Creatine clearance approximates GFR (slightly overestimates)
PAH clearance = eRPF (eRPF slightly underestimates true RPF)
eRPF = UPAH x V/PPAH = CPAH.
Renal blood flow (RBF) = RPF/(1 - Hct).
Plasma volume = TBV x (1 – Hct)
RPF = RBF x (1 - Hct)
Cinulin = GFR = Uinulin V/Pinulin
Cpah = eRPF = Upah V/Ppah.

PSGN - LM—glomeruli enlarged and hypercellular. IF - (“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition
along GBM and mesangium. EM—subepithelial IC humps.
Type 1 MPGN - subendothelial IC deposits + granular IF. Type 2 MPGN - intramembranous deposits.
DPGN - LM—“wire looping” of capillaries. IF—granular; EM—subendothelial, sometimes subepithelial or intramembranous IgG-based ICs often
with C3 deposition.

Berger ds - LM—mesangial proliferation IF—IgA-based IC deposits in mesangium; EM—mesangial IC deposition.

Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
Diabetic glomerulonephropathy - LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions).
Minimal change ds - LM—Normal glomeruli (lipid may be seen in PCT cells). IF—⊖. EM—effacement of podocyte foot processes.
FSGS - LM—segmental sclerosis and hyalinosis. IF—often ⊖ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1. EM—EFFACEMENT OF
FOOT PROCESSES SIMILAR TO MINIMAL CHANGE DS. Membranous nephropathy - LM—diffuse capillary and GBM thickening. IF—granular
due to immune complex (IC) deposition. EM—“Spike and dome” appearance of subepithelial deposits. Amyloidosis - LM—Congo red stain shows
apple-green birefringence under polarized light due to amyloid deposition in the mesangium.
PSGN - subepithelial IC humps
Membranous nephropathy - EM—“Spike and dome” appearance of subepithelial deposits.
Type 1 MPGN - subendothelial IC deposits + granular IF
Type 2 MPGN - intramembranous deposits
DPGN - MC subendothelial, sometimes subepithelial or intramembranous deposits
Berger ds - mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.

(In proliferative GN (MPGN and DPGN) deposits are subendothelial/intramembranous. In PSGN and membranous nephropathy deposits are
subepithelial.)
Fanconi syndrome - DEFECTS Generalized reabsorption defect in PCT > inc excretion of amino acids, glucose, HCO3 – , and PO4 3–, and all
substances reabsorbed by the PCT.
Bartter syndrome - DEFECTS Reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter).
Gitelman syndrome - DEFECTS Reabsorption defect of NaCl in DCT.
Liddle syndrome - DEFECTS Gain of function mutation > dec Na+ channel degradation > inc Na+ reabsorption in collecting tubules.
Syndrome of Apparent Mineralocorticoid Excess - DEFECTS - Hereditary 11β-HSD deficiency > inc cortisol > inc mineralocorticoid receptor activity.
Fanconi - EFFECTS Metabolic acidosis (proximal RTA), hypokalemia, HYPOPHOSPHATEMIA
(like loops) Bartter - EFFECTS Metabolic alkalosis, hypokalemia, HYPERCALCIURIA.
(like thiazides) Gittelman - EFFECTS Metabolic alkalosis, hypokalemia, HYPOMAGNESEMIA, HYPOCALCIURIA.
Liddle - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
SAME - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
(All have hypokalemia. All have metabolic alkalosis except fanconi syndrome (proximal RTA).)
(First is fanconi, rest are alphabetical)
See diagram on page 611. [TF/P] > 1 = KCU-ICP. [TF/P] < 1 = HAG. [TF/P] = 1 = Na+.
(K+,Cl-,urea,inulin, creatinine,PAH) (HCO3-,amino acids,glucose)
Distal renal tubular acidosis (RTA type 1) - Inability of -intercalated cells to secrete H+ > no new HCO3 – is generated > metabolic acidosis. URINE
pH > 5.5. SERUM K+ dec.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption > inc excretion of HCO3 – in urine > metabolic acidosis. Urine pH
- < 5.5 when plasma HCO3 – below reduced resorption threshold. > 5.5 when filtered HCO3 – exceeds resorptive threshold. SERUM K+ dec.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia > dec NH3 synthesis in PCT > dec NH4 +
excretion. Urine pH - < 5.5 (or variable). SERUM K+ inc.
If > 12 mEq/L then Inc Anion gap Metabolic acidosis - GOLDMARK: Glycols (ethylene glycol, proplyene glycol) Oxoproline (toxic metabolite of
acetaminophen) L-lactate (lactic acidosis) D-lactate (exogenous lactic acid) Methanol (and other alcohols) Aspirin (late e ect) Renal failure Keytones
(diabetic, alcoholic, starvation).
If 8–12 mEq/L then Normal anion gap - HARDASS Hyperchloremia/hyperalimentation Addison disease Renal tubular acidosis Diarrhea
Acetazolamide Spironolactone Saline infusion
Distal renal tubular acidosis (RTA type 1) - Inability of a-intercalated cells to secrete H+.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia.
MPGN - Type I may be 2° to hepatitis B or C infection. May also be idiopathic. Subendothelial IC deposits with granular IF. Type II is associated with
C3 nephritic factor (IgG autoantibody that stabilizes C3 convertase > persistent complement activation > dec C3 levels). Intramembranous deposits,
also called dense deposit disease. Both types: mesangial ingrowth > GBM splitting > “tram- track” on H&E and PAS stains.
Glomerular diseases-
Nephritic syndrome PGI-AM - Examples Acute poststreptococcal glomerulonephritis Goodpasture syndrome IgA nephropathy (Berger disease) Alport
syndrome Membranoproliferative glomerulonephritis.
Nephrotic syndrome MAD-FM - EXAMPLES May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process): Focal
segmental glomerulosclerosis (1° or 2°) Minimal change

disease (1° or 2°) Membranous nephropathy (1° or 2°) Amyloidosis (2°) Diabetic glomerulonephropathy (2°)
Nephritic-nephrotic syndrome DPGN and MPGN - Diffuse proliferative glomerulonephritis, Membranoproliferative glomerulonephritis.
Calcium oxalate: hypocitraturia.
Calcium phosphate: inc pH.
Ammonium magnesium phosphate (struvite) - inc pH.
Uric acid - dec pH.
Cystine - dec pH.
Calcium oxalate: hypocitraturia - Radiopaque - Radiopaque - Shaped like envelope or dumbbell. Treatment: thiazides, citrate, low-sodium diet.
Calcium phosphate: inc pH. Xray-Radiopaque, CT-Radiopaque. Wedgeshaped prism. Treatment: low-sodium diet, thiazides.
Ammonium magnesium phosphate (struvite) - inc pH. XRAY - Radiopaque. CT - Radiopaque. Coffin lid. Treatment: eradication of underlying
infection, surgical removal of stone.
Uric acid - dec pH. XRAY - Radiolucent. CT - Visible. Rhomboid or rosettes. Treatment: alkalinization of urine, allopurinol.
Cystine - dec pH. XRAY - Faintly radiopaque. CT - Moderately radiopaque. Hexagonal. Treatment: low sodium diet, alkalinization of urine, chelating
agents (eg, tiopronin, penicillamine) if refractory. Prerenal - URINE OSMOLALITY (mOsm/kg) >500. URINE Na+ (mEq/L) <20. FENa <1%.
SERUM BUN/Cr >20.
Intrinsic - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) >40. FENa >2%. SERUM BUN/Cr <15.
Postrenal - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) Varies. FENa Varies. SERUM BUN/Cr Varies.
Prerenal azotemia - URINE OSMOLALITY (mOsm/kg) >500.
Postrenal azotemia, Intrinsic renal failure - URINE OSMOLALITY (mOsm/kg) <350.
ATN - 3 stages: 1. Inciting event 2. Maintenance phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia 3. Recovery phase
—polyuric; BUN and serum creatinine fall; risk of hypokalemia and renal wasting of other electrolytes and minerals.
Autosomal dominant tubulointerstitial kidney disease - Also called medullary cystic kidney disease. Causes tubulointerstitial fbrosis and progressive
renal insuffciency with inability to concentrate urine. Medullary cysts usually not visualized; smaller kidneys on ultrasound. Poor prognosis.
Renal oncocytoma - Benign epithelial cell tumor arising from collecting ducts (arrows in A point to wellcircumscribed mass with central scar). Large
eosinophilic cells with abundant mitochondria without perinuclear clearing B (vs chromophobe renal cell carcinoma). Presents with painless hematuria,
fank pain, abdominal mass. Often resected to exclude malignancy (eg, renal cell carcinoma). Renal cell carcinoma - Originates from PCT.
Renal oncocytoma - Benign epithelial cell tumor arising from collecting ducts.

Renal papillary necrosis A Sloughing of necrotic renal papillae A p gross hematuria. May be triggered by recent infection or immune stimulus.
Associated with:
Sickle cell disease or trait Acute pyelonephritis Analgesics (eg, NSAIDs) Diabetes mellitus
SAAD papa with papillary necrosis.
WAGR complex (WT1 deletion)—Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, Range of developmental delays (WT1
deletion).
Denys-Drash syndrome (WT1 mutation)—Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male
pseudohermaphroditism). Beckwith-Wiedemann syndrome (WT2 mutation)—Wilms tumor, macroglossia, organomegaly, hemihyperplasia,
omphalocele. (everything is getting larger)

Urothelial carcinoma of the bladder - Associated with problems in your Pee SAC: Phenacetin, tobacco Smoking, Aromatic amines (found in dyes),
Cyclophosphamide.
Squamous cell carcinoma of the bladder - Risk factors include 4 S’s: Schistosoma haematobium infection (Middle East), chronic cystitis (“systitis”),
smoking, chronic nephrolithiasis (stones).
Sonic hedgehog (SHH) gene - base of limb buds - Anterior-posterior axis patterning.
Wnt-7 gene - distal end of each limb - Dorsal-ventral axis patterning.
Fibroblast growth factor (FGF) gene - Apical ectodermal ridge - Limb lengthening.
Homeobox (Hox) genes - Segmental organization in cranial-caudal direction, TRANSCRIPTION FACTOR CODING.
Early embryonic development-
Within week 1 - hCG secretion begins around the time of implantation of blastocyst. Blastocyst “sticks” at day 6.
Within week 2 - Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers.
Within week 3 - Gastrulation forms trilaminar embryonic disc. Cells from epiblast invaginate > primitive streak > endoderm, mesoderm, ectoderm.
Notochord arises from midline mesoderm and induces overlying ectoderm to become neural plate. 3 weeks = 3 layers.
Weeks 3–8 (embryonic period) - Neural tube formed by neuroectoderm and closes by week 4. Organogenesis. Extremely susceptible to teratogens.
Week 4 - Heart begins to beat. Cardiac activity visible by transvaginal ultrasound. Upper and lower limb buds begin to form. 4 weeks = 4 limbs and 4
heart chambers.
Week 6 - Fetal movements start.
Week 8 - Genitalia have male/female characteristics.
Ectoderm - External/outer layer
Surface ectoderm Epidermis; adenohypophysis (from Rathke pouch); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactory
epithelium; anal canal below the pectinate line; parotid, sweat, mammary glands.
Craniopharyngioma—benign Rathke pouch tumor with cholesterol crystals, calcifcations.
Neural tube Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland), retina, spinal cord. Neuroectoderm—
think CNS.
Neural crest Enterochromaffn cells, Leptomeninges (arachnoid, pia), Melanocytes, Odontoblasts, PNS ganglia (cranial, dorsal root, autonomic),
Adrenal medulla, Schwann cells, Spiral membrane (aorticopulmonary septum), Endocardial cushions (also derived partially from mesoderm), Skull
bones. ELMO PASSES Neural crest—think PNS and non-neural structures nearby.
Mesoderm-
Muscle, bone, connective tissue, serous linings of body cavities (eg, peritoneum, pericardium, pleura), spleen (develops within foregut mesentery),
cardiovascular structures, lymphatics, blood, wall of gut tube, upper 2/3 of vagina, kidneys, adrenal cortex, dermis, testes, ovaries, microglia, dura
mater, tracheal cartilage. Notochord induces ectoderm to form neuroectoderm (neural plate); its only postnatal derivative is the nucleus pulposus of the
intervertebral disc. Middle/“meat” layer. Mesodermal defects = VACTERL association: Vertebral defects Anal atresia Cardiac defects Tracheo-
Esophageal fstula Renal defects Limb defects (bone and muscle).
Endoderm-
Gut tube epithelium (including anal canal above the pectinate line), most of urethra and lower 1/3 of vagina (derived from urogenital sinus), luminal
epithelial derivatives (eg, lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular and parafollicular [C] cells).
“Enternal” layer.
Medications
ACE inhibitors - Renal failure, oligohydramnios, hypocalvaria
Alkylating agents - Absence of digits, multiple anomalies
Aminoglycosides - Ototoxicity A mean guy hit the baby in the ear
Antiepileptic drugs - Neural tube defects, cardiac defects, cleft palate, skeletal abnormalities (eg, phalanx/nail hypoplasia, facial dysmorphism) High-
dose folate supplementation recommended; most commonly valproate, carbamazepine, phenytoin, phenobarbital
Diethylstilbestrol - Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies
Fluoroquinolones - Cartilage damage
Folate antagonists - Neural tube defects Antiepileptics, trimethoprim, methotrexate
Isotretinoin - Craniofacial (eg, microtia, dysmorphism), CNS, cardiac, and thymic defects Contraception mandatory. Pronounce “isoteratinoin.”
Lithium - Ebstein anomaly
Methimazole - Aplasia cutis congenita (congenital absence of skin, particularly on scalp)
Tetracyclines - Discolored teeth, inhibited bone growth “Teethracyclines”
Thalidomide - Limb defects (phocomelia, micromelia— “fipper” limbs) Limb defects with “tha-limb-domide”
Warfarin - Bone and cartilage deformities (stippled epiphyses, nasal and limb hypoplasia), optic nerve atrophy, fetal cerebral hemorrhage. Do not wage
warfare on the baby; keep it heppy with heparin (does not cross placenta).
Diabetes in pregnancy - Caudal regression syndrome, cardiac defects (eg, VSD), neural tube defects, macrosomia, neonatal hypoglycemia (due to islet
cell hyperplasia), polycythemia, neonatal respiratory distress syndrome.
Methylmercury - Neurotoxicity. Higher concentrations in top-predator fsh (eg, shark, swordfsh, king mackerel, tilefsh).
1st pharyngeal arch - Maxillary process > maxilla, zygomatic bone. Mandibular process > meckel cartilage > mandible, malleus and incus,
sphenomandibular ligament. Muscles of mastication (temporalis, masseter, lateral and medial pterygoids), mylohyoid, anterior belly of digastric, tensor
tympani, anterior 2/3 of tongue, tensor veli palatini CN V3 chew.

2nd pharyngeal arch - Reichert cartilage: stapes, styloid process, lesser horn of hyoid, stylohyoid ligament. Muscles of facial expression, stapedius,
stylohyoid, platysma, posterior belly of digastric. CN VII (seven) smile (facial expression).
3rd pharyngeal arch - Greater horn of hyoid. Stylopharyngeus. CN IX (stylopharyngeus) swallow stylishly.
4th and 6th pharyngeal arches - Arytenoids, Cricoid, Corniculate, Cuneiform, Thyroid (used to sing and ACCCT). 4th arch: most pharyngeal
constrictors; cricothyroid, levator veli palatini. 6th arch: all intrinsic muscles of larynx except cricothyroid. 4th arch: CN X (superior laryngeal branch)
simply swallow. 6th arch: CN X (recurrent/ inferior laryngeal branch) speak.

1st pharyngeal arch - anterior belly of digastric, tensor veli palatini. 2nd pharyngeal arch - lesser horn of hyoid, posterior belly of digastric. 3rd
pharyngeal arch - Greater horn of hyoid.
4th arch - levator veli palatini.

Pharyngeal pouch derivatives - Ear, tonsils, bottom-to-top: 1 (ear), 2 (tonsils), 3 dorsal (bottom for inferior parathyroids), 3 ventral (to = thymus), 4
(top = superior parathyroids) POUCH DERIVATIVES NOTES
1st pharyngeal pouch - Middle ear cavity, eustachian tube, mastoid air cells. 1st pouch contributes to endoderm-lined structures of ear.
2nd pharyngeal pouch - Epithelial lining of palatine tonsil.

3rd pharyngeal pouch - Dorsal wings > inferior parathyroids. Ventral wings > thymus. Third pouch contributes to thymus and both inferior
parathyroids. Structures from 3rd pouch end up below those from 4th pouch.
4th pharyngeal pouch - Dorsal wings > superior parathyroids. Ventral wings > ultimopharyngeal body > parafollicular (C) cells of thyroid. 4th
pharyngeal pouch forms para“4”llicular cells.
Orofacial clefts - Cleft lip and cleft palate have distinct, multifactorial etiologies, but often occur together. Cleft lip - Due to failure of fusion of the
maxillary and merged medial nasal processes (formation of 1° palate).
Cleft palate - Due to failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelf with the nasal septum and/or 1°
palate (formation of 2° palate).
Paramesonephric (Müllerian) duct - Develops into female internal structures— fallopian tubes, uterus, upper portion of vagina (lower portion from
urogenital sinus). Male remnant is appendix testis. Mesonephric (Wolfan) duct - Develops into male internal structures (except prostate)—Seminal
vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED). Female remnant is Gartner duct. Müllerian agenesis (Mayer-RokitanskyKüster-
Hauser syndrome)—may present as 1° amenorrhea (due to a lack of uterine development) in females with fully developed 2° sexual characteristics
(functional ovaries).

Clostridium perfringens - α-toxin (lecithinase, a phospholipase) and heat-labile enterotoxin. Infant botulism - spores (toxin formed in-vivo)
Adult botulism - preformed toxin
Anthrax - Prophylaxis with ciprofoxacin or doxycycline when exposed.

Diphtheria Rx - diphtheria antitoxin +/– erythromycin or penicillin.

Listera - Treatment: ampicillin.
SNAP: Sulfonamides—Nocardia; Actinomyces—Penicillin.
Leprosy - Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
N. gonorrheae - Treatment: ceftriaxone + azithromycin (to cover possible chlamydial coinfection, ceftriaxone-resistant strains). Erythromycin eye
ointment prevents neonatal blindness. Meningococci - Prophylaxis - Rifampin, ciprofloxacin, or ceftriaxone. Treatment: ceftriaxone or penicillin G.

H. influenzae - Treatment: amoxicillin +/ clavulanate for mucosal infections; ceftriaxone for meningitis; rifampin prophylaxis for close contacts.
Pertussis - Treatment: macrolides; if allergic use TMP-SMX.
Brucella - Treatment: doxycycline + rifampin or streptomycin.
Legionella - Treatment: macrolide or quinolone.

Pseudomonas Treatments: Antipseudomonal penicillins in combination with -lactamase inhibitor (eg, piperacillintazobactam) 3rd- and 4th-generation
cephalosporins (eg, ceftazidime, cefepime) Monobactams Fluoroquinolones Carbapenems
Salmonella typhi - treat with ceftriaxone or fuoroquinolone
S. agalactae - GBS - Patients with culture receive intrapartum penicillin/ampicillin prophylaxis.

H. pylori - Most common initial treatment is triple therapy: amoxicillin (metronidazole if penicillin allergy) + clarithromycin + proton pump inhibitor;
antibiotics cure Pylori. Bismuth-based quadruple therapy if concerned about macrolide resistance.
Lyme ds - Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Rx Penicillin G

Congenital syphilis - To prevent, treat patient early in pregnancy, as placental transmission typically occurs after first trimester.
Gardnerella vaginalis - Treatment: metronidazole or clindamycin.
Chlamydia - Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for possible concomitant gonorrhea.
Rickettsial diseases and vector-borne illnesses Treatment: doxycycline.
Mycoplasma pneumoniae - Treatment: macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since Mycoplasma has no cell wall).
C difficile - Treatment: oral vancomycin or fidaxomicin. For recurrent cases, consider repeating prior regimen or fecal microbiota transplant.
Lab diagnosis based on gram ⊕ rods with metachromatic (blue and red) granules and ⊕ Elek test for toxin. Club shaped (metachromatic granules on
Löffler media). Black colonies on cystine-tellurite agar. Treatment: diphtheria antitoxin +/– erythromycin or penicillin.
Listeria - Facultative intracellular rod; Unpasteurized dairy products and cold deli meats, transplacental transmission, vaginal transmission during birth.
Grows well at refrigeration temperatures (“cold enrichment”). Forms “rocket tails” via actin polymerization. Characteristic tumbling motility in broth.
Amnionitis, septicemia, and spontaneous abortion in pregnant patients; granulomatosis infantiseptica; meningitis in immunocompromised patients,
neonates, and older adults; mild, self- limited gastroenteritis in healthy individuals.
M avium–intracellulare (causes disseminated, non-TB disease in AIDS; often resistant to multiple drugs). Prophylaxis with azithromycin when CD4+
count < 50 cells/mm3
Mycobacterium tuberculosis - Cord factor creates a “serpentine cord” appearance in virulent M tuberculosis strains; activates macrophages (promoting
granuloma formation) and induces release of TNF-α. Sulfatides (surface glycolipids) inhibit phagolysosomal fusion.
Acid production: meningococci—maltose and glucose; gonococci— glucose.
Mycobacteria - Sulfatides (surface glycolipids) inhibit phagolysosomal fusion.
Leprosy Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
Acid production: meningococci—maltose and glucose; gonococci— glucose.
H. influenzae type b - Epiglottitis (“thumb sign” on lateral neck x-ray)
Croup - parainfluenza; “seal-like” barking cough and inspiratory stridor. Steeple sign on x-ray.
Bordetella pertusis - inspiratory “whoop” (“whooping cough”), posttussive vomiting.
Legionella - Ella sisters - (Cysteine) chapel out of charcoal and iron
Pseudomonas aeruginosa - aerobic; motile, catalase ⊕, gram ⊖ rod. Non-lactose fermenting. Oxidase ⊕.
Salmonella typhi (ty-Vi) - Monocytes
Salmonella spp. except S typhi - PMNs
Shigella - PMNs
Anthrax - Prophylaxis with ciprofoxacin or doxycycline when exposed.
Diphtheria Rx - diphtheria antitoxin +/– erythromycin or penicillin.
Listera - Treatment: ampicillin.
SNAP: Sulfonamides—Nocardia; Actinomyces—Penicillin.
Leprosy - Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
N. gonorrheae - Treatment: ceftriaxone + azithromycin (to cover possible chlamydial coinfection, ceftriaxone-resistant strains). Erythromycin eye
ointment prevents neonatal blindness.
Meningococci - Prophylaxis - Rifampin, ciprofloxacin, or ceftriaxone. Treatment: ceftriaxone or penicillin G.
H. influenzae - Treatment: amoxicillin +/ clavulanate for mucosal infections; ceftriaxone for meningitis; rifampin prophylaxis for close contacts.
Pertussis - Treatment: macrolides; if allergic use TMP-SMX.
Brucella - Treatment: doxycycline + rifampin or streptomycin.

Legionella - Treatment: macrolide or quinolone.

Pseudomonas Treatments: Antipseudomonal penicillins in combination with -lactamase inhibitor (eg, piperacillintazobactam) 3rd- and 4th-generation
cephalosporins (eg, ceftazidime, cefepime) Monobactams Fluoroquinolones Carbapenems (AACCMQ)
Salmonella typhi - treat with ceftriaxone or fuoroquinolone
S. agalactae - GBS - Patients with culture receive intrapartum penicillin/ampicillin prophylaxis.
H. pylori - Most common initial treatment is triple therapy: amoxicillin (metronidazole if penicillin allergy) + clarithromycin + proton pump inhibitor;
antibiotics cure Pylori. Bismuth-based quadruple therapy if concerned about macrolide resistance.
Lyme ds - Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Rx Penicillin G
Congenital syphilis - To prevent, treat patient early in pregnancy, as placental transmission typically occurs after first trimester.
Gardnerella vaginalis - Treatment: metronidazole or clindamycin.
Chlamydia - Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for possible concomitant gonorrhea.
Rickettsial diseases and vector-borne illnesses Treatment: doxycycline.
Mycoplasma pneumoniae - Treatment: macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since Mycoplasma has no cell wall).
Systemic mycosis - Treatment: fluconazole or itraconazole for local infection; amphotericin B for systemic infection.
Tinea (pityriasis) versicolor - Treatment: selenium sulfide, topical and/or oral antifungal medications.
Candida - Treatment: oral fluconazole/topical azoles for vaginal; nystatin, azoles, or, rarely, echinocandins for oral; fluconazole, echinocandins, or
amphotericin B for esophageal or systemic disease. Aspergillus - Treatment: voriconazole or echinocandins (2nd-line).
Cryptococcus - Treatment: amphotericin B + flucytosine followed by fluconazole for cryptococcal meningitis.
Mucor and Rhizopus spp - Treatment: surgical debridement, amphotericin B or isavuconazole
Pneumocystis jirovecii - Treatment/prophylaxis: TMP-SMX, pentamidine, dapsone (prophylaxis as single agent, or treatment in combination with
TMP), atovaquone. Start prophylaxis when CD4+ cell count drops to < 200 cells/mm3 in people living with HIV.
Sporothrix schenckii - Treatment: itraconazole or potassium iodide (only for cutaneous/lymphocutaneous). Think of a rose gardener who smokes a
cigar and pot.
Giardia lamblia - Rx Metronidazole.
Entamoeba histolytica - Rx Metronidazole; paromomycin or iodoquinol for asymptomatic cyst passers.
Cryptosporidium - Rx Prevention (by filtering city water supplies); nitazoxanide in immunocompetent hosts.
Protozoa—CNS infections-
Toxoplasma gondii - Rx Sulfadiazine + pyrimethamine. Prophylaxis with TMP-SMX when CD4+ cell count < 100 cells/mm3.
Naegleria fowleri - Rx Amphotericin B has been effective for a few survivors.
Trypanosoma brucei - Rx Suramin for bloodborne disease or melarsoprol for CNS penetration.
Protozoa—hematologic infections-
Plasmodium - TREATMENT Chloroquine (for sensitive species); if resistant, use mefloquine or atovaquone/ proguanil. If life-threatening, use
intravenous quinidine or artesunate (test for G6PD deficiency). For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency).
Babesia - Rx Atovaquone + azithromycin.
Visceral infections-
Trypanosoma cruzi - Rx Benznidazole or nifurtimox; cruzing in my Benz, with a fur coat on.
Leishmania spp - Rx Amphotericin B, sodium stibogluconate.
Sexually transmitted infections-
Trichomonas vaginalis - Rx Metronidazole for patient and partner(s) (prophylaxis; check for STI).
Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin).
Cestode/tapeworm Rx - (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole).
Nematodes (roundworms)
Intestinal-
Enterobius vermicularis (pinworm) - Bendazoles, pyrantel pamoate.
Ascaris lumbricoides (giant roundworm) - Bendazoles.
Strongyloides stercoralis (threadworm) - Ivermectin or bendazoles.
Ancylostoma spp, Necator americanus (hookworms) - Bendazoles or pyrantel pamoate.
Trichinella spiralis - Bendazoles.
Trichuris trichiura (whipworm) - Bendazoles.
Tissue-
Toxocara canis - Visceral larva migrans. Bendazoles.
Onchocerca volvulus - Ivermectin (ivermectin for river blindness).
Loa loa - Diethylcarbamazine.
Wuchereria bancrofti, Brugia malayi - Diethylcarbamazine.
Cestodes (tapeworms)
Taenia solium1 - Praziquantel.
Taenia solium2 - Praziquantel; albendazole for neurocysticercosis.
Diphyllobothrium latum - Praziquantel, niclosamide.
Echinococcus granulosus - Albendazole; surgery for complicated cysts.
Trematodes (flukes)
Schistosoma - Praziquantel.
Clonorchis sinensis - Praziquantel.
Ectoparasites
Sarcoptes scabiei - Treatment: permethrin cream, oral ivermectin, washing/drying all clothing/bedding, treat close contacts.
Pediculus humanus/ Phthirus pubis - Treatment: pyrethroids, malathion, or ivermectin lotion, and nit combing. Children with head lice can be treated at
home without interrupting school attendance.

insulin inc Na+ retention in kidneys

insulin inc K+ uptake in cells
INSULIN release dec by α2, inc by β2 stimulation
insulin and c-peptide released equally
GLUT1 - P-RBC
GLUT2 - LKG-B
GLUT3 - BP
GLUT4 - AS
GLUT5 - GS
SGLT1/2 - SK
insulin dependent - GLUT4
insulin independent - GLUT1,2,3,5; SGLT1,2 (BRICK-LIPS) GLUT-2 - bidirectional
GLUT-5 - fructose
GLUT1: RBCs, brain, cornea, placenta.
GLUT2 (bidirectional): B-islet cells, liver, kidney, GI tract. GLUT3: brain, placenta.

GLUT4: adipose tissue, striated muscle.

GLUT5 (fructose): spermatocytes, GI tract.
SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine.
Receptor tyrosine kinase - IGF-1, FGF, PDGF, EGF, Insulin. MAP kinase pathway. Get Found In the MAP.
Nonreceptor tyrosine kinase - G-CSF, Erythropoietin, Thrombopoietin Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH. JAK/STAT
pathway. Think acidophils and cytokines. GET a JAKed PIG.
Signaling pathways of endocrine hormones-
cAMP - FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2- receptor), MSH, PTH, Calcitonin, Histamine (H2-receptor), Glucagon, GHRH. FLAT
ChAMPs CHuGG.
cGMP - BNP, ANP, EDRF (NO). BAD GraMPa. Think vasodilation and diuresis.
IP3 - GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin. GOAT HAG.
Intracellular receptor - Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4,Vitamin D. PET CAT in TV.
Serine/threonine kinase receptor - TGF-B
Receptor tyrosine kinase - IGF-1, FGF, PDGF, EGF, Insulin. MAP kinase pathway. Get Found In the MAP. (Growth factors and insulin).
Nonreceptor tyrosine kinase - G-CSF, Erythropoietin, Thrombopoietin Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH. JAK/STAT
pathway. Think acidophils and cytokines. GET a JAKed PIG.
Inc estrogen (eg, OCPs, pregnancy) > inc SHBG.
Cortisol - Eosinopenia, lymphopenia
Signaling pathways of endocrine hormones-
cAMP - FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2- receptor), MSH, PTH, Calcitonin, Histamine (H2-receptor), Glucagon, GHRH. FLAT
ChAMPs CHuGG.
cGMP - BNP, ANP, EDRF (NO). BAD GraMPa. Think vasodilation and diuresis.
IP3 - GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin. GOAT HAG.
Intracellular receptor - Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4,Vitamin D. PET CAT in TV.
Serine/threonine kinase receptor - TGF-B
Receptor tyrosine kinase - IGF-1, FGF, PDGF, EGF, Insulin. MAP kinase pathway. Get Found In the MAP. (Growth factors and insulin).
Nonreceptor tyrosine kinase - G-CSF, Erythropoietin, Thrombopoietin Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH. JAK/STAT
pathway. Think acidophils and cytokines. GET a JAKed PIG.
Nephrogenic DI Rx - TREATMENT Manage the underlying cause. Low-solute diet, HCTZ, amiloride, indomethacin.
CAUSES - Hereditary (ADH receptor mutation), drugs (eg, lithium, demeclocycline), hypercalcemia, hypokalemia.
DESMOPRESSIN ADMINISTRATION Minimal change in urine osmolality.
pegvisomant - (GH receptor antagonist)
Primary polydipsia and diabetes insipidus - Urine specifc gravity <1.006. Urine osmolality usually <300 mOsm/kg.
Nephrogenic DI Rx - TREATMENT Manage the underlying cause. Low-solute diet, HCTZ, amiloride, indomethacin.
CAUSES - Hereditary (ADH receptor mutation), drugs (eg, lithium, demeclocycline), hypercalcemia, hypokalemia.
DESMOPRESSIN ADMINISTRATION Minimal change in urine osmolality
failure to suppress serum GH following oral glucose tolerance test;
GH secreting adenoma - failure to suppress serum GH following oral glucose tolerance test. TREATMENT Pituitary adenoma resection. If not cured,
treat with octreotide (somatostatin analog), pegvisomant (GH receptor antagonist), or dopamine agonists (eg, cabergoline).

Hypothyroid myopathy (proximal weakness, inc CK)

Thyrotoxic myopathy (proximal weakness, normal CK)
Wolff-Chaikoff effect—protective autoregulation; sudden exposure to excess iodine temporarily turns off thyroid peroxidase > dec T3/T4 production.
Jod-Basedow phenomenon - Iodine-induced hyperthyroidism. Occurs when a patient with iodine defciency and partially autonomous thyroid tissue (eg,
autonomous nodule) is made iodine replete. Can happen after iodine IV contrast or amiodarone use. Opposite to Wolff- Chaikoff effect.
Hyperthyroidism - inc number and sensitivity of B-adrenergic receptors, inc expression of cardiac sarcolemmal ATPase and dec expression of
phospholamban.
Postpartum thyroiditis—mild, self-limited variant of Hashimoto thyroiditis arising < 1 year after delivery.
Hypothyroidism - hypercholestrolemia
Hyperthyroidism - dec cholestrol
Congenita hypothyroidism - cretinism - Findings (6 P’s): pot-bellied, pale, puffy-faced child with protruding umbilicus, protuberant tongue, and poor
brain development.
Euthyroid sick syndrome - nonthyroidal illness syndrome - dec T3 with normal/dec T4 and TSH in critically ill patients).

Hypothyroid myopathy (proximal weakness, inc CK)

Thyrotoxic myopathy (proximal weakness, normal CK)
Euthyroid sick syndrome - nonthyroidal illness syndrome - dec T3 with normal/dec T4 and TSH in critically ill patients).
Hashimoto - Associated with HLA-DR3, inc risk of primary thyroid lymphoma (typically diffuse large B-cell lymphoma).
Graves - Associated with HLA-DR3 and HLA-B8.
Fine needle aspiration cytology may not be able to distinguish between follicular adenoma and carcinoma
Follicular carcinoma - Associated with RAS mutation and PAX8-PPAR-y translocations.
Thyroid storm Rx - Treat with the 4 P’s: B-blockers (eg, propranolol), propylthiouracil, corticosteroids (eg, prednisolone), potassium iodide (Lugol
iodine). Iodide load > dec T4 synthesis > Wolff- Chaikoff effect.
Papillary carcinoma - Most common. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes), psamMoma bodies, nuclear grooves (Papi
and Moma adopted Orphan Annie). Inc risk with RET/ PTC rearrangements and BRAF mutations, childhood irradiation.
Tertiary hyperparathyroidism - Refractory (autonomous) hyperparathyroidism resulting from chronic kidney disease. Inc inc PTH, inc Ca2+.
Familial hypocalciuric hypercalcemia - Defective G-coupled Ca2+-sensing receptors in multiple tissues (eg, parathyroids, kidneys). Higher than normal
Ca2+ levels required to suppress PTH. Excessive renal Ca2+ reabsorption > mild hypercalcemia and hypocalciuria with normal to inc PTH levels.
Pseudohypoparathyroidism type 1A—autosomal dominant, maternally transmitted mutations (imprinted GNAS gene). GNAS1-inactivating mutation
(coupled to PTH receptor) that encodes the Gs protein subunit > inactivation of adenylate cyclase when PTH binds to its receptor > end-organ
resistance (kidney and bone) to PTH. Physical fndings: Albright hereditary osteodystrophy (shortened 4th/5th digits, short stature, round face,
subcutaneous calcifcations, developmental delay). Labs: inc PTH, dec Ca2+, inc PO4 3–.
Pseudopseudohypoparathyroidism—autosomal dominant, paternally transmitted mutations (imprinted GNAS gene) but WITHOUT end-organ
resistance to PTH due to normal maternal allele maintaining renal responsiveness to PTH. Physical fndings: same as Albright hereditary
osteodystrophy. Labs: normal PTH, Ca2+, PO4 3–.
Pseudohypoparathyroidism type 1A—end-organ resistance (kidney and bone) to PTH. Labs: inc PTH, dec Ca2+, inc PO4 3–.
Pseudopseudohypoparathyroidism—WITHOUT end-organ resistance to PTH. Labs: normal PTH, Ca2+, PO4 3–.
HbA1c - >6.5% - Refects average blood glucose over prior 3 months (infuenced by RBC turnover)
Fasting plasma glucose - >126 mg/dL - Fasting for > 8 hours
2-hour oral glucose tolerance test - >200 mg/dL - 2 hours after consumption of 75 g of glucose in water
Random plasma glucose - >200 mg/dL - Presence of hyperglycemic symptoms is required.
Type 1 - GLUCOSE INTOLERANCE Severe
Type 2 - GLUCOSE INTOLERANCE Mild to moderate
Nelson syndrome - Enlargement of pre-existing ACTH–secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease > inc
ACTH (hyperpigmentation), mass effect (headaches, bitemporal hemianopia). Treatment: transsphenoidal resection, postoperative pituitary irradiation
for residual tumor.
Pheochromocytoma - rule of 10s
Carcinoid tumor - rule of thirds
Meckel diverticulum - rule of 2s
Neuroblastoma - (neuroblastoma is normotensive). Can also present with opsoclonus-myoclonus syndrome (“dancing eyes-dancing feet”). Inc HVA
and VMA (catecholamine metabolites) in urine. Homer-Wright rosettes (neuroblasts surrounding a central lumen) characteristic of neuroblastoma and
medulloblastoma. Bombesin and NSE +. Associated with amplifcation of N-myc oncogene. Addison ds - chronic primary adrenal insufficiency

Adrenal/addisonian crisis - acute adrenal insufficiency

Primary adrenal insufficiency - dec aldosterone synthesis.
Sec/Ter adrenal insufficiency - normal aldosterone synthesis (intact RAAS).
1° hyperaldosteronism does not directly cause edema due to aldosterone escape mechanism. However, certain 2° causes of hyperaldosteronism (eg,
heart failure) impair the aldosterone escape mechanism, leading to worsening of edema.
Neuroblastoma - Most common presentation is abdominal distension and a firm, irregular mass that can cross the midline (vs Wilms tumor, which is
smooth and unilateral).
Insulinoma - Whipple triad: low blood glucose, symptoms of hypoglycemia (eg, lethargy, syncope, diplopia), and resolution of symptoms after
normalization of plasma glucose levels. Zollinger-Ellison syndrome - Positive secretin stimulation test: inc gastrin levels after administration of
secretin, which normally inhibits gastrin release.
Carcinoid tumor Rx - Treatment: surgical resection, somatostatin analog (eg, octreotide) or tryptophan hydroxylase inhibitor (eg, telotristat) for
symptom control.
ZES - Positive secretin stimulation test: inc gastrin levels after administration of secretin, which normally inhibits gastrin release.
Most OHAs classes are avoided in renal insufficiency.
PTU used in Primary (first) trimester of pregnancy (due to methimazole teratogenicity); methimazole used in second and third trimesters of pregnancy
(due to risk of PTU-induced hepatotoxicity). Not used to treat Graves ophthalmopathy (treated with corticosteroids). ADVERSE EFFECTS Skin rash,
agranulocytosis (rare), aplastic anemia, hepatotoxicity. PTU use has been associated with ANCA-positive vasculitis. Methimazole is a possible
teratogen (can cause aplasia cutis).
Pheochromocytoma - rule of 10s
Carcinoid tumor - rule of thirds
Meckel diverticulum - rule of 2s
Metformin - lactic acidosis (use with caution in renal insufficiency).

Rosiglitazone: inc risk of MI, cardiovascular death.

GLP-1 analogs, DPP-4 inhibitors - dec glucagon release, dec gastric emptying, inc glucose-dependent insulin release. SE GLP-1 analogs - Pancreatitis,
weight loss, Inc satiety. SE DPP-4 inh - Respiratory and urinary infections, weight neutral, Inc satiety. (DPP-4 inhibitors - Inhibit DPP-4 enzyme that
deactivates GLP-1).
Zollinger-Ellison syndrome - Positive secretin stimulation test: inc gastrin levels after administration of secretin, which normally inhibits gastrin
release.
6th week - herniation
10th week - returns and rotates around SMA 270 counterclockwise
Gastroschisis - Not associated with chromosome abnormalities;
Omphalocele - Associated with trisomies 13 and 18, Beckwith-Wiedemann & cardiac, GU, neural tube defects.
Rostral fold defect - sternal defects (-ectopia cordis)
Lateral fold defect - omphalocele, gastroschisis
Caudal fold defect - bladder exstrophy
Esophageal atresia (EA) with distal tracheoesophageal fstula (TEF) is the most common (85%)
Ventral pancreatic bud - main duct and uncinate process
Dorsal pancreatic bud - body, tail, isthmus, accessory duct
Both buds - head
Hypertrophic pyloric stenosis - associated with exposure to macrolides.
Duodenal atresia—X-ray A shows “double bubble” (dilated stomach, proximal duodenum).
Jejunal and ileal atresia—X-ray may show “triple bubble” (dilated stomach, duodenum, proximal jejunum).
Hypertrophic pyloric stenosis - hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and subsequent volume contraction).
Pancreas divisum—fail to fuse at 7 weeks
Submucosa—includes submucosal nerve plexus (Meissner), secretes fuid.
Muscularis externa—includes myenteric nerve plexus (Auerbach), motility.
Hepatoduodenal - Borders the omental foramen, which connects the greater and lesser sacs. Pringle maneuver.
Hepatogastric - Separates greater and lesser sacs on the right, CUT TO ACCESS LESSER SAC.
Gastrosplenic - Separates greater and lesser sacs on the left.
Ventral mesentry - falciform, hepatoduodenal, hepatogastric
Dorsal mesentry - gastrocolic, gastrosplenic, splenorenal
(all related to liver are derived from ventral mesentry)
Plicae circulares - distal duodenum, jejunum, proximal ileum.
Ileum - Largest number of goblet cells in the small intestine.
Esophagus - Upper 1/3, striated muscle; middle and lower 2/3 smooth muscle.
Colon - no villi.
Watershed regions - Splenic flexure—SMA and IMA
Rectosigmoid junction—the last sigmoid arterial branch from the IMA and superior rectal artery.
Nutcracker syndrome—compression of left renal vein between superior mesenteric artery and aorta.
Superior mesenteric artery syndrome—SMA and aorta compress transverse (third) portion of duodenum.
PANS innervation-
foregut, midgut - vagus N
hindgut - pelvic N
Foregut - Celiac - Vagus - T12/L1
Midgut - SMA - Vagus - L1
Hindgut - IMA - Pelvic - L3
Branches of celiac trunk: common hepatic, splenic, and left gastric.
*common hepatic > gastroduodenal > ant and post sup pancreaticoduodenal > right gastroepiploic.
*common hepatic > proper hepatic > right gastric.
*splenic > short gastric and left gastroepiploic.
*left gastric > esophageal.
Branches of celiac trunk: common hepatic, splenic, and left gastric.
Above pectinate - visceral N, sup rectal A(IMA), sup rectal V(IMV), internal iliac LN
Below pectinate - pudendal N, inf rectal A(internal pudendal A), inf rectal V(internal pudendal V), superficial inguinal LN
External hemorrhoids - inferior rectal branch of pudendal nerve
zone 1 (periportal) - best oxygenated, viral hepatitis, ingested toxins
zone 2 - yellow fever
zone 3 (pericentral (centrilobular)) - ischemia, cyt P-450, alcoholic hepatitis, metabolic toxins
Hepatic stellate (Ito) cells in space of Disse store vitamin A (when quiescent) and produce extracellular matrix (when activated). Responsible for
hepatic fibrosis.
apical surface of hepatocytes faces bile canaliculi
basolateral surface faces sinusoids
Double duct sign - gall stone at ampulla of vater blocks both CBD and pancreatic duct.
Ca Head of pancreas - commonly ductal adenocarcinoma.
Femoral triangle - adductor longus, sartorius and inguinal ligament; contains NAV.
Femoral sheath - NO NERVE. Contains vein, artery and deep inguinal LN.
Hiatal hernia-
sliding - gastric cardia
paraesophageal - gastric fundus
Spermatic cord (ICE-tie)-
Internal spermatic fascia (transversalis fascia)
Cremasteric muscle and fascia (internal oblique)
External spermatic fascia (external oblique)
External iliac vessels > inferior epigastric vessels
Inguinal (hesselbach) triangle - inf epigastric vessels, inguinal ligament and rectus abdominis. Infants - pleuroperitoneal membrane; left sided hernia.

Adults - phrenoesophageal membrane; hiatal hernia (through esophageal hiatus).

Right horn of sinus venosus - Smooth part of right atrium

Primitive pulmonary vein - Smooth part of left atrium
Bulbus cordis - Smooth parts (outfow tract) of left and right ventricles
Catecholamine stimulation via β1 receptor:
1. Activated protein kinase A > phospholamban phosphorylation > active Ca2+ ATPase > inc Ca2+ storage in sarcoplasmic reticulum. 2. Activated
protein kinase A > Ca2+ channel phosphorylation > inc Ca2+ entry > inc Ca2+-induced Ca2+ release.
Coronary blood fow to LV and interventricular septum peaks in early diastole.
Vasodilators (eg, nitroglycerin/nitrates) dec preload.
Arterial vasodilators (eg, hydralazine) dec afterload.
ACE inhibitors and ARBs dec both preload and afterload.
Nitroprusside - Short acting vasodilator (arteries = veins).
Contractility (and SV) dec with: Acidosis, Hypoxia/hypercapnia.

Inc wall tension per Laplace’s law > inc pressure > inc afterload.
LV compensates for inc afterload by thickening (hypertrophy) in order to dec wall stress.
Narcotic overdose dec contractility
Spinal anesthesia dec venous return
Exercise dec TPR via arteriolar vasodilation
AR and MR - no true isovolumetric phase
Rapid flling—period just after mitral valve opening
Reduced flling—period just before mitral valve closing
x descent—Reduced or absent in tricuspid regurgitation and right HF because pressure gradients are reduced. y descent—RA emptying into RV.
Prominent in constrictive pericarditis, absent in cardiac tamponade.

PP directly proportional to SV and inversely proportional to arterial compliance.

In early stages of exercise, CO maintained by inc HR and inc SV. In later stages, CO maintained by inc HR only (SV plateaus)
Inc PP in hyperthyroidism, aortic regurgitation, aortic stiffening (isolated systolic hypertension in elderly), obstructive sleep apnea ( inc sympathetic
tone), anemia, exercise (transient). Dec PP in aortic stenosis, cardiogenic shock, cardiac tamponade, advanced HF.
Mean arterial pressure MAP = CO x total peripheral resistance (TPR). MAP (at resting HR) = 2/3 DBP + 1/3 SBP = DBP + 1/3 PP.
Resistance = driving pressure (ΔP)/Q = (8η (viscosity) × length)/πr4
Isovolumetric contraction (period between mitral valve closing and aortic valve opening)—period of highest O2 consumption
Rapid flling—period just after mitral valve opening
Reduced flling—period just before mitral valve closing
x descent - Reduced or absent in tricuspid regurgitation and right HF
y descent—RA emptying into RV. Prominent in constrictive pericarditis, absent in cardiac tamponade.
Loss of dichrotic notch in AR
AR - inc EDV, inc SV
MR - Inc SV, dec ESV, inc EDV
AR and MR - no true isovolumetric phase
Hand grip-
MURMURS THAT INCREASE WITH MANEUVER Most other left-sided murmurs (AR, MR, VSD).
MURMURS THAT DECREASE WITH MANEUVER AS (dec transaortic valve pressure gradient) HCM (inc LV volume).
AR murmur - Best heard at base (aortic root dilation) or left sternal border (valvular disease).
Inspiration - inc venous return to right heart, dec venous return to left heart.
ASD murmur - pulmonic area.
MVP murmur - Loudest just before S2.
PDA murmur - loudest at S2.
AS mumur - loudest at heart base.
MR - loudest at apex.
MS murmur - (dec interval between S2 and OS correlates with inc severity).
Patent ductus arteriosus - Best heard at left infraclavicular area. Loudest at S2.

AS - “Pulsus parvus et tardus”—pulses are weak with a delayed peak.

Component of Cushing reflex (triad of hypertension, bradycardia, and respiratory depression)— inc intracranial pressure constricts arterioles > cerebral
ischemia > inc pCO2 and dec pH > central reflex sympathetic inc in perfusion pressure (hypertension) > inc stretch > peripheral reflex baroreceptor–
induced bradycardia.
U wave—prominent in hypokalemia (think hyp“U”kalemia), bradycardia.

If channels (funny current) responsible for a slow, mixed Na+ /K+ inward current. ST segment—isoelectric, ventricles depolarized.
U wave—prominent in hypokalemia (think hyp“U”kalemia), bradycardia.

BNP blood test used for diagnosing HF (very good negative predictive value). Available in recombinant form (nesiritide) for treatment of HF. Skeletal
muscle - Local metabolites during exercise (vasodilatory): CO2, H+ , Adenosine, Lactate, K+ (CHALK).
TGA - (“egg on a string” appearance on CXR).
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.

Infant of patient with diabetes during pregnancy - Transposition of great vessels, VSD Williams syndrome - Supravalvular aortic stenosis
22q11 syndromes - Truncus arteriosus, tetralogy of Fallot.
Fetal alcohol syndrome - VSD, PDA, ASD, tetralogy of Fallot

Uncorrected PDA (Eisenmenger syndrome) can eventually result in late cyanosis in the lower extremities (differential cyanosis).
HOCM - Asymmetric septal hypertrophy and systolic anterior motion of mitral valve.
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.
Stanford type A (proximal): involves Ascending aorta. May extend to aortic arch or descending aorta. May result in acute aortic regurgitation or cardiac
tamponade. Treatment: surgery. Stanford type B (distal): involves only descending aorta (Below left subclavian artery). Treatment: β-blockers, then
vasodilators. (to prevent reflex tachycardia)

AAA - Most often infrarenal (distal to origin of renal arteries).

Abdominal aortic aneurysm - Usually associated with atherosclerosis.
Thoracic aortic aneurysm - Associated with cystic medial degeneration.
Subclavian steal syndrome: >15 mm Hg difference in systolic BP between arms.
Myocardial hibernation—potentially reversible LV systolic dysfunction in the setting of chronic ischemia. Contrast with myocardial stunning, a
transient LV systolic dysfunction after a brief episode of acute ischemia.

Vasospastic (also called Prinzmetal or Variant)—transient ST elevation on ECG. STEMI - Q waves

3-14 days - LV pseudoaneurysm (risk of rupture).
>2 weeks - True ventricular aneurysm (risk of mural thrombus).

Kussmaul sign - Paradoxical inc in JVP on inspiration.

Brugada syndrome - Autosomal dominant; most commonly due to loss of function mutation of Na+ channels. Inc prevalence in Asian males. ECG
pattern of pseudo-right bundle branch block and ST- segment elevations in leads V1-V2.
In the first 6 hours, ECG is the gold standard. Cardiac troponin I rises after 4 hours (peaks at 24 hr) and is inc for 7–10 days; more specifc than other
protein markers. CK-MB rises after 6–12 hours (peaks at 16–24 hr) and is predominantly found in myocardium but can also be released from skeletal
muscle. Useful in diagnosing reinfarction following acute MI because levels return to normal after 48 hours.
Lateral (LCX) I, aVL
InFerior (RCA) II, III, aVF
Posterior (PDA) V7–V9, ST depression in V1–V3 with tall R waves.

Holiday heart syndrome - Atrial fibrillation seen after episodes of excessive alcohol consumption.
Atrial flutter - Treat like atrial fbrillation +/– catheter ablation of region between tricuspid annulus and IVC. Mobitz type I (Wenckebach) - Progressive
lengthening of PR interval until a beat is “dropped”. Regularly irregular. Mobitz type II - Dropped beats that are not preceded by a change in the length
of the PR interval (as in type I).

Holiday heart syndrome - Atrial fibrillation seen after episodes of excessive alcohol consumption.
Ventricular pseudoaneurysm formation 3–14 days: free wall rupture contained by adherent pericardium or scar tissue. True ventricular aneurysm 2
weeks to several months: outward bulge with contraction (“dyskinesia”), associated with fibrosis.
Takotsubo cardiomyopathy: broken heart syndrome—ventricular apical ballooning likely due to increased sympathetic stimulation (eg, stressful
situations).
HOCM - Asymmetric septal hypertrophy and systolic anterior motion of mitral valve.
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.
Löffer endocarditis—associated with hypereosinophilic syndrome; histology shows eosinophilic infltrates in myocardium.
Aschoff bodies (granuloma with giant cells).
Anitschkow cells (enlarged macrophages with ovoid, wavy, rod-like nucleus).
Myocarditis - arrhythmias (persistent tachycardia out of proportion to fever is characteristic).
Pericarditis - ECG changes include widespread ST-segment elevation and/or PR depression.
Endocarditis - If culture -ve, most likely Coxiella burnetii, Bartonella spp.
Native valve endocarditis may be due to HACEK organisms (Haemophilus, Aggregatibacter [formerly Actinobacillus], Cardiobacterium, Eikenella,
Kingella).
Cardiac Tamponade - pulsus paradoxus, electrical alternans.
Pulsus paradoxus—dec in amplitude of systolic BP by > 10 mm Hg during inspiration.
Primary (essential) hypertension - (CATA)
Hypertension with heart failure - (DABAA)
Hypertension with diabetes mellitus - (B-CATA)
Hypertension in asthma - (C-CAT)
Hypertension in pregnancy - Nifedipine, methyldopa, labetalol, hydralazine. New moms love hugs.
Nitrates - Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5 inhibitor use.
Flushing-
Niacin - prostaglandin mediated
Vancomycin - histamine mediated
(niacin-lipids-inflammation)
(antibiotics-allergic reactions)
Hypertensive emergency - Treat with (CNN-FL) labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside.
Verapamil SE - hyperprolactinemia
Nesiritide - recombinant BNP.
Vasodilators (eg, nitroglycerin/nitrates) dec preload.
Arterial vasodilators (eg, hydralazine) dec afterload.
ACE inhibitors and ARBs dec both preload and afterload.
Nitroprusside - Short acting vasodilator (arteries = veins).
Ranolazine - MECHANISM Inhibits the late phase of inward sodium current thereby reducing diastolic wall tension and oxygen consumption.
Sacubitril - MECHANISM A neprilysin inhibitor; prevents degradation of bradykinin, natriuretic peptides, angiotensin II, and substance P -- > inc
vasodilation, dec ECF volume.
Flushing-
Niacin - prostaglandin mediated
Vancomycin - histamine mediated
(niacin-lipids-inflammation)
(antibiotics-allergic reactions)
Digoxin - ADVERSE EFFECTS Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (think van Glow), arrhythmias, AV block. Can
lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to digoxin toxicity: renal failure (dec excretion), hypokalemia (permissive
for digoxin binding at K+-binding site on Na+ /K+ ATPase), drugs that displace digoxin from tissue- binding sites, and dec clearance (eg, verapamil,
amiodarone, quinidine).
Fibrates - SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7a -hydroxylase).
Niacin - SE - Flushed face (prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia, Hyperuricemia.
Statins - SE - Hepatotoxicity (inc LFTs), myopathy (esp when used with fibrates or niacin).
PCSK-9 inh - SE - Myalgias, delirium, dementia, other neurocognitive effects.
Adenosine - inc K+ out of cells > hyperpolarizing the cell and dec ICa, decreasing AV node conduction.
IVabradine - prolongs slow depolarization (phase “IV”) by selectively inhibiting “funny” sodium channels (If).

Esmolol and adenosine - very short acting.

Vasodilators (eg, nitroglycerin/nitrates) dec preload.
Arterial vasodilators (eg, hydralazine) dec afterload.
ACE inhibitors and ARBs dec both preload and afterload.
Nitroprusside - Short acting vasodilator (arteries = veins).
Fibrates - Gemfibrozil, bezafibrate, fenofibrate - LDL dec; HDL inc; TGs dec dec dec. Activate PPAR-α > upregulate LPL > inc TG clearance. Activate
PPAR-α > induce HDL synthesis. SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7α-hydroxylase).

Niacin - LDL dec dec; HDL inc inc; TGs dec. Inhibits lipolysis (hormone- sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis. SE -
Flushed face (prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia Hyperuricemia.
follicular cells - endoderm
parafollicular cells - 4th pharyngeal pouch

Subclavian artery --> inf thyroid artery

ECA --> sup thyroid artery
post pituitary - neuroectoderm.
ant pituitary - oral ectoderm (Rathke pouch).

tesamorelin - GHRH analog

leuprolide - GnRH analog
octreotide - somatostatin analog
Dopamine - dec prolactin and TSH
TRH - inc prolactin and TSH
DESMOPRESSIN - Rx NOCTURNAL ENURESIS & Central DI bromocriptine - dopamine agonist

dopamine antagonists - antipsychotics, metoclopramide

Nipple stimulation and chest wall injury (via ANS) inhibits dopamine.
Prolactin in turn inhibits its own secretion by inc dopamine synthesis and secretion from hypothalamus.
estrogen - inc prolactin
Dopamine agonists (eg, bromocriptine) inhibit prolactin secretion and can be used in treatment of prolactinoma.
Dopamine antagonists (eg, most antipsychotics, metoclopramide) and estrogens (eg, OCPs, pregnancy) stimulate prolactin secretion. inc TBG -
pregnancy, estrogen
dec TBG - steroid use, nephrotic syndrome
PTH - inc urine cAMP
aminoglycosides dec serum Mg2+
Common causes of dec Mg2+ include diarrhea, aminoglycosides, diuretics, alcohol use disorder

dec serum Ca2+ > inc PTH secretion

Inc serum PO4 3− > inc PTH secretion
Dec serum Mg2+ > inc PTH secretion
Dec dec serum Mg2+ > dec PTH secretion
Alkaline environment - dec ionized Ca2+
Acidic environment - inc ionized Ca2+
inhibit peripheral conversion- steroids, beta blocker, PTU wolf-chaikoff - turn off TPO

GH and steroids inc rT3

5-deiodinase - peripheral conversion of T4 to T3
Somatostatin, dopamine and glucocorticoids inhibit TSH release from anterior pituitary

CL = rate of elimination of drug/plasma drug concentration = Vd x Ke (elimination constant) = UV/P t1/2 = (0.7 x Vd)/CL in first-order elimination
Loading dose = (Cp x Vd)/F
Maintenance dose = (Cp x CL x t)/F

Bioavailability F = [AUCoral x DoseIV] / [Doseoral x AUCIV]

Irreversible competitive inhibitor behaves like noncompetitve inhibitor. It resembles substrate and binds active site of substrate but its effects are like
noncompetitve inhibitor.
TI = TD50/ED50 = median toxic dose/median effective dose
Competitive inhibitors (reversible) - dec potency
Competitive inhibitors (irreversible) - dec efficacy
Noncompetitive inhibitors - dec efficacy
Tachyphylaxis - Hydralazine, nitrates, niacin, phenylephrine, LSD, MDMA.
Sweat glands are part of the sympathetic pathway but are innervated by cholinergic fibers.
Gi - dec sympathetic (adrenergic) outfow, dec insulin release, dec lipolysis, inc platelet aggregation, dec aqueous humor production.
Drugs with lower TI values frequently require monitoring (eg, warfarin, theophylline, digoxin, antiepileptic drugs, lithium.
Tachyphylactic Acute decrease in response to a drug after initial/repeated administration Hydralazine, nitrates, niacin, phenylephrine, LSD, MDMA
Gq - (q-tie), HAVe 1 M&M! - H1, α1, V1, M1, M3
Gi - too (2) MAD - M2, α2, D2
Gs - HD-BV - β1, β2, β3, D1, H2, V2
ANS RECEPTORS-
↑ IP3 - alpha-1 - Peripheral vasoconstriction, Urethral constriction, Pupillary dilation
↓ cAMP - alpha-2 - CNS sympatholytic, ↓ INSULIN RELEASE & INTESTINAL MOTILITY
↑ cAMP - beta-1 - ↑ Cardiac contractility & heart rate, ↑ Renin release by JG cells of kidney
↑ cAMP - beta-2 - Peripheral vasodilation, Bronchodilation, inc INSULIN RELEASE
↓ cAMP - M2 - ↓ Cardiac contractility & heart rate
↑ IP3 - M3 - Bronchoconstriction, ↑ INSULIN RELEASE & INTESTINAL MOTILITY, Bladder contraction, Pupillary constriction, Peripheral
vasodilation* (*Via release of nitric oxide).
↑ IP3 - alpha-1, M3
↑ cAMP - beta-1, beta-2
↓ cAMP - alpha-2, M2
M3 - inc INSULIN RELEASE & INTESTINAL MOTILITY
a2 - dec INSULIN RELEASE & INTESTINAL MOTILITY
B2 - inc INSULIN RELEASE
M3 and B2 - inc insulin release.
M3 and B2 - inc insulin release and vasodialtion.
Physostigmine - crosses BBB (tertiary amine)
Neostigmine and pyridostigmine - dont cross BBB (quarternary amine)
Pyridostigmine - Used with glycopyrrolate, hyoscyamine, or propantheline to control pyridostigmine side effects.
Pilocarpine can cross BBB (tertiary amine).
Muscarinic effects - relieved by atropine
Nicotinic effects - relieved by pralidoxime
Atropine - Blocks muscarinic effects (DUMBBELSS) of anticholinesterases, but not the nicotinic effects.
Pilocarpine - Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma); resistant to AChE, can cross
bloodbrain barrier (tertiary amine). Rx Potent stimulator of sweat, tears, and saliva. Open-angle and closed-angle glaucoma, xerostomia (Sjögren
syndrome).
Jimson weed (Datura) (anticholinergic) > gardener’s pupil (mydriasis due to plant alkaloids).
Mirtazapine - Rx Depression. SE - Sedation, inc serum cholesterol, inc appetite.
Metoprolol SE - dyslipidemia.
All 3 inc CO and HR.
Dopamine/epinephrine - inc BP (high dose)
Dobutamine - no effect or dec
Fenoldopam - dec BP

isoproterenol (rarely used) has little a effect but causes B2-mediated vasodilation, resulting in dec mean arterial pressure and inc heart rate through B1
and reflex activity. Pindolol and acebutolol - partial agonist
Nonselective a- and B-antagonists—carvedilol, labetalol.
Nebivolol combines cardiac-selective B1-adrenergic blockade with stimulation of B3-receptors (activate NO synthase in the vasculature and dec SVR).

PDE-3 inhibitor - Milrinone - In cardiomyocytes: inc cAMP > inc Ca2+ influx > inc ionotropy and chronotropy. In vascular smooth muscle: inc cAMP
> MLCK inhibition > vasodilation > dec preload and afterload.
PDE-4 inhibitor - Rofumilast - inc cAMP in neutrophils, granulocytes, and bronchial epithelium. Rx Severe COPD.
Sildenafl only: cyanopia (blue-tinted vision) via inhibition of PDE-6 (six) in retina.

Age-related changes in pharmacokinetics - It’s how aging bodies are MADE.

Metabolism - dec hepatic mass, dec hepatic blood flow and dec drug metabolism. Phase I metabolism lost first with aging. Drugs metabolized during
phase II (eg, lorazepam, acetaminophen) are safer than drugs metabolized during phase I (eg, diazepam). Thus therapeutic doses may suffce in elderly.
Absorption - inc gastric pH, dec gastric emptying. Drug absorption influenced via drug-drug/food interactions.
Distribution - inc body fat content (inc Vd for lipophilic drugs, eg, propofol). Dec albumin (dec binding of acidic drugs). Dec total body water (dec Vd
for hydrophilic drugs, eg, digoxin). Elimination - dec GFR and dec tubular secretion. Inc plasma concentration of renally excreted drugs; thus dec
therapeutic doses may suffice in elderly.
Beers criteria - Examples:
a-blockers (inc risk of hypotension)
Anticholinergics, antidepressants, antihistamines, opioids (inc risk of delirium, sedation, falls, constipation, urinary retention) Benzodiazepines (inc
risk of delirium, sedation, falls)
NSAIDs (inc risk of GI bleeding, especially with concomitant anticoagulation)
PPIs (inc risk of C diffcile infection)
Arsenic (DS) - Dimercaprol, succimer
Mercury (DS) - Dimercaprol, succimer
Copper - “Penny”cillamine (penicillamine), trientine (3 copper pennies)
Lead (PEDS) - Calcium disodium EDTA, dimercaprol, succimer, penicillamine
Physostigmine - crosses BBB (tertiary amine)
Neostigmine and pyridostigmine - dont cross BBB (quarternary amine)
Weak acids - Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to
alkalinize urine.
Weak bases - Examples: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride to acidify urine.
TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channel blocking activity of TCAs, but not for accelerating drug
elimination.
TCA toxicity Rx ammonium chloride and sodium bicarbonate.
Imipenem-cilastatin
Cisplatin-amifostine
Cyclophosphamide-mesna
Meperidine is an opioid but causes mydriasis.
Muscarinic antagonists - Benztropine, trihexyphenidyl - CNS - Parkinson disease (“park my Benz”). Acute dystonia.
(different from tetrabenazine)
Metabolic-
-glifozin SGLT-2 inhibitor Dapaglifozin
-glinide Meglitinide Repaglinide
-gliptin DPP-4 inhibitor Sitagliptin
-glitazone PPAR-γ activator Rosiglitazone
-glutide GLP-1 analog Liraglutide
-ximab Chimeric human-mouse monoclonal antibody Rituximab
-zumab Humanized monoclonal antibody Bevacizumab
-umab Human monoclonal antibody Denosumab
-leukin Interleukin-2 agonist/analog Aldesleukin
-kinra Interleukin receptor antagonist Anakinra
Inducers - SGPC-CMRN-P
Substrates - The OCPs are anti-war
Inhibitors - [Link]-RAG
Ecological study - Measures population data not necessarily applicable to individuals (ecological fallacy).
Intention-to-treat analysis: All patients are analyzed. Attempts to avoid misleading bias from patients dropping out.
Per protocol analysis: Only patients who complete the study “per protocol” are included. Risk of bias from non-random noncompliance.
For rare diseases (low prevalence), OR approximates RR.
Precision - The absence of random variation in a test.
Accuracy - The absence of systematic error or bias in a test.
Sensitivity and specifcity are fxed properties of a test. PPV and NPV vary depending on disease prevalence in population being tested.
LR+ > 10 indicates a highly specifc test (LR+ = sensitivity / 1 – specificity).
LR– < 0.1 indicates a highly sensitive test (LR- = 1-sensitivity / specificity).
SN-N-OUT = highly SeNsitive test, when Negative, rules OUT disease.
SP-P-IN = highly SPecifc test, when Positive, rules IN disease.
Inc prevalence > inc PPV and dec NPV.
Berkson bias (bedside bias)—cases and/or controls selected from hospitals (bedside bias) are less healthy and have different exposures.
Attrition bias (attri is a lost personality) —participants lost to follow up have a different prognosis than those who complete the study.
Hawthorne effect—participants change behavior upon awareness of being observed.
Pygmalion effect (aalam is a pig and researcher) - Researcher’s belief in the efficacy of a treatment changes the outcome of that treatment.
(Pygmalion effect = Observer-expectancy bias)
Confounding bias - Factor related to both exposure and outcome (but not on causal path) distorts effect of exposure on outcome
(vs effect modification - in which the exposure leads to different outcomes in subgroups stratifed by the factor).
Procedure bias - Subjects in different groups are not treated the same.
Selection bias - Randomization (creates groups with similar distributions of known and unknown variables). Ensure the choice of the right
comparison/reference group.
Recall bias - Decrease time from exposure to follow-up
Measurement bias - Use objective, standardized, and previously tested methods of data collection that are planned ahead of time. Use placebo group.
Procedure bias - Blinding (masking) and use of placebo reduce infuence of participants and researchers on procedures and interpretation of outcomes as
neither are aware of group assignments. Observer-expectancy bias - Blinding (masking) and use of placebo reduce infuence of participants and
researchers on procedures and interpretation of outcomes as neither are aware of group assignments.
Confounding bias - Multiple/repeated studies Crossover studies (subjects act as their own controls) Matching (patients with similar characteristics in
both treatment and control groups) Lead-time bias - Measure “back-end” survival (adjust survival according to the severity of disease at the time of
diagnosis)
Length-time bias - A randomized controlled trial assigning subjects to the screening program or to no screening.

If p < a, then assuming H0 is true, the probability of obtaining the test results would be less than the probability of making a type I error. H0 is
therefore rejected as false. Power = (1 – β)
CI= 1 – α
Mata-analysis - Limited by quality of individual studies and bias in study selection.

Capacity is determined by a physician. Competency is determined by a judge. (mental capacity/legal competency) capacity - MASSIVE

Exceptions to informed consent - (WIPE it away)

Do not resuscitate order - DNR order prohibits cardiopulmonary resuscitation (CPR). Patient may still consider other lifesustaining measures (eg,
intubation, feeding tube, chemotherapy). Capacity - MASSIVE
Exceptions to informed consent - WIPE it away
Exceptions to patient confdentiality - SAVED

Situations in which parental consent is usually not required: Sex (contraception, STIs, prenatal care— usually not abortion), Drugs (substance use
disorder treatment), Rock and roll (emergency/trauma)
Goals - Specific, Measurable, Achievable, Relevant, and Time bound (SMART).
Patient-centered interviewing techniques (VR-FAIR / IAR-VRF)

Introduction Agenda Reflection Validation Recapitulation Facilitation Expressing empathy PEARLS

Partnership Empathy Apology Respect Legitimization Support Delivering bad news SPIKES

Setting Perception Invitation Knowledge Emotions Strategy

Exceptions to patient confdentiality - SAVED
Goals - Specific, Measurable, Achievable, Relevant, and Time bound (SMART).

For in-person spoken language interpretation, the interpreter should ideally be next to or slightly behind the patient. For sign language interpretation,
the interpreter should be next to or slightly behind the physician.
Limited panel & cheaper - EPO and HMO
Outside network & expensive - POS and PPO

No referral reqd - EPO and PPO

Referral reqd - POS and HMO
(Start with P - outside network and expensive)
(PO-provider organisation - no referral required)
(when u pee outside u get fined and its expensive)
Bundled payment - (like medicity hospital)
Accountable care organization-
Providers voluntarily enroll
Medicare Specialists voluntarily enroll
Medicaid is like ayushmann bharat
This prioritization of positive effects over negative effects is called the principle of double effect. Human factors design-
Forcing functions - those that prevent undesirable actions
Standardization improves process reliability
Simplification reduces wasteful activities

Abductors Gluteus medius, gluteus minimus

Adductors Adductor magnus, adductor longus, adductor brevis
Extensors (SSG) Gluteus maximus, semitendinosus, semimembranosus
Flexors (TRIPS) Iliopsoas, rectus femoris, tensor fascia lata, pectineus, sartorius
Internal rotation (GGT) Gluteus medius, gluteus minimus, tensor fascia latae
External rotation (GOPI) Iliopsoas, gluteus maximus, piriformis, obturator
Osgood-schlatter ds - avulsion of secondary ossification centre of proximal tibial tubercle.
Legg-calve-perthes ds - Idiopathic avascular necrosis of femoral head.
SCFE - Displaced epiphysis relative to femur neck due to axial force on femoral head.
Developmental dysplasia of the hip - Abnormal acetabulum; ortolani and barlow maneuver.
Nursemaid’s elbow - radial head subluxation.
Medial tibial stress syndrome - shin splints.
Iliotibial band syndrome - lateral femoral epicondyle.
De Quervain tenosynovitis - AbPL and EPB tendons; + Finkelstein test - tender radial styloid with stretch of thumb tendons.
IECN
epidermis - impetigo
upper dermis - erysipelas
deeper dermis - cellulitis
deeper tissue - necrotizing fascitis
Recurrent branch of median nerve is purely motor. No loss of sensation with injury of Recurrent branch of median nerve. Recurrent branch of median
nerve is different from palmar cutaneous branch. lunate - median N injury
hamate - ulnar N injury
Ulnar nerve - ulnar claw; loss of ulnar flexors, ulnar lumbricals, interossei & thumb adductor; loss of sensation.
Median nerve - ape hand and hand of benediction; loss of wrist flexion and function of LOAF; loss of sensation.
Recurrent branch of median nerve - ape hand; loss of thenar muscles; no loss of sensation. Recurrent branch of median nerve is purely motor.
Interossei - finger adduction and abduction.
Lumbricals - flexion of MCP joint, extension of interphalangeal joint.
Thenar muscles (OAF) - opposition, abduction and flexion of thumb.
ULNAR nerve - Medial epicondyle of humerus “funny bone” (proximal lesion). Fractured hook of hamate (distal lesion).
Recurrent branch of median nerve is different from palmar cutaneous branch.
lunate - median N injury
hamate - ulnar N injury
Erb palsy (“waiter’s tip”) - upper trunk
Klumpke palsy (claw hand / total claw hand) - lower trunk
Wrist drop - posterior cord, radial nerve
Winged scapula - SALT
Deltoid paralysis - axillary nerve
“Saturday night palsy” (wrist drop) - radial nerve, posterior cord
Difficulty flexing elbow, variable C8 sensory loss - musculocutaneous N
Decreased thumb function “hand of benediction” - median nerve
Intrinsic muscles of hand, claw hand (ulnar claw) - ulnar nerve
Thoracic outlet syndrome - Compression of lower trunk and subclavian vessels, most commonly within the scalene triangle.
Carpal tunnel contents-
FDP tendon
FDS tendon
FPL tendon
Median nerve
Complications of proximal scaphoid fractures include avascular necrosis and nonunion due to retrograde blood supply from a branch of the radial
artery.

For both ulnar and median nerve - loss of flexors with proximal lesion; loss of extensors with distal lesion. (ED-PF)

(check distal lesion with extension. check proximal lesion with flexion.) distal median - claw
distal ulnar - claw

proximal median - hand of benediction

proximal ulnar - ok gesture/ape hand
(check distal lesion with extension.
check proximal lesion with flexion.)
Clawing more pronounced with distal lesions, less with proximal lesions Anterior drawer/Lachman - ACL

Posterior drawer - PCL

AP abduction (valgus stress test) - MCL
AP adduction (varus stress test) - LCL
McMurray test (LIME) - menisci
Surgical neck of humerus -
Axillary NERVE.
Posterior circumflex ARTERY.
Surgical neck of humerus - POSTERIOR circumflex artery.
Femoral head - MEDIAL circumfex femoral artery.
Iliohypogastric (T12-L1) - IT
Genitofemoral nerve (L1-L2) - cremaster
Lateral femoral cutaneous (L2-L3)
Obturator (L2-L4) - AAA-GOP
Femoral (L2-L4) - SQIP
Sciatic (L4-S3) - BASS
Common (fibular) peroneal (L4-S2) - PPT
(superficial peroneal - PP; deep peroneal - T)
Tibial (L4-S3) - TB-PPF
Superior gluteal (L4-S1) - GGT
Inferior gluteal (L5-S2) - G maximus
Pudendal (S2-S4) - ext sphincters of urethra and anus
Anterior talofibular ligament—most common ankle sprain overall, classifed as a low ankle sprain.
Anterior inferior tibiofbular ligament—most common high ankle sprain.
Common peroneal injury - Foot drop—inverted and plantarfexed at rest, loss of eversion and dorsifexion; “steppage gait”.
Superior gluteal (L4-S1) - Motor—gluteus medius, gluteus minimus, tensor fascia latae. Iatrogenic injury during intramuscular injection to
superomedial gluteal region (prevent by choosing superolateral quadrant, preferably anterolateral region). Trendelenburg sign/gait— pelvis tilts
because weightbearing leg cannot maintain alignment of pelvis through hip abduction. Lesion is contralateral to the side of the hip that drops,
ipsilateral to extremity on which the patient stands.
Pudendal (S2-S4) Sensory—perineum. Motor—external urethral and anal sphincters. Stretch injury during childbirth, prolonged cycling, horseback
riding. Dec sensation in perineum and genital area; can cause fecal and/or urinary incontinence. Can be blocked with local anesthetic during childbirth
using ischial spine as a landmark for injection.
Surgical neck of humerus - POSTERIOR circumflex artery.
Femoral head - MEDIAL circumfex femoral artery.
Pi is released to initiate the power stroke.
ADP is released at the end of power stroke.
Binding of new ATP detaches myosin from actin.
ATP hydrolysis converts myosin to high energy position (cocked), ready to bind actin if Ca2+ is available.
HIZ shortens. A band remains the same.
DHPR and ryanodine receptor are mechanically coupled.
Ca2+ reuptake by SERCA —> muscle relaxation
Contraction initiation in cardiac and SMCs is dependent on extracellular Ca influx through L-type Ca channels, which can be prevented by CCBs (eg,
verapamil). Skeletal muscle is resistant to CCBs, as Ca release by the SR is triggered by a mechanical interaction b/w L-type and RyR Ca channels.
There is no influx of Ca in skeletal muscles.
Pi is released to initiate the power stroke.
ADP is released at the end of power stroke.
Type 1 muscles - red
Type 2 muscles - white
OPG (osteoprotegerin, a RANKL decoy receptor) binds RANKL to prevent RANK-RANKL interaction > dec osteoclast activity
Carpal tunnel syndrome - Suggested by ⊕ Tinel sign (percussion of wrist causes tingling) and Phalen maneuver (90° flexion of wrist causes tingling).
Muscle stretch receptors - Body of muscle/type Ia and II sensory axons.
Golgi tendon organ - Tendons/type Ib sensory axons.
Muscle stretch receptors-
PATHWAY inc stretch > via dorsal root ganglion (DRG) > activation of inhibitory interneuron and α motor neuron > simultaneous inhibition of
antagonist muscle (prevents overstretching) and activation of agonist muscle (contraction). LOCATION/INNERVATION Body of muscle/type Ia and II
sensory axons. ACTIVATION BY inc muscle stretch. Responsible for deep tendon refexes.
Golgi tendon organ-
PATHWAY Inc tension > via DRG > activation of inhibitory interneuron > inhibition of agonist muscle (reduced tension within muscle and tendon).
LOCATION/INNERVATION Tendons/type Ib sensory axons. ACTIVATION BY Inc muscle tension.
Endochondral ossifcation - Cartilaginous model of bone is frst made by chondrocytes. Osteoclasts and osteoblasts later replace with woven bone and
then remodel to lamellar bone.
Membranous ossifcation - Woven bone formed directly without cartilage. Later remodeled to lamellar bone.
Osteoblastic activity measured by bone ALP, osteocalcin, propeptides of type I procollagen.
Estrogen - Inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing osteoclasts.
Recurrent branch of median nerve is purely motor. No loss of sensation with injury of Recurrent branch of median nerve. Recurrent branch of median
nerve is different from palmar cutaneous branch. Carpal tunnel syndrome - Suggested by ⊕ Tinel sign (percussion of wrist causes tingling) and Phalen
maneuver (90° flexion of wrist causes tingling).
Unhappy triad (MMA) - Consists of damage to the ACL, MCL, and medial meniscus (attached to MCL).
De Quervain tenosynovitis - AbPL and EPB tendons; + Finkelstein test - tender radial styloid with stretch of thumb tendons.
ToRuS (buckle) fracture - tension(convex) side remains solid(intact), compression(concave) side buckles/fractures.
Greenstick fracture - tension(convex) side fractures, compression(concave) side intact.
Avascular necrosis of bone - Most common site is femoral head (watershed zone) - due to insuffciency of medial circumfex femoral artery.
Osteoporosis - Diagnosed by bone mineral density measurement by DEXA (dual-energy X-ray absorptiometry) at the lumbar spine, total hip, and
femoral neck, with a T-score of ≤ 2.5 or by a fragility fracture (eg, fall from standing height, minimal trauma) at hip or vertebra.
Surgical neck of humerus - POSTERIOR circumflex artery.
Femoral head - MEDIAL circumfex femoral artery.

Osteomalacia/rickets - Defective mineralization of OSTEOID (osteomalacia) or CARTILAGINOUS GROWTH PLATES (rickets, only in children).
Avascular necrosis of bone - Most common site is femoral head (watershed zone) - due to insuffciency of medial circumfex femoral artery. Femoral
head - Medial circumfex femoral artery.
Epiphysis - giant cell tumor.

Metaphysis - osteosarcoma, osteochondroma, simple bone cyst.

Diaphysis - ewings, myeloma, osteoid osteoma, fibrous dysplasia.
Osteoid osteoma - Presents as bone pain (worse at night) that is relieved by NSAIDs. Bony mass (< 2 cm) with radiolucent osteoid core.
Osteoblastoma - Larger size (> 2 cm), pain unresponsive to NSAIDs.
Ewing sarcoma - t(11;22) (fusion protein EWS-FLI1). “Onion skin” periosteal reaction in bone.
Giant cell tumor - “Osteoclastoma” “Soap bubble” appearance on x-ray.
OA - 1st CMC, DIP, PIP; not MCP
RA - MCP, PIP, wrist; not DIP or 1st CMC.
POLYMYOSITIS - characterized by endomysial inflammation with CD8+ T cells.
DERMATOMYOSITIS - Perimysial inflammation and atrophy with CD4+ T cells.
Polymyalgia rheumatica - normal CK
Polymyositis/dermatomyositis - inc CK
Reactive arthritis (YES-SCC) - Classic triad: Conjunctivitis Urethritis Arthritis. Associated with infections by Shigella, Campylobacter, E coli,
Salmonella, Chlamydia, Yersinia.
Myasthenia gravis - Spared reflexes; Worsens with muscle use.
Lambert-eaton - Hyporeflexia; Improves with muscle use
parakeratosis (retention of nuclei) - psoriasis, actinic keratosis
hypergranulosis - lichen planus
psoriasis - hyperkeratosis(inc stratum corneum) , parakeratosis(retention of nuclei) , acanthosis(inc spinosum)
Spongiosis - eczema
Hyperkeratosis inc thickness of stratum corneum Psoriasis, calluses
Hypergranulosis inc thickness of stratum granulosum Lichen planus
Acanthosis Epidermal hyperplasia (inc spinosum) Acanthosis nigricans, psoriasis
Intradermal nevi are papular.
Junctional nevi are flat macules.
Kaposi sarcoma - lymphocytic infiltrate
Bacillary angiomatosis - neutrophilic infiltrate
Psoriasis - Acanthosis with parakeratotic scaling (nuclei still in stratum corneum), Munro microabscesses. Inc stratum spinosum, stratum granulosum.
Staphylococcal scalded skin syndrome - Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which
destroys epidermal-dermal junction). SSSS - Stratum granulosum only
Nikolsky sign ⊕ Pemphigus vulgaris and SJS
Nikolsky sign ⊖ Bullous pemphigoid
UVB is dominant in sunBurn, UVA in tAnning and photoAging.
Venous ulcer - Irregular border, shallow, exudative
Arterial ulcer - Symmetric with well-defned punched out appearance
Neuropathic ulcer - Hyperkeratotic edge with undermined borders
Neuropatic ulcer - ASSOCIATED SIGNS Claw toes, Charcot joints, absent refexes.
Pityriasis rosea “Herald patch” followed days later by other scaly erythematous plaques, often in a “Christmas tree” distribution on trunk.
Tinea (pityriasis) versicolor - Caused by Malassezia spp. (Pityrosporum spp.), a yeast-like fungus (not a dermatophyte despite being called tinea)
Advanced melanoma Rx - immunotherapy (eg, ipilimumab (CTLA-4 inhibitor)) and/or BRAF inhibitors (eg, vemurafenib, encorafenib, dabrafenib).

4 different types of melanoma - superficial spreading, nodular, lentigo maligna, and acral lentiginous (darker skin tones). Aspirin -
Low dose (< 300 mg/day): dec platelet aggregation.
Intermediate dose (300–2400 mg/day): antipyretic and analgesic.

High dose (2400–4000 mg/day): anti- inflammatory.

TNF-a inhibitors can cause drug induced lupus.
Low-dose salicylates - inhibit tubular secretion of uric acid (can cause gout)

High-dose salicylates - inhibit tubular reabsorption of uric acid (can cause uric acid stones) Diuretics, low-dose salicylates - inhibit tubular secretion
Probenecid, high-dose salicylates - inhibit tubular reabsorption

Acanthocytes (“spur cells”) - (ALE) Liver disease, abetalipoproteinemia, vitamin E defciency. Echinocytes (“burr cells”) - (EPL) Liver disease, ESRD,
pyruvate kinase defciency. Dacrocytes (“teardrop cells”)
Degmacytes (“bite cells”)

Target cells (HALT) - HbC disease, Asplenia, Liver disease, Thalassemia. Howell-jolly bodies - Basophilic nuclear remnants (do not contain iron).
Heinz bodies - Denatured and precipitated hemoglobin (contain iron). Basophilic stippling - Basophilic ribosomal precipitates (do not contain iron).
Pappenheimer bodies - Basophilic granules (contain iron).

Iron granules - Sideroblastic anemias (eg, lead poisoning, myelodysplastic syndromes, chronic alcohol overuse). HEINZ - Hb ppts
BASOPHILIC STIPPLING - RIBOSOMAL PPTS
HOWELL-JOLLY - NUCLEAR REMNANTS

Contain iron - Heinz bodies, Pappenheimer bodies

Do not contain iron - Howell-jolly bodies, Basophilic stippling
Sideroblastic anemia - ringed sideroblasts (iron granules), basophilic stippling, pappenheimer bodies.
Iron granules - Require Prussian blue stain to be visualized.
Heinz bodies (Hb ppts) - Requires supravital stain (eg, crystal violet) to be visualized.
nonmegaloblastic macrocytic-
diamond-blackfan, liver ds, chronic alcohol
Nonmegaloblastic -
•Diamond-Blackfan anemia
•Liver disease
•Chronic alcohol overuse.
1 (α α/α –) - α-thalassemia minima.
2 (α –/α –; trans) or (α α/– –; cis) - α-thalassemia minor.
3 (– –/– α) - Hemoglobin H disease (HbH); excess β -globin forms β4.
4 (– –/– –) - Hemoglobin Barts disease; no α-globin, excess γ-globin forms γ4 - Hydrops fetalis; incompatible with life. Microcytic (MCV < 80 fL) -

Hemoglobin affected (TAIL) -

Defective globin chain: •Thalassemias
Defective heme synthesis: •Anemia of chronic disease •Iron deficiency (late) •Lead poisoning.

Normocytic (MCV 80–100 fL) -

Nonhemolytic (low reticulocyte index) -
•Iron deficiency (early) •Anemia of chronic disease •Aplastic anemia •Chronic kidney disease. Hemolytic (high reticulocyte index) -
Intrinsic -
Membrane defects •Hereditary spherocytosis •Paroxysmal nocturnal hemoglobinuria.
Enzyme deficiencies •G6PD deficiency •Pyruvate kinase deficiency.
Hemoglobinopathies •Sickle cell anemia •HbC disease.
Extrinsic -
•Autoimmune •Microangiopathic •Macroangiopathic •Infections.
Macrocytic (MCV > 100 fL) -
Megaloblastic - DNA affected-
Defective DNA synthesis •Folate deficiency •Vitamin B12 deficiency •Orotic aciduria.
Defective DNA repair •Fanconi anemia.
Nonmegaloblastic -
•Diamond-Blackfan anemia •Liver disease •Chronic alcohol overuse.
RPI = (reticulocyte % × actual Hct)/normal Hct (≈ 45%)
B-thalassemia - Point mutations in splice sites and promoter sequences on chromosome 11.
Sideroblastic anemia - ringed sideroblasts (iron granules), basophilic stippling, pappenheimer bodies.
Nonmegaloblastic macrocytic (CLD)-
•Diamond-Blackfan anemia
•Liver disease
•Chronic alcohol overuse.
B12 def - Historically diagnosed with the Schilling test, a test that determines if the cause is dietary insuffciency vs malabsorption.
Hereditary spherocytosis - Labs: dec mean fluorescence of RBCs in eosin 5-maleimide (EMA) binding test, inc fragility in osmotic fragility test.
Aplastic anemia - pacytopenia
Aplastic crisis - anemia only
Diamond-Blackfan anemia - A congenital form of pure red cell aplasia (vs Fanconi anemia, which causes pancytopenia). Due to intrinsic defect in a
progenitor cells. Inc % HbF (but dec total Hb). Short stature, craniofacial abnormalities, and upper extremity malformations (triphalangeal thumbs).
Fanconi anemia - defective homologous recombination DNA repair pathway.
Nonmegaloblastic - Diamond-Blackfan anemia
Aplastic anemia - Viral agents (eg, EBV, HIV, hepatitis viruses). Causative drugs (eg, benzene, chloramphenicol, alkylating agents, antimetabolites).

Aplastic crisis (pure RBC aplasia) - parvovirus B19.

Aplastic anemia - Causative drugs (eg, benzene, chloramphenicol, alkylating agents, antimetabolites).
Aplastic anemia - Carbamazepine, methimazole, NSAIDs, benzene, chloramphenicol, propylthiouracil. (Can’t make New blood cells properly)
PNH - Treatment: eculizumab (targets terminal complement protein C5).
Pyruvate kinase deficiency - Increases levels of 2,3-BPG > dec hemoglobin affnity for O2.
Corticosteroids cause neutrophilia, despite causing eosinopenia and lymphopenia.
AIP - Neuropsychiatric manifestations
Port-wine urine
PCT - Dermatologic manifestations
Tea-colored urine
Acute intermittent porphyria - Porphobilinogen deaminase, previously called uroporphyrinogen I synthase (PBG AIP-le khaalo)
Porphyria cutanea tarda - Uroporphyrinogen decarboxylase (PCT-uro)
AIP - Neuropsychiatric manifestations, Port-wine urine.
PCT - Dermatologic manifestations, Tea-colored urine.
(Ristocetin failure seen in both vWd and bernard-soulier syndrome).
(normally ristocetin functions to activate vWf)
Hemophilia B: defciency of factor IX (christmas factor) - Rx emicizumab
Emici sounds like mistletoe and factor 9 is christmas factor.
TTP - Inhibition or defciency of ADAMTS13 (a vWF metalloprotease) > dec degradation of vWF multimers > inc large vWF multimers > inc platelet
adhesion and aggregation (microthrombi formation). (Ristocetin failure seen in both vWd and bernard-soulier syndrome).
(normally ristocetin functions to activate vWf)
Antithrombin defciency - Has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following standard heparin dosing.
Protein C or S defciency - dec ability to inactivate factors Va and VIIIa. Inc risk of warfarin-induced skin necrosis.
FFP contains all coagulation factors and plasma proteins;
PCC (prothrombin complex concentrate) generally contains factors II, VII, IX, and X, as well as protein C and S.
Cryoprecipitate - Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin.
FFP - all factors and plasma proteins
PCC - 2, 7, 9, 10, c and s
Cryoprecipitate - fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
MM > 10%
Waldenstrom >10%
MGUS <10%
MDS <20%
AML >20%
Mycosis fungoides - cutaneous T-cell lymphoma characterized by atypical CD4+ cells with “cerebriform” nuclei and intraepidermal neoplastic cell
aggregates (Pautrier microabscess).
Richter transformation—CLL/SLL transformation into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).
Pseudo-Pelger-Huët anomaly—neutrophils with bilobed (“duet”) nuclei. Associated with myelodysplastic syndromes or drugs (eg,
immunosuppressants).
ALL - TdT+ (marker of pre-T and pre-B cells), CD10+ (marker of pre-B cells).
CLL - CD20+, CD23+, CD5+ B-cell neoplasm.
Leukemoid reaction - LAP score inc
CML - LAP score dec
Hemophagocytic lymphohistiocytosis - Systemic overactivation of macrophages and cytotoxic T cells > fever, pancytopenia, hepatosplenomegaly, inc
inc serum ferritin levels. Bone marrow biopsy shows macrophages phagocytosing marrow elements.
Alemtuzumab - CD52 (Aalam house no 52)
Bevacizumab - VEGF (inhibits blood vessel formation)

Cetuximab, panitumumab - EGFR (ram setu in pani to bring back eGFr) Rituximab - CD20 (Ritu house no 20)
Trastuzumab - HER2 (“trust HER”)
(PNC) (Pembrolizumab, nivolumab, cemiplimab - PD-1)

(ADA Laila) (Atezolizumab, durvalumab, avelumab - PD-L1) (Ipilimumab - CTLA-4) (ipill kha aur cut le)
Alectinib - ALK (sounds similar)
(EGF) Erlotinib, Gefitinib, aFatinib - EGFR

(DIN) Imatinib, dasatinib, nilotinib - BCR-ABL (nice din in philadelphia) Ruxolitinib - JAK1/2 (Ruxar and jack got married)
Bortezomib, ixazomib, carfilzomib - Proteasome
(DEV) Vemurafenib, encorafenib, dabrafenib - BRAF (dev removes bra) MEK inhibitors (eg, trametinib) (trams make in india)

Palbociclib - Cyclin-dependent kinase 4/6

Olaparib - Poly(ADP-ribose) polymerase (dec DNA repair)
Langerhans cell histiocytosis - Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (“tennis rackets” or rod shaped on EM) are
characteristic. 5-FU SE - palmar-plantar erythrodysesthesia (hand-foot syndrome).
(PNC - Pembrolizumab, nivolumab, cemiplimab - PD-1).
(ADA Laila - Atezolizumab, durvalumab, avelumab - PD-L1).
(Ipilimumab - CTLA-4).
Anthracyclines (Doxorubicin, daunorubicin) - Dilated cardiomyopathy (often irreversible).
Trastuzumab - Dilated cardiomyopathy (often reversible).

Ticlopidine SE - Neutropenia
DEV (BRAF) + trametinib (MEK inh) - Rx Melanoma
Bleomycin: DNA strand breakage via free radicals. (bleo blows up the DNA)
Busulfan - Cross-links DNA. (bus crosses links)
Paclitaxel - microtubule ko pakad ke rakhta hai
Taxanes - Docetaxel, paclitaxel - Hyperstabilize polymerized microtubules
Anthracyclines (Doxorubicin, daunorubicin) - Dilated cardiomyopathy (often irreversible).
Trastuzumab - Dilated cardiomyopathy (often reversible).
cladribine, pentostatin - purine analogs
cytarabine - pyrimidine analogs
Antimetabolites (5-MTP-HCC) - Cladribine(Cell cycle nonspecific) Cytarabine 5-fluorouracil Hydroxyurea Methotrexate Pentostatin Thiopurines - S
phase
Cell cycle–independent drugs - (NP-NP-ABD) - Platinum compounds, Alkylating agents: Anthracyclines Busulfan Dactinomycin Nitrogen mustards
Nitrosoureas Procarbazine Topoisomerase inhibitors - S and G2 phase
Bleomycin - M and G2 phase
Antimetabolites (5-MTP-HCC) - S phase
Microtubule inhibitors - M phase
Cell cycle–independent drugs - (NP-NP-ABD)
Warfarin - crosses placenta, monitor PT/INR (extrinsic pathway)
Heparin - does not cross placenta, monitor PTT (intrinsic pathway)
RADIAL NERVE-
Injury above elbow - wrist drop;
Injury below elbow - no wrist drop.
Tricep function and posterior arm sensation spared in midshaft fracture.
Supraspinatus (suprascapular nerve) - abducts - 0-15 - “empty/full can” test.
Infraspinatus (suprascapular nerve) - ext rotates - pitching injury.
Teres minor (axillary nerve) - adducts and ext rotates.
Subscapularis (upper and lower subscapular nerves) - adducts and int rotates.
Thenar muscles (OAF) - opposition, abduction and flexion of thumb.

Erb palsy (“waiter’s tip”)- DIBs Iliohypogastric (T12-L1) - IT Genitofemoral nerve (L1-L2) - cremaster Lateral femoral cutaneous (L2-L3) Obturator
(L2-L4) - AAA-GOP

Femoral (L2-L4) - SQIP

Sciatic (L4-S3) - BASS
Common (fibular) peroneal (L4-S2) - PPT
(superficial peroneal - PP; deep peroneal - T)
Tibial (L4-S3) - TB-PPF
Superior gluteal (L4-S1) - GGT
Inferior gluteal (L5-S2) - G maximus
Pudendal (S2-S4) - ext sphincters of urethra and anus
Erb palsy (“waiter’s tip”) - upper trunk
Klumpke palsy (claw hand / total claw hand) - lower trunk
Wrist drop - posterior cord, radial nerve
Winged scapula - SALT
Deltoid paralysis - axillary nerve
“Saturday night palsy” (wrist drop) - radial nerve, posterior cord Difficulty flexing elbow, variable C8 sensory loss - musculocutaneous N Decreased
thumb function “hand of benediction” - median nerve Intrinsic muscles of hand, claw hand (ulnar claw) - ulnar nerve

For both ulnar and median nerve - loss of flexors with proximal lesion; loss of extensors with distal lesion. (ED-PF)

(check distal lesion with extension. check proximal lesion with flexion.)

Indirect - lateral to inferior epigastric vessels, both rings, covered by all 3 layers, processus vaginalis failure.
Direct - medial to inferior epigastric vessels, through inguinal (hesselbach) triangle, superficial ring only, covered by external spermatic fascia only, due
to acquired weakness of transversalis fascia.

inguinal - males MC
femoral - females MC
MC overall inguinal > femoral
Femoral triangle - adductor longus, sartorius and inguinal ligament; contains NAV.
Inguinal (hesselbach) triangle - inf epigastric vessels, inguinal ligament and rectus abdominis.
Sliding hiatal hernia—gastroesophageal junction is displaced upward as gastric cardia slides into hiatus; “hourglass stomach.” Most common type.
Associated with GERD.
Paraesophageal hiatal hernia— gastroesophageal junction is usually normal but gastric fundus protrudes into the thorax.
Glucose-dependent insulinotropic peptide K cells (duodenum, jejunum). Exocrine: Dec gastric H+ secretion. Also called gastric inhibitory peptide
(GIP).
Motilin - Produces migrating motor complexes (MMCs). Inc in fasting state. Erythromycin - motilin receptor agonist.
VIP - from Parasympathetic ganglia. Dec by adrenergic input. VIPoma - Watery Diarrhea, Hypokalemia, Achlorhydria (WDHA syndrome).
Cholestrol-7a-hydroxylase catalyzes RL step of bile acid synthesis.
Dec absorption of enteric bile salts at distal ileum (as in short bowel syndrome, Crohn disease) prevents normal fat absorption and may cause bile acid
diarrhea. Calcium, which normally binds oxalate, binds fat instead, so free oxalate is absorbed by gut > inc frequency of calcium oxalate kidney stones.
Major pathway - vagus > GRP > gastrin > ECL cells > histamine > parietal cells > acid.
pancreas-
low flow - high chloride
high flow - high bicarbonate
Glucose and galactose are taken up by SGLT1 (Na+ dependent). Fructose is taken up via facilitated diffusion by GLUT5. All are transported to blood
by GLUT2. d-xylose test: abnormal with mucosal damage, normal in pancreatic insufficiency.
Enterokinase/enteropeptidase converts trypsinogen to trypsin.
Peyer patches - Unencapsulated lymphoid tissue found in lamina propria and submucosa of ileum. Contain specialized M cells.
Thymus and lymph nodes are encapsulated.
iron - duodenum
folate - jejunum
B12 - ileum
Hepcidin inhibts ferroportin-1 on basolateral surface of enterocyte.
Dec iron absorption (by degrading ferroportin) and dec iron release (from macrophages).
Cholestrol-7a-hydroxylase catalyzes RL step of bile acid synthesis.
Direct bilirubin > urobilinogen in gut > 80% stercobilin in feces , 20% absorbed (out of 20% > 90% enterohepatic circulation + 10% urobilin in urine).
Single stone more common in submandibular gland (Wharton duct).
Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor. Composed of chondromyxoid stroma and epithelium and recurs if
incompletely excised or ruptured intraoperatively. May undergo malignant transformation.
Mucoepidermoid carcinoma—most common malignant tumor, has mucinous and squamous components.
Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal centers. Associated with tobacco smoking. Bilateral in
10%; multifocal in 10%.
Chagas disease - Presents with progressive dysphagia to solids and liquids (vs obstruction—primarily solids), Inc risk of esophageal cancer.
Eosinophilic esophagitis - Esophageal rings and linear furrows
Esophagitis - (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers).
Pill-induced esophagitis (eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).
Scleroderma esophageal involvement - Esophageal smooth muscle atrophy
Barrett esophagus - replacement of nonkeratinized stratifed squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells).
Esophageal cancer - Aggressive course due to lack of serosa in esophageal wall.
Achalasia - esophageal squamous cell carcinoma
Menetrier disease - WAVEE Weight loss, Anorexia, Vomiting, Epigastric pain, Edema (due to protein loss). Hyperplasia of gastric mucosa >
hypertrophied rugae. Excess mucus production with resultant protein loss and parietal cell atrophy with dec acid production. Precancerous.
Chronic gastritis - Chronic inflammation > atrophy (> hypochlorhydria > hypergastrinemia) and metaplasia.
Intestinal type - [Link], nitrosamines, smoking, achlorhydria, gastritis; lesser curvature; raised margin ulcer.
Diffuse type - E-cadherin mutation; linitis plastica; signet ring cells.
Blumer shelf— palpable mass on digital rectal exam suggesting metastasis to rectouterine pouch (pouch of Douglas).
Gastric ulcer - Biopsy margins to rule out malignancy.
Duodenal ulcer - not routinely biopsied.
Hemorrhage - Duodenal (posterior > anterior).
Perforation - Duodenal (anterior > posterior).
Ruptured gastric ulcer on the lesser curvature of stomach > bleeding from left gastric artery. An ulcer on the posterior wall of duodenum > bleeding
from gastroduodenal artery.
Celiac ds - HLA-DQ2, HLA-DQ8, d-xylose test abnormal (villous atrophy); assc. T-cell lymphoma, dermatitis herpetiformis; + Anti-tTG, Anti-
deamidated gliadin peptide, Anti-endomesial abs. Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis.
Primarily affects distal duodenum and/or proximal jejunum.
Gliadin (gluten protein found in wheat, barley, rye).
Lactose intolerance - Osmotic diarrhea with dec stool pH (colonic bacteria ferment lactose). Lactose hydrogen breath test: ⊕ for lactose malabsorption
if post-lactose breath hydrogen value rises > 20 ppm compared with baseline.
Pancreatic insufficiency - Causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12. Dec duodenal bicarbonate (and
pH) and fecal elastase. d-xylose test: normal. Whipple disease - Infection with Tropheryma whipplei (intracellular gram ⊕); PAS ⊕ foamy
macrophages in intestinal lamina propria, mesenteric nodes. Cardiac symptoms, Arthralgias, and Neurologic symptoms are common.
Upper GI bleeding—originates proximal to ligament of Treitz. Usually presents with hematemesis and/or melena.
Lower GI bleeding—originates distal to ligament of Treitz. Usually presents with hematochezia.
Hemorrhage - Duodenal (posterior > anterior).
Perforation - Duodenal (anterior > posterior).
Crohn - Th1 mediated (noncaseatinng granulomas).
UC - Th2 mediated.
Crohn disease - Th1 mediated, + for ASCA, calcium oxalate kidney stones, gall stones; azathioprine, steroids, antibiotics, biologics; non caseating
granulomas, Skip lesions, rectal sparing, transmural infammation > fistulas. Cobblestone mucosa, creeping fat, bowel wall thickening (“string sign” on
small bowel follow-through), linear ulcers, fissures.
UC - Th2 mediated; assc primary sclerosing cholangitis, MPO-ANCA/p-ANCA; bloody diarrhea; 5-ASA - mesalamine, 6-MP, infliximab; lead pipe
colon, crypt abscesses, ulcers, no granulomas. Continuous colonic lesions, always with rectal involvement. Mucosal and submucosal infammation only.
Microscopic colitis - Histology shows infammatory infltrate in lamina propria with thickened subepithelial collagen band or intraepithelial
lymphocytes.
Appendicitis - obstruction by fecalith (in adults) or lymphoid hyperplasia (in children). May elicit psoas, obturator, and Rovsing signs.
Zenker diverticulum - at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor.
Midgut volvulus - infants/children.
Sigmoid volvulus - elderly, coffee bean sign.
Hirschsprung ds - Associated with loss of function mutations in RET.
Zenker - false
Meckel - true
Colonic ischemia - Thumbprint sign on imaging due to mucosal edema/hemorrhage.
Angiodysplasia - Associated with end-stage renal disease, von Willebrand disease, aortic stenosis.
Necrotizing enterocolitis - pneumatosis intestinalis, pneumoperitoneum, portal venous gas.

Ascending colon CRC—exophytic mass, iron defciency anemia, weight loss.

Descending colon CRC—infiltrating mass, partial obstruction, colicky pain, hematochezia.
1. APC
2. K-RAS
3. Tumor suppressor gene(s) (TP53, DCC)
ALP - inc in bone ds
GGT - not inc in bone ds
Biliary atresia - Most common reason for pediatric liver transplantation.
Reye syndrome - Rare, often fatal childhood hepatic encephalopathy. Aspirin metabolites dec B-oxidation by reversible inhibition of mitochondrial
enzymes.
Rigler triad of gallstone ileus: radiographic fndings of pneumobilia, small bowel obstruction, gallstone (usually in iliac fossa).
Charcot triad of cholangitis includes jaundice, fever, RUQ pain.
Reynolds pentad of cholangitis is Charcot triad plus altered mental status and shock (hypotension).
Acute pancreatitis - Diagnosis by 2 of 3 criteria: acute epigastric pain often radiating to the back, inc serum amylase or lipase (more specific) to 3x
upper limit of normal, or characteristic imaging findings.
Rigler triad of gallstone ileus: radiographic fndings of pneumobilia, small bowel obstruction, gallstone (usually in iliac fossa).
Charcot triad of cholangitis includes jaundice, fever, RUQ pain.
Reynolds pentad of cholangitis is Charcot triad plus altered mental status and shock (hypotension).
Sulfasalazine - reversible oligospermia
B-PM
O-PMLM
S-BS
E-D
Neutrophils-
Specific granules - LAP, lactoferrin, collagenase, lysozyme.
Azurophilic granules (lysosomes) - proteinases, acid phosphatase, MPO, B-glucuronidase.
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.
Eosinophils - Produce histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and eosinophil-
derived neurotoxin.
Embryonic globins: ζ and ε.
Fetal hemoglobin (HbF) = α2γ2.
Adult hemoglobin (HbA1) = α2β2.

HbA2 = (α2δ2)
Platelats - Contain dense granules (Ca2+, ADP, Serotonin, Histamine; CASH) and α granules (vWF, fibrinogen, fibronectin, platelet factor 4). vWF
receptor: GpIb. Fibrinogen receptor: GpIIb/IIIa.
Left shift - inflammation, CML
Leukoerythroblastic reaction - suggests marrow infiltration - mets, myelofibrosis
Toxic granulation - dark blue coarse granules
Dohle bodies - light blue peripheral inclusions
Rh hemolytic disease - PRESENTATION Hydrops fetalis, jaundice shortly after birth, [Link] by administration of anti-D IgG to Rh ⊖
pregnant patients during third trimester and early postpartum period (if fetus Rh ⊕). Prevents maternal anti-D IgG production.
RBC - Membranes contain Cl− /HCO3 − antiporter, which allow RBCs to export HCO3 − and transport CO2 from the periphery to the lungs for
elimination.
Left shift— inc neutrophil precursors (eg, band cells, metamyelocytes) in peripheral blood. Reflects states of myeloid proliferation (eg, infammation,
CML).
Leukoerythroblastic reaction—left shift accompanied by immature RBCs. Suggests bone marrow infltration (eg, myelofibrosis, metastasis).
Monocytes - Kidney shaped nucleus; frosted glass cytoplasm.
Basophils - Mediate allergic reaction. Densely basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes
synthesized and released on demand.
Mast cells - histamine, heparin, tryptase, eosinophil chemotactic factor.
Mastocytosis - inc serum tryptase; c-KIT mutations.
Vancomycin, opioids, and radiocontrast dye can elicit IgE-independent mast cell degranulation.
Dendritic cells - Express MHC class II and Fc receptors on surface. Can present exogenous antigens on MHC class I (cross-presentation).
Plasma cell - “Clock-face” chromatin distribution and eccentric nucleus, abundant RER, and well-developed Golgi apparatus. Found in bone marrow
and normally do not circulate in peripheral blood. (Hb has negative charge)
Hemoglobin electrophoresis - On a gel, hemoglobin migrates from the negatively charged cathode to the positively charged anode.
Coombs reagent - anti human globulin.
Direct coombs - Only anti-IgG (COOMBS REAGENT) is added. Tests antibody coated RBCs.
Indirect coombs - Both anti-IgG and test RBCs are added. Tests antibodies in serum.
Direct coombs - AIHA diagnosis
Indirect coombs - pretransfusion testing.
Coombs reagent - anti-Ig antibody
NK cells - lytic granules (perforins and granzymes), CD56, CD16 (FcR).
CD28 (costimulatory signal) necessary for T-cell activation.
A: normal hemoglobin β chain (HbA, adult)
F: normal hemoglobin y chain (HbF, fetal)
S: sickle cell hemoglobin β chain (HbS)
C: hemoglobin C β chain (HbC)
Coombs reagent - anti human globulin.
Direct coombs - Only anti-IgG is added. Tests antibody coated RBCs.
Indirect coombs - Both anti-IgG and test RBCs are added. Tests antibodies in serum.
Direct coombs - AIHA diagnosis
Indirect coombs - pretransfusion testing.
Negatively charged cathode to the positively charged anode.
Cations are positively charged, anions are negatively charged.
Pro-aggregation factors: TXA2 (released by platelets), ↓ blood flow, ↑ platelet aggregation.
Anti-aggregation factors: PGI2 and NO (released by endothelial cells), ↑ blood flow, ↓ platelet aggregation.
Gp1b def - bernard-soulier
Gp2b/3a def - glanzmann thrombasthenia
vWF def - von Willebrand ds
Aspirin irreversibly inhibits cyclooxygenase, thereby inhibiting TXA2 synthesis.
PTCT (Clopidogrel, prasugrel, ticagrelor, ticlopidine) - blocks P2Y12(ADP) receptor thus inhibiting ADP-induced expression of GpIIb/IIIa.
TEA (Abciximab, eptifibatide, tirofiban) - inhibits Gp2b/3a directly.
Ristocetin - activates vWF to bind GpIb.
Ristocetin failure - von Williebrand ds and bernard-soulier synd.
Desmopressin - releases vWF and F8 from endothelium.
vWF carries/protects factor VIII.
Factor V Leiden mutation produces a factor V resistant to inhibition by activated protein C.
Antithrombin(AT3) - inhibts factors 2a, 7a, 9a, 10a, 11a, 12a

(principal targets 2a and 10a). Warfarin reversal-

delayed - vit K
immediate - FFP/PCC

Warfarin inhibits - epoxide reductase

F7 - shortest half life
F2 - longest half life
intrinsic pathway - contact activation
extrinsic pathway - tissue factor
PROTEIN C and S - cleaves and inhibits 5a and 8a. C1 esterase inhibtor - inhibits 12a, 11a and kallikrein. Heparin and LMWH inhibit both 10a and 2a.

F13 - fibrin stabilizng factor.

10a inhibition - fondaparinux, direct 10a inh (apixaban).
2a(thrombin) inhibition - direct thrombin inh (bivalirudin, argatroban, dabigatran). (BAD THROMBIN). tPA stimulation - THROMBOLYTICS:
alteplase, reteplase, streptokinase, tenecteplase.
tPA inhibition - ANTIFIBRINOLYTICS: aminocaproic acid, tranexamic acid.

Extinction - elimination of target behavior.

Isolation (of affect) Separating feelings from ideas and events. Describing murder in graphic detail with no emotional response. eg in policemen,
lawyers
Repression and regression are involuntary.
Suppression is voluntary.
Reinforcement = increase behaviour
Punishment = decrease behaviour
Positive - add stimulus
Negative - remove stimulus
The fIve stages of grief per the Kübler-Ross model are (BAD-AD) denial, anger, bargaining, depression, and acceptance (may occur in any order).
Persistent complex bereavement disorder is diagnosed if severe grief interferes with functioning for > 12 months.
Intellectualization - Using facts and logic to emotionally distance oneself from a stressful situation. A patient diagnosed with cancer discusses the
pathophysiology of the disease.
Rationalization - Asserting plausible explanations for events that actually occurred for other reasons, usually to avoid self-blame. An employee who
was recently fired claims that the job was not important anyway.
Isolation (of affect) - Separating feelings from ideas and events. Describing murder in graphic detail with no emotional response.
Repression Involuntarily withholding an idea or feeling from conscious awareness (vs suppression).
Suppression Intentionally withholding an idea or feeling from conscious awareness (vs repression).
Repression and regression are involuntary.
MATURE DEFENSES - SASH
Kubler-ross grief - BAD-AD
As with child abuse, suspected child neglect must be reported to local child protective services.
Infant deprivation effects-
Reactive attachment disorder - (infant withdrawn/unresponsive to comfort).
Disinhibited social engagement (child indiscriminately attaches to strangers).
As with child abuse, suspected child neglect must be reported to local child protective services.
ADHD - ≥ 6 months of limited attention span and/or poor impulse control. Treatment: stimulants (eg, methylphenidate) +/– behavioral therapy;
alternatives include atomoxetine and α2 -agonists (eg, clonidine, guanfacine).
Conduct disorder <18 yrs; After age 18, often reclassifed as antisocial personality disorder.
Disruptive mood dysregulation disorder (children) - Onset before age 10. Severe, recurrent temper outbursts out of proportion to situation. Child is
constantly angry and irritable between outbursts. Treatment: CBT, stimulants, antipsychotics.
Intermittent explosive disorder (adults) - Onset after age 6. Recurrent verbal or physical outbursts representing a failure to control aggressive impulses.
Outbursts are out of proportion to provocation and may lead to legal, fnancial, or social consequences. Episodes are not premeditated and last < 30
minutes. Treatment: psychotherapy, SSRIs.
Diagnostic criteria by symptom duration-
Narcolepsy > 3m
> 1m Selective mutism, Separation anxiety
ADHD, Specific learning, Oppositional defiant > 6m
Tic disorder, Disruptive mood dysregulation > 1y
< 1 m Acute stress
> 1m Panic, Posttraumatic stress disorder
Adjustment < 6m
Phobias, Generalized anxiety disorder > 6m
< 1 m Brief psychotic disorder
Delusional disorder > 1 m
Schizophreniform disorder 1-6 m
Schizophrenia > 6 m
Dysthymic disorder, Cyclothymic disorder > 2y
> 2w Major depressive disorder
> 1 w Manic sx of bipolar disorder
(DHD-ND)
1. Delusions
2. Hallucinations, often auditory
3. Disorganized speech
4. Disorganized or catatonic behavior
* 5. Negative symptoms
Cyclothymia - mild bipolar - Must last ≥ 2 years with symptoms present at least half of the time, with any remission lasting ≤ 2 months.
Dysthymia - mild MDD - ≥ 2 depressive symptoms lasting ≥ 2 years (≥ 1 year in children), with any remission lasting ≤ 2 months.
OCD - Ego-dystonic: behavior inconsistent with one’s beliefs and attitudes (vs obsessive-compulsive personality disorder, ego-syntonic).
Panic disorder - Diagnosis requires attack followed by ≥ 1 month of ≥ 1 of the following:
1. Persistent concern of additional attacks
2. Worrying about consequences of attack
3. Behavioral change related to attacks
Treatment: CBT, SSRIs, and venlafaxine are first line. Benzodiazepines occasionally used in acute setting.
Schizophrenia - Diagnosis requires ≥ 2 of the following active symptoms, including ≥ 1 from symptoms #1–3:
(DHD-ND)
1. Delusions
2. Hallucinations, often auditory

3. Disorganized speech
4. Disorganized or catatonic behavior
* 5. Negative symptoms
Symptom onset ≥ 6 months prior to diagnosis; requires ≥ 1 month of active symptoms over the past 6 months.
Brief psychotic disorder—≥ 1 positive symptom(s) lasting < 1 month, usually stress-related.
Schizophreniform disorder—≥ 2 symptoms lasting 1–6 months.
MDD with seasonal pattern - Major depressive episodes occurring only during a particular season (usually winter) in ≥ 2 consecutive years and in most
years across a lifetime. OCD - Treatment: CBT and SSRIs; clomipramine and venlafaxine are second line.
Acute stress disorder—lasts between 3 days and 1 month. Treatment: CBT.
Manic episode -
Diagnosis requires hospitalization or marked functional impairment
with ≥ 3 of the following (manics DIG FAST):
Distractibility
Impulsivity/Indiscretion—seeks pleasure without regard to consequences (hedonistic)
Grandiosity—inflated self-esteem
Flight of ideas—racing thoughts
Inc goal-directed Activity/psychomotor Agitation
Dec need for Sleep
Talkativeness or pressured speech
Diagnostic criteria by symptom duration-
Narcolepsy > 3m
> 1m Selective mutism, Separation anxiety
ADHD, Specific learning, Oppositional defiant > 6m
Tic disorder, Disruptive mood dysregulation > 1y
< 1 m Acute stress
> 1m Panic, Posttraumatic stress disorder
Adjustment < 6m
Phobias, Generalized anxiety disorder > 6m
< 1 m Brief psychotic disorder
Delusional disorder > 1 m
Schizophreniform disorder 1-6 m
Schizophrenia > 6 m
Dysthymic disorder, Cyclothymic disorder > 2y
> 2w Major depressive disorder
> 1 w Manic sx of bipolar disorder
MDD - Recurrent episodes lasting ≥ 2 weeks characterized by ≥ 5 of 9 diagnostic symptoms including depressed mood or anhedonia (or irritability in
children). SIG E CAPS:
Sleep disturbances
Dec Interest in pleasurable activities (anhedonia)
Guilt or feelings of worthlessness
Dec Energy
Dec Concentration
Appetite/weight changes
Psychomotor retardation or agitation
Suicidal ideation
Treatment: CBT and SSRIs are first line; alternatives include SNRIs, MIRTAZAPINE, BUPROPION, electroconvulsive therapy (ECT), ketamine.
Adjustment disorder - Occur within 3 months of an identifiable psychosocial stressor (eg, divorce, illness) lasting < 6 months once the stressor has
ended. Rx CBT.
MDD with peripartum onset - Meets MDD criteria with onset no later than 1 year after delivery.
PTSD - (HARD) - persistent Hyperarousal, Avoidance of associated stimuli, intrusive Re-experiencing of the event (eg, nightmares, flashbacks),
changes in cognition or mood (eg, fear, horror, Distress). Disturbance lasts > 1 month with significant distress or impaired functioning. Treatment:
CBT, SSRIs, and venlafaxine are first line. PRAZOSIN can reduce nightmares.
Cyclothymia - mild bipolar - Must last ≥ 2 years with symptoms present at least half of the time, with any remission lasting ≤ 2 months.
Dysthymia - mild MDD - ≥ 2 depressive symptoms lasting ≥ 2 years (≥ 1 year in children), with any remission lasting ≤ 2 months.
GAD - For most days of ≥ 6 months. Associated with ≥ 3 of the following for adults (≥ 1 for kids): restlessness, irritability, sleep disturbance, fatigue,
muscle tension, difficulty concentrating. Treatment: CBT, SSRIs, SNRIs are first line. Buspirone, TCAs, benzodiazepines are second line.
Phobia - ≥ 6 months; Treatment: CBT with exposure therapy.
Social anxiety disorder - Treatment: CBT, SSRIs, venlafaxine. For perforamance type use β-blockers or benzodiazepines as needed.
Agoraphobia - Treatment: CBT, SSRIs.
Bipolar 1 - mania +/- hypomania/depression.
Bipolar 2 - hypomania + depression (no mania).
Bipolar not time bound.
Treatment: mood stabilizers (eg, lithium, valproic acid, carbamazepine, lamotrigine), atypical antipsychotics.
OCD - ego-dystonic
OC personality disorder - ego-syntonic
Ego-dystonic: behavior inconsistent with one’s beliefs and attitudes
Ego-syntonic: behavior consistent with one’s own beliefs and attitudes
Factitious disorder imposed on another - Formerly called Munchausen syndrome by proxy - Form of child/elder abuse.
Somatic symptom disorder - Treatment: regular office visits with the same physician in combination with psychotherapy.
Conversion disorder - patient may be aware of but indifferent toward symptoms (“la belle indifférence”).
Malingering - specific 2° (external) gain.
Factitious disorder - (1° [internal] gain).
Refeeding syndrome—often occurs in signifcantly malnourished patients with sudden inc calorie intake > inc insulin > dec PO4 3 , dec K+ , dec Mg2+
> cardiac complications, rhabdomyolysis, seizures.
Illness anxiety disorder - Hypochondriasis
Anorexia nervosa - Treatment: nutritional rehabilitation, psychotherapy, olanzapine.
Bulimia nervosa - Treatment: psychotherapy, nutritional rehabilitation, antidepressants (eg, SSRIs). Bupropion is CONTRAINDICATED due to seizure
risk.
Binge-eating disorder - Most common eating disorder in adults. Treatment: psychotherapy (first line); SSRIs; lisdexamfetamine.
Pica - Treatment: psychotherapy and nutritional rehabilitation (first line); SSRIs (second line).
Narcolepsy - Due to dec orexin (hypocretin) production in lateral hypothalamus and dysregulated sleep-wake cycles. Treatment: good sleep hygiene
(scheduled naps, regular sleep schedule), daytime stimulants (eg, amphetamines, modafnil) and/or nighttime sodium oxybate (GHB).
REM sleep - Nightmares. Memory of nightmare present.
N3 - Night terrors, bed-wetting, sleep-walking. No memory of the arousal episode.
Acute dystonia - Typical antipsychotics, anticonvulsants (eg, carbamazepine), metoclopramide.
Rx - Benztropine or diphenhydramine.
Serotonin syndrome - Psychiatric drugs: MAOIs, SSRIs, SNRIs, TCAs, vilazodone, vortioxetine, buspirone. Nonpsychiatric drugs: tramadol,
ondansetron, triptans, linezolid, MDMA, dextromethorphan,

meperidine, St. John’s wort.

Serotonin syndrome Rx Cyproheptadine (5-HT2 receptor antagonist). Prevention: avoid simultaneous serotonergic drugs, and allow a washout period
between them.

Hypertensive crisis - Rx Phentolamine.

Neuroleptic malignant syndrome - Rx Dantrolene, dopaminergics (eg, bromocriptine, amantadine), benzodiazepines; discontinue causative agent.
Delirium tremens - Rx Longer-acting benzodiazepines.
Acute dystonia - Rx Benztropine or diphenhydramine.
Lithium toxicity - Rx Discontinue lithium, hydrate aggressively with isotonic sodium chloride, consider hemodialysis.
Tricyclic antidepressant toxicity - Rx Supportive treatment, monitor ECG, NaHCO3 (prevents arrhythmia), activated charcoal.
3-36 hrs - Tremors, insomnia, diaphoresis, agitation, GI upset
6-48 hrs - Withdrawal seizures
12-48 hrs - Alcoholic hallucinosis (usually visual)
48-96 hrs - Delirium tremens
PCP - miosis
LSD, MDMA - mydriasis
MDMA - hyponatremia
TCAs, SNRIs, bupropion - inh NE reuptake.
TCAs, SSRIs, SNRIs, trazodone - inh 5-HT reuptake.
Mirtazapine - inh α2 (autoreceptor) adrenergic receptor.
MDD - bupropion;
GAD - buspirone;
buprenorphine - opioid partial agonist
Bupropion - Bupropion - Inhibits NE and DA reuptake. Also used for smoking cessation. Toxicity: stimulant effects (tachycardia, insomnia), headache,
seizures in patients with bulimia and anorexia nervosa. Dec risk of sexual side effects and weight gain compared to other antidepressants.
Buspirone - Partial 5-HT1A receptor agonist. Rx Generalized anxiety disorder. Does not cause sedation, addiction, or tolerance. Begins to take effect
after 1–2 weeks. Does not interact with alcohol (vs barbiturates, benzodiazepines).
Buprenorphine - Sublingual form (partial opioid agonist) used to prevent relapse. Can precipitate withdrawal symptoms when combined with full
agonist.
High-potency vs Low-potency typical antipsychotics:
flu’s hal? > tri pi and get HIGH - haloperidol, trifluoperazine, pimozide, fluphenazine
CH-i-THI is a low-potency mode of - chlorpromazine, thioridazine
Extrapyramidal symptoms—ADAPT-
Hours to days:
Acute Dystonia (muscle spasm, stiffness, oculogyric crisis). Treatment: benztropine, diphenhydramine.
Days to months:
Akathisia (restlessness). Treatment: β-blockers, benztropine, benzodiazepines. Parkinsonism (bradykinesia). Treatment: benztropine, amantadine.
Months to years:
Tardive dyskinesia (chorea, especially orofacial). Treatment: benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine.
Bupropion - Inhibits NE and DA reuptake.
Mirtazapine - a2-antagonist (inc release of NE and 5-HT), potent 5-HT2 and 5-HT3 receptor antagonist, and H1 antagonist.
Trazodone - Primarily blocks 5-HT2, a1-adrenergic, and H1 receptors; also weakly inhibits 5-HT reuptake.
Varenicline - Nicotinic ACh receptor partial agonist.
Vilazodone - Inhibits 5-HT reuptake; 5-HT1A receptor partial agonist.
Vortioxetine - Inhibits 5-HT reuptake; 5-HT1A receptor agonist and 5-HT3 receptor antagonist.

Cremasteric refex = L1, L2

Patellar refex = L2-L4
Achilles refex = S1, S2
Anal wink refex = S3, S4
Biceps and brachioradialis refexes = C5, C6 Triceps refex = C6, C7, C8

(Ascending tracts synapse and then cross.)

(Descending tracts cross and then synapse.)
Fine touch - dorsal column
Crude touch - anterior spinothalamic tract
Medial longitudinal fasciculus - Internuclear ophthalmoplegia - (impaired adduction of ipsilateral eye; nystagmus of contralateral eye with abduction).
Multiple sclerosis.

INO = Ipsilateral adduction failure, Nystagmus Opposite. Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3 nucleus of adducting eye
via MLF. Alar plate - dorsal - TGF-B, BMP
Basal plate - ventral - SHH
lissencephaly - neuronal migration failure - smooth brain

ENDONEURIUM - GBS, individual nerve fiber.

PERINEURIUM - blood-nerve permeability barrier; surrounds fascicle of fibres.
EPINEURIUM - entire nerve (fascicle + vessels).
Preoptic nucleus - thermoregulation, sexual behaviour, releases GnRH.
MGN (auditory) - superior olive and inferior colliculus of tectum.
superior colliculus - conjugate gaze.
eyes - superior colliculus
ears - inferior colliculus
Frontal lobe - broca, frontal eye field, primary motor, premotor, prefrontal.
Parietal cortex - primary somatosensory, somatosensory association.
Temporal lobe - wernicke, primary auditory, limbic association.
Occipital lobe - primary visual cortex
man in a barrel syndrome - ACA-MCA watershed infarct
ACA-MCA watershed infarct—proximal upper and lower extremity weakness (“man- in-a-barrel syndrome”). PCA-MCA watershed infarct—higher-
order visual dysfunction.
S2, S3, S4 Sensation of penile and anal zones
4 CN nuclei are medial (III, IV, VI, XII).
“Factors of 12, except 1 and 2.”

Inducing hypocapnia via hyperventilation reduces the partial pressure of arterial carbon dioxide (PaCO2), which incites vasoconstriction in the cerebral
resistance arterioles. This constriction decrease cerebral blood flow, which reduces cerebral blood volume and, ultimately, decreases the patient’s ICP.
PO2 less than 50 mm Hg increases cerebral blood flow.
Rising PCO2 increases cerebral blood flow until 90 mmHg.

MAP plateaus cerebral blood flow between 70-160 mmHg. Below 70 it reduces cerebral blood flow and above 160 it increases cerebral blood flow
CUSHING REFLEX-
inc ICP -> dec CPP -> central autoregulation to inc BP (central HTN) -> peripheral strech receptor stimulation -> inc PANS -> bradycardia and resp
depression .

3 - levator palpebrae superioris

5 - tensor tympani, muscles of masticationn
7 - chorda tympani, orbicularis oculi, stapedius, submandibular and sublingual glands
9 - stylopharyngeus - pharynx/larynx elevation, gag reflex - afferent, swallowing, parotid gland
10 - palatoglossus - soft palate elevation, cough reflex - afferent and efferent, gag reflex - efferent, swallowing.
(9” - gag. 10” - cough.)
Cerebellum/4th ventricle/posterior fossa - pilocytic astrocytoma, medulloblastoma, ependymoma
Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3 nucleus of adducting eye via MLF.
PCA arises from basilar artery
ACA and MCA arise from ICA
PICA arises from vertebral artery
AICA arises at junction of vertebral and basilar artery
SCA arises from basilar artery
pontine arises from basilar artery
lenticulostriate arise from MCA
anterior choroidal arise from ICA
PCom connects PCA and ICA.
amaurosis fugax (transient visual loss) - retinal artery occlusion
Basilar artery (pons) - locked-in syndrome
AICA - lateral pontine syndrome
PICA - lateral medullary (wallenberg) synd
ASA - medial medullary syndrome
Alexia without agraphia (pure word blindness or acquired pure alexia) is the inability to read despite preserved ability to write.
Alexia without agraphia - reading lost, writing preserved.
Prosopagnosia - inability to recognises faces.
PCA stroke - alexia without agraphia (dominant hemisphere);
prosopagnosia (non-dominant hemisphere).
MCA stroke dominant hemisphere - aphasia, agraphia, acalculia (Gerstmann).
MCA stroke nondominant hemisphere - hemispatial neglect.
Lenticulostriate artery - absence of cortical signs; pure motor stroke.
Multiple sclerosis, GCA - Marcus-Gunn pupil (RAPD)
Tertiary syphilis - Argyll-Robertson pupil
Neurofibromin - negative RAS regulator.
pVHL - ubiquitinates hypoxia- inducible factor 1a.
MC primary brain tumor in childhood - pilocytic astrocytoma
MC malignant brain tumor in childhood - medulloblastoma
MC childhoood supratentorial tumor - craniopharyngioma
Uncal transtentorial herniation-
Early herniation - ipsilateral blown pupil (unilateral CN III compression), contralateral hemiparesis.
Late herniation - coma, Kernohan phenomenon (misleading contralateral blown pupil and ipsilateral hemiparesis due to contralateral compression
against Kernohan notch). Normal RInne (ACDC) - AC > BC
Normal Weber - no localization
Ischemia - Most vulnerable: hippocampus, neocortex, cerebellum (Purkinje cells), watershed areas.
Medial longitudinal fasciculus - Internuclear ophthalmoplegia - (impaired adduction of ipsilateral eye; nystagmus of contralateral eye with abduction).
Multiple sclerosis.

INO = Ipsilateral adduction failure, Nystagmus Opposite. Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3 nucleus of adducting eye
via MLF.
Stroke imaging: noncontrast CT to exclude hemorrhage (before tPA can be given). CT detects ischemic changes in 6–24 hr. Diffusion-weighted MRI
can detect ischemia within 3–30 min.
Stroke Treatment: tPA (if within 3–4.5 hr of onset and no hemorrhage/risk of hemorrhage) and/or thrombectomy (if large artery occlusion). Reduce risk
with medical therapy (eg, aspirin, clopidogrel); optimum control of blood pressure, blood sugars, lipids; smoking cessation; and treat conditions that
inc risk (eg, atrial fibrillation, carotid artery stenosis).
Mood stabilizers - VLLC - valproate, lithium, lamotrigine, carbamazepine.
amygdala lesion - kluver-bucy syndrome
pineal lesion (dorsal midbrain) - parinaud synd
Parinaud syndrome (VLLC)—vertical gaze palsy, pupillary light-near dissociation, lid retraction, convergence-retraction nystagmus.
Damage to cerebellum - ipsilateral deficits; fall toward side of lesion
Frontal eye field lesion - eye looks towards lesion
PPRF lesion - eye looks away from lesion
Decorticate (flexor) posturing—lesion above red nucleus
Decerebrate (extensor) posturing—lesion at or below red nucleus�
Parinaud syndrome (pinealoma) - vertical gaze palsy
PPRF lesion - horizontal gaze palsy
Hypertensive hemorrhages (Charcot-Bouchard microaneurysm) most often occur in putamen of basal ganglia (lenticulostriate vessels), followed by
thalamus, pons, and cerebellum.
Parinaud syndrome (pinealoma) - vertical gaze palsy
PPRF lesion - horizontal gaze palsy
Alexia without agraphia - reading lost, writing preserved.
Prosopagnosia - inability to recognises faces.
Pons lesion - locked in syndrome.
Basilar artery (think lower midbrain and upper pons) - Pons, medulla, lower midbrain - Reticular activating system (RAS). Corticospinal and
corticobulbar tracts. Ocular cranial nerve nuclei, paramedian pontine reticular formation. Locked-in syndrome.
(tongue muscles have pushing action)
Anterior spinal artery - (Medial medulla)
Fever (<40) - Febrile seizure (benign, usually self-limiting).
Heat stroke (>40) - CNS dysfunction (eg, confusion), end-organ damage, acute respiratory distress syndrome, rhabdomyolysis.
Aneurysms-
ACom—compression > bitemporal hemianopia (compression of optic chiasm); visual acuity defcits; rupture > ischemia in ACA distribution >
contralateral lower extremity hemiparesis, sensory defcits. MCA—rupture > ischemia in MCA distribution > contralateral upper extremity and lower
facial hemiparesis, sensory defcits.
PCom—compression > ipsilateral CN III palsy > mydriasis (“blown pupil”); may also see ptosis (LPS), “down and out” eye.
Simple seizures - consciousness intact.
Complex - consciousness impaired.

Reversible causes of dementia: Depression, hypothyroidism, vitamin B12 defciency, neurosyphilis, normal pressure hydrocephalus.
Normal pressure hydrocephalus - CSF pressure elevated only episodically; does not result in increased subarachnoid space volume. Expansion of
ventricles distorts the fbers of the corona radiata > triad of urinary incontinence, gait apraxia (magnetic gait), and cognitive dysfunction.
Parinaud syndrome (pinealoma) - vertical gaze palsy
PPRF lesion - horizontal gaze palsy
Uncal transtentorial herniation - Uncus = medial temporal lobe. Early herniation > ipsilateral blown pupil (unilateral CN III compression), contralateral
hemiparesis. Late herniation > coma, Kernohan

phenomenon (misleading contralateral blown pupil and ipsilateral hemiparesis due to contralateral compression against Kernohan notch).
Can cause Parinaud syndrome (compression of tectum vertical gaze palsy); obstructive hydrocephalus (compression of cerebral aqueduct); precocious
puberty in males (hCG production). Similar to germ cell tumors (eg, testicular seminoma).
Polio - asymmetric weakness (vs symmetric weakness in spinal muscular atrophy).
Cauda-equina syndrome - Radicular pain, absent knee and ankle refexes, loss of bladder and anal sphincter control, saddle anesthesia.
Normal Rinne - AC>BC (ACDC)
Central vertigo - Findings: directional or purely VERTICAL nystagmus, skew deviation (VERTICAL misalignment of the eyes), diplopia, dysmetria.
Focal neurologic findings.
Outer - cornea, sclera
Middle - iris, ciliary body, choroid
Inner - retina
Anterior segment = anterior chamber + posterior chamber
Hyperopia - convex (converging) lens
Myopia - concave (diverging) lens
Astigmatism - cylindrical lens
Trabecular outflow (90%) - inc with M3 agonist (eg, carbachol, pilocarpine).
Uveoscleral outflow (10%) - inc with prostaglandin agonists (eg latanoprost, bimatoprost).
Iris - Dilator muscle (α1), Sphincter muscle (M3).
Aqueous humour production - dec by B-blockers (eg, timolol), α2-agonists (eg, brimonidine), and carbonic anhydrase inhibitors (eg, acetazolamide).
Miosis - 1st neuron: Edinger-Westphal nucleus to ciliary ganglion via CN III
2nd neuron: short ciliary nerves to sphincter pupillae muscles
Mydriasis - 1st neuron: hypothalamus to ciliospinal center of Budge (C8–T2)
2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels)
3rd neuron: plexus along internal carotid, through cavernous sinus; enters orbit as long ciliary nerve to pupillary dilator muscles. Sympathetic fibers
also innervate smooth muscle of eyelids (minor retractors - superior tarsal muscles) and sweat glands of forehead and face.
Pupillary light reflex - Light in either retina sends a signal via CN II to PRETECTAL nuclei in midbrain that activates bilateral Edinger- Westphal
nuclei; pupils constrict bilaterally (direct and consensual reflex).
Marcus Gunn pupil - Also called relative afferent pupillary defect (RAPD). When the light shines into a normal eye, constriction of the ipsilateral
(direct reflex) and contralateral eye (consensual reflex) is observed. When the light is then swung to the affected eye, both pupils DILATE instead of
constrict due to impaired conduction of light signal along the injured optic nerve. Associated with optic neuritis (eg, multiple sclerosis), optic
neuropathies (eg, giant cell arteritis).
Horner syndrome- Sympathetic denervation of face. Ptosis (slight drooping of eyelid: superior tarsal muscle). Anhidrosis (absence of sweating) and
flushing of affected side of face. Miosis (pupil constriction). Associated with lesions along the sympathetic chain: 1st neuron: pontine hemorrhage,
lateral medullary syndrome, spinal cord lesion above T1 (eg, Brown-Séquard syndrome, late-stage syringomyelia). 2nd neuron: stellate ganglion
compression by Pancoast tumor. 3rd neuron: carotid dissection (painful); anhidrosis is usually absent.
Blowout fracture - May lead to infraorbital nerve injury.
Cavernous sinus - (CNs III, IV, VI, V1 & V2 plus postganglionic sympathetic pupillary fibers)
Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3 nucleus of adducting eye via MLF.
Succinylcholine - Reversal of blockade: Phase I (prolonged depolarization)—no antidote. Block potentiated by cholinesterase inhibitors. Phase II
(repolarized but blocked; ACh receptors are available, but desensitized)—may be reversed with cholinesterase inhibitors. Complications include
hypercalcemia,
Local anesthetics - Order of loss (PTTP) : (1) pain, (2) temperature, (3) touch, (4) pressure.
Full agonist: morphine, heroin, meperidine (long acting), methadone, codeine (prodrug; activated by CYP2D6), fentanyl.
Partial agonist: buprenorphine.
Mixed agonist/antagonist: nalbuphine, pentazocine, butorphanol.
Antagonist: naloxone, naltrexone, methylnaltrexone.
P5S3O3; C5R3W; D3F2L2. (SOaP CRoW DLF)
P5S3O3 (INFANT 0–12 mo);
Primitive reflexes (MRPB - 3,4,6,12), Posture, Picks 6, Pincer grasp 10, Points to objects 12.
(Posture—lifts head 1, rolls and sits 6, crawls 8, stands 10, walks 12–18)
Social smile 2, Stranger anxiety 6, Separation anxiety 9.
Orients (voice 4, names/gestures 9), Object permanence 9, Oratory 10.

C5R3W (TODDLER 12–36 mo);

Cruises 12, Climbs stairs 18, Cubes age x 3, Cutlery 20, Kicks ball 24. Recreation 24-36, Rapproachment 24, Realization 36.
Words 200-2, 300-3.

D3F2L2 (PRE-SCHOOL 3–5 yr);

Drive 3, Dexterity 4 (buttons/zippers/grooms self 5), Drawings 4 Freedom 3, Friends 4.
Language (1000 words 3, sentences/prepositions 4), Legends 4.

Alar plate (dorsal): sensory; regulated by TGF-β (including bone morphogenetic protein [BMP])
Basal plate (ventral): motor; regulated by sonic hedgehog gene (SHH)
Posterior cerebral artery - Occipital lobe. Contralateral hemianopia with macular sparing; alexia without agraphia (dominant hemisphere, extending to
splenium of corpus callosum); prosopagnosia (nondominant hemisphere).

Basilar artery (think lower midbrain and upper pons) - Pons, medulla, lower midbrain - Reticular activating system (RAS). Corticospinal and
corticobulbar tracts. Ocular cranial nerve nuclei, paramedian pontine reticular formation. Locked-in syndrome.

Anterior inferior cerebellar artery - Facial nucleus. Vestibular nuclei. Spinothalamic tract, spinal trigeminal nucleus. Sympathetic fbers. Middle and
inferior cerebellar peduncles. Labyrinthine artery. Lateral pontine syndrome.

Posterior inferior cerebellar artery - Nucleus ambiguus (CN IX, X, XI). Vestibular nuclei. Lateral spinothalamic tract, spinal trigeminal nucleus.
Sympathetic fbers. Inferior cerebellar peduncle. Lateral medullary (Wallenberg) syndrome.

Anterior spinal artery - Corticospinal tract. Medial lemniscus. Caudal medulla—hypoglossal nerve (tongue deviates ipsilaterally - pushing effect).
Medial Medullary syndrome— caused by infarct of paramedian branches of ASA and/or vertebral arteries.
Neural crest - melanocytes, face/ branchial arch mesenchyme.
NTDs - Inc acetylcholinesterase (AChE) in amniotic fluid is a helpful confirmatory test.

CN 12 (HSG) - hyoglossus - retracts and depresses; genioglossus - protrudes tongue; styloglossus - sides of tongue upwards to create trough. CN 10 -
palatoglossus - elevates posterior tongue.
Myelin wraps and insulates axons: dec membrane capacitance, inc membrane resistance, inc space (length) constant, dec time constant. HIV-infected
microglia fuse to form multinucleated giant cells in CNS seen in HIV-associated dementia.

Field defect - holoprosencephaly

Syringomyelia - “capelike,” bilateral, symmetrical loss of pain and temperature sensation in upper extremities (fine touch sensation is preserved).

(fine touch is via dorsal columns)

Chiari 1 - spinal cavitations (eg, syringomyelia).
Chiari 2 - aqueductal stenosis, lumbosacral myelomeningocele, noncommunicating hydrocephalus.
Dandy-Walker malformation - noncommunicating hydrocephalus, spina bifda.
Fine touch - dorsal column
Crude touch - anterior spinothalamic tract
Neuron markers: neuroflament protein, synaptophysin.
Astrocyte marker: GFAP.
Specialized ependymal cells (choroid plexus) produce CSF.
Schwann cell marker: S100.
(RMP-MF)
R - JS
Mer (Mr) - DP
P - PH
Meis (Miss)- D-PILL
F - PT
(RMP-MF)
R - JS - Finger tips, joints
Mer (Mr) - DP - Finger tips, superficial skin
P - PH - Deep skin layers, ligaments, joints
Meis (Miss)- D-PILL - Glabrous (hairless) skin
F - PT - All tissues except cartilage and eye lens
P and Meis(Miss) - adapt quickly
Mer(Mr) and R - adapt slowly
(PMs adapt quickly, MRs adapt slowly)
Chromatolysis-
cellular swelling,
nucleus displacement,
nissl dispersion
Distal to injury - wallerian degeneration.
Proximal to injury - axonal retraction and chromatolysis.
Wallerian degeneration—disintegration of the axon and myelin sheath distal to site of axonal injury with macrophages removing debris. Proximal to the
injury, the axon retracts, and the cell body sprouts new protrusions that grow toward other neurons for potential reinnervation.
PARKINSON DISEASE - Acetylcholine inc; Dopamine dec; Serotonin dec.
Mesoderm - duramater
Neural crest - arachnoid and pia mater
NO BBB - area postrema, OVLT, neurohypophysis
BBB components -
Endothelial tight junction
Basement membrane
Astrocyte foot processes
Pericytes
Glucose and amino acids cross slowly by carriermediated transport mechanisms. Nonpolar/lipid-soluble substances cross rapidly via diffusion
Alcohol, benzodiazepines, and barbiturates - dec REM sleep and dec N3 sleep;
Norepinephrine - dec REM sleep.
Alcohol, benzodiazepines, and barbiturates - dec REM sleep and dec N3 sleep;
Norepinephrine - dec REM sleep.
Benzodiazepines are useful for night terrors and sleepwalking by dec N3 and REM sleep.
(N3 - sleepwalking, bedwetting, night terrors)
CTZ and adjacent vomiting center nuclei receive input from 5 major receptors: muscarinic (M1), dopamine (D2), histamine (H1), serotonin (5-HT3),
and neurokinin (NK-1) receptors.
NTS (medulla) inputs-
CTZ (area postrema)
GI system (via vagus)
Vestibular system
CNS
Rx Chemo vomiting - 5HT3, D2, NK-1 blockers
Rx Motion sickness - H1, M1 blockers
Rx Hyperemesis gravidarum - H1 blocker
N2 - bruxism; sleep spindles and K complexes.
N3 - sleepwalking, bedwetting, night terrors.
REM - Loss of motor tone, inc brain O2 use, variable pulse/BP, inc ACh, dreaming, nightmares, penile tumescence, memory processing, extraocular
movements.
delta - high amplitude, low frequency
beta - low amplitude, high frequency
(delta airlines - high noise amplitude)
Changes in elderly: dec REM, dec N3, inc sleep latency, inc early awakenings.

Changes in depression: inc REM sleep time, dec REM latency, dec N3, repeated nighttime awakenings, early morning awakening (terminal insomnia).

Change in narcolepsy: dec REM latency.

Benzodiazepines are useful for night terrors and sleepwalking by dec N3 and REM sleep. (N3 - sleepwalking, bedwetting, night terrors)
waveforms - BATS-DB

N3 - night terrors REM - nightmares

N1 - 5
N2 - 45
N3 - 25
REM - 25
REM sleep (25%) Loss of motor tone, inc brain O2 use, variable pulse/BP, inc ACh. REM is when dreaming, nightmares, and penile/clitoral
tumescence occur; may serve memory processing function. Extraocular movements due to activity of PPRF (paramedian pontine reticular formation/
conjugate gaze center). Occurs every 90 minutes, and duration inc through the night.

Hypothalamus Inputs (areas not protected by blood-brain barrier): OVLT (senses change in osmolarity), area postrema (found in dorsal medulla,
responds to emetics).

Preoptic nucleus - Thermoregulation, sexual behavior. Releases GnRH. Failure of GnRH-producing neurons to migrate from olfactory pit > Kallmann
syndrome. Thalamic nuclei-
VPL - INPUT Spinothalamic and dorsal columns/medial lemniscus. Vibration, proprioception, pain, temp, pressure, light touch.
VPM - INPUT Trigeminal and gustatory pathway. Face sensation, taste.

VAL - INPUT Basal ganglia, cerebellum. Motor.

LGN - INPUT CN II, optic chiasm, optic tract. Light
MGN - INPUT Superior olive and inferior colliculus of tectum. Music.
Eyes - superior colliculi. Ears - inferior colliculi.
Ventral anterior and lateral nuclei - INPUT Basal ganglia, cerebellum. Motor. DESTINATION Motor cortices (frontal lobe).
Limbic system - Collection of neural structures involved in emotion, long-term memory, olfaction, behavior modulation, ANS function. Consists of
hippocampus, amygdalae, mammillary bodies, anterior thalamic nuclei, cingulate gyrus, entorhinal cortex.
LATERAL NUCLEUS - inhibited by leptin.
Ventromedial nucleus - Stimulated by leptin.
Superior colliculus - eyes
Inferior colliculus - ears
VPL - INPUT Spinothalamic and dorsal columns/medial lemniscus. Vibration, proprioception, pain, temp, pressure, light touch.
VPM - INPUT Trigeminal and gustatory pathway. Face sensation, taste.
VAL - INPUT Basal ganglia, cerebellum. Motor.
LGN - INPUT CN II, optic chiasm, optic tract. Light
MGN - INPUT Superior olive and inferior colliculus of tectum. Music.
Mesocortical - dec activity > “negative” symptoms

Mesolimbic - inc activity > “positive” symptoms Nigrostriatal - dec activity > extrapyramidal symptoms

Tuberoinfundibular - dec activity > inc prolactin

Cerebellar input - Middle cerebellar peduncle, Inferior cerebellar peduncle.
Cerebellar output - Superior cerebellar peduncle.
Mesocortical - dec activity > “negative” symptoms
Mesolimbic - inc activity > “positive” symptoms
Nigrostriatal - dec activity > extrapyramidal symptoms
Tuberoinfundibular - dec activity > inc prolactin
Mesolimbic pathway - 1° therapeutic target of antipsychotic drugs > dec positive symptoms (eg, in schizophrenia).
CEREBELLUM -
Lateral lesion - affects extremities; fall towards injured side.
Medial lesion - affects axial and proximal limbs.
Direct (excitatory) pathway—SNc input to the striatum via the nigrostriatal dopaminergic pathway releases GABA, which inhibits GABA release from
the GPi, disinhibiting the Thalamus via the GPi (inc motion).
Indirect (inhibitory) pathway—SNc input to the striatum via the nigrostriatal dopaminergic pathway releases GABA that disinhibits STN via GPe
inhibition, and STN stimulates GPi to inhibit the thalamus (dec motion).
DIRECT - striatum > GPi > thalamus > inc motion.
INDIRECT - striatum > GPe > STN > GPi > thalamus > dec motion.
(LEARN WIT REVERSE ENGINEERING)
Lateral lesions—affect voluntary movement of extremities (lateral structures); when injured, propensity to fall toward injured (ipsilateral) side.
Medial lesions (eg, vermis, fastigial nuclei, focculonodular lobe)—truncal ataxia (widebased cerebellar gait), nystagmus, head tilting. Generally result
in bilateral motor defcits affecting axial and proximal limb musculature (medial structures).
Dopamine increases motion via both direct and indirect pathway.
It stimulates direct excitatory pathway and inhibits indirect inhibitory pathway.
GABA is the primary neurotransmitter in basal ganglia.

Cushing refex—triad of hypertension, bradycardia, and respiratory depression in response to inc ICP. Lateral nuclei = sensory (alar plate).
—Sulcus limitans—
Medial nuclei = motor (basal plate).

(LSA-MMB)
Vagal nuclei-
NTS (vomiting) - visceral sensory info, vomiting - CN 7, 9, 10
NA(Nucleus ambiguus) - motor to pharynx, larynx, upper esophagus - CN 9, 10, 11(cranial portion) DMN - PANS to heart, lungs, upper GI - CN 10
tongue-
ant 2/3 - taste-7, sensation-5
post 1/3 - taste and sensation-9
pharynx/larynx elevation (stylopharyngeus) - 9
soft palate elevation - 10
swallowing - 9 and 10
Sensory-1,2,8.
Motor-3,4,6,11,12.
Both-5,7,9,10.
Sensory-1,2,8. Motor-3,4,6,11,12. Both-5,7,9,10.
parotid-9, submandibular, sublingual-7
pharynx/larynx elevation - 9. soft palate elevation - 10.
7 - auditory volume modulation (stapedius)
5 - dampening of loud noises (tensor tympani)
parotid-9, submandibular, sublingual-7
(facial nerve passes through parotid but it doesnt supply parotid)
(parotid supplied by CN 9)
Gag - 9’’
Cough - 10’’
(Lateral lowers the jaw)
LP Needle passes through: SF-SILEDAS
Tracts - (cervical is always close to the horns)

Peripheral precocious puberty - McCune-Albright syndrome.

Klienfelter syndrome - Dysgenesis of seminiferous tubules > dec inhibin B > inc FSH. Abnormal Leydig cell function > dec testosterone > inc LH >
inc estrogen.
Placenta previa - Attachment of placenta over internal cervical os.
Low-lying placenta - is located < 2 cm from, but not covering, the internal cervical os.
Müllerian agenesis (Mayer-RokitanskyKüster-Hauser syndrome)—may present as 1° amenorrhea (due to a lack of uterine development) in females
with fully developed 2° sexual characteristics (functional ovaries).

Vasa previa - Frequently associated with velamentous umbilical cord insertion (cord inserts in chorioamniotic membrane rather than placenta > fetal
vessels travel to placenta unprotected by Wharton jelly).
Complete mole- STAINING FOR P57 PROTEIN ⊖ (paternally imprinted).
Partial mole- STAINING FOR P57 PROTEIN ⊕ (maternally expressed). Partial mole is P57 positive.

H-mole - Associated with hCG-mediated sequelae: early preeclampsia (before 20 weeks of gestation), theca-lutein cysts, hyperemesis gravidarum,
hyperthyroidism.
HELLP syndrome Preeclampsia with thrombotic microangiopathy of the liver. Hemolysis, Elevated Liver enzymes, Low Platelets.
Gynecologic tumor epidemiology - Incidence (US)—endometrial > ovarian > cervical; cervical cancer is more common worldwide due to lack of
screening or HPV vaccination. Prognosis: Cervical (best prognosis, diagnosed < 45 years old) > Endometrial (middleaged, about 55 years old) >
Ovarian (worst prognosis, > 65 years).
Complete mole-
COMPONENTS Most commonly enucleated egg + single sperm (subsequently duplicates paternal DNA).
STAINING FOR P57 PROTEIN ⊖ (paternally imprinted).
Partial mole-
COMPONENTS 2 sperm + 1 egg
STAINING FOR P57 PROTEIN ⊕ (maternally expressed) Partial mole is P57 positive
Lichen sclerosus Thinning of epidermis with fbrosis/sclerosis of dermis. Presents with porcelain-white plaques with a red or violet border. Skin
fragility with erosions can be observed. Most common in postmenopausal females. Benign, but slightly increased risk for SCC.
Lichen simplex chronicus Hyperplasia of vulvar squamous epithelium. Presents with leathery, thick vulvar skin with enhanced skin markings due to
chronic rubbing or scratching. Benign, no risk of SCC.
Sarcoma botryoides - Embryonal rhabdomyosarcoma variant. Affects females < 4 years old; spindle-shaped cells; desmin ⊕. Presents with clear, grape-
like, polypoid mass emerging from vagina. HPV - Associated with HPV-16 and HPV-18, which produce both the E6 gene product (inhibits TP53) and
E7 gene product (inhibits pRb) (6 before 7; P before R). Koilocytes (cells with wrinkled “raisinoid” nucleus and perinuclear halo) are pathognomonic
of HPV infection.
Polycystic ovarian syndrome - Hyperinsulinemia and/or insulin resistance hypothesized to alter hypothalamic hormonal feedback response > inc
LH:FSH, inc androgens (eg, testosterone) from theca interna cells, dec rate of follicular maturation > unruptured follicles (cysts) + anovulation.
Follicular cyst - Most common ovarian mass in young females.
Ovarian tumors - Most common adnexal mass in females > 55 years old.
Serous cystadenoma - Most common ovarian neoplasm.
Serous carcinoma - Most common malignant ovarian neoplasm.
Mature cystic teratoma (dermoid cyst) - Most common ovarian tumor in young females.
Dysgerminoma - Malignant. Most common in adolescents. Sheets of uniform “fried egg” cells. Tumor markers: inc hCG, inc LDH.
Yolk sac tumor (endodermal sinus tumor) - Schiller-Duval bodies (resemble glomeruli). Tumor marker: inc AFP.
Granulosa cell tumor - Most common malignant sex cord stromal tumor. Call-Exner bodies (granulosa cells arranged haphazardly around collections of
eosinophilic fuid, resembling primordial follicles). Tumor marker: inc inhibin.
Endometrial carcinoma - Most common gynecologic malignancy.
Endometriod type endometrial carcinoma - Early pathogenic events include loss of PTEN or mismatch repair proteins.
Leiomyoma (fibroid) - Most common tumor in females.
Seminoma - Most common testicular tumor.
Testicular yolk sac tumor - Most common testicular tumor in children < 3 years old.
Primary testicular lymphoma - Most common testicular cancer in older males.
Dysgerminoma - Sheets of uniform “fried egg” cells. Tumor markers: inc hCG, inc LDH.
Yolk sac tumor - Also called endodermal sinus tumor. Schiller-Duval bodies (resemble glomeruli). Tumor marker: inc AFP. Occurs in children and
young adult females.
Granulosa cell tumor Most common malignant sex cord stromal tumor. Predominantly occurs in females in their 50s. Often produces estrogen and/or
progesterone. Histology shows Call-Exner bodies (granulosa cells arranged haphazardly around collections of eosinophilic fuid, resembling primordial
follicles). Tumor marker: inc inhibin.
Psammoma bodies -
serous ovarian carcinoma
serous endometrial carcinoma
Lobular carcinoma in situ and invasive lobular carcinoma - Dec E-cadherin expression.
Lobular carcinoma in situ - Dec E-cadherin expression. No mass or calcifcations > incidental biopsy finding. Inc risk of cancer in either breast (vs
DCIS, same breast and quadrant).
Squamous cell carcinoma - Seen in the US, but more common in Asia, Africa, South America. Precursor in situ lesions: Bowen disease (in penile shaft,
presents as leukoplakia “white plaque”), erythroplasia of Queyrat (carcinoma in situ of the glans, presents as erythroplakia “red plaque”), Bowenoid
papulosis (carcinoma in situ of unclear malignant potential, presenting as reddish papules). Associated with uncircumcised males and HPV.
Bowen ds - shaft. Erythroplasia of queyrat - glans.
Cryptorchidism - Dec inhibin B, inc FSH, inc LH; testosterone dec in bilateral cryptorchidism, normal in unilateral.
Embryonal carcinoma - May be associated with inc hCG and normal AFP levels when pure (inc AFP when mixed).
BPH - Inc total PSA, with inc fraction of free PSA.
Prostatic adenocarcinoma - Prostatic acid phosphatase (PAP) and PSA are useful tumor markers (inc total PSA, with dec fraction of free PSA).
BPH - Inc total PSA, with inc fraction of free PSA.
Prostatic adenocarcinoma - Inc total PSA, with dec fraction of free PSA.
Prostatic adenocarcinoma - Arises most often from posterior lobe (peripheral zone) of prostate gland.
BPH - Hyperplasia (not hypertrophy) of periurethral (lateral and middle) lobes.
Progestin challenge: presence of bleeding upon withdrawal of progestins excludes anatomic defects (eg, Asherman syndrome) and chronic anovulation
without estrogen.

Ketoconazole - 17 -hydroxylase/17,20-lyase inhibitor - Prostate cancer. ADVERSE EFFECTS - Gynecomastia. Spironolactone - Androgen receptor
and 17 -hydroxylase/17,20-lyase inhibitor - PCOS. ADVERSE EFFECTS - Amenorrhea. Bronchi and proximal bronchiole - columnar, goblet cells and
cilia
Terminal and respiratory bronchiole - cuboidal, club cells and cilia
Ciliated epithelium persists up to the respiratory bronchioles.
Cilia are last to disappear. Cilia terminate in respiratory bronchioles.
Cartilage and goblet cells extend to the end of bronchi. Pseudostratifed ciliated columnar cells primarily make up epithelium of bronchus and extend to
beginning of terminal bronchioles, then transition to cuboidal cells. Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond
this point). . Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli. Cilia terminate in respiratory bronchioles.
EPCSA - 7, 17 ,25, birth, 8 years

Pneumocytes develop starting at week 20 of development. Respiration capable at ~ week 25. Collapsing pressure (P) = 2 (surface tension)/radius
Bronchi and proximal bronchiole - columnar, goblet cells and cilia
Terminal and respiratory bronchiole - cuboidal, club cells and cilia

Ciliated epithelium persists up to the respiratory bronchioles.

Cilia are last to disappear. Cilia terminate in respiratory bronchioles.

Cartilage and goblet cells extend to the end of bronchi. Pseudostratifed ciliated columnar cells primarily make up epithelium of bronchus and extend to
beginning of terminal bronchioles, then transition to cuboidal cells. Airway smooth muscle cells extend to end of terminal bronchioles (sparse beyond
this point). . Mostly cuboidal cells in respiratory bronchioles, then simple squamous

cells up to alveoli. Cilia terminate in respiratory bronchioles.

Airway resistance highest in the large- to medium-sized bronchi. Small airways consist of bronchioles that further divide into terminal bronchioles
(large numbers in parallel > least airway

resistance).
Therapeutic supplemental O2 can result in Retinopathy of prematurity, Intraventricular hemorrhage, Bronchopulmonary dysplasia (RIB).
Screening tests for fetal lung maturity: lecithinsphingomyelin (L/S) ratio in amniotic fuid ( 2 is healthy; < 1.5 predictive of NRDS), foam stability
index, surfactant-albumin ratio. Collapsing pressure (P) = 2 (surface tension)/radius

Relation of the pulmonary artery to the bronchus at each lung hilum is described by RALS—Right Anterior; Left Superior. If you aspirate a peanut:

While supine—usually enters superior segment of right lower lobe. While lying on right side—usually enters right upper lobe.
While upright—usually enters right lower lobe.
Diaphragm structures - Structures perforating diaphragm:

At T8: IVC, right phrenic nerve

At T10: esophagus, vagus (CN 10; 2 trunks)
At T12: aorta (red), thoracic duct (white), azygos vein (blue)
8,10,12 - IEA
RV and any lung capacity that includes RV cannot be measured by spirometry
Functional residual capacity = RV + ERV. Volume of gas in lungs after normal expiration; outward pulling force of chest wall is balanced with inward
collapsing force of lungs.
Determination of physiologic dead space- VD = VT x (Paco2 – Peco2)/Paco2
Minute ventilation = VE = VT x RR
Alveolar ventilation = VA = (VT - VD) x RR
Determination of physiologic dead space- VD = VT x (Paco2 – Peco2)/Paco2
VD = physiologic dead space = anatomic dead space of conducting airways plus alveolar dead space; apex of healthy lung is largest contributor of
alveolar dead space. Volume of inspired air that does not take part in gas exchange.
VT = tidal volume. Paco2 = arterial Pco2 . Peco2 = expired air Pco2 . Physiologic dead space—approximately equivalent to anatomic dead space in
normal lungs. May be greater than anatomic dead space in lung diseases with V ̇ /Q ̇ mismatch.
Oxygen content of blood O2 content = (1.34 x Hb x Sao2 ) + (0.003 x Pao2 ). Hb = hemoglobin concentration; Sao2 = arterial O2 saturation. Pao2 =
partial pressure of O2 in arterial blood. Normally 1 g Hb can bind 1.34 mL O2 ; normal Hb amount in blood is 15 g/dL. O2 binding capacity = 20 mL
O2 /dL of blood. With dec Hb there is dec O2 content of arterial blood, but no change in O2 saturation and Pao2 .
O2 delivery to tissues = cardiac output x O2 content of blood.
Respiratory system changes in the elderly - Aging is associated with progressive dec in lung function. TLC remains the same.
INCREASED-
Lung compliance (loss of elastic recoil)
RV
V̇/Q̇ mismatch
A-a gradient
DECREASED-
Chest wall compliance (inc chest wall stiffness)
FVC and FEV1
Respiratory muscle strength (can impair cough)
Ventilatory response to hypoxia/hypercapnia
Elastic recoil - Tendency for lungs to collapse inward and chest wall to spring outward. At FRC, airway and alveolar pressures equal atmospheric
pressure (called zero), and intrapleural pressure is negative (preventing atelectasis). The inward pull of the lung is balanced by the outward pull of the
chest wall. System pressure is atmospheric. Pulmonary vascular resistance (PVR) is at a minimum. Inc compliance = lung easier to flll (eg,
emphysema, aging)
Dec compliance = lung harder to flll (eg, pulmonary fibrosis, pneumonia, ARDS, pulmonary edema).
Hysteresis - Lung infation follows a different pressurevolume curve than lung deflation due to need to overcome surface tension forces in inflation.
Oxygen content of blood = O2 content = (1.34 x Hb x Sao2 ) + (0.003 x Pao2).
O2 delivery to tissues = cardiac output x O2 content of blood.
Oxygen-hemoglobin dissociation curve - ODC has sigmoidal shape due to positive cooperativity (ie, tetrameric Hb molecule can bind 4 O2 molecules
and has higher affnity for each subsequent O2 molecule bound). Myoglobin is monomeric and thus does not show positive cooperativity; curve lacks
sigmoidal appearance.
Shifting ODC to the right > dec Hb affnity for O2 (facilitates unloading of O2 to tissue) > inc P50 (higher Po2 required to maintain 50% saturation). In
peripheral tissue, inc H+ from tissue metabolism shifts curve to right, unloading O2 (Bohr effect).
Shifting ODC to the left > dec O2 unloading > renal hypoxia > inc EPO synthesis > compensatory erythrocytosis.
Fetal Hb (2a and 2y subunits) has higher affnity for O2 than adult Hb (due to dec affnity for 2,3-BPG) > dissociation curve is shifted left, driving
diffusion of O2 across the placenta from pregnant patient to fetus.
Left shift (dec O2 unloading to tissue) - Left = lower - Dec H+ (inc pH, base), dec PCO2 , dec 2,3–BPG, dec Temperature, inc CO, inc MetHb, inc
HbF.
Right shift (inc O2 unloading to tissues) - ACE BATs right handed - Inc H+ (dec pH, Acid), inc PCO2 , Exercise, inc 2,3–BPG, High Altitude, inc
Temperature.
Cyanide vs carbon monoxide poisoning - Both inhibit aerobic metabolism via inhibition of complex IV of ETC (cytochrome c oxidase) > hypoxia that
does not fully correct with supplemental O2 and inc anaerobic metabolism.
Cyanide-
EXPOSURE Synthetic product combustion, amygdalin ingestion (found in apricot seeds), cyanide ingestion (eg, in suicide attempts), fire victims.
PRESENTATION Headache, dyspnea, drowsiness, seizure, coma. May have cherry red skin. Breath may have bitter almond odor. LABS Normal PaO2
. Elevated lactate > metabolic acidosis.
EFFECT ON OXYGEN-HEMOGLOBIN CURVE Curve normal. Oxygen saturation may appear normal initially. Despite ample O2 supply, it cannot
be used due to ineffective oxidative phosphorylation. TREATMENT Decontamination (eg, remove clothing). Hydroxocobalamin (binds cyanide >
cyanocobalamin > renal excretion). Nitrites (oxidize Hb > methemoglobin > binds cyanide > cyanomethemoglobin > dec toxicity). Sodium thiosulfate
(inc cyanide conversion to thiocyanate > renal excretion).
Carbon monoxide-
EXPOSURE Motor exhaust, gas heaters, fire victims.
PRESENTATION Headache, vomiting, confusion, visual disturbances, coma. May have cherry-red skin with bullous skin lesions. Multiple victims
may be involved (eg, family due to faulty furnace). LABS Normal PaO2 . Elevated carboxyhemoglobin on co-oximetry. Classically associated with
bilateral globus pallidus lesions on MRI, although can rarely be seen with cyanide toxicity.
EFFECT ON OXYGEN-HEMOGLOBIN CURVE - Left shift in curve > inc affinity for O2 > dec O2 unloading in tissues. Binds competitively to Hb
with >200 greater affinity than O2 to form carboxyhemoglobin —> dec %O2 saturation of Hb.
TREATMENT - 100% O2 . Hyperbaric oxygen if severe.
Methemoglobin - Iron in Hb is normally in a reduced state (ferrous Fe2+). Oxidized form of Hb (ferric, Fe3+) does not bind O2 as readily as Fe2+, but
has inc affnity for cyanide > tissue hypoxia from dec O2 saturation and dec O2 content. Methemoglobinemia may present with cyanosis (does not
improve with supplemental O2 ) or with chocolate-colored blood. Dapsone, local anesthetics (eg, benzocaine), and nitrites (eg, from dietary intake or
polluted/ high-altitude water sources) cause poisoning by oxidizing Fe2+ to Fe3+. Methemoglobinemia can be treated with methylene blue and vitamin
C.
Carboxyhemoglobin - CO + Hb
Carbaminohemoglobin - CO2 + Hb
Cyanide toxicity-
Hb CONCENTRATION Normal
% O2 SAT OF Hb - Normal
DISSOLVED O2 (PaO2) - Normal

TOTAL O2 CONTENT - Normal

Perfusion limited—O2 (normal health), CO2 , N2O. Gas equilibrates early along the length of the capillary. Exchange can be inc only if blood flow inc.
Diffusion limited—O2 (emphysema, fbrosis, exercise), CO. Gas does not equilibrate by the time blood reaches the end of the capillary. O2 diffuses
slowly, while CO2 diffuses very rapidly across the alveolar membrane. Disease states that lead to diffusion limitation (eg, pulmonary fibrosis) are more
likely to cause early hypoxia than hypercapnia.
Normal A-a gradient - High altitude (dec barometric pressure), Hypoventilation (eg, opioid use, obesity hypoventilation syndrome).
Inc A-a gradient - V ̇ /Q ̇ mismatch, Diffusion limitation (eg, fibrosis), Right-to-left shunt.
R = respiratory quotient = CO2 produced/ O2 consumed
A-a gradient = Pao2 – Pao2 . Normal A-a gradient estimated as (age/4) + 4 (eg, for a person <40 years old, gradient should be <14).
Diffusion: V̇ gas = A × Dk × (P1 – P2)/Δx
Pulmonary vascular resistance
PVR = (Ppulm artery – PL atrium)/Q
Remember: ΔP = Q × R, so R = ΔP / Q
R = 8ηl/πr4
Alveolar gas equation:
PAo2 = PIo2 – (Paco2/R) ≈ 150 mm Hga – (Paco2/0.8)
Pulmonary vascular resistance
PVR = (Ppulm artery – PL atrium)/Q
Remember: ΔP = Q × R, so R = ΔP / Q
R = 8ηl/πr4
Alveolar gas equation
PAo2 = PIo2 – (Paco2/R) ≈ 150 mm Hga – (Paco2/0.8)
Diffusion: V̇ gas = A × Dk × (P1 – P2)/Δx
Lung zones:
V ̇ /Q ̇ at apex of lung = 3 (wasted ventilation)
V ̇ /Q ̇ at base of lung = 0.6 (wasted perfusion)
Both ventilation and perfusion are greater at the base of the lung than at the apex of the lung. With exercise (inc cardiac output), there is vasodilation of
apical capillaries > V̇/Q̇ ratio approaches 1. V̇/Q̇ = 0 = “oirway” obstruction (shunt). In shunt, 100% O2 does not improve Pao2 (eg, foreign body
aspiration).
V̇/Q̇ = infinity = blood flow obstruction (physiologic dead space). Assuming < 100% dead space, 100% O2 improves Pao2 (eg, pulmonary embolus).
Zone 1 = PA>Pa>Pv = decV/dec dec Q > inc V/Q = V̇/Q̇ at apex of lung = 3 (wasted ventilation)
Zone 2 = Pa > PA > Pv = V/Q ~ 1
Zone3=Pa>Pv>PA=incV/incincQ>decV/Q=V̇/Q̇ atbaseoflung=0.6(wastedperfusion)
Response to exercise-
Inc CO2 production.
Inc O2 consumption.
Right shift of ODC.
Inc ventilation to meet O2 demand and remove excess CO2 .
V ̇ /Q ̇ ratio from apex to base becomes more uniform.
Inc pulmonary blood flow due to inc cardiac output.
Dec pH during strenuous exercise (2° to lactic acidosis).
No change in Pao2 and Paco2 , but inc in venous CO2 content and dec in venous O2 content.

PSGN - subepithelial IC humps

Membranous nephropathy - EM—“Spike and dome” appearance of subepithelial deposits.
Type 1 MPGN - subendothelial IC deposits + granular IF
Type 2 MPGN - intramembranous deposits
DPGN - MC subendothelial, sometimes subepithelial or intramembranous deposits
Berger ds - mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
(In proliferative GN (MPGN and DPGN) deposits are subendothelial/intramembranous. In PSGN and membranous nephropathy deposits are
subepithelial.)
PSGN - LM—glomeruli enlarged and hypercellular. IF - (“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition
along GBM and mesangium. EM—subepithelial IC humps.
Type 1 MPGN - subendothelial IC deposits + granular IF. Type 2 MPGN - intramembranous deposits.
DPGN - LM—“wire looping” of capillaries. IF—granular; EM—subendothelial, sometimes subepithelial or intramembranous IgG-based ICs often
with C3 deposition.
Berger ds - LM—mesangial proliferation IF—IgA-based IC deposits in mesangium; EM—mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
Diabetic glomerulonephropathy - LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions).
Minimal change ds - LM—Normal glomeruli (lipid may be seen in PCT cells). IF—⊖. EM—effacement of podocyte foot processes.
FSGS - LM—segmental sclerosis and hyalinosis. IF—often ⊖ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1. EM—effacement of foot
processes similar to minimal change ds.
Membranous nephropathy - LM—diffuse capillary and GBM thickening. IF—granular due to immune complex (IC) deposition. EM—“Spike and
dome” appearance of subepithelial deposits.
Amyloidosis - LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium.
MPGN - Type I may be 2° to hepatitis B or C infection. May also be idiopathic. Subendothelial IC deposits with granular IF. Type II is associated with
C3 nephritic factor (IgG autoantibody that stabilizes C3 convertase > persistent complement activation > dec C3 levels). Intramembranous deposits,
also called dense deposit disease. Both types: mesangial ingrowth > GBM splitting > “tram- track” on H&E and PAS stains.
Glomerular diseases-
Nephritic syndrome PGI-AM - Examples Acute poststreptococcal glomerulonephritis Goodpasture syndrome IgA nephropathy (Berger disease) Alport
syndrome Membranoproliferative glomerulonephritis.
Nephrotic syndrome MAD-FM - EXAMPLES May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process): Focal
segmental glomerulosclerosis (1° or 2°) Minimal change disease (1° or 2°) Membranous nephropathy (1° or 2°) Amyloidosis (2°) Diabetic
glomerulonephropathy (2°)
Nephritic-nephrotic syndrome DPGN and MPGN - Diffuse proliferative glomerulonephritis, Membranoproliferative glomerulonephritis.
Type 1 MPGN - subendothelial IC deposits + granular IF
Type 2 MPGN - intramembranous deposits
Calcium oxalate: hypocitraturia.
Calcium phosphate: inc pH.
Ammonium magnesium phosphate (struvite) - inc pH.
Uric acid - dec pH.
Cystine - dec pH.
FSGS and Membranous nephropathy - 1° disease has poor response to steroids. May progress to CKD.
Minimal change disease - 1° disease has excellent response to corticosteroids.
Calcium oxalate: hypocitraturia - Radiopaque - Radiopaque - Shaped like envelope or dumbbell. Treatment: thiazides, citrate, low-sodium diet.
Calcium phosphate: inc pH. Xray-Radiopaque, CT-Radiopaque. Wedgeshaped prism. Treatment: low-sodium diet, thiazides.
Ammonium magnesium phosphate (struvite) - inc pH. XRAY - Radiopaque. CT - Radiopaque. Coffin lid. Treatment: eradication of underlying
infection, surgical removal of stone.
Uric acid - dec pH. XRAY - Radiolucent. CT - Visible. Rhomboid or rosettes. Treatment: alkalinization of urine, allopurinol.
Cystine - dec pH. XRAY - Faintly radiopaque. CT - Moderately radiopaque. Hexagonal. Treatment: low sodium diet, alkalinization of urine, chelating
agents (eg, tiopronin, penicillamine) if refractory. Prerenal azotemia - URINE OSMOLALITY (mOsm/kg) >500.

Postrenal azotemia, Intrinsic renal failure - URINE OSMOLALITY (mOsm/kg) <350.

Prerenal - URINE OSMOLALITY (mOsm/kg) >500. URINE Na+ (mEq/L) <20. FENa <1%. SERUM BUN/Cr >20.
Intrinsic - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) >40. FENa >2%. SERUM BUN/Cr <15.
Postrenal - URINE OSMOLALITY (mOsm/kg) <350. URINE Na+ (mEq/L) Varies. FENa Varies. SERUM BUN/Cr Varies.
Xanthogranulomatous pyelonephritis—rare; grossly orange nodules that can mimic tumor nodules; characterized by widespread kidney damage due to
granulomatous tissue containing foamy macrophages. Associated with Proteus infection.
Acute cystitis - Labs: ⊕ leukocyte esterase. ⊕ nitrites (indicates presence of Enterobacteriaceae).
Chronic pyelonephritis - . Coarse, asymmetric corticomedullary scarring, blunted calyces. Tubules can contain eosinophilic casts resembling thyroid
tissue (thyroidization of kidney).
ATN - 3 stages: 1. Inciting event 2. Maintenance phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia 3. Recovery phase
—polyuric; BUN and serum creatinine fall; risk of hypokalemia and renal wasting of other electrolytes and minerals.
Autosomal dominant tubulointerstitial kidney disease - Also called medullary cystic kidney disease. Causes tubulointerstitial fbrosis and progressive
renal insuffciency with inability to concentrate urine. Medullary cysts usually not visualized; smaller kidneys on ultrasound. Poor prognosis.
Renal oncocytoma - Benign epithelial cell tumor arising from collecting ducts (arrows in A point to wellcircumscribed mass with central scar). Large
eosinophilic cells with abundant mitochondria without perinuclear clearing B (vs chromophobe renal cell carcinoma). Presents with painless hematuria,
fank pain, abdominal mass. Often resected to exclude malignancy (eg, renal cell carcinoma). Renal cell carcinoma - Originates from PCT.
Renal oncocytoma - Benign epithelial cell tumor arising from collecting ducts.
WAGR complex (WT1 deletion)
Denys-Drash syndrome (WT1 mutation)
Beckwith-Wiedemann syndrome (WT2 mutation)
WAGR complex (WT1 deletion)—Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, Range of developmental delays (WT1
deletion).
Denys-Drash syndrome (WT1 mutation)—Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male
pseudohermaphroditism).
Beckwith-Wiedemann syndrome (WT2 mutation)—Wilms tumor, macroglossia, organomegaly, hemihyperplasia, omphalocele. (everything is getting
larger)
Urothelial carcinoma of the bladder - Associated with problems in your Pee SAC: Phenacetin, tobacco Smoking, Aromatic amines (found in dyes),
Cyclophosphamide.
Squamous cell carcinoma of the bladder - Risk factors include 4 S’s: Schistosoma haematobium infection (Middle East), chronic cystitis (“systitis”),
smoking, chronic nephrolithiasis (stones).
Sonic hedgehog (SHH) gene - base of limb buds - Anterior-posterior axis patterning.
Wnt-7 gene - distal end of each limb - Dorsal-ventral axis patterning.
Fibroblast growth factor (FGF) gene - Apical ectodermal ridge - Limb lengthening.
Homeobox (Hox) genes - Segmental organization in cranial-caudal direction, TRANSCRIPTION FACTOR CODING.
arachnoid, pia - neural crest
dura mater - mesoderm
upper 2/3 of vagina - mesoderm
lower 1/3 of vagina - endoderm (endodermal sinus)
kidneys, adrenal cortex - mesoderm
wall of gut tube - mesoderm
Gut tube epithelium - endoderm
Endoderm - luminal epithelial derivatives (eg, lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular and
parafollicular [C] cells).
Mesodermal defects = VACTERL association: Vertebral defects Anal atresia Cardiac defects Tracheo-Esophageal fstula Renal defects Limb defects
(bone and muscle).
Deformation - occurs after embryonic period.
Malformation - occurs during embryonic period (weeks 3–8 of development).
ACE inhibitors - hypocalvaria
Methimazole - Aplasia cutis congenita (congenital absence of skin, particularly on scalp).
Methylmercury (TKSS) - top-predator fish (eg, shark, swordfsh, king mackerel, tilefsh).
Neonatal abstinence syndrome - Treatment (for opiate use): methadone, morphine, buprenorphine.
Warfarin - Bone and cartilage deformities (stippled epiphyses, nasal and limb hypoplasia), optic nerve atrophy, fetal cerebral hemorrhage.
Diabetes in pregnancy - Caudal regression syndrome, cardiac defects (eg, VSD), neural tube defects, macrosomia, neonatal hypoglycemia (due to islet
cell hyperplasia), polycythemia, neonatal respiratory distress syndrome.
Neonatal abstinence syndrome - Treatment (for opiate use): methadone, morphine, buprenorphine.
Syncytiotrophoblast - Lacks MHC I expression > dec chance of attack by maternal immune system.
Cytotrophoblast - Inner layer.
Syncytiotrophoblast - Outer layer.
Chorion = placenta
Urachus - b/w bladder and umblicus
Vitelline duct - b/w gut and umblicus
1st pharyngeal arch - Maxillary process > maxilla, zygomatic bone. Mandibular process > meckel cartilage > mandible, malleus and incus,
sphenomandibular ligament. Muscles of mastication (temporalis, masseter, lateral and medial pterygoids), mylohyoid, anterior belly of digastric, tensor
tympani, anterior 2/3 of tongue, tensor veli palatini CN V3 chew.
2nd pharyngeal arch - Reichert cartilage: stapes, styloid process, lesser horn of hyoid, stylohyoid ligament. Muscles of facial expression, stapedius,
stylohyoid, platysma, posterior belly of digastric. CN VII (seven) smile (facial expression).
3rd pharyngeal arch - Greater horn of hyoid. Stylopharyngeus. CN IX (stylopharyngeus) swallow stylishly.
4th and 6th pharyngeal arches - Arytenoids, Cricoid, Corniculate, Cuneiform, Thyroid (used to sing and ACCCT). 4th arch: most pharyngeal
constrictors; cricothyroid, levator veli palatini. 6th arch: all intrinsic muscles of larynx except cricothyroid. 4th arch: CN X (superior laryngeal branch)
simply swallow. 6th arch: CN X (recurrent/ inferior laryngeal branch) speak.
1st pharyngeal arch - anterior belly of digastric, tensor veli palatini.
2nd pharyngeal arch - lesser horn of hyoid, posterior belly of digastric.
3rd pharyngeal arch - Greater horn of hyoid.
4th arch - levator veli palatini.
Paramesonephric (Müllerian) duct - Develops into female internal structures— fallopian tubes, uterus, upper portion of vagina (lower portion from
urogenital sinus). Male remnant is appendix testis. Mesonephric (Wolfan) duct - Develops into male internal structures (except prostate)—Seminal
vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED). Female remnant is Gartner duct. Müllerian agenesis (Mayer-RokitanskyKüster-
Hauser syndrome)—may present as 1° amenorrhea (due to a lack of uterine development) in females with fully developed 2° sexual characteristics
(functional ovaries).
Genital tubercle - glans and muscles
Urogenital sinus - glands
Urogenital fold - ventral shaft/labia minora
Labioscrotal swelling - scrotum/labia majora
Hypospadias - Due to failure of urethral folds to fuse. Associated with inguinal hernia, cryptorchidism, chordee. Can be seen in 5α-reductase defciency.
Epispadias - Due to faulty positioning of genital tubercle. Exstrophy of the bladder is associated with epispadias.
Lymphatic drainage -
Ovaries/testes/fundus of uterus > para-aortic lymph nodes.
Body of uterus/cervix/superior part of bladder > external iliac nodes.
Prostate/cervix/corpus cavernosum/proximal vagina > internal iliac nodes.
Distal vagina/vulva/scrotum/distal anus > superfcial inguinal nodes.
Clitoris/glans penis > deep inguinal nodes.
Ureter Course - under gonadal artery; over common iliac artery; under uterine artery/vas deferens (retropeitoneal).
Erection—parasympathetic nervous system (pelvic splanchnic nerves, S2-S4).
Emission—sympathetic nervous system (hypogastric nerve, T11-L2).

Expulsion—visceral and somatic nerves (pudendal nerve).

Pathway of sperm during ejaculation— SEVEN UP: Seminiferous tubules Epididymis Vas deferens Ejaculatory ducts (Nothing) Urethra Penis.
Superior bladder wall (dome) injury—direct trauma to full bladder (eg, seatbelt) > abrupt inc intravesical pressure > dome rupture (weakest part) >
intraperitoneal urine accumulation. Peritoneal absorption of urine > inc BUN, inc creatinine.
Anterior bladder wall or neck injury—pelvic fracture > perforation by bony spicules > extraperitoneal urine accumulation (retropubic space).
Anterior urethral injury—perineal straddle injury > disruption of bulbar (spongy) urethra > scrotal hematoma. If Buck fascia is torn, urine escapes into
perineal space.
Posterior urethral injury—pelvic fracture > disruption at bulbomembranous junction (weakest part) > urine leakage into retropubic space and high-
riding prostate.

Embryonic/developmental age—time since fertilization. Used in embryology.

Gestational age—time since frst day of last menstrual period. Used clinically.
Sertoli cells - Temperature sensitive; dec sperm production and dec inhibin B with inc temperature.
Leydig cells - testosterone production unaffected by temperature.
Meiosis I is arrested in prophase I for years until ovulation (1° oocytes).
Meiosis II is arrested in metaphase II until fertilization (2° oocytes).
Mittelschmerz—transient mid-cycle ovulatory pain (“middle hurts”); classically associated with peritoneal irritation (eg, follicular swelling/rupture,
fallopian tube contraction). Can mimic appendicitis.

hCG - Has identical α subunit as LH, FSH, TSH (states of inc hCG can cause hyperthyroidism). β subunit is unique (pregnancy tests detect β subunit).
hCG is inc in multiple gestations, hydatidiform moles, choriocarcinomas, and Down syndrome; hCG is dec in ectopic/failing pregnancy, Edwards
syndrome, and Patau syndrome.
Stage 1 - Pre-pubertal - No sexual hair, Flat-appearing chest with raised nipple.
Stage 2 - 8 - 11.5 yrs - Pubic hair appears (pubarche), Testicular enlargement, Breast bud forms (thelarche), mound forms.

Stage 3 - 11.5 - 13 yrs - Coarsening of pubic hair, Penis size/length inc, Breast enlarges.
Stage 4 - 13 - 15 yrs - Coarse hair across pubis, sparing thigh; Penis width/glans inc; Breast enlarges, raised areola, mound on mound.
Stage 5 - Usually > 15 years - Coarse hair across pubis and medial thigh; Penis and testis enlarge to adult size; Adult breast contour, areola flattens.
Menopause - Inc inc FSH is specifc for menopause (loss of negative feedback on FSH due to dec estrogen). Hormonal changes: dec estrogen, inc inc
FSH, inc LH (no surge), inc GnRH. Causes HAVOCS: Hot fashes (most common), Atrophy of the Vagina, Osteoporosis, Coronary artery disease,
Sleep disturbances.
DHT:
Early—differentiation of penis, scrotum, prostate
Late—prostate growth, balding, sebaceous gland activity
Earliest detectable secondary sexual characteristic is breast bud development in females, testicular enlargement in males.

Ureteropelvic junction obstruction - Most common pathologic cause of prenatal hydronephrosis wk 3 - pronephros
wk 4 - mesonephros
wk 5 - metanephros

Metanephric mesenchyme (metanephric blastema) - glomerulus to DCT

Ureteric bud (metanephric diverticulum)- collecting duct to ureter
Horseshoe kidney - gets trapped under IMA; assc with chromosomal aneuploidy.
Multicystic dysplastic kidney - Ureteric bud develops, but fails to induce differentiation.
PUV - MCC of bladder outlet obstruction in male infants; present in posterior (prostatic) urethra; assc with Urethral obstruction, B/L hydronephrosis,
dilated/thickened bladder, oligohydramnios. Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens).

Left kidney is taken during living donor transplantation because it has a longer renal vein.
Ureter Course - under gonadal artery; over common iliac artery; under uterine artery/vas deferens (retropeitoneal).
Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens).
Common Ureteral obstructions - UPJ, UVJ, pelvic inlet.
Blood Supply - Proximal - renal A.
Middle - gonadal A, Aorta, common and internal iliac A.
Distal - internal iliac and superior vesical A.
JG apparatus -
1. DCT (macula densa cells)
2. JG cells in the middle
3. Afferent arteriole
Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens).
Left kidney is taken during living donor transplantation because it has a longer renal vein.
Renal blood flow - RSIA-IA-G-EPIAIR
Plasma volume = TBV x (1 – Hct). (TBV=total blood volume).
Renal clearance - Cx = (Ux V)/Px
Cinulin = GFR = Uinulin V/Pinulin = Kf [(PGC – PBS) – ( GC – BS)] (GC = glomerular capillary; BS = Bowman space; BS normally equals zero; Kf
= filtration coefficient).
Inulin clearance = GFR
Creatine clearance approximates GFR (slightly overestimates)
PAH clearance = eRPF (eRPF slightly underestimates true RPF)
eRPF = UPAH x V/PPAH = CPAH.
Renal blood flow (RBF) = RPF/(1 - Hct).
Plasma volume = TBV x (1 – Hct)
RPF = RBF x (1 - Hct)
Cinulin = GFR = Uinulin V/Pinulin
Cpah = eRPF = Upah V/Ppah.
Measure-
Plasma volume - radiolabeled albumin
ECF volume - inulin or mannitol
ECF (1/3 of TBW) - plasma (25% of ECF) + interstitial fluid (75% of ECF)
ICF (2/3 of TBW) - includes RBC volume
ICF - K, Mg, ATP (HiKin)
ECF - Na, Cl, HCO3, albumin
Glomerular filtration barrier-
1. Fenestrated capillary endothelium.
2. Basement membrane with type IV collagen chains and heparan sulfate.
3. Visceral epithelial layer consisting of podocyte foot processes (FPs).
Fenestrated capillary endothelium (prevents entry of > 100 nm molecules/blood cells);
Slit diaphragm (prevents entry of molecules > 4–5 nm).
Filtration fraction (FF) = GFR/RPF
Filtered load (mg/min) = GFR (mL/min) × plasma concentration (mg/mL).
Inulin clearance = GFR.
Creatine clearance approximates GFR (slightly overestimates).
PAH clearance = eRPF (eRPF slightly underestimates true RPF).
PSGN - LM—glomeruli enlarged and hypercellular. IF - (“starry sky”) granular appearance (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition
along GBM and mesangium. EM—subepithelial IC

humps.
Type 1 MPGN - subendothelial IC deposits + granular IF. Type 2 MPGN - intramembranous deposits.
DPGN - LM—“wire looping” of capillaries. IF—granular; EM—subendothelial, sometimes subepithelial or intramembranous IgG-based ICs often
with C3 deposition.
Berger ds - LM—mesangial proliferation IF—IgA-based IC deposits in mesangium; EM—mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
Diabetic glomerulonephropathy - LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions).
Minimal change ds - LM—Normal glomeruli (lipid may be seen in PCT cells). IF—⊖. EM—effacement of podocyte foot processes.
FSGS - LM—segmental sclerosis and hyalinosis. IF—often ⊖ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1. EM—EFFACEMENT OF
FOOT PROCESSES SIMILAR TO MINIMAL CHANGE DS. Membranous nephropathy - LM—diffuse capillary and GBM thickening. IF—granular
due to immune complex (IC) deposition. EM—“Spike and dome” appearance of subepithelial deposits. Amyloidosis - LM—Congo red stain shows
apple-green birefringence under polarized light due to amyloid deposition in the mesangium.
PSGN - subepithelial IC humps
Membranous nephropathy - EM—“Spike and dome” appearance of subepithelial deposits.
Type 1 MPGN - subendothelial IC deposits + granular IF
Type 2 MPGN - intramembranous deposits
DPGN - MC subendothelial, sometimes subepithelial or intramembranous deposits
Berger ds - mesangial IC deposition.
Alport syndrome - “basket-weave” appearance due to irregular thickening of GBM.
(In proliferative GN (MPGN and DPGN) deposits are subendothelial/intramembranous. In PSGN and membranous nephropathy deposits are
subepithelial.)
Thick ascending loop of henle and DCT are impermeable to water.
Inc plasma protein concentration - dec GFR, no change in RPF, dec FF (GFR/RPF)
Dec plasma protein concentration - inc GFR, no change in RPF, inc FF (GFR/RPF)
Dehydration - dec GFR, dec dec RPF, inc FF (GFR/RPF)
Plasma volume = TBV x (1 – Hct). (TBV=total blood volume).
Renal clearance - Cx = (Ux V)/Px
Cinulin = GFR = Uinulin V/Pinulin = Kf [(PGC – PBS) – ( GC – BS)] (GC = glomerular capillary; BS = Bowman space; BS normally equals zero; Kf
= filtration coefficient).
Inulin clearance = GFR
Creatine clearance approximates GFR (slightly overestimates)
PAH clearance = eRPF (eRPF slightly underestimates true RPF)
eRPF = UPAH x V/PPAH = CPAH.
Renal blood flow (RBF) = RPF/(1 - Hct).
Plasma volume = TBV x (1 – Hct)
RPF = RBF x (1 - Hct)
Cinulin = GFR = Uinulin V/Pinulin
Cpah = eRPF = Upah V/Ppah.
PCT - PTH—inhibits Na+/PO4 3– cotransport > inc PO4 3– excretion. PCT - AT II—stimulates Na+/H+ exchange > inc Na+, H2O, and HCO3 −
reabsorption (permitting contraction alkalosis).
DCT - PTH—inc Ca2+/Na+ exchange > inc Ca2+ reabsorption
Filtered load = GFR × Px.
Excretion rate = V × Ux.
Reabsorption rate = filtered – excreted.
Secretion rate = excreted – filtered
FeNa = Na+ excreted/Na+ filtered =
(V × UNa)/(GFRxPNa) =
(PCr × UNa)/(UCr × PNa)
where GFR = (UCr × V)/PCr.
FeNA = (PCr × UNa)/(UCr × PNa)
(Una’s PCR/UC pinna)
PCT - PTH—inhibits Na+/PO4 3– cotransport > inc PO4 3– excretion. AT II—stimulates Na+/H+ exchange > inc Na+, H2O, and HCO3 −
reabsorption (permitting contraction alkalosis).
DCT - PTH—inc Ca2+/Na+ exchange > inc Ca2+ reabsorption
Thick ascending loop of henle and DCT are impermeable to water
In adults, at plasma glucose of ∼ 200 mg/dL, glucosuria begins (threshold). At rate of ∼ 375 mg/min, all transporters are fully saturated (Tm).
Sodium- glucose cotransporter 2 (SGLT2) inhibitors (eg, - ozin drugs) result in glucosuria at plasma concentrations < 200 mg/dL.
Splay phenomenon—Tm for glucose is reached gradually rather than sharply due to the heterogeneity of nephrons (ie, different Tm points); represented
by the portion of the titration curve between threshold and Tm.
In principal cells: inc apical K+ conductance, inc Na+/K+ pump, inc epithelial Na+ channel (ENaC) activity > lumen negativity > K+ secretion.
In α-intercalated cells: lumen negativity > inc H+ ATPase activity > inc H+ secretion > inc HCO3 −/Cl− exchanger activity.
Nephrotoxins/drugs (eg, ifosfamide, cisplatin) can cause FANCONI SYNDROME, bcoz they affect PCT.
Fanconi - EFFECTS Metabolic acidosis (proximal RTA), hypokalemia, HYPOPHOSPHATEMIA
(like loops) Bartter - EFFECTS Metabolic alkalosis, hypokalemia, HYPERCALCIURIA.
(like thiazides) Gittelman - EFFECTS Metabolic alkalosis, hypokalemia, HYPOMAGNESEMIA, HYPOCALCIURIA.
Liddle - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
SAME - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
(All have hypokalemia. All have metabolic alkalosis except fanconi syndrome (proximal RTA).)
(First is fanconi, rest are alphabetical)
Fanconi syndrome - DEFECTS Generalized reabsorption defect in PCT > inc excretion of amino acids, glucose, HCO3 – , and PO4 3–, and all
substances reabsorbed by the PCT.
Bartter syndrome - DEFECTS Reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter).
Gitelman syndrome - DEFECTS Reabsorption defect of NaCl in DCT.
Liddle syndrome - DEFECTS Gain of function mutation > dec Na+ channel degradation > inc Na+ reabsorption in collecting tubules.
Syndrome of Apparent Mineralocorticoid Excess - DEFECTS - Hereditary 11β-HSD deficiency > inc cortisol > inc mineralocorticoid receptor activity.
SAME - Can acquire disorder from glycyrrhetinic acid (present in licorice), which blocks activity of 11 -hydroxysteroid dehydrogenase.
AT II - Helps maintain blood volume and blood pressure. Affects baroreceptor function; limits re ex bradycardia, which would normally accompany its
pressor effects.
See diagram on page 611. [TF/P] > 1 = KCU-ICP. [TF/P] < 1 = HAG. [TF/P] = 1 = Na+.
(K+,Cl-,urea,inulin, creatinine,PAH) (HCO3-,amino acids,glucose)
TF - tubular fluid. P - plasma.
macula densa cells in DCT
Juxtaglomerular apparatus - Consists of mesangial cells, JG cells (modified smooth muscle of afferent arteriole), and the macula densa (NaCl sensor
located at the DCT).
AT-2 - efferent arteriole vasoconstriction
Juxtaglomerular apparatus - Consists of mesangial cells, JG cells (modified smooth muscle of afferent arteriole), and the macula densa (NaCl sensor
located at the DCT).
JG cells secrete renin in response to dec renal blood pressure and inc sympathetic tone ( B1 ).
Macula densa cells sense dec NaCl delivery to DCT > inc renin release > efferent arteriole vasoconstriction > inc GFR.
Fanconi syndrome - DEFECTS Generalized reabsorption defect in PCT > inc excretion of amino acids, glucose, HCO3 – , and PO4 3–, and all
substances reabsorbed by the PCT.
Bartter syndrome - DEFECTS Reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter).
Gitelman syndrome - DEFECTS Reabsorption defect of NaCl in DCT.
Liddle syndrome - DEFECTS Gain of function mutation > dec Na+ channel degradation > inc Na+ reabsorption in collecting tubules.

Syndrome of Apparent Mineralocorticoid Excess - DEFECTS - Hereditary 11β-HSD deficiency > inc cortisol > inc mineralocorticoid receptor activity.
Fanconi - EFFECTS Metabolic acidosis (proximal RTA), hypokalemia, HYPOPHOSPHATEMIA
(like loops) Bartter - EFFECTS Metabolic alkalosis, hypokalemia, HYPERCALCIURIA.
(like thiazides) Gittelman - EFFECTS Metabolic alkalosis, hypokalemia, HYPOMAGNESEMIA, HYPOCALCIURIA.

Liddle - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE. SAME - EFFECTS Metabolic alkalosis,
hypokalemia, HYPERTENSION, DEC ALDOSTERONE. (All have hypokalemia. All have metabolic alkalosis except fanconi syndrome (proximal
RTA).) (First is fanconi, rest are alphabetical)

Dopamine - Secreted by PCT cells, promotes natriuresis. At low doses; dilates interlobular arteries, afferent arterioles, efferent arterioles > inc RBF,
little or no change in GFR. At higher doses; acts as vasoconstrictor.
HYPOKALEMIA - Hypo-osmolarity, Alkalosis, β-adrenergic agonist (inc Na+/K+ ATPase), Insulin (inc Na+/K+ ATPase), Insulin shifts K+ into cells.
(BHAI).
HYPERKALEMIA - Digoxin (blocks Na+/K+ ATPase), HyperOsmolarity, Lysis of cells (eg, crush injury, rhabdomyolysis, tumor lysis syndrome),
Acidosis, β-blocker, High blood Sugar (insulin deficiency), Succinylcholine (inc risk in burns/muscle trauma). (Hyperkalemia? DO LAβSS).

HYPOKALEMIA - HypoOsmolarity, Alkalosis.

HYPERKALEMIA - HyperOsmolarity, Acidosis.
(As water moves towards hyperosmolarity, it takes some potassium alongwith it causing hypokalemia).
Acid–base balance affects serum potassium by the exchange of hydrogen ions for potassium across the cell membrane. A rise in the serum pH
(decrease in H+ concentration) will result in a shift of H+ out of the cell and potassium into the cell. The reverse occurs during acidemia with a shift of
potassium out of the cell. A sudden increase in plasma osmolality will shift water out of the cell and drag some potassium with the water. This will
result in a significant rise in serum potassium.
AT-2 - Net effect: preservation of renal function (↑ FF) in low-volume state with simultaneous Na+ reabsorption (both proximal and distal) to maintain
circulating volume.
Dopamine -
low dose - vasodilator
high dose - vasoconstrictor
HYPOKALEMIA - HypoOsmolarity, Alkalosis.
HYPERKALEMIA - HyperOsmolarity, Acidosis.
(K travels with water; K is exchanged with H+)
(K travels with water;
K is exchanged with H+)
Acid–base balance affects serum potassium by the exchange of hydrogen ions for potassium across the cell membrane. A rise in the serum pH
(decrease in H+ concentration) will result in a shift of H+ out of the cell and potassium into the cell. The reverse occurs during acidemia with a shift of
potassium out of the cell. A sudden increase in plasma osmolality will shift water out of the cell and drag some potassium with the water. This will
result in a significant rise in serum potassium.
Bartter - HYPERCALCIURIA.
Gittelman - HYPOCALCIURIA, HYPOMAGNESEMIA.
Fanconi - EFFECTS Metabolic acidosis (proximal RTA), hypokalemia, HYPOPHOSPHATEMIA
(like loops) Bartter - EFFECTS Metabolic alkalosis, hypokalemia, HYPERCALCIURIA.
(like thiazides) Gittelman - EFFECTS Metabolic alkalosis, hypokalemia, HYPOMAGNESEMIA, HYPOCALCIURIA.
Liddle - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
SAME - EFFECTS Metabolic alkalosis, hypokalemia, HYPERTENSION, DEC ALDOSTERONE.
(All have hypokalemia. All have metabolic alkalosis except fanconi syndrome (proximal RTA).)
(First is fanconi, rest are alphabetical)
Fanconi syndrome - DEFECTS Generalized reabsorption defect in PCT > inc excretion of amino acids, glucose, HCO3 – , and PO4 3–, and all
substances reabsorbed by the PCT.
Bartter syndrome - DEFECTS Reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter).
Gitelman syndrome - DEFECTS Reabsorption defect of NaCl in DCT.
Liddle syndrome - DEFECTS Gain of function mutation > dec Na+ channel degradation > inc Na+ reabsorption in collecting tubules.
Syndrome of Apparent Mineralocorticoid Excess - DEFECTS - Hereditary 11β-HSD deficiency > inc cortisol > inc mineralocorticoid receptor activity.
Distal renal tubular acidosis (RTA type 1) - Inability of -intercalated cells to secrete H+ > no new HCO3 – is generated > metabolic acidosis. URINE
pH > 5.5. SERUM K+ dec.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption > inc excretion of HCO3 – in urine > metabolic acidosis. Urine pH
- < 5.5 when plasma HCO3 – below reduced resorption threshold. > 5.5 when filtered HCO3 – exceeds resorptive threshold. SERUM K+ dec.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia > dec NH3 synthesis in PCT > dec NH4 +
excretion. Urine pH - < 5.5 (or variable). SERUM K+ inc.
Distal renal tubular acidosis (RTA type 1) - Inability of a-intercalated cells to secrete H+.
Proximal renal tubular acidosis (RTA type 2) - Defect in PCT HCO3 – reabsorption.
Hyperkalemic tubular acidosis (RTA type 4) - Hypoaldosteronism or aldosterone resistance; hyperkalemia.
If > 12 mEq/L then Inc Anion gap Metabolic acidosis - GOLDMARK: Glycols (ethylene glycol, proplyene glycol) Oxoproline (toxic metabolite of
acetaminophen) L-lactate (lactic acidosis) D-lactate (exogenous lactic acid) Methanol (and other alcohols) Aspirin (late e ect) Renal failure Keytones
(diabetic, alcoholic, starvation).
If 8–12 mEq/L then Normal anion gap - HARDASS Hyperchloremia/hyperalimentation Addison disease Renal tubular acidosis Diarrhea
Acetazolamide Spironolactone Saline infusion

Atria -
[Link] primum grows toward endocardial cushions, narrowing ostium primum.
[Link] secundum forms in septum primum due to cell death (ostium primum regresses).
[Link] secundum develops on the right side of septum primum, as ostium secundum maintains right-to-left shunt.
[Link] secundum expands and covers most of ostium secundum. The residual foramen is the foramen ovale.
[Link] portion of septum primum forms the one-way valve of the foramen ovale.
6. Septum primum closes against septum secundum, sealing the foramen ovale soon after birth because of inc LA pressure and dec RA pressure.
7. Septum secundum and septum primum fuse during infancy/early childhood, forming the atrial septum.
Ventricles-
[Link] interventricular septum forms. Opening is called interventricular foramen.
[Link] septum rotates and fuses with muscular ventricular septum to form membranous interventricular septum, closing interventricular
foramen.
[Link] of endocardial cushions separates atria from ventricles and contributes to both atrial septation and membranous portion of the interventricular
septum.
Outfow tract formation - Neural crest cell migrations > truncal and bulbar ridges that spiral and fuse to form aorticopulmonary septum > ascending
aorta and pulmonary trunk. Aortic arch derivatives Develop into arterial system.
1st Part of maxillary artery (branch of external carotid). 1st arch is maximal.
2nd Stapedial artery and hyoid artery. Second = stapedial.
3rd Common carotid artery and proximal part of internal carotid artery. C is 3rd letter of alphabet.
4th On left, aortic arch; on right, proximal part of right subclavian artery. 4th arch (4 limbs) = systemic.
6th Proximal part of pulmonary arteries and (on left only) ductus arteriosus. 6th arch = pulmonary and the pulmonary-to-systemic shunt (ductus
arteriosus).
EMBRYONIC STRUCTURE GIVES RISE TO
Truncus arteriosus Ascending aorta and pulmonary trunk
Bulbus cordis Smooth parts (outfow tract) of left and right ventricles
Primitive ventricle Trabeculated part of left and right ventricles
Primitive atrium Trabeculated part of left and right atria
Left horn of sinus venosus Coronary sinus
Right horn of sinus venosus Smooth part of right atrium (sinus venarum)

Endocardial cushion Atrial septum, membranous interventricular septum; AV and semilunar valves Right common cardinal vein and right anterior
cardinal vein Superior vena cava (SVC)
Posterior, subcardinal, and supracardinal veins Inferior vena cava (IVC)
Primitive pulmonary vein Smooth part of left atrium
At birth, infant takes a breath > dec resistance in pulmonary vasculature > inc left atrial pressure vs right atrial pressure > foramen ovale closes (now
called fossa ovalis); inc in O2 (from respiration) and dec in prostaglandins (from placental separation) > closure of ductus arteriosus.

Indomethacin helps close the patent ductus arteriosus > ligamentum arteriosum (remnant of ductus arteriosus). “Endomethacin” ends the PDA.
Prostaglandins E1 and E2 kEEp PDA open. Allantois > urachus Median umbilical ligament. Urachus is part of allantois between bladder and umbilicus
Umbilical arteries Medial umbilical ligaments
Umbilical vein Ligamentum teres hepatis (round ligament). Contained in falciform ligament

RV is the most anterior part of the heart and most commonly injured in trauma.
LA is the most posterior part of the heart;
Pericardium innervated by phrenic nerve. Pericarditis can cause referred pain to the neck, arms, or one or both shoulders (often left).
Coronary blood supply LAD and its branches supply anterior 2/3 of interventricular septum, anterolateral papillary muscle, and anterior surface of LV.
Most commonly occluded. PDA supplies posterior 1/3 of interventricular septum, posterior 2/3 walls of ventricles, and posteromedial papillary muscle.
RCA supplies AV node and SA node. Infarct may cause nodal dysfunction (bradycardia or heart block). Right (acute) marginal artery supplies RV.
Coronary blood fow to LV and interventricular septum peaks in early diastole.
Digoxin (blocks Na+ /K+ pump > inc intracellular Na+ > dec Na+ /Ca2+ exchanger activity > inc intracellular Ca2+).
Cardiac output CO = SV x HR.
Fick principle: CO = rate of O2 consumption/(arterial O2 content – venous O2 content)
In early stages of exercise, CO maintained by inc HR and inc SV. In later stages, CO maintained by inc HR only (SV plateaus).
Inc PP in hyperthyroidism, aortic regurgitation, aortic stiffening (isolated systolic hypertension in elderly), obstructive sleep apnea ( inc sympathetic
tone), anemia, exercise (transient). Dec PP in aortic stenosis, cardiogenic shock, cardiac tamponade, advanced HF.
Mean arterial pressure MAP = CO x total peripheral resistance (TPR). MAP (at resting HR) = 2/3 DBP + 1/3 SBP = DBP + 1/3 PP.
Capillaries have highest total cross-sectional area and lowest fow velocity.

Arterioles account for most of TPR. Veins provide most of blood storage capacity. Viscosity depends mostly on hematocrit. Viscosity inc in
hyperproteinemic states (eg, multiple myeloma), polycythemia. Viscosity dec in anemia.
S3—in early diastole during rapid ventricular flling phase. Turbulence caused by blood from LA mixing with inc ESV.
S4—in late diastole (“atrial kick”). Turbulence caused by blood entering stiffened LV.

Jugular venous pulse (JVP):

a wave—atrial contraction. Absent in atrial fbrillation.
c wave—RV contraction (closed tricuspid valve bulging into atrium).
x descent—atrial relaxation and downward displacement of closed tricuspid valve during rapid ventricular ejection phase. Reduced or absent in
tricuspid regurgitation and right HF because pressure gradients are reduced.
v wave— inc RA pressure due to inc volume against closed tricuspid valve.
y descent—RA emptying into RV. Prominent in constrictive pericarditis, absent in cardiac tamponade.
Physiologic splitting - Inspiration > drop in intrathoracic pressure > inc venous return > inc RV flling > inc RV stroke volume > inc RV ejection time >
delayed closure of pulmonic valve. Dec pulmonary impedance (inc capacity of the pulmonary circulation) also occurs during inspiration, which
contributes to delayed closure of pulmonic valve.
Fixed splitting - Heard in ASD.
Paradoxical splitting - Heard in conditions that delay aortic valve closure (eg, aortic stenosis, left bundle branch block). Normal order of semilunar
valve closure is reversed: in paradoxical splitting P2 occurs before A2. On inspiration, P2 closes later and moves closer to A2, “paradoxically”
eliminating the split. On expiration, the split can be heard (opposite to physiologic splitting).
Auscultation of the heart
Aortic area: Systolic murmur - Aortic stenosis, Flow murmur (eg, physiologic murmur), Aortic valve sclerosis.
Left sternal border: Diastolic murmur - Aortic regurgitation (valvular), Pulmonic regurgitation. Systolic murmur - Hypertrophic cardiomyopathy.
Pulmonic area: Systolic ejection murmur - Pulmonic stenosis, Atrial septal defect, Flow murmur.
Tricuspid area: Holosystolic murmur - Tricuspid regurgitation, Ventricular septal defect. Diastolic murmur - Tricuspid stenosis.
Mitral area (apex): Holosystolic murmur - Mitral regurgitation. Systolic murmur - Mitral valve prolapse. Diastolic murmur - Mitral stenosis.
Hand grip inc inc afterload > inc reverse flow across aortic valve (inc LV volume). MURMURS THAT INCREASE WITH MANEUVER Most other
left-sided murmurs (AR, MR, VSD). MURMURS THAT DECREASE WITH MANEUVER AS (dec transaortic valve pressure gradient) HCM (inc LV
volume).
Inspiration inc venous return to right heart, dec venous return to left heart. MURMURS THAT INCREASE WITH MANEUVER Most right- sided
murmurs. MURMURS THAT DECREASE WITH MANEUVER Most left-sided murmurs.
Aortic regurgitation - High-pitched “blowing” early diastolic decrescendo murmur. Best heard at base (aortic root dilation) or left sternal border
(valvular disease).
MS - Delayed rumbling mid-to-late diastolic murmur (dec interval between S2 and OS correlates with inc severity).
Myocardium - Phase 2 = plateau—Ca2+ infux through voltagegated Ca2+ channels balances K+ effux. Ca2+ infux triggers Ca2+ release from
sarcoplasmic reticulum and myocyte contraction (excitationcontraction coupling).
In contrast to skeletal muscle:
Cardiac muscle action potential has a plateau due to Ca2+ infux and K+ effux.
Cardiac muscle contraction requires Ca2+ infux from ECF to induce Ca2+ release from sarcoplasmic reticulum (Ca2+-induced Ca2+ release).
Cardiac myocytes are electrically coupled to each other by gap junctions. Occurs in all cardiac myocytes except for those in the SA and AV nodes.
Pacemaker action potential - Occurs in the SA and AV nodes. Key differences from the ventricular action potential include:
Phase 0 = upstroke—opening of voltage-gated Ca2+ channels. Fast voltage-gated Na+ channels are permanently inactivated because of the less
negative resting potential of these cells. Results in a slow conduction velocity that is used by the AV node to prolong transmission from the atria to
ventricles. Phases 1 and 2 are absent.
Phase 3 = repolarization—inactivation of the Ca2+ channels and inc activation of K+ channels > inc K+ effux.
Phase 4 = slow spontaneous diastolic depolarization due to If (“funny current”). If channels responsible for a slow, mixed Na+ /K+ inward current;
different from INa in phase 0 of ventricular action potential. Accounts for automaticity of SA and AV nodes. The slope of phase 4 in the SA node
determines HR. ACh/adenosine dec the rate of diastolic depolarization and dec HR, while catecholamines inc depolarization and inc HR. Sympathetic
stimulation inc the chance that If channels (funny current) are open and thus inc HR.
SA node—located at junction of RA and SVC; “pacemaker” inherent dominance with slow phase of upstroke.
AV node—located in posteroinferior part of interatrial septum. Blood supply usually from RCA. 100-msec delay allows time for ventricular flling.
T-wave inversion may indicate ischemia or recent MI.
U wave—prominent in hypokalemia (think hyp“U”kalemia), bradycardia.
ANP - Acts via cGMP. Causes vasodilation and dec Na+ reabsorption at the renal collecting tubule. Dilates afferent renal arterioles and constricts
efferent arterioles, promoting diuresis and contributing to “aldosterone escape” mechanism.

BNP blood test used for diagnosing HF (very good negative predictive value). Available in recombinant form (nesiritide) for treatment of HF.
BaroReceptors:
Aortic arch transmits via vagus nerve to solitary nucleus of medulla (responds to changes in BP).
Carotid sinus (dilated region superior to bifurcation of carotid arteries) transmits via glossopharyngeal nerve to solitary nucleus of medulla (responds to
changes in BP). Chemoreceptors:

Peripheral—carotid and aortic bodies are stimulated by inc Pco2, dec pH of blood, and dec Po2 (< 60 mm Hg).
Central—are stimulated by changes in pH and Pco2 of brain interstitial fuid, which in turn are infuenced by arterial CO2 as H+ cannot cross the blood-
brain barrier. Do not directly respond to Po2. Central chemoreceptors become less responsive with chronically inc Pco2 (eg, COPD) > inc dependence
on peripheral chemoreceptors to detect dec O2 to drive respiration.
Hypotension— dec arterial pressure > dec stretch > dec afferent baroreceptor fring > inc efferent sympathetic fring and dec efferent parasympathetic
stimulation > vasoconstriction, inc HR, inc contractility, inc BP. Important in the response to severe hemorrhage.
Carotid massage— inc pressure on carotid sinus > inc stretch > inc afferent baroreceptor fring > inc AV node refractory period > dec HR.
Component of Cushing refex (triad of hypertension, bradycardia, and respiratory depression)— inc intracranial pressure constricts arterioles > cerebral
ischemia > inc pCO2 and dec pH > central

refex sympathetic inc in perfusion pressure (hypertension) > inc stretch > peripheral refex baroreceptor– induced bradycardia. ORGAN - FACTORS
DETERMINING AUTOREGULATION
Lungs - Hypoxia causes vasoconstriction
Heart - Local metabolites (vasodilatory): NO, CO2, dec O2

Brain - Local metabolites (vasodilatory): CO2 (pH)

Kidneys - Myogenic and tubuloglomerular feedback
Skeletal muscle - Local metabolites during exercise (vasodilatory): CO2, H+ , Adenosine, Lactate, K+ (CHALK). At rest: sympathetic tone in arteries.
Skin - Sympathetic vasoconstriction most important mechanism for temperature control.

Thyroglossal duct cyst presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs persistent cervical sinus
leading to pharyngeal cleft cyst in lateral neck). Thyroid follicular cells derived from endoderm. Parafollicular cells arise from 4th pharyngeal pouch.
FLAT PiG: FSH, LH, ACTH, TSH, PRL, GH.
B-FLAT: Basophils—FSH, LH, ACTH, TSH.

Acid PiG: Acidophils — PRL, GH.

Anterior pituitary (adenohypophysis) - Secretes FSH, LH, ACTH, TSH, prolactin, GH, and B-endorphin. Melanotropin (MSH) secreted from
intermediate lobe of pituitary. Derived from oral ectoderm (Rathke pouch).
Proopiomelanocortin derivatives— -endorphin, ACTH, and MSH.
Adrenal cortex and medulla - Adrenal cortex (derived from mesoderm) and medulla (derived from neural crest).
Dopamine - dec prolactin, TSH. Also called prolactin-inhibiting factor.
GHRH Analog (tesamorelin) used to treat HIV-associated lipodystrophy.

Tonic GnRH analog (eg, leuprolide) suppresses hypothalamic–pituitary–gonadal axis. Pulsatile GnRH leads to puberty, fertility.
TRH - inc TSH, prolactin.
GH - Secretion inc during exercise, deep sleep, puberty, hypoglycemia. Secretion dec by glucose, somatostatin, somatomedin (regulatory molecule
secreted by liver in response to GH acting on target tissues).
Desmopressin (ADH analog) is a treatment for central DI and nocturnal enuresis.
REGULATION Prolactin secretion from anterior pituitary is tonically inhibited by dopamine from tuberoinfundibular pathway of hypothalamus.
Prolactin in turn inhibits its own secretion by inc dopamine synthesis and secretion from hypothalamus. TRH inc prolactin secretion (eg, in 1° or 2°
hypothyroidism). Dopamine agonists (eg, bromocriptine) inhibit prolactin secretion and can be used in treatment of prolactinoma. Dopamine
antagonists (eg, most antipsychotics, metoclopramide) and estrogens (eg, OCPs, pregnancy) stimulate prolactin secretion.
Peripheral conversion is inhibited by glucocorticoids, -blockers, and propylthiouracil (PTU). Reverse T3 (rT3) is a metabolically inactive byproduct of
the peripheral conversion of T4 and its production is increased by growth hormone and glucocorticoids. Functions of thyroid peroxidase include
oxidation, organifcation of iodine, and coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT). Inhibited by PTU and methimazole.
Wolff-Chaikoff effect—protective autoregulation; sudden exposure to excess iodine temporarily turns off thyroid peroxidase > dec T3/T4 production.
Posterior pituitary - Derived from neuroectoderm.
Dopamine - dec prolactin, TSH. Also called prolactin-inhibiting factor. Dopamine antagonists (eg, antipsychotics) can cause galactorrhea due to
hyperprolactinemia.
MSH - inc melanogenesis by melanocytes. Causes hyperpigmentation in Cushing disease, as MSH and ACTH share the same precursor molecule,
proopiomelanocortin.
Breastfeeding > inc prolactin > dec GnRH > delayed postpartum ovulation (natural contraception).
Growth hormone - Also called somatotropin. Secreted by anterior pituitary. Stimulates linear growth and muscle mass through IGF-1 (somatomedin C)
secretion by liver. Inc insulin resistance (diabetogenic).
Thyroxine - Stimulates surfactant synthesis in Babies
Thyroxine-binding globulin (TBG) binds most T3/T4 in blood. Bound T3/T4 = inactive. Inc TBG in pregnancy, OCP use (estrogen > inc TBG) > inc
total T3/T4
Dec TBG in steroid use, nephrotic syndrome.
PTH inc serum Ca2+, dec serum PO4 3–, inc urine PO4 3– , inc urine cAMP.
PTH - Inc RANK-L (receptor activator of NF- B ligand) secreted by osteoblasts and osteocytes; binds RANK (receptor) on osteoclasts and their
precursors to stimulate osteoclasts and inc Ca2+ > bone resorption (intermittent PTH release can also stimulate bone formation).
Plasma Ca2+ exists in three forms:
Ionized/free (~ 45%, active form) Bound to albumin ( 40%) Bound to anions ( 15%)
Inc pH (less H+ ) > albumin binds more Ca2+ > dec ionized Ca2+ (eg, cramps, pain, paresthesias, carpopedal spasm) > inc PTH. Dec pH (more H+ ) >
albumin binds less Ca2+ > inc ionized Ca2+ > dec PTH.
Ionized/free Ca2+ is 1° regulator of PTH; changes in pH alter PTH secretion, whereas changes in albumin concentration do not.

Preproinsulin (synthesized in RER of pancreatic cells) > cleavage of “presignal” > proinsulin (stored in secretory granules) > cleavage of proinsulin >
exocytosis of insulin and C-peptide equally. Insulin and C-peptide are inc in insulinoma and sulfonylurea use, whereas exogenous insulin lacks C-
peptide.
Insulin - inc cellular uptake of K+ and amino acids. Unlike glucose, insulin does not cross placenta.
Insulin-dependent glucose transporters: GLUT4: adipose tissue, striated muscle (exercise can also GLUT4 expression) Insulin-independent
transporters: GLUT1: RBCs, brain, cornea, placenta. GLUT2 (bidirectional): islet cells, liver, kidney, GI tract (think 2-way street). GLUT3: brain,
placenta. GLUT5 (fructose): spermatocytes, GI tract. SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine.

Glucose enters B cells > ATP generated from glucose metabolism closes K+ channels (target of sulfonylureas) and depolarizes cell membrane .
Voltage-gated Ca2+ channels open > Ca2+ infux and stimulation of insulin exocytosis .
17-hydroxylase def -LABS dec androstenedione. PRESENTATION XY: ambiguous genitalia, undescended testes. XX: lacks 2° sexual development.
21-hydroxylase def - LABS inc renin activity; inc 17-hydroxyprogesterone PRESENTATION Most common. Presents in infancy (salt wasting) or
childhood (precocious puberty). XX: virilization.

LABS dec renin activity

11 -hydroxylase def - MINERALOCORTICOIDS dec aldosterone; inc 11-deoxycorticosterone (results in inc BP). PRESENTATION Presents in
infancy (severe hypertension) or childhood (precocious puberty). XX: virilization.
Cortisol -
Upregulates 1-receptors on arterioles > inc sensitivity to norepinephrine and epinephrine (permissive action)
At high concentrations, can bind to mineralocorticoid (aldosterone) receptors
Inc Insulin resistance (diabetogenic)
Inc Gluconeogenesis, lipolysis, and proteolysis (dec glucose utilization).
Dec Fibroblast activity (poor wound healing, dec collagen synthesis, inc striae).
Dec Infammatory and Immune responses:
Inhibits production of leukotrienes and prostaglandins
Inhibits WBC adhesion > neutrophilia
Blocks histamine release from mast cells
Eosinopenia, lymphopenia
Blocks IL-2 production
Exogenous corticosteroids can cause reactivation of TB and candidiasis (blocks IL-2 production).
Ghrelin - Acts on lateral area of hypothalamus (hunger center) to inc appetite.
Leptin - Acts on ventromedial area of hypothalamus (satiety center) to dec appetite.
Endocannabinoids Act at cannabinoid receptors in hypothalamus and nucleus accumbens.
In males, inc sex hormone–binding globulin (SHBG) lowers free testosterone > gynecomastia.
In females, dec SHBG raises free testosterone > hirsutism.
Inc estrogen (eg, OCPs, pregnancy) > inc SHBG.
Midgut: 6th week of development—physiologic herniation of midgut through umbilical ring. 10th week of development—returns to abdominal cavity
+ rotates around superior mesenteric artery (SMA), total 270° counterclockwise.

Failure of rostral fold closure (eg, sternal defects [ectopia cordis]), lateral fold closure (eg, omphalocele, gastroschisis), or caudal fold closure (eg,
bladder exstrophy).
Gastroschisis- ETIOLOGY Extrusion of abdominal contents through abdominal folds (typically right of umbilicus). COVERAGE Not covered by
peritoneum or amnion A ; “the guts come out of the gap (schism) in the letter G”. ASSOCIATIONS Not associated with chromosome abnormalities;
favorable prognosis.
Omphalocele- ETIOLOGY Failure of lateral walls to migrate at umbilical ring > persistent midline herniation of abdominal contents into umbilical
cord. COVERAGE Covered by peritoneum and amnion B (light gray shiny sac); “abdominal contents are sealed in the letter O”. ASSOCIATIONS
Associated with congenital anomalies (eg, trisomies 13 and 18, Beckwith-Wiedemann syndrome) and other structural abnormalities (eg, cardiac, GU,
neural tube).
Congenital umbilical hernia - Failure of umbilical ring to close after physiologic herniation of midgut. Covered by skin.
Tracheoesophageal anomalies - Esophageal atresia (EA) with distal tracheoesophageal fstula (TEF) is the most common (85%) and often presents as
polyhydramnios in utero (due to inability of fetus to swallow amniotic fuid). Neonates drool, choke, and vomit with frst feeding. TEFs allow air to
enter stomach (visible on CXR). Cyanosis is 2° to laryngospasm (to avoid refux-related aspiration). Clinical test: failure to pass nasogastric tube into
stomach.
Duodenal atresia—failure to recanalize. X-ray A shows “double bubble” (dilated stomach, proximal duodenum). Associated with Down syndrome.
Jejunal and ileal atresia—disruption of mesenteric vessels (typically SMA) > ischemic necrosis of fetal intestine > segmental resorption: bowel
becomes discontinuous. X-ray may show “triple bubble” (dilated stomach, duodenum, proximal jejunum) and gasless colon.
Hypertrophic pyloric stenosis - More common in firstborn males; associated with exposure to macrolides.
Ventral pancreatic bud contributes to uncinate process and main pancreatic duct. The dorsal pancreatic bud alone becomes the body, tail, isthmus, and
accessory pancreatic duct. Both the ventral and dorsal buds contribute to pancreatic head.
Spleen—arises in mesentery of stomach (hence is mesodermal) but has foregut supply (celiac trunk > splenic artery)
Retroperitoneal structures - SAD PUCKER:
Suprarenal (adrenal) glands [not shown]
Aorta and IVC
Duodenum (2nd through 4th parts) Pancreas (except tail)
Ureters [not shown]
Colon (descending and ascending) Kidneys
Esophagus (thoracic portion) [not shown] Rectum (partially) [not shown].
Hepatoduodenal - Borders the omental foramen, which connects the greater and lesser sacs. Pringle maneuver.
Hepatogastric - Separates greater and lesser sacs on the right, CUT TO ACCESS LESSER SAC.
Gastrosplenic - Separates greater and lesser sacs on the left.
Ventral mesentry - falciform, hepatoduodenal, hepatogastric
Dorsal mesentry - gastrocolic, gastrosplenic, splenorenal
(all related to liver are derived from ventral mesentry)
Falciform ligament - Liver to anterior abdominal wall - Ligamentum teres hepatis (derivative of fetal umbilical vein), patent paraumbilical veins -
Derivative of ventral mesentery.
Hepatoduodenal ligament - Liver to duodenum - Portal triad: proper hepatic artery, portal vein, common bile duct. Derivative of ventral mesentery.
Pringle maneuver—ligament is compressed manually or with a vascular clamp in omental foramen to control bleeding from hepatic inflow source.
Borders the omental foramen, which connects the greater and lesser sacs. Part of lesser omentum.
Hepatogastric ligament - Liver to lesser curvature of stomach - Gastric vessels - Derivative of ventral mesentery. Separates greater and lesser sacs on
the right. May be cut during surgery to access lesser sac. Part of lesser omentum.
Gastrocolic ligament - Greater curvature and transverse colon - Gastroepiploic arteries - Derivative of dorsal mesentery. Part of greater omentum.
Gastrosplenic ligament - Greater curvature and spleen - Short gastrics, left gastroepiploic vessels - Derivative of dorsal mesentery. Separates greater
and lesser sacs on the left. Part of greater omentum.
Splenorenal ligament - Spleen to left pararenal space - Splenic artery and vein, tail of pancreas - Derivative of dorsal mesentery.
Submucosa—includes submucosal nerve plexus (Meissner), secretes fuid
Muscularis externa—includes myenteric nerve plexus (Auerbach), motility
Serosa (when intraperitoneal), adventitia (when retroperitoneal).
Frequency of basal electric rhythm (slow waves), which originate in the interstitial cells of Cajal: duodenum > ileum > stomach. DIS
Duodenum Villi and microvilli inc absorptive surface. Brunner glands (bicarbonate-secreting cells of submucosa) and crypts of Lieberkühn (contain
stem cells that replace enterocytes/goblet cells and Paneth cells that secrete defensins, lysozyme, and TNF).
Two areas of the colon have dual blood supply from distal arterial branches (“watershed regions”) > susceptible in colonic ischemia: Splenic flexure—
SMA and IMA
Rectosigmoid junction—the last sigmoid arterial branch from the IMA and superior rectal artery.
Nutcracker syndrome—compression of left renal vein between superior mesenteric artery and aorta. May cause abdominal (fank) pain, gross hematuria
(from rupture of thin-walled renal varicosities), left-sided varicocele.
Superior mesenteric artery syndrome— characterized by intermittent intestinal obstruction symptoms (primarily postprandial pain) when SMA and
aorta compress transverse (third) portion of duodenum. Typically occurs in conditions associated with diminished mesenteric fat (eg, low body
weight/malnutrition).
Foregut - Celiac - Vagus - T12/L1 - Pharynx (vagus nerve only) and lower esophagus (celiac artery only) to proximal duodenum; liver, gallbladder,
pancreas, spleen (mesoderm).
Midgut - SMA - Vagus - L1 - Distal duodenum to proximal 2/3 of transverse colon.
Hindgut - IMA - Pelvic - L3 - Distal 1/3 of transverse colon to upper portion of anal canal.
Celiac trunk - Branches of celiac trunk: common hepatic, splenic, and left gastric.
Fetal erythropoiesis occurs in (YLSB): Yolk sac (3–8 weeks), Liver (6 weeks–birth), Spleen (10–28 weeks), Bone marrow (18 weeks to adult).
HbF has higher affnity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2 ) across
the placenta. HbA2 ( a2 d2 ) is a form of adult hemoglobin present in small amounts.
. Infammatory states (eg, bacterial infection) cause neutrophilia and changes in neutrophil morphology, such as left shift, toxic granulation (dark blue,
coarse granules), Döhle bodies (light blue, peripheral inclusions, arrow in B ), and cytoplasmic vacuoles. Neutrophil chemotactic agents: C5a, IL-8,
LTB4 , 5-HETE (leukotriene precursor), kallikrein, platelet-activating factor, N- formylmethionine (bacterial proteins).
Left shift— inc neutrophil precursors (eg, band cells, metamyelocytes) in peripheral blood. Refects states of myeloid proliferation (eg, infammation,
CML).
Leukoerythroblastic reaction—left shift accompanied by immature RBCs. Suggests bone marrow infltration (eg, myelofbrosis, metastasis).
RBC - Membranes contain Cl /HCO3 antiporter, which allow RBCs to export HCO3 and transport CO2 from the periphery to the lungs for elimination.
Bluish color (polychromasia) on Wright-Giemsa stain of reticulocytes represents residual ribosomal RNA.
Neutrophils-
Specific granules - LAP, lactoferrin, collagenase, lysozyme. Azurophilic granules (lysosomes) - proteinases, acid phosphatase, MPO, B-glucuronidase.
Platelats - Contain dense granules (Ca2+, ADP, Serotonin, Histamine; CASH) and α granules (vWF, fibrinogen, fibronectin, platelet factor 4). vWF
receptor: GpIb. Fibrinogen receptor: GpIIb/IIIa. Monocytes - Kidney shaped nucleus; frosted glass cytoplasm.
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.
Eosinophils - Produce histaminase, major basic protein (MBP, a helminthotoxin), eosinophil peroxidase, eosinophil cationic protein, and
eosinophilderived neurotoxin. Causes of eosinophilia (PACMAN Eats): Parasites Asthma Chronic adrenal insuffciency Myeloproliferative disorders
Allergic processes Neoplasia (eg, Hodgkin lymphoma) Eosinophilic granulomatosis with polyangiitis. Basophils - Mediate allergic reaction. Densely
basophilic granules contain heparin (anticoagulant) and histamine (vasodilator). Leukotrienes synthesized and released on demand.
Mast cells - Activated by tissue trauma, C3a and C5a, surface IgE cross-linking by antigen (IgE receptor aggregation) > degranulation > release of
histamine, heparin, tryptase, and eosinophil chemotactic factors. Vancomycin, opioids, and radiocontrast dye can elicit IgE-independent mast cell
degranulation.
Mastocytosis—rare; proliferation of mast cells in skin and/or extracutaneous organs. Associated with c-KIT mutations and inc serum tryptase.
NK cells - lytic granules (perforins and granzymes), CD56, CD16 (FcR).
Rotator cuf muscles - Shoulder muscles that form the rotator cuff:
Supraspinatus (suprascapular nerve)— abducts arm initially (before the action of the deltoid); most common rotator cuff injury (trauma or degeneration
and impingement tendinopathy or tear [arrow in A ]), assessed by “empty/full can” test
Infraspinatus (suprascapular nerve)— externally rotates arm; pitching injury
teres minor (axillary nerve)—adducts and externally rotates arm

Subscapularis (upper and lower subscapular nerves)—internally rotates and adducts arm Innervated primarily by C5-C6. Arm abduction DEGREE
MUSCLE NERVE 0°–15° Supraspinatus Suprascapular 15°–90° Deltoid Axillary
> 90° Trapezius Accessory
> 90° Serratus Anterior Long Thoracic (SALT)

Radial (C5-T1) - Compression of axilla, eg, due to crutches or sleeping with arm over chair (“Saturday night palsy”), Midshaft fracture of humerus ,
Repetitive pronation/supination of forearm, eg, due to screwdriver use (“fnger drop”) - Injuries above the elbow cause loss of sensation over posterior
arm/forearm and dorsal hand, wrist drop (loss of elbow, wrist, and fnger extension) with dec grip strength (wrist extension necessary for maximal
action of fexors). Injuries below the elbow cause distal paresthesias without wrist drop. Tricep function and posterior arm sensation spared in midshaft
fracture.

Ulnar - thumb adduction

Median - thumb opposition, abduction, flexion
Recurrent branch of median nerve (C5-T1) - Superfcial laceration of palm. “Ape hand”. Loss of thenar muscle group: opposition, abduction, and
flexion of thumb. No loss of sensation.
Klumpke palsy- Traction or tear of lower trunk: C8-T1 roots. Infants—upward force on arm during delivery. Adults—trauma (eg, grabbing a tree
branch to break a fall). Intrinsic hand muscles: lumbricals, interossei, thenar, hypothenar. Claw hand: lumbricals normally fex MCP joints and extend
DIP and PIP joints.
Scaphoid (palpable in anatomic snuff box) is the most commonly fractured carpal bone, typically due to a fall on an outstretched hand. Complications
of proximal scaphoid fractures include avascular necrosis and nonunion due to retrograde blood supply from a branch of the radial artery. Occult
fracture not always seen on initial x-ray. Dislocation of lunate may impinge median nerve and cause carpal tunnel syndrome.
Hand muscles-
Thenar (median)—Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis, superfcial head (deep head by ulnar nerve). Hypothenar (ulnar)
—Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi brevis. Both groups perform the same functions: Oppose, Abduct, and Flex
(OAF).
Dorsal interossei (ulnar)—abduct the fngers. Palmar interossei (ulnar)—adduct the fngers. (DAB = Dorsals ABduct. PAD = Palmars ADduct.)
Lumbricals (1st/2nd, median; 3rd/4th, ulnar)— flex at the MCP joint, extend PIP and DIP joints.
Alar plate (dorsal): sensory; regulated by TGF- (including bone morphogenetic protein [BMP])
Basal plate (ventral): motor; regulated by sonic hedgehog gene (SHH)
Five secondary vesicles
Telencephalon - Cerebral hemispheres, Basal ganglia; Lateral ventricles
Diencephalon - Thalamus, Hypothalamus, Retina; Third ventricle Mesencephalon - Midbrain; Cerebral aqueduct
Metencephalon - Pons Cerebellum; Upper part of fourth ventricle Myelencephalon - Medulla; Lower part of fourth ventricle
Neural crest—PNS neurons (dorsal root ganglia, autonomic ganglia [sympathetic, parasympathetic, enteric]), PNS glial cells (Schwann cells, satellite
cells), adrenal medulla, melanocytes, face/ branchial arch mesenchyme.
NTDs - Associated with diabetes and folate defciency during pregnancy. Inc -fetoprotein (AFP) in amniotic fuid and serum (except spina bifda occulta
= normal AFP). Inc acetylcholinesterase (AChE) in amniotic fuid is a helpful confrmatory test.
Chiari I malformation Ectopia of cerebellar tonsils inferior to foramen magnum (1 structure). Congenital, usually asymptomatic in childhood, manifests
in adulthood with headaches and cerebellar symptoms. Associated with spinal cavitations (eg, syringomyelia).
Chiari II malformation Herniation of cerebellum (vermis and tonsils) and medulla (2 structures) through foramen magnum > noncommunicating
hydrocephalus. Usually associated with aqueductal stenosis, lumbosacral myelomeningocele (may present as paralysis/sensory loss at and below the
level of the lesion). More severe than Chiari I, usually presents early in life.
Tongue development-
1st pharyngeal arch forms anterior 2/3 of tongue (sensation via CN V3 , taste via CN VII). 3rd and 4th pharyngeal arches form posterior 1/3 of tongue
(sensation and taste mainly via CN IX, extreme posterior via CN X). Motor innervation is via CN XII to hyoglossus (retracts and depresses tongue),
genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing). Motor innervation is via CN X to
palatoglossus (elevates posterior tongue during swallowing).

GLUT1 - P-RBC
GLUT2 - LKG-B
GLUT3 - BP
GLUT4 - AS
GLUT5 - GS
SGLT1/2 - SK
insulin dependent - GLUT4
insulin independent - GLUT1,2,3,5; SGLT1,2 (BRICK-LIPS)
. Inc insulin response with oral vs IV glucose due to incretins (eg, glucagon- like peptide 1 [GLP-1], glucose-dependent insulinotropic polypeptide
[GIP]), which are released after meals and inc B cell sensitivity to glucose. Release dec by a2, inc by B2 stimulation (2 = regulates insulin).

Extinction Discontinuation of reinforcement (positive or negative) eventually eliminates behavior. Can occur in operant or classical conditioning.
Dissociation Temporary, drastic change in personality, memory, consciousness, or motor behavior to avoid emotional stress. Patient has incomplete or
no memory of traumatic event. A survivor of sexual abuse sees the abuser and suddenly becomes numb and detached.
Intellectualization Using facts and logic to emotionally distance oneself from a stressful situation. A patient diagnosed with cancer discusses the
pathophysiology of the disease.
Rationalization Asserting plausible explanations for events that actually occurred for other reasons, usually to avoid self-blame. An employee who was
recently fred claims that the job was not important anyway.
Reaction formation Replacing a warded-off idea or feeling with an emphasis on its opposite (vs sublimation). A stepfather treats a child he resents with
excessive nurturing and overprotection. Repression Involuntarily withholding an idea or feeling from conscious awareness (vs suppression).
Suppression Intentionally withholding an idea or feeling from conscious awareness (vs repression).
Grief The fve stages of grief per the Kübler-Ross model are denial, anger, bargaining, depression, and acceptance (may occur in any order). Other
common grief symptoms include shock, guilt, sadness, anxiety, yearning, and somatic symptoms that usually occur in waves. Auditory or visual
hallucinations can occur in the context of normal bereavement (eg, hearing the deceased speaking). Duration varies widely. Persistent complex
bereavement disorder is diagnosed if severe grief interferes with functioning for > 12 months.
Pronephros—week 3 of development; then degenerates. Mesonephros—week 4 of development; functions as interim kidney for 1st trimester; persists
in the male genital system as Wolffian duct, forming ductus deferens and epididymis. Metanephros— permanent; first appears in week 5 of
development; nephrogenesis is normally completed by week 36 of gestation.
Ureteropelvic junction—last to canalize > congenital obstruction. Can be unilateral or bilateral. Most common pathologic cause of prenatal
hydronephrosis. Detected by prenatal ultrasound. Horseshoe kidney - Inferior poles of both kidneys fuse abnormally. As they ascend from pelvis during
fetal development, horseshoe kidneys get trapped under inferior mesenteric artery and remain low in the abdomen. Kidneys can function normally, but
associated with hydronephrosis (eg, ureteropelvic junction obstruction), renal stones, infection, inc risk of renal cancer. Higher incidence in
chromosomal aneuploidy (eg, Turner syndrome, trisomies 13, 18, 21).
Unilateral renal agenesis - Ureteric bud fails to develop and induce differentiation of metanephric mesenchyme > complete absence of kidney and
ureter.
Multicystic dysplastic kidney - Ureteric bud develops, but fails to induce differentiation of metanephric mesenchyme > nonfunctional kidney consisting
of cysts and connective tissue. Predominantly nonhereditary and usually unilateral; bilateral leads to Potter sequence.
Posterior urethral valves - Membrane remnant in the posterior (prostatic) urethra in males; its persistence can lead to urethral obstruction. Can be
diagnosed prenatally by bilateral hydronephrosis and dilated or thick-walled bladder on ultrasound. Most common cause of bladder outlet obstruction
in male infants. Associated with oligohydramnios in cases of severe obstruction.
Water (ureters) flows over the iliacs and under the bridge (uterine artery or vas deferens).
Left kidney is taken during living donor transplantation because it has a longer renal vein.

Blood supply to ureter: Proximal—renal arteries Middle—gonadal artery, aorta, common and internal iliac arteries Distal—internal iliac and superior
vesical arteries. 3 common points of ureteral obstruction: ureteropelvic junction, pelvic inlet, ureterovesical junction. Water (ureters) flows over the
iliacs and under the bridge (uterine artery or vas deferens).

Plasma volume can be measured by radiolabeling albumin. Extracellular volume can be measured by inulin or mannitol. Serum osmolality = 275– 295
mOsm/kg H2 O. Plasma volume = TBV x (1 – Hct). (TBV=total blood volume).
Glomerular filtration barrier - Responsible for filtration of plasma according to size and charge selectivity. Composed of: Fenestrated capillary
endothelium Basement membrane with type IV collagen chains and heparan sulfate Visceral epithelial layer consisting of podocyte foot processes
(FPs). Charger barrier—glomerular filtration barrier contains charged glycoproteins that prevent entry of charged molecules (eg, albumin). Size barrier
—fenestrated capillary endothelium (prevents entry of > 100 nm molecules/blood cells); podocyte foot processes interpose with glomerular basement
membrane (GBM); slit diaphragm (prevents entry of molecules > 4–5 nm).

Filtration fraction (FF) = GFR/RPF

Filtered load (mg/min) = GFR (mL/min) × plasma concentration (mg/mL).
Inulin clearance = GFR.
Creatine clearance approximates GFR (slightly overestimates).
PAH clearance = eRPF (eRPF slightly underestimates true RPF).
Cinulin = GFR = Uinulin V/Pinulin
Cpah = eRPF = Upah V/Ppah.
GFR can be estimated with creatinine clearance. RPF is best estimated with PAH clearance. Prostaglandins Dilate Afferent arteriole (PDA).
Angiotensin II Constricts Efferent arteriole (ACE). Prostaglandins preferentially dilate afferent arteriole ( inc RPF, inc GFR, so no change in FF).
Angiotensin II preferentially constricts efferent arteriole (dec RPF, inc GFR, so inc FF). Dehydration - dec GFR, dec dec RPF, inc FF (GFR/RPF)

In adults, at plasma glucose of 200 mg/dL, glucosuria begins (threshold). At rate of 375 mg/min, all transporters are fully saturated (Tm). Normal
pregnancy is associated with inc GFR. With inc filtration of all substances, including glucose, the glucose threshold occurs at lower plasma glucose
concentrations > glucosuria at normal plasma glucose levels. Sodium- glucose cotransporter 2 (SGLT2) inhibitors (eg, - ozin drugs) result in glucosuria
at plasma concentrations < 200 mg/dL. Glucosuria is an important clinical clue to diabetes mellitus. Splay phenomenon—Tm for glucose is reached
gradually rather than sharply due to the heterogeneity of nephrons (ie, different Tm points); represented by the portion of the titration curve between
threshold and Tm.

Sonic hedgehog (SHH) gene - Zone of polarizing activity at base of limb buds - Anterior-posterior axis patterning, CNS development - Mutations >
holoprosencephaly.
Wnt-7 gene - Apical ectodermal ridge at distal end of each limb - Dorsal-ventral axis patterning, limb development - “Vnt-7”
Fibroblast growth factor (FGF) gene - Apical ectodermal ridge - Limb lengthening (via mitosis of mesoderm) - “Look at that Fetus, Growing Fingers”.
Homeobox (Hox) genes - Multiple - Segmental organization in cranial-caudal direction, transcription factor coding - Mutations > appendages in wrong
locations. Isotretinoin > inc Hox gene expression.

Early embryonic development-

Within week 1 - hCG secretion begins around the time of implantation of blastocyst. Blastocyst “sticks” at day 6.
Within week 2 - Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers.
Within week 3 - Gastrulation forms trilaminar embryonic disc. Cells from epiblast invaginate > primitive streak > endoderm, mesoderm, ectoderm.
Notochord arises from midline mesoderm and induces overlying ectoderm to become neural plate. 3 weeks = 3 layers.
Weeks 3–8 (embryonic period) - Neural tube formed by neuroectoderm and closes by week 4. Organogenesis. Extremely susceptible to teratogens.
Week 4 - Heart begins to beat. Cardiac activity visible by transvaginal ultrasound. Upper and lower limb buds begin to form. 4 weeks = 4 limbs and 4
heart chambers.
Week 6 - Fetal movements start.
Week 8 - Genitalia have male/female characteristics.
Surface ectoderm Epidermis; adenohypophysis (from Rathke pouch); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactory
epithelium; anal canal below the pectinate line; parotid, sweat, mammary glands.
Neural crest Enterochromaffn cells, Leptomeninges (arachnoid, pia), Melanocytes, Odontoblasts, PNS ganglia (cranial, dorsal root, autonomic),
Adrenal medulla, Schwann cells, Spiral membrane (aorticopulmonary septum), Endocardial cushions (also derived partially from mesoderm), Skull
bones. ELMO PASSES Neural crest—think PNS and non-neural structures nearby.
Mesoderm- Muscle, bone, connective tissue, serous linings of body cavities (eg, peritoneum, pericardium, pleura), spleen (develops within foregut
mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, upper 2/3 of vagina, kidneys, adrenal cortex, dermis, testes, ovaries,
microglia, dura mater, tracheal cartilage.
Mesodermal defects = VACTERL association: Vertebral defects Anal atresia Cardiac defects Tracheo-Esophageal fstula Renal defects Limb defects
(bone and muscle).
Endoderm-
Gut tube epithelium (including anal canal above the pectinate line), most of urethra and lower 1/3 of vagina (derived from urogenital sinus), luminal
epithelial derivatives (eg, lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular and parafollicular [C] cells).
“Enternal” layer.
Agenesis Absent organ due to absent primordial tissue.
Aplasia Absent organ despite presence of primordial tissue.
Deformation Extrinsic mechanical distortion (eg, congenital torticollis); occurs after embryonic period.
Malformation Intrinsic developmental defect; occurs during embryonic period (weeks 3–8 of development).
Alkylating agents - Absence of digits, multiple anomalies
Antiepileptic drugs - Neural tube defects, cardiac defects, cleft palate, skeletal abnormalities (eg, phalanx/nail hypoplasia, facial dysmorphism) High-
dose folate supplementation recommended; most commonly valproate, carbamazepine, phenytoin, phenobarbital
Isotretinoin - Craniofacial (eg, microtia, dysmorphism), CNS, cardiac, and thymic defects Contraception mandatory.
Methimazole - Aplasia cutis congenita (congenital absence of skin, particularly on scalp)
Warfarin - Bone and cartilage deformities (stippled epiphyses, nasal and limb hypoplasia), optic nerve atrophy, fetal cerebral hemorrhage. Do not wage
warfare on the baby; keep it heppy with heparin (does not cross placenta).
Diabetes in pregnancy - Caudal regression syndrome, cardiac defects (eg, VSD), neural tube defects, macrosomia, neonatal hypoglycemia (due to islet
cell hyperplasia), polycythemia, neonatal respiratory distress syndrome.
Methylmercury - Neurotoxicity. Higher concentrations in top-predator fsh (eg, shark, swordfsh, king mackerel, tilefsh). TKSS
Neonatal abstinence syndrome - Treatment (for opiate use): methadone, morphine, buprenorphine.
Syncytiotrophoblast - Lacks MHC I expression > dec chance of attack by maternal immune system.
Cytotrophoblast - Inner layer.
Syncytiotrophoblast - Outer layer.
Cytotrophoblast - Inner layer of chorionic villi; makes cells.
Syncytiotrophoblast - Outer layer of chorionic villi; synthesizes and secretes hormones, eg, hCG (structurally similar to LH; stimulates corpus luteum
to secrete progesterone during frst trimester). Lacks MHC I expression > dec chance of attack by maternal immune system.
Splitting 0–4 days: separate chorion and amnion (di-di)
Splitting 4–8 days: shared Chorion (mo-di)
Splitting 8–12 days: shared Chorion and Amnion (mo-mo)
Splitting 13+ days: shared Body (conjoined)

Umbilical arteries and vein are derived from allantois.

Urachus - Allantois forms from hindgut and extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and umbilicus.
Failure of urachus to involute can lead to anomalies that may increase risk of infection and/or malignancy (eg, adenocarcinoma) if not treated.
Obliterated urachus is represented by the median umbilical ligament after birth, which is covered by median umbilical fold of the peritoneum.
Patent urachus - Total failure of urachus to obliterate > urine discharge from umbilicus.
Urachal cyst - Partial failure of urachus to obliterate; fuid-flled cavity lined with uroepithelium, between umbilicus and bladder. Cyst can become
infected and present as painful mass below umbilicus.
Vesicourachal diverticulum - Slight failure of urachus to obliterate > outpouching of bladder.
Vitelline duct - Also called omphalomesenteric duct. Connects yolk sac to midgut lumen. Obliterates during week 7 of development.
Patent vitelline duct Total failure of vitelline duct to obliterate > meconium discharge from umbilicus.
Vitelline duct cyst Partial failure of vitelline duct to obliterate. Inc risk for volvulus.
Meckel diverticulum Slight failure of vitelline duct to obliterate > outpouching of ileum (true diverticulum). Usually asymptomatic. May have
heterotopic gastric and/or pancreatic tissue > melena, hematochezia, abdominal pain.
Lung development - Occurs in five stages. Begins with the formation of lung bud from distal end of respiratory diverticulum during week 4 of
development.
EPCSA - 7, 17 ,25, birth, 8 years
Embryonic (weeks 4–7) Lung bud > trachea > bronchial buds > mainstem bronchi > secondary (lobar) bronchi > tertiary (segmental) bronchi. Errors at
this stage can lead to tracheoesophageal fistula.
Pseudoglandular (weeks 5–17) Endodermal tubules > terminal bronchioles. Surrounded by modest capillary network. Respiration impossible,
incompatible with life.
Canalicular (weeks 16–25) Terminal bronchioles > respiratory bronchioles > alveolar ducts. Surrounded by prominent capillary network. Airways
increase in diameter. Pneumocytes develop starting at

week 20 of development. Respiration capable at ~ week 25.

Saccular (week 24–birth) Alveolar ducts > terminal sacs. Terminal sacs separated by 1° septae.
Alveolar (week 36–8 years) Terminal sacs > adult alveoli (due to 2° septation). In utero, “breathing” occurs via aspiration and expulsion of amniotic
fluid > inc pulmonary vascular resistance through gestation. At birth, air replaces fluid > dec pulmonary vascular resistance.
Club cells - Nonciliated; low columnar/cuboidal with secretory granules. Located in bronchioles. Degrade toxins via cytochrome P-450; secrete
component of surfactant; progenitor cells for club and ciliated cells.
Type II pneumocytes - Cuboidal and clustered.
2 functions:
1. Serve as stem cell precursors for 2 cell types (type I and type II cells); proliferate during lung damage. 2. Secrete surfactant from lamellar bodies
(arrowheads in B ).
Surfactant— dec alveolar surface tension, dec alveolar collapse, dec lung recoil, and inc compliance. Composed of multiple lecithins, mainly
dipalmitoylphosphatidylcholine (DPPC). Synthesis begins ~20 weeks’ gestation and achieves mature levels ~35 weeks of gestation. Corticosteroids
important for fetal surfactant synthesis and lung development.
Collapsing pressure (P) = 2 (surface tension)/radius
Law of Laplace—Alveoli have inc tendency to collapse on expiration as radius dec.

Hemosiderin-laden macrophages (heart failure cells) may be found in the setting of pulmonary edema or alveolar hemorrhage.
Neonatal respiratory distress syndrome - Surfactant defciency > inc surface tension > alveolar collapse (“ground-glass” appearance of lung felds). Risk
factors: prematurity, diabetes during pregnancy (due to inc fetal insulin), C-section delivery (dec release of fetal glucocorticoids; less stressful than
vaginal delivery). Treatment: maternal steroids before birth; exogenous surfactant for infant. Therapeutic supplemental O2 can result in Retinopathy of
prematurity, Intraventricular hemorrhage, Bronchopulmonary dysplasia (RIB). Screening tests for fetal lung maturity: lecithinsphingomyelin (L/S) ratio
in amniotic fuid ( 2 is healthy; < 1.5 predictive of NRDS), foam stability index, surfactant-albumin ratio. Persistently low O2 tension > risk of PDA.
Airway resistance highest in the large- to medium-sized bronchi. Small airways consist of bronchioles that further divide into terminal bronchioles
(large numbers in parallel > least airway resistance). Warms, humidifes, and flters air but does not participate in gas exchange > “anatomic dead space.”
Cartilage and goblet cells extend to the end of bronchi. Pseudostratifed ciliated columnar cells primarily make up epithelium of bronchus and extend to
beginning of terminal bronchioles, then transition to cuboidal cells. Clear mucus and debris from lungs (mucociliary escalator). Airway smooth muscle
cells extend to end of terminal bronchioles (sparse beyond this point).
Mostly cuboidal cells in respiratory bronchioles, then simple squamous cells up to alveoli. Cilia terminate in respiratory bronchioles.

Relation of the pulmonary artery to the bronchus at each lung hilum is described by RALS—Right Anterior; Left Superior.
Right lung is a more common site for inhaled foreign bodies because right main stem bronchus is wider, more vertical, and shorter than the left. If you
aspirate a peanut:

While supine—usually enters superior segment of right lower lobe. While lying on right side—usually enters right upper lobe. While upright—usually
enters right lower lobe.
Diaphragm structures - Structures perforating diaphragm:
At T8: IVC, right phrenic nerve

At T10: esophagus, vagus (CN 10; 2 trunks)

At T12: aorta (red), thoracic duct (white), azygos vein (blue) (“At T-1-2 it’s the red, white, and blue”)
C3, 4, 5 keeps the diaphragm alive. Other bifurcations: The Common Carotid bifourcates at C4. The Trachea bifourcates at T4. The abdominal aorta
bifourcates at L4.
Lymph node -
Follicle Site of B-cell localization and proliferation. In outer cortex. 1° follicles are dense and quiescent. 2° follicles have pale central germinal centers
and are active.
Medulla Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses. Medullary sinuses communicate with
efferent lymphatics and contain reticular cells and macrophages.
Paracortex Contains T cells. Region of cortex between follicles and medulla. Contains high endothelial venules through which T and B cells enter from
blood. Not well developed in patients with DiGeorge syndrome. Paracortex enlarges in an extreme cellular immune response (eg, EBV and other viral
infections > paracortical hyperplasia > lymphadenopathy).

Sleep physiology - Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian
rhythm controls nocturnal release of ACTH, prolactin, melatonin, norepinephrine: SCN > norepinephrine release > pineal gland > inc melatonin. SCN
is regulated by environment (eg, light). Two stages: rapid-eye movement (REM) and non-REM. Alcohol, benzodiazepines, and barbiturates are
associated with REM sleep and N3 sleep; norepinephrine also dec REM sleep. Benzodiazepines are useful for night terrors and sleepwalking by dec N3
and REM sleep.

SLEEP STAGE (% OF TOTAL SLEEP TIME IN YOUNG ADULTS) DESCRIPTION EEG WAVEFORM AND NOTES
Awake (eyes open) Alert, active mental concentration. Beta (highest frequency, lowest amplitude). Awake (eyes closed) Alpha.
Non-REM sleep
Stage N1 (5%) Light sleep. Theta.
Stage N2 (45%) Deeper sleep; when bruxism (“twoth” [tooth] grinding) occurs. Sleep spindles and K complexes.
Stage N3 (25%) Deepest non-REM sleep (slow-wave sleep); sleepwalking, night terrors, and bedwetting occur (wee and fee in N3). Delta (lowest
frequency, highest amplitude), deepest sleep stage. REM sleep (25%) Loss of motor tone, inc brain O2 use, variable pulse/BP, inc ACh. REM is when
dreaming, nightmares, and penile/clitoral tumescence occur; may serve memory processing function. Extraocular movements due to activity of PPRF
(paramedian pontine reticular formation/ conjugate gaze center). Occurs every 90 minutes, and duration inc through the night. Beta. Changes in elderly:
dec REM, dec N3, inc sleep latency, inc early awakenings. Changes in depression: inc REM sleep time, dec REM latency, dec N3, repeated nighttime
awakenings, early morning awakening (terminal insomnia). Change in narcolepsy: dec REM latency. At night, BATS Drink Blood.
N2 - bruxism; sleep spindles and K complexes.
N3 - sleepwalking, bedwetting, night terrors.
REM - Loss of motor tone, inc brain O2 use, variable pulse/BP, inc ACh, dreaming, nightmares, penile tumescence, memory processing, extraocular
movements.
Changes in elderly: dec REM, dec N3, inc sleep latency, inc early awakenings.

Changes in depression: inc REM sleep time, dec REM latency, dec N3, repeated nighttime awakenings, early morning awakening (terminal insomnia).

Change in narcolepsy: dec REM latency.

Alcohol, benzodiazepines, and barbiturates - dec REM sleep and dec N3 sleep; Norepinephrine - dec REM sleep.
Benzodiazepines are useful for night terrors and sleepwalking by dec N3 and REM sleep. (N3 - sleepwalking, bedwetting, night terrors)
waveforms - BATS-DB

N3 - night terrors REM - nightmares

N1 - 5
N2 - 45
N3 - 25
REM - 25
Hypothalamus -
Lateral nucleus Hunger. Destruction > anorexia, failure to thrive (infants). Stimulated by ghrelin, inhibited by leptin. Lateral injury makes you lean.
Ventromedial nucleus Satiety. Destruction (eg, craniopharyngioma) > hyperphagia. Stimulated by leptin. Ventromedial injury makes you very massive.
Anterior nucleus Cooling, parasympathetic. A/C = Anterior Cooling.

Posterior nucleus Heating, sympathetic. Heating controlled by posterior nucleus (“hot pot”).
Suprachiasmatic nucleus Circadian rhythm. SCN is a Sun-Censing Nucleus.
Supraoptic and paraventricular nuclei Synthesize ADH and oxytocin. SAD POX: Supraoptic = ADH, Paraventricular = OXytocin. ADH and oxytocin
are carried by neurophysins down axons to posterior pituitary, where these hormones are stored and released.
Preoptic nucleus Thermoregulation, sexual behavior. Releases GnRH. Failure of GnRH-producing neurons to migrate from olfactory pit > Kallmann
syndrome.

Thalamic nuclei-
VPL - INPUT Spinothalamic and dorsal columns/medial lemniscus. Vibration, proprioception, pain, temp, pressure, light touch. VPM - INPUT
Trigeminal and gustatory pathway. Face sensation, taste.
VAL - INPUT Basal ganglia, cerebellum. Motor.
LGN - INPUT CN II, optic chiasm, optic tract. Light
MGN - INPUT Superior olive and inferior colliculus of tectum. Music.

Mesocortical - dec activity > “negative” symptoms Mesolimbic - inc activity > “positive” symptoms Nigrostriatal - dec activity > extrapyramidal
symptoms

Tuberoinfundibular - dec activity > inc prolactin

Direct (excitatory) pathway—SNc input to the striatum via the nigrostriatal dopaminergic pathway releases GABA, which inhibits GABA release from
the GPi, disinhibiting the Thalamus via the GPi (inc motion).
Indirect (inhibitory) pathway—SNc input to the striatum via the nigrostriatal dopaminergic pathway releases GABA that disinhibits STN via GPe
inhibition, and STN stimulates GPi to inhibit the thalamus (dec motion).
DIRECT - striatum > GPi > thalamus > inc motion.
INDIRECT - striatum > GPe > STN > GPi > thalamus > dec motion.
(LEARN WIT REVERSE ENGINEERING)
Watershed zones - Cortical border zones occur between anterior and middle cerebral arteries and posterior and middle cerebral arteries (blue areas in A
). Internal border zones occur between the superfcial and deep vascular territories of the middle cerebral artery (red areas in A ). Common locations for
brain metastases. Infarct due to severe hypoperfusion:
ACA-MCA watershed infarct—proximal upper and lower extremity weakness (“manin-a-barrel syndrome”). PCA-MCA watershed infarct—higher-
order visual dysfunction.
Brain stem—ventral view
4 CN are above pons (I, II, III, IV).
4 CN exit the pons (V, VI, VII, VIII).
4 CN are in medulla (IX, X, XI, XII).
4 CN nuclei are medial (III, IV, VI, XII). “Factors of 12, except 1 and 2.”
Cranial nerve nuclei - Located in tegmentum portion of brain stem (between dorsal and ventral portions): Midbrain—nuclei of CN III, IV
Pons—nuclei of CN V, VI, VII, VIII
Medulla—nuclei of CN IX, X, XII
Spinal cord—nucleus of CN XI Lateral nuclei = sensory (alar plate). —Sulcus limitans—
Medial nuclei = motor (basal plate).
Vagal nuclei-
NTS (vomiting) - visceral sensory info, vomiting - CN 7, 9, 10
NA(Nucleus ambiguus) - motor to pharynx, larynx, upper esophagus - CN 9, 10, 11(cranial portion)
DMN - PANS to heart, lungs, upper GI - CN 10
Cranial nerves and vessel pathways-
Anterior cranial fossa (through ethmoid bone) - Cribriform plate - CN I
Middle cranial fossa (through sphenoid bone) - Optic canal CN 2, Ophthalmic artery
Superior orbital fissure - CN III, CN IV, CN VI, CN V1. Foramen Rotundum - CN V2
Foramen Ovale - CN V3
Foramen spinosum - Middle meningeal artery
Posterior cranial fossa (through temporal or occipital bone)- Internal auditory meatus - 7, 8
Jugular foramen - 9, 10, 11, jugular vein
Hypoglossal canal - 12
Foramen magnum - Brain stem, Spinal root of CN XI, vertebral arteries
Sensory-1,2,8. Motor-3,4,6,11,12. Both-5,7,9,10.
parotid-9, submandibular, sublingual-7
pharynx/larynx elevation - 9. soft palate elevation - 10.
7 - auditory volume modulation (stapedius)
5 - dampening of loud noises (tensor tympani)
Cranial nerve reflexes- REFLEX AFFERENT EFFERENT
Corneal AFFERENT V1 ophthalmic (nasociliary branch) EFFERENT Bilateral VII (temporal branch—orbicularis oculi) Cough AFFERENT X
EFFERENT X (also phrenic and spinal nerves)
Gag AFFERENT IX EFFERENT X
Jaw jerk AFFERENT V3 (sensory—muscle spindle from masseter) EFFERENT V3 (motor—masseter)
Lacrimation AFFERENT V1 (loss of refex does not preclude emotional tears). EFFERENT VII Pupillary AFFERENT II EFFERENT III
LP Needle passes through: SF-SILEDAS

Needle passes through:

skin
fascia and fat
supraspinous ligament
interspinous ligament
ligamentum favum
epidural space (epidural anesthesia needle stops here) dura mater arachnoid mater

subarachnoid space (CSF collection occurs here) (cervical is always close to the horns) (Ascending tracts synapse and then cross.) (Descending tracts
cross and then synapse.) Cremasteric refex = L1, L2

Patellar refex = L2-L4

Achilles refex = S1, S2
Anal wink refex = S3, S4
Biceps and brachioradialis refexes = C5, C6 Triceps refex = C6, C7, C8

Medial longitudinal fasciculus - Internuclear ophthalmoplegia - (impaired adduction of ipsilateral eye; nystagmus of contralateral eye with abduction).
Multiple sclerosis. INO = Ipsilateral adduction failure, Nystagmus Opposite. Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3
nucleus of adducting eye via MLF.

Frontal lobe - broca, frontal eye field, primary motor, premotor, prefrontal. Parietal cortex - primary somatosensory, somatosensory association.

Temporal lobe - wernicke, primary auditory, limbic association. Occipital lobe - primary visual cortex

ASCENDING Dorsal column (pressure, vibration, fine touch, [conscious] proprioception) • Fasciculus graciLis (Lower body, legs) • Fasciculus
cUneatus (Upper body, arms). DESCENDING Lateral corticospinal tract (voluntary motor) • Sacral • Cervical. Anterior corticospinal tract (voluntary
motor).
ASCENDING Lateral spinothalamic tract (pain, temperature) • Sacral • Cervical. Anterior spinothalamic tract (crude touch, pressure). (cervical is
always close to the horns) Spinal tract anatomy and functions - Ascending tracts synapse and then cross.

TRACT FUNCTION 1ST-ORDER NEURON SYNAPSE 1 2ND-ORDER NEURON SYNAPSE 2 + PROJECTIONS

Ascending tracts-
Dorsal column Pressure, vibration, fne touch, (conscious) proprioception. 1ST-ORDER NEURON Sensory nerve ending > bypasses pseudounipolar
cell body in dorsal root ganglion > enters spinal cord > ascends ipsilaterally in dorsal columns. SYNAPSE 1 Nucleus gracilis, nucleus cuneatus
(ipsilateral medulla). 2ND-ORDER NEURON Decussates in medulla > ascends contralaterally as the medial lemniscus. SYNAPSE 2 +
PROJECTIONS VPL (thalamus) > sensory cortex. (synapse in ipsilateral medulla and then decussates in medulla)
Spinothalamic tract Lateral: pain, temperature Anterior: crude touch, pressure. 1ST-ORDER NEURON Sensory nerve ending (A and C fbers) >
bypasses pseudounipolar cell body in dorsal root ganglion > enters spinal cord. SYNAPSE 1 Ipsilateral gray matter (spinal cord). 2ND-ORDER
NEURON Decussates in spinal cord as the anterior white commissure > ascends contralaterally. SYNAPSE 2 + PROJECTIONS VPL (thalamus) >
sensory cortex.
(synapse in ipsilateral gray matter and then decussates in anterior white commisure)
Descending tract-
Lateral corticospinal tract Voluntary movement of contralateral limbs. 1ST-ORDER NEURON UMN: cell body in 1° motor cortex > descends
ipsilaterally (through posterior limb of internal capsule and cerebral peduncle), most fbers decussate at caudal medulla (pyramidal decussation) >
descends contralaterally. SYNAPSE 1 Cell body of anterior horn (spinal cord). 2ND-ORDER NEURON LMN: leaves spinal cord. SYNAPSE 2 +
PROJECTIONS NMJ > muscle fbers. (decussates in caudal medulla (pyramidal decussation) and then synapse at anterior horn)
Clinical refexes - Refexes count up in order (main nerve root in bold): Achilles refex = S1, S2 (“buckle my shoe”)
Patellar refex = L2-L4 (“kick the door”)
Biceps and brachioradialis refexes = C5, C6 (“pick up sticks”) Triceps refex = C6, C7, C8 (“lay them straight”)
Additional refexes:
Cremasteric refex = L1, L2 (“testicles move”)
Anal wink refex = S3, S4 (“winks galore”)
Reflex grading: 0: absent 1: hypoactive 2: normal 3: hyperactive 4: clonus.
Primitive refexes - CNS refexes that are present in a healthy infant, but are absent in a neurologically intact adult. Normally disappear within 1st year
of life. These primitive refexes are inhibited by a mature/ developing frontal lobe. They may reemerge in adults following frontal lobe lesions > loss of
inhibition of these refexes.
Moro refex “Hang on for life” refex—abduct/extend arms when startled, and then draw together.
Rooting refex Movement of head toward one side if cheek or mouth is stroked (nipple seeking).
Sucking refex Sucking response when roof of mouth is touched.
Palmar refex Curling of fngers if palm is stroked.
Plantar refex Dorsifexion of large toe and fanning of other toes with plantar stimulation. Babinski sign—presence of this refex in an adult, which may
signify a UMN lesion.
Galant refex Stroking along one side of the spine while newborn is in ventral suspension (face down) causes lateral fexion of lower body toward
stimulated side.

Inducing hypocapnia via hyperventilation reduces the partial pressure of arterial carbon dioxide (PaCO2), which incites vasoconstriction in the cerebral
resistance arterioles. This constriction decrease cerebral blood flow, which reduces cerebral blood volume and, ultimately, decreases the patient’s ICP.

PO2 less than 50 mm Hg increases cerebral blood flow.

Rising PCO2 increases cerebral blood flow until 90 mmHg.
MAP plateaus cerebral blood flow between 70-160 mmHg. Below 70 it reduces cerebral blood flow and above 160 it increases cerebral blood flow

CUSHING REFLEX-
inc ICP -> dec CPP -> central autoregulation to inc BP (central HTN) -> peripheral strech receptor stimulation -> inc PANS -> bradycardia and resp
depression .

3 - levator palpebrae superioris

5 - tensor tympani, muscles of masticationn
7 - chorda tympani, orbicularis oculi, stapedius, submandibular and sublingual glands
9 - stylopharyngeus - pharynx/larynx elevation, gag reflex - afferent, swallowing, parotid gland
10 - palatoglossus - soft palate elevation, cough reflex - afferent and efferent, gag reflex - efferent, swallowing. (9” - gag. 10” - cough.)
amygdala lesion - kluver-bucy syndrome
pineal lesion (dorsal midbrain) - parinaud synd

Parinaud syndrome (VLLC)—vertical gaze palsy, pupillary light-near dissociation, lid retraction, convergence-retraction nystagmus. Damage to
cerebellum - ipsilateral deficits; fall toward side of lesion

Frontal eye field lesion - eye looks towards lesion PPRF lesion - eye looks away from lesion

Decorticate (flexor) posturing—lesion above red nucleus

Decerebrate (extensor) posturing—lesion at or below red nucleus�
Normal RInne (ACDC) - AC > BC
Normal Weber - no localization
Ischemia - Most vulnerable: hippocampus, neocortex, cerebellum (Purkinje cells), watershed areas.
Medial longitudinal fasciculus - Internuclear ophthalmoplegia - (impaired adduction of ipsilateral eye; nystagmus of contralateral eye with abduction).
Multiple sclerosis.

INO = Ipsilateral adduction failure, Nystagmus Opposite. Normal - Signal goes from CN 6 nucleus of abducting eye to CN 3 nucleus of adducting eye
via MLF.
Stroke imaging: noncontrast CT to exclude hemorrhage (before tPA can be given). CT detects ischemic changes in 6–24 hr. Diffusion-weighted MRI
can detect ischemia within 3–30 min.
Stroke Treatment: tPA (if within 3–4.5 hr of onset and no hemorrhage/risk of hemorrhage) and/or thrombectomy (if large artery occlusion). Reduce risk
with medical therapy (eg, aspirin, clopidogrel); optimum control of blood pressure, blood sugars, lipids; smoking cessation; and treat conditions that
inc risk (eg, atrial fibrillation, carotid artery stenosis).

Pyrimidine synthesis:
Lefunomide: inhibits dihydroorotate dehydrogenase
5-fuorouracil (5-FU) and its prodrug capecitabine: form 5-F-dUMP, which inhibits thymidylate synthase ( dTMP) Purine synthesis:
6-mercaptopurine (6-MP) and its prodrug azathioprine: inhibit de novo purine synthesis
Mycophenolate and ribavirin: inhibit inosine monophosphate dehydrogenase Purine and pyrimidine synthesis:
Hydroxyurea: inhibits ribonucleotide reductase
Methotrexate (MTX), trimethoprim (TMP), and pyrimethamine: inhibit dihydrofolate reductase ( deoxythymidine monophosphate [dTMP]) in humans,
bacteria, and protozoa, respectively CPS1 = m1tochondria (urea cycle) CPS2 = cytwosol
DNA repair

Double strand
Nonhomologous end joining Brings together 2 ends of DNA fragments to repair double-stranded breaks. Defective in ataxia- telangiectasia. Homology
not required. Some DNA may be lost. Homologous recombination Requires 2 homologous DNA duplexes. A strand from damaged dsDNA is repaired
using a complementary strand from intact homologous dsDNA as a template. Defective in breast/ovarian cancers with BRCA1 mutation and in Fanconi
anemia. Restores duplexes accurately without loss of nucleotides.
Single strand
Nucleotide excision repair Specifc endonucleases release the oligonucleotides containing damaged bases; DNA polymerase and ligase fll and reseal the
gap, respectively. Repairs bulky helix- distorting lesions. Occurs in G1 phase of cell cycle. Defective in xeroderma pigmentosum (inability to repair
DNA pyrimidine dimers caused by UV exposure). Presents with dry skin, photosensitivity, skin cancer. Base excision repair Base-specifc Glycosylase
removes altered base and creates AP site (apurinic/apyrimidinic). One or more nucleotides are removed by AP-Endonuclease, which cleaves 5 end.
APLyase cleaves 3 end. DNA Polymerase- flls the gap and DNA ligase seals it. Occurs throughout cell cycle. Important in repair of spontaneous/toxic
deamination. “GEL Please.” Mismatch repair Mismatched nucleotides in newly synthesized (unmethylated) strand are removed and gap is flled and
resealed. Occurs predominantly in S phase of cell cycle. Defective in Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]).
INITIATION
1. eIFs identify 5’ cap
2. 40s + initiator tRNA
3. mRNA + 60s + 40s/tRNA complex. GTP.

ELONGATION
1. Charged tRNA binds A site. EF & GTP.
2. rRNA - peptide bond formation, transfers polypeptide to A site’s amino acid. 3. Moves peptidyl tRNA to P site (translocation).

TERMINATION
eRFs recognise stop codon > release completed polypeptide. GTP.
Rough endoplasmic reticulum Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to lysosomal and other
proteins. Nissl bodies (RER in neurons)—synthesize peptide neurotransmitters for secretion. Free ribosomes—unattached to any membrane; site of
synthesis of cytosolic, peroxisomal, and mitochondrial proteins. N-linked glycosylation occurs in the eNdoplasmic reticulum. Mucus-secreting goblet
cells of small intestine and antibody-secreting plasma cells are rich in RER. Proteins within organelles (eg, ER, Golgi bodies, lysosomes) are formed in
RER.
Smooth endoplasmic reticulum Site of steroid synthesis and detoxifcation of drugs and poisons. Lacks surface ribosomes. Location of glucose-6-
phosphatase (last step in both glycogenolysis and gluconeogenesis). Liver hepatocytes and steroid hormone– producing cells of the adrenal cortex and
gonads are rich in SER.
Cell trafficking
GOlgi is distribution center for proteins and lipids from ER to vesicles and plasma membrane. Posttranslational events in O- oligosaccharides include
modifying N-oligosaccharides on asparagine, adding O-oligosaccharides on serine and threonine, and adding mannose-6-phosphate to proteins for
lysosomal and other proteins.
Endosomes are sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the
membrane/Golgi for further use.
I-cell disease (inclusion cell disease/mucolipidosis type II)—inherited lysosomal storage disorder (autosomal recessive); defect in N-
acetylglucosaminyl-1-phosphotransferase failure of the Golgi to phosphorylate mannose residues (dec mannose-6-phosphate) on glycoproteins
enzymes secreted extracellularly rather than delivered to lysosomes > lysosomes defcient in digestive enzymes > build-up of cellular debris in
lysosomes (inclusion bodies). Results in coarse facial features, gingival hyperplasia, corneal clouding, restricted joint movements, claw hand
deformities, kyphoscoliosis, and inc plasma levels of lysosomal enzymes. Often fatal in childhood.
Vesicular trafcking proteins
COPI: Golgi > Golgi (retrograde); cis-Golgi > ER.
COPII: ER > cis-Golgi (anterograde).
“Two (COPII) steps forward (anterograde); one (COPI) step back (retrograde).”
Clathrin: trans-Golgi > lysosomes; plasma membrane > endosomes (receptormediated endocytosis [eg, LDL receptor activity]).
Zellweger syndrome—autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes. Hypotonia, seizures, hepatomegaly, early
death.
Refsum disease—autosomal recessive disorder of -oxidation buildup of phytanic acid due to inability to degrade it. Scaly skin, ataxia, cataracts/night
blindness, shortening of 4th toe, epiphyseal dysplasia. Treatment: diet, plasmapheresis.
Adrenoleukodystrophy—X-linked recessive disorder of -oxidation due to mutation in ABCD1 gene VLCFA buildup in adrenal glands, white (leuko)
matter of brain, testes. Progressive disease that can lead to adrenal gland crisis, progressive loss of neurologic function, death
Drugs that act on microtubules (microtubules get constructed very terribly): Mebendazole (antihelminthic)
Griseofulvin (antifungal) Colchicine (antigout)
Vinca alkaloids (anticancer) Taxanes (anticancer)
Collagen - Most abundant protein in the human body. Extensively modifed by posttranslational modifcation. Organizes and strengthens extracellular
matrix. Type I - Skeleton Type II - Cartilage Type III - Arteries Type IV - Basement membrane SCAB
Type I Most common (90%)—Bone (made by osteoblasts), Skin, Tendon, dentin, fascia, cornea, late wound repair. Type I: bone, tendone. Dec
production in osteogenesis imperfecta type I.
Type II Cartilage (including hyaline), vitreous body, nucleus pulposus. Type II: cartwolage.
Type III Reticulin—skin, blood vessels, uterus, fetal tissue, early wound repair. Type III: defcient in vascular type of EhlersDanlos syndrome (threE D).
Type IV Basement membrane (basal lamina), lens. Type IV: under the foor (basement membrane). Defective in Alport syndrome; targeted by
autoantibodies in Goodpasture syndrome.
Collagen synthesis and structure
[Link]—translation of collagen chains (preprocollagen)—usually Gly-X-Y (X and Y are proline or lysine). Collagen is 1 ⁄3 glycine; glycine
content of collagen is less variable than that of lysine and proline. [Link] is used for lab quantifcation of collagen. Hydroxylation—
hydroxylation (“hydroxCylation”) of specifc proline and lysine residues. Requires vitamin C; defciency scurvy. [Link]—glycosylation of pro-
-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfde bonds (triple helix of 3 collagen chains). Problems forming
triple helix > osteogenesis imperfecta.
[Link]—exocytosis of procollagen into extracellular space.
[Link] processing—cleavage of disulfde-rich terminal regions of procollagen > insoluble tropocollagen. [Link]-linking—reinforcement of many
staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by copper- containing lysyl oxidase) to make collagen fbrils. Cross-
linking of collagen increases with age. Problems with crosslinking > Menkes disease. CRISPR/Cas9 - A genome editing tool derived from bacteria.
Consists of a guide RNA (gRNA) , which is complementary to a target DNA sequence, and an endonuclease (Cas9), which makes a single- or double-
strand break at the target site .
a. Break imperfectly repaired by nonhomologous end joining (NHEJ) > accidental frameshift mutations (“knock-out”) ,
b. Or a donor DNA sequence can be added to fll in the gap using homology-directed repair (HDR) .
Molecular cloning Production of a recombinant DNA molecule in a bacterial host. Steps: 1. Isolate eukaryotic mRNA (post-RNA processing) of
interest. 2. Add reverse transcriptase (an RNA- dependent DNA polymerase) to produce complementary DNA (cDNA, lacks introns). 3. Insert cDNA
fragments into bacterial plasmids containing antibiotic resistance genes. 4. Transform (insert) recombinant plasmid into bacteria. 5. Surviving bacteria
on antibiotic medium produce cloned DNA (copies of cDNA).
Hardy-Weinberg law assumptions include:
No mutation occurring at the locus Natural selection is not occurring Completely random mating
No net migration
Large population
DISEASE TRINUCLEOTIDE REPEAT MODE OF INHERITANCE MNEMONIC
Huntington disease (CAG)n AD Caudate has ACh and GABA
Myotonic dystrophy (CTG)n AD Cataracts, Toupee (early balding in males), Gonadal atrophy in males, reduced fertility in females Fragile X syndrome
(CGG)n XD Chin (protruding), Giant Gonads Friedreich ataxia (GAA)n AR Ataxic GAAit
Down’s
1st trimester - β-hCG inc only
2nd trimester - β-hCG and Inhibin A inc only
rest everything is dec irrespective of trimester

Edward’s
everything dec in 1st and 2nd trimester
Patau’s
everything dec in 1st and normal/NA in 2nd trimester
PKD1-16, PKD2-4
TSC1-9, TSC2-16
NF1-17, NF2-22
β-globin 11, α-globin 16
BRCA1-17, BRCA2-13
RB1-13, TP53-17(sum 8)
williams - 7
wilms - 11
wilson - 13
CHROMOSOME SELECTED EXAMPLES
3 von Hippel-Lindau disease, renal cell carcinoma
4 ADPKD (PKD2), achondroplasia, Huntington disease
5 Cri-du-chat syndrome, familial adenomatous polyposis
6 Hemochromatosis (HFE)
7 Williams syndrome, cystic fbrosis
9 Friedreich ataxia, tuberous sclerosis (TSC1)
11 Wilms tumor, -globin gene defects (eg, sickle cell disease, -thalassemia), MEN1
13 Patau syndrome, Wilson disease, retinoblastoma (RB1), BRCA2
15 Prader-Willi syndrome, Angelman syndrome, Marfan syndrome
16 ADPKD (PKD1), -globin gene defects (eg, -thalassemia), tuberous sclerosis (TSC2) 17 Neurofbromatosis type 1, BRCA1, TP53 (Li-Fraumeni
syndrome)
18 Edwards syndrome
21 Down syndrome
22 Neurofbromatosis type 2, DiGeorge syndrome (22q11)
X Fragile X syndrome, X-linked agammaglobulinemia, Klinefelter syndrome (XXY)
Ethanol metabolism inc NADH/ NAD+ ratio in liver, causing:
[Link] acidosis— pyruvate conversion to lactate
[Link] hypoglycemia— gluconeogenesis due to conversion of OAA to malate
[Link]—diversion of acetyl-CoA into ketogenesis rather than TCA cycle
[Link]— conversion of DHAP to glycerol-3-P (4A) ; acetyl-CoA diverges into fatty acid synthesis (4B) , which combines with glycerol-3-P
to synthesize triglycerides
Metabolism sites
Mitochondria Fatty acid oxidation ( -oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation, ketogenesis. Cytoplasm Glycolysis,
HMP shunt, and synthesis of cholesterol (SER), proteins (ribosomes, RER), fatty acids, and nucleotides. Both Heme synthesis, urea cycle,
gluconeogenesis. Hugs take two (both).
Glycolysis Phosphofructokinase-1 (PFK-1) AMP ⊕, fructose-2,6-bisphosphate ⊕ ATP ⊖, citrate ⊖
Gluconeogenesis Fructose-1,6-bisphosphatase 1 AMP ⊖, fructose-2,6-bisphosphate ⊖
TCA cycle Isocitrate dehydrogenase ADP ⊕ ATP ⊖, NADH ⊖
Glycogenesis Glycogen synthase Glucose-6-phosphate ⊕, insulin ⊕, cortisol ⊕ Epinephrine ⊖, glucagon ⊖
Glycogenolysis Glycogen phosphorylase Epinephrine ⊕, glucagon ⊕, AMP ⊕ Glucose-6-phosphate ⊖, insulin ⊖, ATP ⊖
HMP shunt Glucose-6-phosphate dehydrogenase (G6PD) NADP+ ⊕ NADPH ⊖
De novo pyrimidine synthesis Carbamoyl phosphate synthetase II (cytoplasm) ATP ⊕, PRPP ⊕ UTP ⊖
De novo purine synthesis Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase AMP ⊖, inosine monophosphate (IMP) ⊖, GMP ⊖
Urea cycle Carbamoyl phosphate synthetase I (mitochondria) N-acetylglutamate ⊕
Fatty acid synthesis Acetyl-CoA carboxylase (ACC) Insulin ⊕, citrate ⊕ Glucagon ⊖, palmitoyl-CoA ⊖
Fatty acid oxidation Carnitine acyltransferase I Malonyl-CoA ⊖
Ketogenesis HMG-CoA synthase
Cholesterol synthesis HMG-CoA reductase Insulin ⊕, thyroxine ⊕, estrogen ⊕ Glucagon ⊖, cholesterol ⊖
cortisol ⊕ GLYCOGENESIS
UTP ⊖ de novo pyrimidine synthesis
palmitoyl-CoA ⊖ fatty acid synthesis
Malonyl-CoA ⊖ fatty acid oxidation
Palmitoyl-CoA ⊖ fatty acid synthesis (Acetyl-CoA carboxylase (ACC))
Malonyl-CoA ⊖ fatty acid oxidation (Carnitine acyltransferase I)
Glucagon inhibits glycogen synthesis, fatty acid synthesis and cholestrol synthesis
Cholestrol synthesis stimulated by Insulin ⊕, thyroxine ⊕, estrogen ⊕
glucokinase - liver, b-cells
hexokinase - other tissues
glucokinase feedback F6P
hexokinase feedback G6P
Glucokinase deficiency is a cause of maturity onset diabetes of the young (MODY) and gestational diabetes.
Glucokinase is induced by insulin but hexokinase is not.
Hexokinase
Location Most tissues, except liver and pancreatic Km Lower (inc affnity)
Vmax Lower (dec capacity)
Induced by insulin No
Feedback inhibition by Glucose-6-phosphate
Glucokinase Location Liver, cells of pancreas Km Higher (dec affnity)
Vmax Higher (inc capacity)
Induced by insulin Yes
Feedback inhibition by Fructose-6-phosphate
FBPase-2 active in fasting state, stimulating gluconeogenesis. (F for fasting)
PFK-2 active in fed state, stimulating glycolysis. (P for peth is full)
PFK-2 makes frustose-2,6-BP which stimulates PFK-1 which stimulates glycolysis in fed state
PFK-1 and PFK-2 stimulate glycolysis
FBPase-1 and FBPase-2
stimulate gluconeogenesis
Gluconeogenesis, irreversible enzymes - Pathway Produces Fresh Glucose.
[Link] carboxylase In mitochondria. Pyruvate > oxaloacetate. Requires biotin, ATP. Activated by acetyl-CoA. [Link]
carboxykinase In cytosol. Oxaloacetate > phosphoenolpyruvate (PEP). Requires GTP.
[Link]-1,6- bisphosphatase 1 In cytosol. Fructose-1,6-bisphosphate > fructose-6-phosphate. Citrate , AMP , fructose 2,6- bisphosphate .
[Link]-6- phosphatase In ER. Glucose-6-phosphate > glucose.

Amino acids Only l-amino acids are found in proteins.

Essential PVT TIM HaLL: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Leucine, Lysine. Glucogenic: Methionine,
histidine, valine. We met his valentine, who is so sweet (glucogenic). Glucogenic/ketogenic: Isoleucine, phenylalanine, threonine, tryptophan.
Ketogenic: leucine, lysine. The only purely ketogenic amino acids.
Acidic Aspartic acid, glutamic acid. Negatively charged at body pH.
Basic Arginine, histidine, lysine. Arginine is most basic. Histidine has no charge at body pH. Arginine and histidine are required during
periods of growth. Arginine and lysine are in histones which bind negatively charged DNA. His lys (lies) are basic.

DISEASE FINDINGS DEFICIENT ENZYME COMMENTS

Von Gierke disease (type I) Severe fasting hypoglycemia, inc inc Glycogen in liver and kidneys, inc blood lactate, inc triglycerides, inc uric acid
(Gout), and hepatomegaly, renomegaly. Liver does not regulate blood glucose. DEFICIENT ENZYME Glucose-6-phosphatase. Treatment: frequent
oral glucose/cornstarch; avoidance of fructose and galactose. Impaired gluconeogenesis and glycogenolysis.
Pompe disease (type II) Cardiomyopathy, hypotonia, exercise intolerance, and systemic fndings lead to early death. DEFICIENT ENZYME Lysosomal
acid -1,4- glucosidase (acid maltase) with -1,6- glucosidase activity. Pompe trashes the pump (1st and 4th letter; heart, liver, and muscle).
Cori disease (type III) Similar to von Gierke disease, but milder symptoms and normal blood lactate levels. Can lead to cardiomyopathy. Limit dextrin–
like structures accumulate in cytosol. DEFICIENT ENZYME Debranching enzymes ( -1,6-glucosidase and 4- -d- glucanotransferase).
Gluconeogenesis is intact.
Andersen disease (type IV) Most commonly presents with hepatosplenomegaly and failure to thrive in early infancy. Other fndings include infantile
cirrhosis, muscular weakness, hypotonia, cardiomyopathy early childhood death. DEFICIENT ENZYME Branching enzyme. Neuromuscular form can
present at any age. Hypoglycemia occurs late in the disease.
McArdle disease (type V) inc glycogen in muscle, but muscle cannot break it down > painful muscle cramps, myoglobinuria (red urine) with strenuous
exercise, and arrhythmia from electrolyte abnormalities. Second-wind phenomenon noted during exercise due to inc muscular blood flow. Skeletal
muscle glycogen phosphorylase (myophosphorylase). Characterized by a fat venous lactate curve with normal rise in ammonia levels during exercise.
Blood glucose levels typically unaffected. McArdle = muscle.
Lysosomal storage diseases Lysosomal enzyme defciency > accumulation of abnormal metabolic products. Inc incidence of Tay-Sachs, Niemann-Pick,
and some forms of Gaucher disease in Ashkenazi Jews.
DISEASE FINDINGS DEFICIENT ENZYME ACCUMULATED SUBSTRATE INHERITANCE
Sphingolipidoses
Tay-Sachs disease - Progressive neurodegeneration, developmental delay, hyperrefexia, hyperacusis, “cherry-red” spot on macula A (lipid
accumulation in ganglion cell layer), lysosomes with onion skin, no hepatosplenomegaly (vs Niemann-Pick). DEFICIENT ENZYME Hexosaminidase
A (“TAy-Sax”). ACCUMULATED SUBSTRATE GM2 ganglioside. AR
Fabry disease Early: triad of episodic peripheral neuropathy, angiokeratomas B , hypohidrosis. Late: progressive renal failure, cardiovascular disease.
DEFICIENT ENZYME -galactosidase A. ACCUMULATED SUBSTRATE Ceramide trihexoside (globotriaosylceramide). XR
Metachromatic leukodystrophy Central and peripheral demyelination with ataxia, dementia. DEFICIENT ENZYME Arylsulfatase A.
ACCUMULATED SUBSTRATE Cerebroside sulfate. AR
Krabbe disease Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells. DEFICIENT ENZYME
Galactocerebrosidase (galactosylceramidase). ACCUMULATED SUBSTRATE Galactocerebroside, psychosine. AR
Gaucher disease Most common. Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of femur, bone crises, Gaucher cells C (lipid-
laden macrophages resembling crumpled tissue paper). DEFICIENT ENZYME Glucocerebrosidase ( -glucosidase); treat with recombinant
glucocerebrosidase. ACCUMULATED SUBSTRATE Glucocerebroside. AR
Niemann-Pick disease Progressive neurodegeneration, hepatosplenomegaly, foam cells (lipid-laden macrophages) D, “cherry-red” spot on macula A .
DEFICIENT ENZYME Sphingomyelinase. ACCUMULATED SUBSTRATE Sphingomyelin. AR.
Mucopolysaccharidoses
Hurler syndrome Developmental delay, skeletal abnormalities, airway obstruction, corneal clouding, hepatosplenomegaly. DEFICIENT ENZYME -l-
iduronidase. ACCUMULATED SUBSTRATE Heparan sulfate, dermatan sulfate. AR
Hunter syndrome Mild Hurler + aggressive behavior, no corneal clouding. DEFICIENT ENZYME Iduronate-2 (two)- sulfatase. ACCUMULATED
SUBSTRATE Heparan sulfate, dermatan sulfate. XR. Hunters see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive).
Fatty acid metabolism

Fasting and starvation Priorities are to supply suffcient glucose to the brain and RBCs and to preserve protein.
Fed state (after a meal) - Glycolysis and aerobic respiration. Insulin stimulates storage of lipids, proteins, and glycogen.
Fasting (between meals) - Hepatic glycogenolysis (major); hepatic gluconeogenesis, adipose release of FFA (minor). Glucagon and epinephrine
stimulate use of fuel reserves.
Starvation days 1–3 - Blood glucose levels maintained by:
Hepatic glycogenolysis
Adipose release of FFA
Muscle and liver, which shift fuel use from glucose to FFA
Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionylCoA (from odd-chain
FFA—the only triacylglycerol components that contribute to gluconeogenesis). Glycogen reserves depleted after day 1. RBCs lack
mitochondria and therefore cannot use ketones.
Starvation after day 3 - Adipose stores (ketone bodies become the main source of energy for the brain). After these are depleted, vital protein
degradation accelerates, leading to organ failure and death. Amount of excess stores determines survival time.
Lipid transport
[Link] enters lymphatics
[Link] transfers Apo CII and Apo E
[Link] Apo CII activates LPL (impaired in type I familia dyslipidemia) [Link] releases VLDL (overproduction in type IV familial
dyslipidemia) [Link] Apo CII activates LPL
[Link] delivers TGs and cholesterol to the liver via Apo E
[Link] of LDL (impaired in type II familial dyslipidemia)
Major apolipoproteins
E - Mediates remnant uptake (everything except LDL) - Chylomicron Chylomicron remnant VLDL IDL HDL.
A-I - Found only on alphalipoproteins (HDL), activates LCAT - HDL.
C-II - Lipoprotein lipase cofactor that catalyzes cleavage. - Chylomicron VLDL IDL HDL.
B-48 - Mediates chylomicron secretion into lymphatics Only on particles originating from the intestines - Chylomicron Chylomicron remnant.
B-100 - Binds LDL receptor Only on particles originating from the liver - VLDL IDL LDL.
Familial dyslipidemias
TYPE INHERITANCE PATHOGENESIS BLOOD LEVEL CLINICAL
I—Hyperchylomicronemia - AR. Lipoprotein lipase or ApoC-2 defciency. INC BLOOD LEVEL Chylomicrons, TG, cholesterol. Pancreatitis,
hepatosplenomegaly, and eruptive/pruritic xanthomas (no risk for atherosclerosis). Creamy layer in supernatant.
II—Hypercholesterolemia - AD. Absent or defective LDL receptors, or defective ApoB-100. INC BLOOD LEVEL IIa: LDL, cholesterol. IIb: LDL,
cholesterol, VLDL. Heterozygotes (1 500) have cholesterol 300 mg/dL; homozygotes (very rare) have cholesterol 700 mg/dL. Accelerated
atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus. III—Dysbetalipoproteinemia - AR. ApoE (defective in
type thrEE). INC BLOOD LEVEL Chylomicrons, VLDL. Premature atherosclerosis, tuberoeruptive and palmar xanthomas. ApE’s palms. IV—
Hypertriglyceridemia - AD. Hepatic overproduction of VLDL. INC BLOOD LEVEL VLDL, TG. Hypertriglyceridemia (> 1000 mg/dL) can cause
acute pancreatitis. Related to insulin resistance. Lymphatic drainage associations
Submandibular Oral cavity Malignancy of oral cavity
Deep cervical Head, neck, oropharynx Upper respiratory tract infection Infectious mononucleosis Kawasaki disease Malignancy of head, neck,
oropharynx
Supraclavicular (Virchow node) Abdomen, pelvis Malignancy of abdomen, pelvis
Mediastinal Trachea, esophagus Pulmonary TB (unilateral hilar) Sarcoidosis (bilateral hilar) Lung cancer Granulomatous disease
Hilar Lungs Pulmonary TB (unilateral hilar) Sarcoidosis (bilateral hilar) Lung cancer Granulomatous disease
Axillary Upper limb, breast, skin above umbilicus Mastitis Metastasis (especially breast cancer)
Epitrochlear Hand, forearm Secondary syphilis
Periumbilical (Sister Mary Joseph node) Abdomen, pelvis Gastric cancer

Celiac Liver, stomach, spleen, pancreas, upper duodenum - Mesenteric lymphadenitis Inflammatory bowel disease Celiac disease Superior mesenteric
Lower duodenum, jejunum, ileum, colon to splenic flexure - Mesenteric lymphadenitis Inflammatory bowel disease Celiac disease
Inferior mesenteric Colon from splenic flexure to upper rectum - Mesenteric lymphadenitis Inflammatory bowel disease Celiac disease Para-aortic Pair
of testes, ovaries, kidneys, fallopian tubes (uterus) Metastasis

External iliac Cervix, superior bladder, body of uterus Sexually transmitted infections Medial foot/leg cellulitis (superficial inguinal). Internal iliac
Lower rectum to anal canal (above pectinate line), bladder, vagina (middle third), cervix, prostate. Sexually transmitted infections Medial foot/leg
cellulitis (superficial inguinal).
Superficial inguinal Anal canal (below pectinate line), skin below umbilicus (except popliteal area), scrotum, vulva. Sexually transmitted infections
Medial foot/leg cellulitis (superficial inguinal). Popliteal (“pop-lateral”) Dorsolateral foot, posterior calf Lateral foot/leg cellulitis

Right lymphatic duct drains right side of body above diaphragm into junction of the right subclavian and internal jugular vein
Thoracic duct drains below the diaphragm and left thorax and upper limb into junction of left subclavian and internal jugular veins (rupture of thoracic
duct can cause chylothorax)
The lymphatic drainage of the vulva is initially to the inguinofemoral nodes, which consists of a superficial inguinal and a deeper femoral node.
(Choices A and B) Lymph from the uterine corpus and inguinal nodes (which drain the lower extremities, buttocks, and external genitalia) subsequently
drain to the external iliac nodes. The external iliac nodes and internal iliac nodes both drain to the common iliac nodes. (Choice D) The bladder, uterus,
and portions of the cervix can drain to the obturator nodes, which are located in the obturator fossa medial to the external iliac vessels. The obturator
nodes are 1 of 3 pelvic lymph node groups (ie, obturator, external iliac, internal iliac) that together drain the pelvis, lower extremities, and lower
abdominal wall.
(Choice E) Lymph from the ovary and common iliac node drain to the paraaortic lymph nodes.
(Choice F) The anal canal and rectum drain to the presacral lymph nodes.
Primary lymph node drainage of the female reproductive system(UWorld)
Uterus - External iliac
Cervix - Internal iliac
Vagina - Proximal: internal iliac
Distal: inguinofemoral
Vulva - Inguinofemoral
Ovaries - Paraaortic
Colon from splenic flexure to upper rectum - inferior mesentric
lower rectum to anal canal (above pectinate line) - internal iliac
anal canal (below pectinate line) - superficial inguinal
skin above umblicus - axillary
skin below umblicus (except popliteal area) - superficial inguinal
HLA SUBTYPE DISEASE MNEMONIC
B27 Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis PAIR. Also called seronegative arthropathies B57 Abacavir
hypersensitivity
DQ2/DQ8 Celiac disease I ate (8) too (2) much gluten at Dairy Queen
DR3 DM type 1, SLE, Graves disease, Hashimoto thyroiditis, Addison disease 2-3, S-L-E DM type 1: HLA-3 and -4 (1 + 3 = 4)
DR4 Rheumatoid arthritis, DM type 1, Addison disease
Th17- + by TGF- , IL-1, IL-6; - by IFN- , IL-4; secrete IL-17, IL-21, IL-22; induce neutrophils.
Treg (express CD3, CD4, CD25, FOXP3)- + by TGF- , IL-2; - by IL-6; secrete TGF- , IL-10, IL-35; Prevent autoimmunity (maintain tolerance).
Th1- + by IFN- , IL-12; - by IL-4, IL-10; secrete IFN- , IL-2; Activate macrophages and cytotoxic T cells.
Th2- + by IL-2, IL-4; - by IFN- ; secrete IL-4, IL-5, IL-6, IL-10, IL-13; Activate eosinophils, IgE.
Generation of antibody diversity (antigen independent)-
1. Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes
2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT)
3. Random combination of heavy chains with light chains
Generation of antibody specifcity (antigen dependent)-
4. Somatic hypermutation and affnity maturation (variable region)
5. Isotype switching (constant region).
Cell surface proteins-
T cells - TCR (binds antigen-MHC complex), CD3 (signal transduction), CD28 (binds B7 on APC).
Helper T cells - CD4, CD40L, CXCR4/CCR5 (co-receptors for HIV).
Cytotoxic T cells - CD8.
Regulatory T cells - CD4, CD25.
B cells - Ig (binds antigen), CD19, CD20, CD21 (receptor for Epstein-Barr virus), CD40, MHC II, B7.
Macrophages - CD14 (receptor for PAMPs, eg, LPS), CD40, CCR5, MHC II, B7 (CD80/86), Fc and C3b receptors (enhanced phagocytosis). NK cells -
CD16 (binds Fc of IgG), CD56 (suggestive marker for NK).
Hematopoietic stem cells - CD34.
Live attenuated vaccines (TRAPS BY MIC) - Adenovirus (nonattenuated, given to military recruits), typhoid (Ty21a, oral), polio (Sabin), varicella
(chickenpox), smallpox, BCG, yellow fever, influenza (intranasal), MMR, rotavirus.
Killed or inactivated vaccine (H-TRIP) - Hepatitis A, Typhoid (Vi polysaccharide, intramuscular), Rabies, Influenza, Polio (SalK).
Subunit vaccine (NASHHH) - HBV (antigen = HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP), Neisseria meningitidis (various
strains), Streptococcus pneumoniae, Haemophilus influenzae type b.
Toxoid - Clostridium tetani, Corynebacterium diphtheriae.

Blood transfusion reactions-

TYPE PATHOGENESIS TIMING CLINICALPRESENTATION DONOR BLOOD HOST BLOOD
Allergic/anaphylactic reaction - Type I hypersensitivity reaction against plasma proteins in transfused blood. IgA-de cient individuals should receive
blood products without IgA. Within minutes to 2-3 hr (due to release of preformed inflammatory mediators in degranulating mast cells). CLINICAL
PRESENTATION - Allergies: urticaria, pruritus. Anaphylaxis: wheezing, hypotension, respiratory arrest, shock. DONOR BLOOD - Donor plasma
proteins, including IgA. HOST BLOOD - Host mast cell.
Acute hemolytic transfusion reaction - Type II hypersensitivity reaction. Typically causes intravascular hemolysis (ABO blood group incompatibility).
During transfusion or within 24 hr (due to preformed antibodies). CLINICAL PRESENTATION - Fever, hypotension, tachypnea, tachycardia, flank
pain, hemoglobinuria (intravascular), jaundice (extravascular). DONOR BLOOD - Donor RBC with A and/or B group antigens. HOST BLOOD - Host
anti-A, anti-B IgG, IgM.
Febrile nonhemolytic transfusion reaction - Cytokines created by donor WBCs accumulate during storage of blood products. Reactions prevented by
leukoreduction of blood products. Within 1-6 hr (due to preformed cytokines). CLINICAL PRESENTATION - Fever, headaches, chills, flushing. More
common in children. DONOR BLOOD - Donor WBC releases preformed cytokines. Transfusion-related acute lung injury - Two-hit mechanism: 1.
Neutrophils are sequestered and primed in pulmonary vasculature due to recipient risk factors. 2. Neutrophils are activated by a product (eg,
antileukocyte antibodies) in the transfused blood and release inflammatory mediators > inc capillary permeability > pulmonary edema. Within minutes
to 6 hr. CLINICAL PRESENTATION - Respiratory distress, noncardiogenic pulmonary edema. DONOR BLOOD - Donor antileukocyte IgG. HOST
BLOOD - Host neutrophils.
Delayed hemolytic transfusion reaction - Anamnestic response to a foreign antigen on donor RBCs (Rh [D] or other minor blood group antigens)
previously encountered by recipient. Typically causes extravascular hemolysis. Onset over 24 hr. Usually presents within 1-2 wk (due to slow
destruction by reticuloendothelial system). Generally self limited and clinically silent. CLINICAL PRESENTATION - Mild fever, hyperbilirubinemia.
DONOR BLOOD - Donor RBC with foreign antigens. HOST BLOOD - Host IgG.

Autoantibodies
AUTOANTIBODY ASSOCIATED DISORDER
Anti-postsynaptic ACh receptor Myasthenia gravis
Anti-presynaptic voltage-gated calcium channel Lambert-Eaton myasthenic syndrome Anti- 2 glycoprotein I Antiphospholipid syndrome

Antinuclear (ANA) Nonspecifc screening antibody, often associated with SLE Anticardiolipin, lupus anticoagulant SLE, antiphospholipid syndrome
Anti-dsDNA, anti-Smith SLE
Antihistone Drug-induced lupus

Anti-U1 RNP (ribonucleoprotein) Mixed connective tissue disease

Rheumatoid factor (IgM antibody against IgG Fc region), anti-CCP (more specifc) Rheumatoid arthritis
Anti-Ro/SSA, anti-La/SSB Sjögren syndrome
Anti-Scl-70 (anti-DNA topoisomerase I) Scleroderma (diffuse)
Anticentromere Limited scleroderma (CREST syndrome)
Antisynthetase (eg, anti-Jo-1), anti-SRP, anti- helicase (anti-Mi-2) Polymyositis, dermatomyositis
Antimitochondrial 1° biliary cholangitis
Anti-smooth muscle, anti-liver/kidney microsomal-1 Autoimmune hepatitis
Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)/perinuclear ANCA (p-ANCA) - Microscopic polyangiitis, eosinophilic
granulomatosis with polyangiitis, ulcerative colitis, 1° sclerosing cholangitis
PR3-ANCA/cytoplasmic ANCA (c-ANCA) Granulomatosis with polyangiitis
Anti-phospholipase A2 receptor 1° membranous nephropathy
Anti-hemidesmosome Bullous pemphigoid
Anti-desmoglein (anti-desmosome) Pemphigus vulgaris
Antithyroglobulin, antithyroid peroxidase (antimicrosomal) Hashimoto thyroiditis
Anti-TSH receptor Graves disease
IgA anti-endomysial, IgA anti-tissue transglutaminase, IgA and IgG deamidated gliadin peptide Celiac disease
Anti-glutamic acid decarboxylase, islet cell cytoplasmic antibodies Type 1 diabetes mellitus
Antiparietal cell, anti-intrinsic factor Pernicious anemia
Anti-glomerular basement membrane Goodpasture syndrome

Infections in immunodeficiency-
Bacteria
dec T CELLS - Sepsis
dec B CELLS - Encapsulated (Please SHINE my SKiS): Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus Influenzae type b,
Neisseria meningitidis, Escherichia coli, Salmonella, Klebsiella pneumoniae, group B Streptococcus

dec GRANULOCYTES - (SBP-NS) Some Bacteria Produce No Serious granules: Staphylococcus, Burkholderia cepacia, Pseudomonas aeruginosa,
Nocardia, Serratia dec COMPLEMENT - Encapsulated species with early complement deficiencies; Neisseria with late complement (C5– C9)
deficiencies.
Viruses
dec T CELLS - CMV, EBV, JC virus, VZV, chronic infection with respiratory/GI viruses dec B CELLS - Enteroviral encephalitis, poliovirus (live
vaccine contraindicated) dec GRANULOCYTES - N/A

dec COMPLEMENT - N/A

Fungi/parasites
dec T CELLS - (PCC) - Candida (local), PCP, Cryptococcus
dec B CELLS - GI giardiasis (no IgA)
dec GRANULOCYTES - (CAM) - Candida (systemic), Aspergillus, Mucor
dec COMPLEMENT - N/A
Note: B-cell defciencies tend to produce recurrent bacterial infections, whereas T-cell defciencies produce more fungal and viral infections.
Transplant rejection-
Hyperacute - Within minutes Pre-existing recipient antibodies react to donor antigen (type II hypersensitivity reaction), activate complement.
Widespread thrombosis of graft vessels > ischemia and fibrinoid necrosis. Graft must be removed.
Acute - Weeks to months Cellular: CD8+ T cells and/or CD4+ T cells activated against donor MHCs (type IV hypersensitivity reaction). Humoral:
similar to hyperacute, except antibodies develop after transplant (associated with C4d deposition). Vasculitis of graft vessels with dense interstitial
lymphocytic infiltrate. Prevent/reverse with immunosuppressants.
Chronic - Months to years CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC. Both cellular and humoral
components (type II and IV hypersensitivity reactions). Recipient T cells react and secrete cytokines > proliferation of vascular smooth muscle,
parenchymal atrophy, interstitial fibrosis.
Dominated by arteriosclerosis - Organ-speci c examples: Chronic allograft nephropathy, Bronchiolitis obliterans, Accelerated atherosclerosis (heart),
Vanishing bile duct syndrome.
Graft-versus-host disease - Onset varies. Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with
“foreign” proteins > severe organ dysfunction. Type IV hypersensitivity reaction. Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usually
in bone marrow and liver transplants (rich in lymphocytes). Potentially bene cial in bone marrow transplant for leukemia (graft-versus-tumor effect).
For patients who are immunocompromised, irradiate blood products prior to transfusion to prevent GVHD.
Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis
P-selectin (released from Weibel- palade bodies) + sialyl lewis
GlyCAM-1/CD34 + L-selectin

Adhesion-
defective in LAD type 1 (dec CD18 integrin subunit) ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1) VCAM-1 (CD106) + VLA-4 integrin

Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
Cyclosporine - Toxicity - Nephrotoxicity, neurotoxicity, hypertension, hyperlipidemia, gingival hyperplasia, hirsutism. Both calcineurin inhibitors are
highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Tacrolimus (FK506) - Toxicity - Similar to cyclosporine, inc risk of diabetes and neurotoxicity; no gingival hyperplasia or hirsutism. Both calcineurin
inhibitors are highly nephrotoxic, especially in higher doses or in patients with dec renal function.
Sirolimus (Rapamycin) - Toxicity - “Pansirtopenia” (pancytopenia), insulin resistance, hyperlipidemia; not nephrotoxic.
Basiliximab - Toxicity - Edema, hypertension, tremor.
Azathioprine - TOXICITY - Pancytopenia. 6-MP degraded by xanthine oxidase; toxicity inc by allopurinol. Pronounce “azathiopurine”
Mycophenolate Mofetil - TOXICITY - GI upset, pancytopenia, hypertension, hyperglycemia. Less nephrotoxic and neurotoxic. Associated with
invasive CMV infection.
Glucocorticoids - TOXICITY - Cushing syndrome, osteoporosis, hyperglycemia, diabetes, amenorrhea, adrenocortical atrophy, peptic ulcers,
psychosis, cataracts, avascular necrosis (femoral head). Toll-like receptor 7 - Imiquimod - CLINICAL USES Anogenital warts, actinic keratosis.
Interleukin-2 - Aldesleukin - CLINICAL USES Renal cell carcinoma, metastatic melanoma.

IFN-α - CLINICAL USES Chronic hepatitis C (not preferred) and B, renal cell carcinoma IFN-β - CLINICAL USES Multiple sclerosis
IFN-γ - CLINICAL USES Chronic granulomatous disease

Natalizumab, Vedolizumab - α4-integrin.

Vedolizumab - gut-specific anti integrin

IBD (via) - Adalimumab, infliximab, Vedolizumab.
Crohn ds - Natalizumab
Natalizumab, Vedolizumab - α4-integrin. (Natalia and Ved use A4 paper)
Adalimumab, infiximab - Soluble TNF-α.
Etanercept - decoy TNF-α receptor.
Eculizumab - Complement protein C5.
Guselkumab - IL-23. (angry beckham)
Ixekizumab, secukinumab - IL-17A. (17 is exactly secular)
Ustekinumab - IL-12/IL-23. (ustaad can bind two)
Denosumab - RANKL.
Emicizumab - Factor IXa and X.
Omalizumab - IgE.
Palivizumab - RSV F protein.
Psoriasis -
Guselkumab (IL-23),
Ixekizumab (IL-17A),
secukinumab (IL-17A),
Ustekinumab (IL-12/23),
Adalimumab, infiximab (soluble TNF-α).
(gusail abdali infiltrates secular uzbekistan exactly)
BUG MEDIA USED FOR ISOLATION MEDIA CONTENTS/OTHER
H infuenzae Chocolate agar Factors V (NAD+ ) and X (hematin)
N gonorrhoeae, N meningitidis Thayer-Martin agar Selectively favors growth of Neisseria by inhibiting growth of gram organisms with vancomycin,
gram organisms except Neisseria with trimethoprim and colistin, and fungi with nystatin Very typically cultures Neisseria B pertussis Bordet-Gengou
agar (Bordet for Bordetella) Regan-Lowe medium Potato extract Charcoal, blood, and antibiotic
C diphtheriae Tellurite agar, Löffer medium
M tuberculosis Löwenstein-Jensen medium, Middlebrook medium, rapid automated broth cultures
M pneumoniae Eaton agar Requires cholesterol
Lactose-fermenting enterics MacConkey agar Fermentation produces acid, causing colonies to turn pink
E coli Eosin–methylene blue (EMB) agar Colonies with green metallic sheen
Brucella, Francisella, Legionella, Pasteurella Charcoal yeast extract agar buffered with cysteine and iron The Ella siblings, Bruce, Francis, a
legionnaire, and a pasteur (pastor), built the Sistine (cysteine) chapel out of charcoal and iron
Fungi Sabouraud agar “Sab’s a fun guy ”
Giemsa - RCT-BPH
dont gram stain well - MALT-CRUMBLE
Encapsulated bacteria - Please SHiNE my SKiS
Aerobes - Nocardia, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Bordetella pertussis
Anaerobes - Clostridium, Bacteroides, Fusobacterium, and Actinomyces israelii.
Facultative anaerobes - Streptococci, staphylococci, and enteric gram ⊖ bacteria.
Obligate intracellular - RCC - Rickettsia, Chlamydia, Coxiella
Thayer-Martin agar - CNTV - Selectively favors growth of Neisseria by inhibiting growth of gram organisms with vancomycin, gram organisms except
Neisseria with trimethoprim and colistin, and fungi with nystatin
Catalase-positive organisms - BB CHESS PLAN - Nocardia, Staphylococci, Serratia, Candida, Listeria, E coli, Burkholderia cepacia, Pseudomonas,
Aspergillus, Helicobacter pylori, Bordetella pertussis.
F+ x F- —> No transfer of chromosomal DNA.
Hfr x F- —> few fanking chromosomal genes transferred.
Hfr × F– and Specialized transduction commonality-
Incorporation into bacterial chromosomal DNA
Transduction-
(GP-SE)
Generalized - Packaging error, Lytic phage.
Speciaized - Excision error, Lysogenic phage.

Generalized transduction - GP
packaging error;
lytic phage;
Bacterial DNA cleaved > parts of DNA packaged in phage capsid > phage infects another bacterium > transfer. There is NO incorporation of phage
DNA into bacterial chromosomal DNA.

Speciaized transduction - SE
Excision error;
Lysogenic phage;
Viral DNA INCORPORATES into bacterial chromosome > phage DNA is excised with flanking bacterial genes > DNA is packaged into phage capsid
> phage infects another bacterium > transfer

LYSOGENIC PHAGE - (ABCD’S): Group A strep erythrogenic toxin, Botulinum toxin, Cholera toxin, Diphtheria toxin, Shiga toxin.

Lyme disease - Caused by Borrelia burgdorferi, which is transmitted by the Ixodes deer tick (also vector for Anaplasma spp. and protozoa Babesia).
Natural reservoir is the mouse; deer are essential to tick life cycle but do not harbor Borrelia. Common in northeastern United States.
Stage 1—early localized: erythema migrans (typical “bulls-eye” configuration is pathognomonic but not always present), flu-like symptoms.
Stage 2—early disseminated: secondary lesions, carditis, AV block, facial nerve (Bell) palsy, migratory myalgias/transient arthritis. Stage 3—late
disseminated: encephalopathy, chronic arthritis, peripheral neuropathy.

(FACE): Facial nerve palsy (typically bilateral), Arthritis, Cardiac block, Erythema migrans.
Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Caused by spirochete Treponema pallidum. Treatment: penicillin G.
Primary syphilis - Localized disease presenting with painless chancre. Use fluorescent or dark-field microscopy to visualize treponemes in fluid from
chancre. VDRL in ~ 80%.
Secondary syphilis - Disseminated disease with constitutional symptoms, maculopapular rash (including palms and soles), condylomata lata (smooth,
painless, wart-like white lesions on genitals), lymphadenopathy, patchy hair loss; also confirmable with dark-field microscopy. Serologic testing:
VDRL/RPR (nonspecific), confirm diagnosis with specific test (eg, FTA-ABS). Secondary syphilis = systemic. Latent syphilis ( serology without
symptoms) may follow.
Tertiary syphilis - Gummas (chronic granulomas), aortitis (vasa vasorum destruction), neurosyphilis (tabes dorsalis, “general paresis”), Argyll
Robertson pupil (constricts with accommodation but is not reactive to light). Signs: broad-based ataxia, Romberg, Charcot joint, stroke without
hypertension. For neurosyphilis: test spinal fluid with VDRL, FTA-ABS, and PCR.
Congenital syphilis - Presents with facial abnormalities such as rhagades (linear scars at angle of mouth), snuffles (nasal discharge), saddle nose,
notched (Hutchinson) teeth, mulberry molars, and short maxilla; saber shins; CN VIII deafness. To prevent, treat patient early in pregnancy, as
placental transmission typically occurs after first trimester.
Chlamydiae - Chlamydiae cannot make their own ATP. They are obligate intracellular organisms that cause mucosal infections. 2 forms: Elementary
body (small, dense) is “enfectious” and enters cell

via endocytosis; transforms into reticulate body. Reticulate body replicates in cell by fission; reorganizes into elementary bodies.
Chlamydia trachomatis causes neonatal and follicular adult conjunctivitis, nongonococcal urethritis, PID, and reactive arthritis.
Chlamydophila pneumoniae and Chlamydophila psittaci cause atypical pneumonia; transmitted by aerosol. Chlamydial cell wall lacks classic
peptidoglycan (due to reduced muramic acid), rendering - lactam antibiotics ineffective. Chlamys = cloak (intracellular). C psittaci —has an avian
reservoir (parrots), causes atypical pneumonia. Lab diagnosis: PCR, nucleic acid amplification test. Cytoplasmic inclusions (reticulate bodies) seen on
Giemsa or fluorescent antibody– stained smear. Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for
possible concomitant gonorrhea.
Chlamydia trachomatis serotypes - Types A, B, and C - Chronic infection, cause blindness due to follicular conjunctivitis in resource- limited areas.
ABC = Africa, Blindness, Chronic infection.
Types D–K - Urethritis/PID, ectopic pregnancy, neonatal pneumonia (staccato cough) with eosinophilia, neonatal conjunctivitis (1–2 weeks after birth).
D–K = everything else. Neonatal disease can be acquired during vaginal birth if pregnant patient is infected. Types L1, L2, and L3 - Lymphogranuloma
venereum—small, painless ulcers on genitals > swollen, painful inguinal lymph nodes that ulcerate (buboes). Treat with doxycycline.
Zoonotic bacteria - Zoonosis—infectious disease transmitted between animals and humans. SPECIES DISEASE TRANSMISSION AND SOURCE
Anaplasma spp Anaplasmosis Ixodes ticks (live on deer and mice)
Bartonella spp Cat scratch disease, bacillary angiomatosis Cat scratch
Borrelia burgdorferi Lyme disease Ixodes ticks (live on deer and mice)
Borrelia recurrentis Relapsing fever Louse (recurrent due to variable surface antigens)
Brucella spp Brucellosis/undulant fever Unpasteurized dairy
Campylobacter Bloody diarrhea Feces from infected pets/animals; contaminated meats/foods/hands
Chlamydophila psittaci Psittacosis Parrots, other birds
Coxiella burnetii Q fever Aerosols of cattle/sheep amniotic fuid
Ehrlichia chafeensis Ehrlichiosis Amblyomma (Lone Star tick)
Francisella tularensis Tularemia Ticks, rabbits, deer fies
Leptospira spp Leptospirosis Animal urine in water; recreational water use
Mycobacterium leprae Leprosy Humans with lepromatous leprosy; armadillo (rare)
Pasteurella multocida Cellulitis, osteomyelitis Animal bite, cats, dogs
Rickettsia prowazekii Epidemic typhus Human to human via human body louse
Rickettsia rickettsii Rocky Mountain spotted fever Dermacentor (dog tick)
Rickettsia typhi Endemic typhus Fleas
Salmonella spp (except S typhi) Diarrhea (which may be bloody), vomiting, fever, abdominal cramps Reptiles and poultry Yersinia pestis Plague Fleas
(rats and prairie dogs are reservoirs)
Ixodes tick - anaplasmosis and lyme disease
louse - relapsing fever (borrelia recurrentis)
fleas - plague, endemic typhus (Rickettsia typhi)
human body louse - epidemic typhus (Rickettsia prowazekii) Aerosols of cattle/sheep amniotic fluid - Q fever Amblyomma (Lone Star tick) -
ehrilichiosis
Dermacentor (dog tick) - RMSF - Rickettsia rickettsii Ticks, rabbits, deer flies - tularemia
Reptiles and poultry - Salmonella spp (except S typhi)
Nematode routes of infection-
Ingested—Enterobius, Ascaris, Toxocara, Trichinella, Trichuris. You’ll get sick if you EATTT these Cutaneous—Strongyloides, Ancylostoma, Necator.
These get into your feet from the SANd. Bites—Loa loa, Onchocerca volvulus, Wuchereria bancrofti. Lay LOW to avoid getting bitten.
Parasite hints-
Biliary tract disease, cholangiocarcinoma - Clonorchis sinensis
Brain cysts, seizures - Taenia solium (neurocysticercosis)
Hematuria, squamous cell bladder cancer - Schistosoma haematobium Liver (hydatid) cysts, exposure to infected dogs - Echinococcus granulosus Iron
deficiency anemia - Ancylostoma, Necator Myalgias, periorbital edema - Trichinella spiralis
Nocturnal perianal pruritus - Enterobius
Portal hypertension - Schistosoma mansoni, Schistosoma japonicum Vitamin B12 deficiency - Diphyllobothrium latum
All are linear except papilloma-, polyoma-, and hepadnaviruses (circular). - PPH
⊕ stranded RNA viruses: (retrovirus) (togavirus) (flavivirus) (coronavirus) (hepevirus) (calicivirus) (picornavirus) - RCT-FHPC
Naked (nonenveloped) viruses include - DNA viruses - papillomavirus, adenovirus, parvovirus, polyomavirus (PAPP); RNA viruses - calicivirus,
picornavirus, reovirus, and hepevirus. (happy rhio khalici naked pic)
Enveloped DNA viruses - (herpesvirus, hepadnavirus, poxvirus) - HHP
CIRCULAR RNA - ARENAVIRUS, BUNYAVIRUS, DELTA VIRUS. - ABD
SEGMENTED VIRUSES - Bunyaviruses (3 segments), Orthomyxoviruses (infuenza viruses) (8 segments), Arenaviruses (2 segments), and Reoviruses
(10-12 segments). - BORA
Purified nucleic acids of most dsDNA viruses (except poxviruses and HBV) and ⊕ strand ssRNA (≈ mRNA) viruses are infectious. Naked nucleic acids
of ⊖ strand ssRNA and dsRNA viruses are not infectious.
DNA viruses - All replicate in the nucleus (except poxvirus). “Pox is out of the box (nucleus).”
RNA viruses - All replicate in the cytoplasm (except retrovirus and influenza virus). “Retro flu is outta cyt (sight).”
Reovirus - RC - Coltivirus —Colorado tick fever. Rotavirus—cause of fatal diarrhea in children.
Picornavirus (PERCH) - Poliovirus—polio-Salk/Sabin vaccines—IPV/OPV. Echovirus—aseptic meningitis. Rhinovirus —“common cold”.
Coxsackievirus—aseptic meningitis; herpangina (mouth blisters, fever); hand, foot, and mouth disease; myocarditis; pericarditis. HAV—acute viral
hepatitis. (PERCH).
Flaviviruses - HYD-SWZ (flavors of hyd and swz) - HCV; Yellow fever; Dengue; St. Louis encephalitis; West Nile virus —meningoencephalitis,
flaccid paralysis; Zika virus.
Togaviruses - Toga CREW—Chikungunya virus (co-infection with dengue virus can occur), Rubella, Eastern and Western equine encephalitis.
Retroviruses - HTLV—T-cell leukemia; HIV—AIDS.
Coronaviruses - “Common cold,” SARS, MERS, COVID-19.
Orthomyxoviruses - Influenza virus
Paramyxoviruses - PaRaMyxovirus: Parainfluenza—croup, RSV—bronchiolitis in babies, Measles, Mumps.
Rhabdoviruses - Rabies.
Filoviruses - Ebola/Marburg hemorrhagic fever—often fatal.
Arenaviruses - LL - LCMV—lymphocytic choriomeningitis virus; Lassa fever encephalitis— spread by rodents.
Bunyaviruses - HSCC (HSBCc) - California encephalitis, Sandfly/Rift Valley fevers, Crimean-Congo hemorrhagic fever, Hantavirus—hemorrhagic
fever, pneumonia.
Delta virus - HDV
Acute laryngotracheobronchitis - Also called croup. Caused by parainfluenza viruses. Results in a “seal-like” barking cough and inspiratory stridor.
Narrowing of upper trachea and subglottis leads to characteristic steeple sign on x-ray.
H. influenzae type b - Epiglottitis (“thumb sign” on lateral neck x-ray)
Croup - parainfluenza; “seal-like” barking cough and inspiratory stridor. Steeple sign on x-ray.
Bordetella pertusis - inspiratory “whoop” (“whooping cough”), posttussive vomiting.

Measles - Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia.
Virus HAV. FAMILY RNA picornavirus. LIVER BIOPSY Hepatocyte swelling, monocyte infiltration, Councilman bodies.
Virus HBV. FAMILY DNA hepadnavirus. LIVER BIOPSY Granular eosinophilic “ground glass” appearance due to accumulation of surface antigen
within infected hepatocytes; cytotoxic T cells mediate damage.
Virus HCV. FAMILY RNA flavivirus. LIVER BIOPSY Lymphoid aggregates with focal areas of macrovesicular steatosis.
Virus HDV. FAMILY RNA deltavirus. LIVER BIOPSY Similar to HBV.
Virus HEV. FAMILY RNA hepevirus. CLINICALCOURSE Fulminant hepatitis in Expectant (pregnant) patients. PROGNOSIS High mortality in
pregnant patients. LIVER BIOPSY Patchy necrosis.
Hepatitis serologic markers-
Anti-HAV (IgM) - IgM antibody to HAV; best test to detect acute hepatitis A.

Anti-HAV (IgG) - IgG antibody indicates prior HAV infection and/or prior vaccination; protects against reinfection. HBsAg - Antigen found on surface
of HBV; indicates hepatitis B infection.
Anti-HBs - Antibody to HBsAg; indicates immunity to hepatitis B due to vaccination or recovery from infection. HBcAg - Antigen associated with
core of HBV.

Anti-HBc - Antibody to HBcAg; IgM = acute/recent infection; IgG = prior exposure or chronic infection. IgM anti-HBc may be the sole marker of
infection during window period. HBeAg - Secreted by infected hepatocyte into circulation. Not part of mature HBV virion. Indicates active viral
replication and therefore high transmissibility and poorer prognosis. Anti-HBe - Antibody to HBeAg; indicates low transmissibility.
Important diagnostic tests-
Incubation period - HBsAg
Prodrome, acute disease - HBsAg (anti-HBc) Convalescence Early - Anti-HBc Convalescence Late - Anti-HBs (anti-HBc)
Acute HBV - HBsAg, HBeAg, Anti-HBc IgM
Window - Anti-HBe, Anti-HBc IgM
Chronic HBV (high infectivity) - HBsAg, HBeAg, Anti-HBc IgG Chronic HBV (low infectivity) - HBsAg, Anti-HBe, Anti-HBc IgG Recovery - Anti-
HBs, Anti-HBe, Anti-HBc IgG Immunized - Anti-HBs
HIV - env (gp120 and gp41): Formed from cleavage of gp160 to form envelope glycoproteins. gp120—attachment to host CD4+ T cell. gp41— fusion
and entry.
Gag (p24 and p17)—capsid and matrix proteins, respectively.
pol—Reverse transcriptase, Integrase, Protease; RIP “Pol” (Paul).

Virus binds CD4 as well as a coreceptor, either CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection). Homozygous CCR5
mutation = immunity. Heterozygous CCR5 mutation = slower course.
HIV diagnosis - Diagnosis made with HIV-1/2 Ag/Ab immunoassays. These immunoassays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.
Very high sensitivity/speci city. Viral load tests determine the amount of viral RNA in the plasma. Use viral load to monitor effect of drug therapy. Use
HIV genotyping to determine appropriate therapy. AIDS diagnosis: 200 CD4+ cells/mm3 (normal: 500–1500 cells/mm3 ) or HIV with AIDS-defining
condition (eg, Pneumocystis pneumonia). Western blot tests are no longer recommended by the CDC for confirmatory testing. HIV-1/2 Ag/Ab testing is
not recommended in babies with suspected HIV due to maternally transferred antibody. Use HIV viral load instead.

CD4+ cell count < 500/mm3 - ECHH

CD4+ cell count < 200/mm3 - JPHH
CD4+ cell count < 100/mm3 - CBCT-MECCA
Common causes of pneumonia
NEONATES(< 4 WK) - Group B streptococci, E coli
CHILDREN (4 WK–18 YR) - Viruses (RSV), Mycoplasma, C trachomatis (infants–3 yr), C pneumoniae (schoolaged children), S pneumoniae. Runts
May Cough Chunky Sputum.
ADULTS(18–40 YR) - Mycoplasma, C pneumoniae, S pneumoniae, Viruses (eg, influenza)
ADULTS(40–65 YR) - S pneumoniae, H influenzae, Anaerobes, Viruses, Mycoplasma
ELDERLY - S pneumoniae, Influenza virus, Anaerobes, H influenzae, Gram ⊖ rods
Special groups-
Alcohol overuse - Klebsiella, anaerobes usually due to aspiration (eg, Peptostreptococcus, Fusobacterium, Prevotella, Bacteroides)
IV drug use - S pneumoniae, S aureus
Aspiration - Anaerobes
Atypical - Mycoplasma, Chlamydophila, Legionella, viruses (RSV, CMV, influenza, adenovirus)
Cystic fibrosis - Pseudomonas, S aureus, S pneumoniae, Burkholderia cepacia
Immunocompromised - S aureus, enteric gram ⊖ rods, fungi, viruses, P jirovecii (with HIV)
Nosocomial - S aureus, Pseudomonas, other enteric gram ⊖ rods
Postviral - S pneumoniae, S aureus, H influenzae
COPD - S pneumoniae, H influenzae, M catarrhalis, Pseudomonas
Common causes of meningitis
NEWBORN (0–6 MO) - Group B Streptococcus E coli Listeria
CHILDREN (6 MO–6YR) - S pneumoniae N meningitidis H influenzae type b Group B Streptococcus Enteroviruses
6–60 YR - S pneumoniae N meningitidis Enteroviruses HSV
60 YR+ - S pneumoniae N meningitidis H influenzae type b Group B Streptococcus Listeria
Give ceftriaxone and vancomycin empirically (add ampicillin if Listeria is suspected).
Viral causes of meningitis: enteroviruses (especially coxsackievirus), HSV-2 (HSV-1 = encephalitis), HIV, West Nile virus (also causes encephalitis),
VZV. In HIV: Cryptococcus spp.
Organisms typically not covered by 1st–4th generation cephalosporins are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and
Enterococci.
Vancomycin - SE - Well tolerated in general but not trouble free: nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing (red man syndrome -
idiopathic reaction largely preventable by pretreatment with antihistamines), DRESS syndrome.
Aminoglycosides - SE - Nephrotoxicity, neuromuscular blockade (absolute contraindication with myasthenia gravis), ototoxicity (especially with loop
diuretics), teratogenicity.
Macrolides - SE - MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash,
eOsinophilia. Increases serum concentration of theophylline, oral anticoagulants.
Polymyxins - SE - Nephrotoxicity, neurotoxicity (eg, slurred speech, weakness, paresthesias), respiratory failure.
Sulfonamides - SE - Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, Stevens-
Johnson syndrome, kernicterus in infants, displace other drugs from albumin (eg, warfarin).
Trimethoprim - SE - Hyperkalemia (high doses), megaloblastic anemia, leukopenia, granulocytopenia, which may be avoided with coadministration of
leucovorin (folinic acid).
Isoniazid - SE - Hepatotoxicity, cytochrome P-450 inhibition, drug-induced SLE, anion gap metabolic acidosis, vitamin B6 deficiency (peripheral
neuropathy, sideroblastic anemia), seizures (in high doses, refractory to benzodiazepines). Administer with pyridoxine (B6).
Aminoglycosides - Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin. “Mean” (aminoglycoside) GNATS cannot kill anaerobes.
Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit. Can cause misreading of mRNA. Also block
translocation. Require O2 for uptake; therefore ineffective against anaerobes.
Tetracyclines - Tetracycline, doxycycline, minocycline. Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA. Limited CNS
penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take tetracyclines with milk (Ca2+), antacids (eg,
Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit drugs’ absorption in the gut.
Tigecycline - Tetracycline derivative. Binds to 30S, inhibiting protein synthesis.
Chloramphenicol - Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
Clindamycin - Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.
Linezolid - Inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.
Macrolides - Azithromycin, clarithromycin, erythromycin. Inhibit protein synthesis by blocking translocation (“macroslides”); bind to the 23S rRNA of
the 50S ribosomal subunit. Bacteriostatic.

Calcium channel blockers - ADVERSE EFFECTS Gingival hyperplasia. Dihydropyridine: peripheral edema, fushing, dizziness. Nondihydropyridine:
cardiac depression, AV block, hyperprolactinemia (verapamil), constipation.
Hydralazine - ADVERSE EFFECTS Compensatory tachycardia (contraindicated in angina/CAD), fuid retention, headache, angina, drug-induced
lupus.
Hypertensive emergency - Treat with (CNN-FL) labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside. Nitroprusside - Can cause cyanide
toxicity (releases cyanide). Fenoldopam - Can cause hypotension, tachycardia, fushing, headache, nausea.

Nitrates - ADVERSE EFFECTS Refex tachycardia (treat with -blockers), hypotension, fushing, headache, “Monday disease” in industrial nitrate
exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend —> tachycardia,
dizziness, headache upon reexposure. Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5
inhibitor use.
Ranolazine - ADVERSE EFFECTS Constipation, dizziness, headache, nausea.

Sacubitril - ADVERSE EFFECTS Hypotension, hyperkalemia, cough, dizziness; contraindicated with ACE inhibitors due to angioedema (both drugs
inc bradykinin). HMG-CoA reductase inhibitors - SE - Hepatotoxicity (inc LFTs), myopathy (esp when used with fibrates or niacin).

Bile acid resins - Cholestyramine, colestipol, colesevelam - SE - GI upset, dec absorption of other drugs and fat- soluble vitamins Ezetimibe - SE -
Rare inc LFTs, diarrhea
Fibrates - SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7 -hydroxylase).
Niacin - SE - Flushed face (prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia Hyperuricemia.

PCSK9 inhibitors - SE - Myalgias, delirium, dementia, other neurocognitive effects.

Fish oil and marine omega-3 fatty acids - SE - Nausea, fish-like taste.
Cardiac glycosides Digoxin. ADVERSE EFFECTS Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (think van Glow),
arrhythmias, AV block. Can lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to toxicity: renal failure ( excretion),
hypokalemia (permissive for digoxin binding at K+-binding site on Na+ /K+ ATPase), drugs that displace digoxin from tissue- binding sites, and dec
clearance (eg, verapamil, amiodarone, quinidine). ANTIDOTE Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+.
1A - Quinidine, procainamide, disopyramide. SE - Cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF
(disopyramide), thrombocytopenia, torsades de pointes due to inc QT interval.
1B - Lidocaine, phenytoin, mexiletine. SE - CNS stimulation/depression, cardiovascular depression.
1C - Flecainide, propafenone. SE - Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.
Antiarrhythmics— -blockers (class II) - ADVERSE EFFECTS Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV
block, HF), CNS effects (sedation, sleep alterations). May mask the signs of hypoglycemia. Metoprolol can cause dyslipidemia. Propranolol can
exacerbate vasospasm in vasospastic angina. B-blockers (except the nonselective - and - antagonists carvedilol and labetalol) cause unopposed 1-
agonism if given alone for pheochromocytoma or for cocaine toxicity (unsubstantiated). Treat B-blocker overdose with saline, atropine, glucagon.
Antiarrhythmics—potassium channel blockers (class III) - ADVERSE EFFECTS Sotalol —torsades de pointes, excessive blockade. Ibutilide—
torsades de pointes. Amiodarone—pulmonary fbrosis, hepatotoxicity, hypothyroidism or hyperthyroidism (amiodarone is 40% iodine by weight), acts
as hapten (corneal deposits, blue/gray skin deposits resulting in photodermatitis), neurologic effects, constipation, cardiovascular effects (bradycardia,
heart block, HF). Remember to check PFTs, LFTs, and TFTs when using amiodarone. Amiodarone is lipophilic and has class I, II, III, and IV effects.
Antiarrhythmics—calcium channel blockers (class IV) - ADVERSE EFFECTS Constipation, fushing, edema, cardiovascular effects (HF, AV block,
sinus node depression).
Adenosine - Adverse effects include flushing, hypotension, chest pain, sense of impending doom, bronchospasm.
IVabradine - SE - Luminous phenomena/visual brightness, hypertension, bradycardia.
GLUT1 - P-RBC
GLUT2 - LKG-B
GLUT3 - BP
GLUT4 - AS
GLUT5 - GS
SGLT1/2 - SK

insulin dependent - GLUT4

insulin independent - GLUT1,2,3,5; SGLT1,2 (BRICK-LIPS)

GLUT-2 - bidirectional GLUT-5 - fructose

GLUT1: RBCs, brain, cornea, placenta.

GLUT2 (bidirectional): B-islet cells, liver, kidney, GI tract.
GLUT3: brain, placenta.
GLUT4: adipose tissue, striated muscle.
GLUT5 (fructose): spermatocytes, GI tract.
SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine.
Signaling pathways of endocrine hormones-
cAMP - FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2- receptor), MSH, PTH, Calcitonin, Histamine (H2-receptor), Glucagon, GHRH. FLAT
ChAMPs CHuGG.
cGMP - BNP, ANP, EDRF (NO). BAD GraMPa. Think vasodilation and diuresis.
IP3 - GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin. GOAT HAG.
Intracellular receptor - Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4,Vitamin D. PET CAT in TV.
Serine/threonine kinase receptor - TGF-B
Receptor tyrosine kinase - IGF-1, FGF, PDGF, EGF, Insulin. MAP kinase pathway. Get Found In the MAP. (Growth factors and insulin).
Nonreceptor tyrosine kinase - G-CSF, Erythropoietin, Thrombopoietin Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH. JAK/STAT
pathway. Think acidophils and cytokines. GET a JAKed PIG.
Wolff-Chaikoff effect—protective autoregulation; sudden exposure to excess iodine temporarily turns off thyroid peroxidase > dec T3/T4 production.
Jod-Basedow phenomenon - Iodine-induced hyperthyroidism. Occurs when a patient with iodine defciency and partially autonomous thyroid tissue (eg,
autonomous nodule) is made iodine replete. Can happen after iodine IV contrast or amiodarone use. Opposite to Wolff- Chaikoff effect.
Hyperthyroidism - inc number and sensitivity of B-adrenergic receptors, inc expression of cardiac sarcolemmal ATPase and dec expression of
phospholamban.
Postpartum thyroiditis—mild, self-limited variant of Hashimoto thyroiditis arising < 1 year after delivery.
Hypothyroidism - hypercholestrolemia
Hyperthyroidism - dec cholestrol
Congenita hypothyroidism - cretinism - Findings (6 P’s): pot-bellied, pale, puffy-faced child with protruding umbilicus, protuberant tongue, and poor
brain development.
Euthyroid sick syndrome - nonthyroidal illness syndrome - dec T3 with normal/dec T4 and TSH in critically ill patients).

Hypothyroid myopathy (proximal weakness, inc CK)

Thyrotoxic myopathy (proximal weakness, normal CK)
Fine needle aspiration cytology may not be able to distinguish between follicular adenoma and carcinoma
Follicular carcinoma - Associated with RAS mutation and PAX8-PPAR-y translocations.
Thyroid storm Rx - Treat with the 4 P’s: B-blockers (eg, propranolol), propylthiouracil, corticosteroids (eg, prednisolone), potassium iodide (Lugol
iodine). Iodide load > dec T4 synthesis > Wolff- Chaikoff effect.
Papillary carcinoma - Most common. Empty-appearing nuclei with central clearing (“Orphan Annie” eyes), psamMoma bodies, nuclear grooves (Papi
and Moma adopted Orphan Annie). Inc risk with RET/ PTC rearrangements and BRAF mutations, childhood irradiation.
HbA1c - >6.5% - Refects average blood glucose over prior 3 months (infuenced by RBC turnover)
Fasting plasma glucose - >126 mg/dL - Fasting for > 8 hours
2-hour oral glucose tolerance test - >200 mg/dL - 2 hours after consumption of 75 g of glucose in water
Random plasma glucose - >200 mg/dL - Presence of hyperglycemic symptoms is required.
Type 1 - GLUCOSE INTOLERANCE Severe
Type 2 - GLUCOSE INTOLERANCE Mild to moderate
Nelson syndrome - Enlargement of pre-existing ACTH–secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushing disease > inc
ACTH (hyperpigmentation), mass effect (headaches, bitemporal hemianopia). Treatment: transsphenoidal resection, postoperative pituitary irradiation
for residual tumor.
Pheochromocytoma - rule of 10s
Carcinoid tumor - rule of thirds
Meckel diverticulum - rule of 2s
Neuroblastoma - (neuroblastoma is normotensive). Can also present with opsoclonus-myoclonus syndrome (“dancing eyes-dancing feet”). Inc HVA
and VMA (catecholamine metabolites) in urine. Homer-Wright rosettes (neuroblasts surrounding a central lumen) characteristic of neuroblastoma and
medulloblastoma. Bombesin and NSE +. Associated with amplifcation of N-myc oncogene. Addison ds - chronic primary adrenal insufficiency
Adrenal/addisonian crisis - acute adrenal insufficiency

Primary adrenal insufficiency - dec aldosterone synthesis.

Sec/Ter adrenal insufficiency - normal aldosterone synthesis (intact RAAS).
1° hyperaldosteronism does not directly cause edema due to aldosterone escape mechanism. However, certain 2° causes of hyperaldosteronism (eg,
heart failure) impair the aldosterone escape mechanism, leading to worsening of edema.
Neuroblastoma - Most common presentation is abdominal distension and a firm, irregular mass that can cross the midline (vs Wilms tumor, which is
smooth and unilateral).
Carcinoid tumor Rx - Treatment: surgical resection, somatostatin analog (eg, octreotide) or tryptophan hydroxylase inhibitor (eg, telotristat) for
symptom control.
ZES - Positive secretin stimulation test: inc gastrin levels after administration of secretin, which normally inhibits gastrin release.
Most OHAs classes are avoided in renal insufficiency.
PTU used in Primary (first) trimester of pregnancy (due to methimazole teratogenicity); methimazole used in second and third trimesters of pregnancy
(due to risk of PTU-induced hepatotoxicity). Not used to treat Graves ophthalmopathy (treated with corticosteroids). ADVERSE EFFECTS Skin rash,
agranulocytosis (rare), aplastic anemia, hepatotoxicity. PTU use has been associated with ANCA-positive vasculitis. Methimazole is a possible
teratogen (can cause aplasia cutis).
Pheochromocytoma - rule of 10s
Carcinoid tumor - rule of thirds
Meckel diverticulum - rule of 2s
Metformin - lactic acidosis (use with caution in renal insufficiency).

Rosiglitazone: inc risk of MI, cardiovascular death.

GLP-1 analogs, DPP-4 inhibitors - dec glucagon release, dec gastric emptying, inc glucose-dependent insulin release. SE GLP-1 analogs - Pancreatitis,
weight loss, Inc satiety. SE DPP-4 inh - Respiratory and urinary infections, weight neutral, Inc satiety. (DPP-4 inhibitors - Inhibit DPP-4 enzyme that
deactivates GLP-1).
Weight loss (GBS) - Biguanides, GLP-1 analogs, SGLT 2 inhibitors.
Weight neutral - DPP-4 inhibitors.
Weight gain (MST) - TZDs, sulfonylureas, meglitinides.
Insulin preparations - SE - Hypoglycemia, lipodystrophy, hypersensitivity reactions (rare), weight gain.
Biguanides - Metformin - SE - GI upset, lactic acidosis (use with caution in renal insufficiency), vitamin B12 deficiency. Weight loss (often desired).
TZDs - “-glits” Pioglitazone, rosiglitazone - SE - Weight gain, edema, HF, inc risk of fractures. Delayed onset of action (several weeks). Rosiglitazone:
inc risk of MI, cardiovascular death. Sulfonylureas (1st gen) - Chlorpropamide, tolbutamide. Sulfonylureas (2nd gen) - Glipizide, glyburide.
Meglitinides “-glins” Nateglinide, repaglinide - SE - Hypoglycemia (inc risk in renal insufficiency), weight gain. Disulfiram-like reaction with first-
generation sulfonylureas only (rarely used).
GLP-1 analogs - Exenatide, liraglutide. DPP-4 inhibitors “-glips” Linagliptin, saxagliptin, sitagliptin - SE GLP-1 analogs - Pancreatitis, weight loss, Inc
satiety. SE DPP-4 inh - Respiratory and urinary infections, weight neutral, Inc satiety. (DPP-4 inhibitors - Inhibit DPP-4 enzyme that deactivates GLP-
1.)
SGLT-2 inh - Sodium-glucose co-transporter 2 inhibitors “-glifs” Canagliflozin, dapagliflozin, empagliflozin - SE - Glucosuria (UTIs, vulvovaginal
candidiasis), dehydration (orthostatic hypotension), weight loss. Use with caution in renal insufficiency (dec efficacy with dec GFR).
-glucosidase inhibitors - Acarbose, miglitol - SE - GI upset, bloating. Not recommended in renal insufficiency.
Amylin analogs - Pramlintide - SE - Hypoglycemia. Inc satiety (often desired).
Weight loss (GBS) - Biguanides, GLP-1 analogs, SGLT 2 inhibitors. Weight neutral - DPP-4 inhibitors. Weight gain (MST) - TZDs, sulfonylureas,
meglitinides.
Thionamides - Propylthiouracil, methimazole - ADVERSE EFFECTS Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity. PTU use has
been associated with ANCA-positive vasculitis. Methimazole is a possible teratogen (can cause aplasia cutis).
Levothyroxine, liothyronine - ADVERSE EFFECTS Tachycardia, heat intolerance, tremors, arrhythmias.
Fludrocortisone - MECHANISM Synthetic analog of aldosterone with glucocorticoid effects.
Cinacalcet - MECHANISM Sensitizes calcium-sensing receptor (CaSR) in parathyroid gland to circulating Ca2+ —> dec PTH.
Sevelamer - MECHANISM Nonabsorbable phosphate binder that prevents phosphate absorption from the GI tract.
Cation exchange resins Patiromer, sodium polystyrene sulfonate, zirconium cyclosilicate. MECHANISM Bind K+ in colon in exchange for other
cations (eg, Na+, Ca2+) —> K+ excreted in feces. Fludrocortisone - ADVERSE EFFECTS Similar to glucocorticoids; also edema, exacerbation of
heart failure, hyperpigmentation
Cinacalcet - ADVERSE EFFECTS Hypocalcemia.
Sevelamer ADVERSE EFFECTS Hypophosphatemia, GI upset.
Cation exchange resins Patiromer, sodium polystyrene sulfonate, zirconium cyclosilicate - ADVERSE EFFECTS Hypokalemia, GI upset.
Above pectinate - visceral N, sup rectal A(IMA), sup rectal V(IMV), internal iliac LN

Below pectinate - pudendal N, inf rectal A(internal pudendal A), inf rectal V(internal pudendal V), superficial inguinal LN Femoral triangle - adductor
longus, sartorius and inguinal ligament; contains NAV.

Femoral sheath - NO NERVE. Contains vein, artery and deep inguinal LN. Spermatic cord (ICE-tie)-
Internal spermatic fascia (transversalis fascia)
Cremasteric muscle and fascia (internal oblique)

External spermatic fascia (external oblique) External iliac vessels > inferior epigastric vessels

Inguinal (hesselbach) triangle - inf epigastric vessels, inguinal ligament and rectus abdominis.
Indirect - lateral to inferior epigastric vessels, both rings, covered by all 3 layers, processus vaginalis failure.
Direct - medial to inferior epigastric vessels, through inguinal (hesselbach) triangle, superficial ring only, covered by external spermatic fascia only, due
to acquired weakness of transversalis fascia. Femoral triangle - adductor longus, sartorius and inguinal ligament; contains NAV.
Inguinal (hesselbach) triangle - inf epigastric vessels, inguinal ligament and rectus abdominis.
Sliding hiatal hernia—gastroesophageal junction is displaced upward as gastric cardia slides into hiatus; “hourglass stomach.” Most common type.
Associated with GERD.
Paraesophageal hiatal hernia— gastroesophageal junction is usually normal but gastric fundus protrudes into the thorax.

Weak acids - Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to
alkalinize urine. Weak bases - Examples: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium chloride to acidify
urine.
TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channel blocking activity of TCAs, but not for accelerating drug
elimination.
TCA toxicity Rx ammonium chloride and sodium bicarbonate.

Zero-order elimination - Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp dec linearly with
time. Examples of drugs— (PEA) Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations). Capacity-limited elimination. Time of t1/2 dec as
concentration dec.
First-order elimination - Rate of first-order elimination is directly proportional to the drug concentration (ie, constant fraction of drug eliminated per
unit time). Cp dec exponentially with time. Applies to most drugs. Flow-dependent elimination. Time of t1/2 is constant as concentration dec.

-ximab Chimeric human-mouse monoclonal antibody Rituximab -zumab Humanized monoclonal antibody Bevacizumab
-umab Human monoclonal antibody Denosumab
-leukin Interleukin-2 agonist/analog Aldesleukin

-kinra Interleukin receptor antagonist Anakinra Inducers - SGPC-CMRN-P

Substrates - The OCPs are anti-war
Inhibitors - [Link]-RAG

OR = (a/c)/(b/d) = ad/bc RR = a/(a + b) / c/(c + d) RRR = 1 − RR

AR = a/a+b - c/c+d
AR% = (RR-1 / RR) x 100
ARR = c/c+d - a/a+b
NNT = 1/ARR
NNH = 1/AR
CFR% = (deaths/cases) x 100
Attack rate = People who become ill / Total people exposed
LR+ = sensitivity / 1 – specificity = TP rate / FP rate
LR- = 1-sensitivity / specificity = FN rate / TN rate
PPV = TP/(TP + FP)
Prevalence = TP + FN / (TP + FN + FP + TN)
NPV = TN/(TN + FN)
Sensitivity = TP / (TP + FN) = 1 – FN rate.
Specifcity = TN / (TN + FP) = 1 – FP rate.
Prevalence / 1 – prevalence = Incidence rate × average duration of disease
Variance = (SD)2 . SE = σ/√n. σ = SD; n = sample size.
CI for sample mean = x ± Z(SE) For the 95% CI, Z = 1.96. For the 99% CI, Z = 2.58.
Coeffcient of determination = r2 (r square)
Selection bias - Randomization (creates groups with similar distributions of known and unknown variables). Ensure the choice of the right
comparison/reference group.

Recall bias - Decrease time from exposure to follow-up

Measurement bias - Use objective, standardized, and previously tested methods of data collection that are planned ahead of time. Use placebo group.
Procedure bias - Blinding (masking) and use of placebo reduce infuence of participants and researchers on procedures and interpretation of outcomes as
neither are aware of group assignments. Observer-expectancy bias - Blinding (masking) and use of placebo reduce infuence of participants and
researchers on procedures and interpretation of outcomes as neither are aware of group assignments.
Confounding bias - Multiple/repeated studies Crossover studies (subjects act as their own controls) Matching (patients with similar characteristics in
both treatment and control groups) Lead-time bias - Measure “back-end” survival (adjust survival according to the severity of disease at the time of
diagnosis)
Length-time bias - A randomized controlled trial assigning subjects to the screening program or to no screening.
Capacity - MASSIVE
Exceptions to informed consent - WIPE it away
Exceptions to patient confdentiality - SAVED
Situations in which parental consent is usually not required: Sex (contraception, STIs, prenatal care— usually not abortion), Drugs (substance use
disorder treatment), Rock and roll (emergency/trauma)
Goals - Specific, Measurable, Achievable, Relevant, and Time bound (SMART).

Patient-centered interviewing techniques (VR-FAIR / IAR-VRF) Introduction Agenda Reflection Validation Recapitulation Facilitation

Expressing empathy PEARLS

Partnership Empathy Apology Respect Legitimization Support

Delivering bad news SPIKES

Setting Perception Invitation Knowledge Emotions Strategy
Limited panel & cheaper - EPO and HMO
Outside network & expensive - POS and PPO
No referral reqd - EPO and PPO
Referral reqd - POS and HMO
(Start with P - outside network and expensive)
(PO-provider organisation - no referral required)
(when u pee outside u get fined and its expensive)
TGA - (“egg on a string” appearance on CXR).
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.
Infant of patient with diabetes during pregnancy - Transposition of great vessels, VSD
Williams syndrome - Supravalvular aortic stenosis
22q11 syndromes - Truncus arteriosus, tetralogy of Fallot.
Fetal alcohol syndrome - VSD, PDA, ASD, tetralogy of Fallot
Uncorrected PDA (Eisenmenger syndrome) can eventually result in late cyanosis in the lower extremities (differential cyanosis).
HOCM - Asymmetric septal hypertrophy and systolic anterior motion of mitral valve.
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.
AAA - Most often infrarenal (distal to origin of renal arteries).
Abdominal aortic aneurysm - Usually associated with atherosclerosis.
Thoracic aortic aneurysm - Associated with cystic medial degeneration.
Subclavian steal syndrome: >15 mm Hg difference in systolic BP between arms.
Myocardial hibernation—potentially reversible LV systolic dysfunction in the setting of chronic ischemia. Contrast with myocardial stunning, a
transient LV systolic dysfunction after a brief episode of acute ischemia.
3-14 days - LV pseudoaneurysm (risk of rupture).
>2 weeks - True ventricular aneurysm (risk of mural thrombus).
Kussmaul sign - Paradoxical inc in JVP on inspiration.
In the first 6 hours, ECG is the gold standard. Cardiac troponin I rises after 4 hours (peaks at 24 hr) and is inc for 7–10 days; more specifc than other
protein markers. CK-MB rises after 6–12 hours (peaks at 16–24 hr) and is predominantly found in myocardium but can also be released from skeletal
muscle. Useful in diagnosing reinfarction following acute MI because levels return to normal after 48 hours.

Lateral (LCX) I, aVL

InFerior (RCA) II, III, aVF
Posterior (PDA) V7–V9, ST depression in V1–V3 with tall R waves.

Holiday heart syndrome - Atrial fibrillation seen after episodes of excessive alcohol consumption.
Atrial flutter - Treat like atrial fbrillation +/– catheter ablation of region between tricuspid annulus and IVC. Mobitz type I (Wenckebach) - Progressive
lengthening of PR interval until a beat is “dropped”. Regularly irregular. Mobitz type II - Dropped beats that are not preceded by a change in the length
of the PR interval (as in type I).

Holiday heart syndrome - Atrial fibrillation seen after episodes of excessive alcohol consumption.
Ventricular pseudoaneurysm formation 3–14 days: free wall rupture contained by adherent pericardium or scar tissue. True ventricular aneurysm 2
weeks to several months: outward bulge with contraction (“dyskinesia”), associated with fibrosis.
Takotsubo cardiomyopathy: broken heart syndrome—ventricular apical ballooning likely due to increased sympathetic stimulation (eg, stressful
situations).

HOCM - Asymmetric septal hypertrophy and systolic anterior motion of mitral valve.
Tetralogy of Fallot - Caused by anterosuperior displacement of the infundibular septum.
Löffer endocarditis—associated with hypereosinophilic syndrome; histology shows eosinophilic infltrates in myocardium.
Aschoff bodies (granuloma with giant cells).
Anitschkow cells (enlarged macrophages with ovoid, wavy, rod-like nucleus).
Myocarditis - arrhythmias (persistent tachycardia out of proportion to fever is characteristic).
Pericarditis - ECG changes include widespread ST-segment elevation and/or PR depression.
Endocarditis - If culture -ve, most likely Coxiella burnetii, Bartonella spp.
Native valve endocarditis may be due to HACEK organisms (Haemophilus, Aggregatibacter [formerly Actinobacillus], Cardiobacterium, Eikenella,
Kingella). Cardiac Tamponade - pulsus paradoxus, electrical alternans.
Pulsus paradoxus—dec in amplitude of systolic BP by > 10 mm Hg during inspiration.

Myocarditis - Infammation of myocardium > global enlargement of heart and dilation of all chambers. Major cause of SCD in adults < 40 years old.
Presentation highly variable, can include dyspnea, chest pain, fever, arrhythmias (persistent tachycardia out of proportion to fever is characteristic).
Multiple causes: Viral (eg, adenovirus, coxsackie B, parvovirus B19, HIV, HHV-6); lymphocytic infltrate with focal necrosis highly indicative of viral
myocarditis
Parasitic (eg, Trypanosoma cruzi, Toxoplasma gondii)

Bacterial (eg, Borrelia burgdorferi, Mycoplasma pneumoniae, Corynebacterium diphtheriae) Toxins (eg, carbon monoxide, black widow venom)
Rheumatic fever
Drugs (eg, doxorubicin, cocaine)
Autoimmune (eg, Kawasaki disease, sarcoidosis, SLE, polymyositis/dermatomyositis) Complications include sudden death, arrhythmias,

heart block, dilated cardiomyopathy, HF, mural thrombus with systemic emboli.
Nitrates - Contraindicated in right ventricular infarction, hypertrophic cardiomyopathy, and with concurrent PDE-5 inhibitor use.
Flushing-
Niacin - prostaglandin mediated
Vancomycin - histamine mediated
(niacin-lipids-inflammation)
(antibiotics-allergic reactions)
Hypertensive emergency - Treat with (CNN-FL) labetalol, clevidipine, fenoldopam, nicardipine, nitroprusside.
Verapamil SE - hyperprolactinemia
Primary (essential) hypertension - (CATA)
Hypertension with heart failure - (DABAA)
Hypertension with diabetes mellitus - (B-CATA)
Hypertension in asthma - (C-CAT)
Hypertension in pregnancy - Nifedipine, methyldopa, labetalol, hydralazine. New moms love hugs.
Vasodilators (eg, nitroglycerin/nitrates) dec preload.
Arterial vasodilators (eg, hydralazine) dec afterload.
ACE inhibitors and ARBs dec both preload and afterload.
Nitroprusside - Short acting vasodilator (arteries = veins).
Ranolazine - MECHANISM Inhibits the late phase of inward sodium current thereby reducing diastolic wall tension and oxygen consumption.
Sacubitril - MECHANISM A neprilysin inhibitor; prevents degradation of bradykinin, natriuretic peptides, angiotensin II, and substance P -- > inc
vasodilation, dec ECF volume.
Digoxin - ADVERSE EFFECTS Cholinergic effects (nausea, vomiting, diarrhea), blurry yellow vision (think van Glow), arrhythmias, AV block. Can
lead to hyperkalemia, which indicates poor prognosis. Factors predisposing to digoxin toxicity: renal failure (dec excretion), hypokalemia (permissive
for digoxin binding at K+-binding site on Na+ /K+ ATPase), drugs that displace digoxin from tissue- binding sites, and dec clearance (eg, verapamil,
amiodarone, quinidine).
Fibrates - SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7a -hydroxylase).
Niacin - SE - Flushed face (prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia, Hyperuricemia.
Statins - SE - Hepatotoxicity (inc LFTs), myopathy (esp when used with fibrates or niacin).
PCSK-9 inh - SE - Myalgias, delirium, dementia, other neurocognitive effects.
Adenosine - inc K+ out of cells > hyperpolarizing the cell and dec ICa, decreasing AV node conduction.
IVabradine - prolongs slow depolarization (phase “IV”) by selectively inhibiting “funny” sodium channels (If).

Esmolol and adenosine - very short acting.

Vasodilators (eg, nitroglycerin/nitrates) dec preload.
Arterial vasodilators (eg, hydralazine) dec afterload.
ACE inhibitors and ARBs dec both preload and afterload.
Nitroprusside - Short acting vasodilator (arteries = veins).
Fibrates - Gemfibrozil, bezafibrate, fenofibrate - LDL dec; HDL inc; TGs dec dec dec. Activate PPAR-α > upregulate LPL > inc TG clearance. Activate
PPAR-α > induce HDL synthesis. SE - Myopathy (inc risk with statins), cholesterol gallstones (via inhibition of cholesterol 7α-hydroxylase).

Niacin - LDL dec dec; HDL inc inc; TGs dec. Inhibits lipolysis (hormone- sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis. SE -
Flushed face (prostaglandin mediated; dec by NSAIDs or long- term use), Hyperglycemia Hyperuricemia.

Ganciclovir - ADVERSE EFFECTS Bone marrow suppression (leukopenia, neutropenia, thrombocytopenia), renal toxicity. More toxic to host
enzymes than acyclovir.
Foscarnet - ADVERSE EFFECTS Nephrotoxicity, electrolyte abnormalities (hypo- or hypercalcemia, hypo- or hyperphosphatemia, hypokalemia,
hypomagnesemia) can lead to seizures.
Cidofovir - ADVERSE EFFECTS Nephrotoxicity (coadminister with probenecid and IV saline to dec toxicity).
Sporicidal - autoclave, chlorine, heat, Ethylene oxide, Hydrogen peroxide
Not sporicidal - alcohols, Quaternary amines
Maybe sporicidal - Iodine and iodophors
Antimicrobials to avoid in pregnancy
ANTIMICROBIAL - ADVERSE EFFECT
Sulfonamides - Kernicterus
Aminoglycosides - Ototoxicity
Fluoroquinolones - Cartilage damage
Clarithromycin - Embryotoxic
Tetracyclines - Discolored teeth, inhibition of bone growth Ribavirin - Teratogenic
Griseofulvin - Teratogenic Chloramphenicol - Gray baby syndrome
Antimicrobial therapy -
FOLIC ACID SYNTHESIS AND REDUCTION (DNA methylation) - Sulfonamides - Sulfamethoxazole Sulfisoxazole Sulfadiazine, Trimethoprim
MEMBRANE INTEGRITY - Daptomycin (gram ⊕) Polymyxins (gram ⊖)
Cell wall synthesis - PEPTIDOGLYCAN SYNTHESIS - Glycopeptides - Vancomycin Bacitracin PEPTIDOGLYCAN CROSS-LINKING -
Penicillinase-sensitive penicillins - Penicillin G, V Ampicillin Amoxicillin Penicillinase-resistant penicillins - Oxacillin Nafcillin Dicloxacillin
Antipseudomonal - Ticarcillin Piperacillin
Cephalosporins (I-V) - 1st—Cefazolin, etc 2nd—Cefoxitin, etc 3rd—Ceftriaxone, etc 4th—Cefepime 5th—Ceftaroline Carbapenems - Imipenem
Meropenem Ertapenem Doripenem
Monobactams - Aztreonam

PROTEIN SYNTHESIS - 50S SUBUNIT - Chloramphenicol Clindamycin Linezolid Macrolides (- Azithromycin Clarithromycin Erythromycin)
Streptogramins (-Quinupristin Dalfopristin) 30S SUBUNIT - Aminoglycosides (-Gentamicin Neomycin Amikacin Tobramycin Streptomycin)
Tetracyclines (-Tetracycline Doxycycline Minocycline) Glycylcycline (Tigecycline) DNA INTEGRITY (via free radicals) - Metronidazole
mRNA SYNTHESIS (RNA polymerase) - Rifampin

Gyrase - Fluoroquinolones (Ciprofloxacin Levofloxacin, etc) Quinolone (Nalidixic acid) Protein synthesis inhibitors -
Aminoglycosides (30S)
Linezolid (50S)

Tetracyclines (30S) - A-site tRNA binding Chloramphenicol (50S) - Peptidyl transferase Macrolides and clindamycin (50S) - Translocation
Sulfonamides, dapsone - inhibit Dihydropteroate synthase Trimethoprim, pyrimethamine - inhibit Dihydrofolate reductase Antimycobacterial therapy-
MYCOLIC ACID SYNTHESIS - Isoniazid

ARABINOGALACTAN SYNTHESIS (arabinosyl transferase) - Ethambutol mRNA SYNTHESIS (DNA-dependent RNA polymerase) - Rifabutin
Rifampin INTRACELLULAR (unclear mechanism) - Pyrazinamide
Antifungal therapy-
LANOSTEROL SYNTHESIS - Terbinafine

ERGOSTEROL SYNTHESIS - Azoles - Clotrimazole Fluconazole Isavuconazole Itraconazole Ketoconazole Miconazole Voriconazole CELL WALL
SYNTHESIS - Echinocandins - Anidulafungin Caspofungin Micafungin
CELL MEMBRANE INTEGRITY - Polyenes -Amphotericin B, Nystatin
NUCLEIC ACID SYNTHESIS - Flucytosine

HIV antiviral therapy-

ENTRY - PENETRATION - Enfuvirtide; ATTACHMENT - Maraviroc
INTEGRASE - Dolutegravir Elvitegravir Raltegravir Bictegravir
PROTEASE - Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir Ritonavir Saquinavir REVERSE TRANSCRIPTASE - NRTIs - Abacavir
(ABC) Emtricitabine (FTC) Lamivudine (3TC) Tenofovir (TDF) Zidovudine (ZDV, formerly AZT); NNRTIs - Delavirdine Efavirenz Nevirapine
OTHER ANTIVIRALS-
NUCLEIC ACID SYNTHESIS -
Guanosine analogs - Acyclovir, etc (HSV, VZV), Ganciclovir (CMV)
Viral DNA polymerase inhibitors - Cidofovir Foscarnet - (HSV(acyclovir resistant) and CMV) Guanine nucleotide synthesis - Ribavirin (RSV, HCV)
Adenosine analog - Remdesivir (SARS-CoV-2)
Endonuclease inhibitor - Baloxavir (influenza virus)
RELEASE OF PROGENY VIRUS-
Neuraminidase inhibitors - Oseltamivir Zanamivir - Influenza A, B.
Anthrax - Prophylaxis with ciprofoxacin or doxycycline when exposed.
Diphtheria Rx - diphtheria antitoxin +/– erythromycin or penicillin.
Listera - Treatment: ampicillin.
SNAP: Sulfonamides—Nocardia; Actinomyces—Penicillin.
Leprosy - Treatment: dapsone and rifampin for tuberculoid form; clofazimine is added for lepromatous form.
N. gonorrheae - Treatment: ceftriaxone + azithromycin (to cover possible chlamydial coinfection, ceftriaxone-resistant strains). Erythromycin eye
ointment prevents neonatal blindness.
Meningococci - Prophylaxis - Rifampin, ciprofloxacin, or ceftriaxone. Treatment: ceftriaxone or penicillin G.
H. influenzae - Treatment: amoxicillin +/ clavulanate for mucosal infections; ceftriaxone for meningitis; rifampin prophylaxis for close contacts.
Pertussis - Treatment: macrolides; if allergic use TMP-SMX.
Brucella - Treatment: doxycycline + rifampin or streptomycin.
Legionella - Treatment: macrolide or quinolone.
Pseudomonas Treatments: Antipseudomonal penicillins in combination with -lactamase inhibitor (eg, piperacillintazobactam) 3rd- and 4th-generation
cephalosporins (eg, ceftazidime, cefepime) Monobactams Fluoroquinolones Carbapenems (AACCMQ)
Salmonella typhi - treat with ceftriaxone or fuoroquinolone
S. agalactae - GBS - Patients with culture receive intrapartum penicillin/ampicillin prophylaxis.
H. pylori - Most common initial treatment is triple therapy: amoxicillin (metronidazole if penicillin allergy) + clarithromycin + proton pump inhibitor;
antibiotics cure Pylori. Bismuth-based quadruple therapy if concerned about macrolide resistance.
Lyme ds - Treatment: doxycycline (1st line); amoxicillin (pregnant patients, children < 8 years old); ceftriaxone if IV therapy required.
Syphilis Rx Penicillin G
Congenital syphilis - To prevent, treat patient early in pregnancy, as placental transmission typically occurs after first trimester.
Gardnerella vaginalis - Treatment: metronidazole or clindamycin.
Chlamydia - Treatment: azithromycin (favored because one-time treatment) or doxycycline. Add ceftriaxone for possible concomitant gonorrhea.
Rickettsial diseases and vector-borne illnesses Treatment: doxycycline.
Mycoplasma pneumoniae - Treatment: macrolides, doxycycline, or fluoroquinolone (penicillin ineffective since Mycoplasma has no cell wall).
Systemic mycosis - Treatment: fluconazole or itraconazole for local infection; amphotericin B for systemic infection.
Tinea (pityriasis) versicolor - Treatment: selenium sulfide, topical and/or oral antifungal medications.
Candida - Treatment: oral fluconazole/topical azoles for vaginal; nystatin, azoles, or, rarely, echinocandins for oral; fluconazole, echinocandins, or
amphotericin B for esophageal or systemic disease. Aspergillus - Treatment: voriconazole/isavuconazole or echinocandins (2nd-line).
Cryptococcus - Treatment: amphotericin B + flucytosine followed by fluconazole for cryptococcal meningitis.
Mucor and Rhizopus spp - Treatment: surgical debridement, amphotericin B or isavuconazole
Pneumocystis jirovecii - Treatment/prophylaxis: TMP-SMX, pentamidine, dapsone (prophylaxis as single agent, or treatment in combination with
TMP), atovaquone. Start prophylaxis when CD4+ cell count drops to < 200 cells/mm3 in people living with HIV.
Sporothrix schenckii - Treatment: itraconazole or potassium iodide (only for cutaneous/lymphocutaneous). Think of a rose gardener who smokes a
cigar and pot.
Giardia lamblia - Rx Metronidazole.
Entamoeba histolytica - Rx Metronidazole; paromomycin or iodoquinol for asymptomatic cyst passers.
Cryptosporidium - Rx Prevention (by filtering city water supplies); nitazoxanide in immunocompetent hosts.
Protozoa—CNS infections-
Toxoplasma gondii - Rx Sulfadiazine + pyrimethamine. Prophylaxis with TMP-SMX when CD4+ cell count < 100 cells/mm3.
Naegleria fowleri - Rx Amphotericin B has been effective for a few survivors.
Trypanosoma brucei - Rx Suramin for bloodborne disease or melarsoprol for CNS penetration.
Protozoa—hematologic infections-
Plasmodium - TREATMENT Chloroquine (for sensitive species); if resistant, use mefloquine or atovaquone/ proguanil. If life-threatening, use
intravenous quinidine or artesunate (test for G6PD deficiency). For P vivax/ovale, add primaquine for hypnozoite (test for G6PD deficiency).
Babesia - Rx Atovaquone + azithromycin.
Visceral infections-
Trypanosoma cruzi - Rx Benznidazole or nifurtimox; cruzing in my Benz, with a fur coat on.
Leishmania spp - Rx Amphotericin B, sodium stibogluconate.
Sexually transmitted infections-
Trichomonas vaginalis -
Rx Metronidazole for patient and partner(s) (prophylaxis; check for STI).

Nematode/roundworm Rx - (all are bendazoles; except loa loa & wuchereria - diethylcarbamazine and onchocerca - ivermectin). Cestode/tapeworm Rx
- (all are praziquantel; except neurocysticercosis and echinococcus granulosus - albendazole). Nematodes (roundworms)
Intestinal-

Enterobius vermicularis (pinworm) - Bendazoles, pyrantel pamoate.

Ascaris lumbricoides (giant roundworm) - Bendazoles.
Strongyloides stercoralis (threadworm) - Ivermectin or bendazoles.
Ancylostoma spp, Necator americanus (hookworms) - Bendazoles or pyrantel pamoate. Trichinella spiralis - Bendazoles.

Trichuris trichiura (whipworm) - Bendazoles.

Tissue-
Toxocara canis - Visceral larva migrans. Bendazoles.
Onchocerca volvulus - Ivermectin (ivermectin for river blindness). Loa loa - Diethylcarbamazine.

Wuchereria bancrofti, Brugia malayi - Diethylcarbamazine. Cestodes (tapeworms)

Taenia solium1 - Praziquantel.
Taenia solium2 - Praziquantel; albendazole for neurocysticercosis. Diphyllobothrium latum - Praziquantel, niclosamide.

Echinococcus granulosus - Albendazole; surgery for complicated cysts. Trematodes (flukes)

Schistosoma - Praziquantel.
Clonorchis sinensis - Praziquantel.

Ectoparasites
Sarcoptes scabiei - Treatment: permethrin cream, oral ivermectin, washing/drying all clothing/bedding, treat close contacts.
Pediculus humanus/ Phthirus pubis - Treatment: pyrethroids, malathion, or ivermectin lotion, and nit combing. Children with head lice can be treated at
home without interrupting school attendance. Ischemia - Inadequate blood supply to meet demand. Mechanisms include dec arterial perfusion (eg,
atherosclerosis), dec venous drainage (eg, testicular torsion, Budd-Chiari syndrome), shock. Regions most vulnerable to hypoxia/ischemia and
subsequent infarction: ORGAN REGION
Brain ACA/MCA/PCA boundary areas.
Heart Subendocardium of LV.
Kidney Straight segment of proximal tubule (medulla), Thick ascending limb (medulla) .
Liver Area around central vein (zone III) .
Colon Splenic fexure (Griffth point),a rectosigmoid junction (Sudeck point).
Watershed areas (border zones) receive blood supply from most distal branches of 2 arteries with limited collateral vascularity. These areas are
susceptible to ischemia from hypoperfusion. Neurons most vulnerable to hypoxic-ischemic insults include Purkinje cells of the cerebellum and
pyramidal cells of the hippocampus and neocortex (zones 3, 5, 6).
TOXICITY SYSTEM DISEASE/CLINICAL MANIFESTATION
Full exposure-
Acute radiation syndrome-
Skin - Hair loss, erythema, desquamation, ulcers/ necrosis
Hematopoietic - Myelosuppression
Gastrointestinal - Mucosal denudation, infammation, edema > abdominal pain, diarrhea, GI bleeding, nausea, vomiting, stomatitis Neurovascular -
Papilledema, seizures, ataxia, impaired refexes, cognitive defcits.
Partial exposure-
Acute local toxicity-
Skin, gonads, eye - Blisters, sterility, dec spermatogenesis, cataracts
Late complication-
Radiation-induced fibrosis-
Skin, subcutaneous tissue - Induration, thickening, loss of elasticity, shrinkage, lymphedema
Lung - Pulmonary fibrosis
Head and neck - Trismus, mucosal fbrosis, ulceration, fstulae
Gastrointestinal - Obstruction, ulcerations, fistulae
Genitourinary - Ureteral and urethral stenosis, fibrotic bladder constriction > obstructive uropathy; fbrosis of ovaries, vulva, vagina; azoospermia.
Radiation-related malignancies-
Thyroid - Papillary thyroid carcinoma
Hematopoietic - Myelodysplastic syndromes, lymphomas, leukemias (eg, CML, AML, ALL)
Skin - Angiosarcoma
Bone - Osteosarcoma
Others - Solid tumors (eg, breast, ovarian, lung)

Margination/rolling-
defective in LAD type-2 (dec sialyl lewis)
E-selectin (upregulated by TNF and IL-1) + sialyl lewis P-selectin (released from Weibel- palade bodies) + sialyl lewis GlyCAM-1/CD34 + L-selectin

Adhesion-
defective in LAD type 1 (dec CD18 integrin subunit) ICAM-1 (CD54) + CD11/18 integrins (LFA-1,Mac-1) VCAM-1 (CD106) + VLA-4 integrin

Transmigration-
PECAM-1 (CD31) + PECAM-1 (CD31)
Wound healing-
Tissue mediators
MEDIATOR ROLE
FGF Stimulates angiogenesis
TGF- Angiogenesis, fibrosis
VEGF Stimulates angiogenesis
PDGF Secreted by activated platelets and macrophages. Induces vascular remodelling and smooth muscle cell migration. Stimulates fibroblast growth
for collagen synthesis. Metalloproteinases Tissue remodeling
EGF Stimulates cell growth via tyrosine kinases (eg, EGFR/ErbB1).
PHASE OF WOUND HEALING - EFFECTOR CELLS - CHARACTERISTICS

Infammatory (up to 3 days after wound) - Platelets, neutrophils, macrophages. Clot formation, inc vessel permeability and neutrophil migration into
tissue; macrophages clear debris 2 days later. Proliferative (day 3–weeks after wound) - Fibroblasts, myofbroblasts, endothelial cells, keratinocytes,
macrophages. Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound
contraction (mediated by myofbroblasts) Delayed second phase of wound healing in vitamin C and copper defciency.
Remodeling (1 week–6+ months after wound) - Fibroblasts. Type III collagen replaced by type I collagen, inc tensile strength of tissue. Collagenases
(require zinc to function) break down type III collagen. Zinc defciency > delayed wound healing.

Cancer epidemiology Skin cancer (basal > squamous >> melanoma) is the most common cancer (not included below). Cancer incidence- MALES 1.
Prostate 2. Lung 3. Colon/rectum
FEMALES 1. Breast 2. Lung 3. Colon/rectum
CHILDREN (0-14) 1. Leukemia 2. CNS 3. Neuroblastoma
Lung cancer incidence has DEC in males, but has not changed signifcantly in females. Cancer mortality- MALES 1. Lung 2. Prostate 3. Colon/rectum
FEMALES 1. Lung 2. Breast 3. Colon/rectum
CHILDREN (0-14) 1. Leukemia 2. CNS 3. Neuroblastoma

Cancer is the 2nd leading cause of death in the United States (heart disease is 1st). Brain - Lung > breast > melanoma, colon, kidney (lots of brain
metastases can kill) Liver - Colon >> stomach > pancreas (cancer sometimes penetrates liver)
Bone - Prostate, breast > kidney, thyroid, lung (painful bones kill the lungs)

Anti PD-1 (PNC) (eg, pembrolizumab, nivolumab, cemiplimab) Anti PD-L1 (ADA) (eg, atezolizumab, durvalumab, avelumab) Ipilimumab (anti-
CTLA-4 antibody).

Oncogenes - Gain of function mutation converts proto-oncogene (normal gene) to oncogene > inc cancer risk. Requires damage to only one allele of a
proto-oncogene. GENE GENE PRODUCT ASSOCIATED NEOPLASM
ALK - Receptor tyrosine kinase Lung adenocarcinoma
HER2/neu (ERBB2) - Receptor tyrosine kinase Breast and gastric carcinomas

RET - REceptor Tyrosine kinase MEN 2A and 2B, medullary and papillary thyroid carcinoma, pheochromocytoma
BCR-ABL - Non-receptor tyrosine kinase CML, ALL
JAK2 - Non-receptor tyrosine kinase Myeloproliferative neoplasms
BRAF - Serine/threonine kinase Melanoma, non-Hodgkin lymphoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia c-KIT -
CytoKIne receptor Gastrointestinal stromal tumor (GIST), mastocytosis

c-MYC - Transcription factor Burkitt lymphoma

MYCL1 - Transcription factor Lung cancer
MYCN (N-myc) - Transcription factor Neuroblastoma
KRAS - RAS GTPase Colorectal, lung, pancreatic cancers
BCL-2 - Antiapoptotic molecule (inhibits apoptosis) Follicular and diffuse large B-Cell Lymphomas
Tumor suppressor genes Loss of function > inc cancer risk; both (two) alleles of a tumor suppressor gene must be lost for expression of disease
(Knudson’s 2-hit hypothesis). GENE GENE PRODUCT ASSOCIATED CONDITION

APC - Negative regulator of β-catenin/WNT pathway Colorectal cancer (associated with FAP)
BRCA1/BRCA2 - BRCA1/BRCA2 proteins BReast, ovarian, prostate, pancreatic CAncers CDKN2A - p16, blocks G1 > S phase Many cancers (eg,
melanoma, lung)
DCC - DCC—Deleted in Colorecta Cancer Colorectal cancer
SMAD4 (DPC4) - DPC—Deleted in Pancreatic Cancer Pancreatic cancer, colorectal cancer MEN1 - MENin Multiple Endocrine Neoplasia type 1
NF1 - Neurofbromin (Ras GTPase activating protein) NeuroFibromatosis type 1
NF2 - Merlin (schwannomin) protein NeuroFibromatosis type 2
PTEN - Negative regulator of PI3k/AKT pathway Prostate, breasT, and ENdometrial cancers
RB1 - Inhibits E2F; blocks G1 > S phase Retinoblastoma, osteosarcoma (bone cancer)
TP53 - p53, activates p21, blocks G1 > S phase Most cancers, Li-Fraumeni syndrome (multiple malignancies at early age, aka, SBLA syndrome:
Sarcoma, Breast, Leukemia, Adrenal gland)
TSC1 - Hamartin protein Tuberous sclerosis
TSC2 - Tuberin (“2berin”) Tuberous sclerosis
VHL - Inhibits hypoxia-inducible factor 1a von Hippel-Lindau disease
WT1 - Urogenital development transcription factor Wilms Tumor (nephroblastoma)
Carcinogens
TOXIN EXPOSURE ORGAN IMPACT
Afatoxins (Aspergillus) Stored grains and nuts Liver Hepatocellular carcinoma
Alkylating agents Oncologic chemotherapy Blood Leukemia/lymphoma
Aromatic amines (eg, benzidine, 2-naphthylamine) Textile industry (dyes), tobacco smoke (2-naphthylamine) Bladder Transitional cell carcinoma
Arsenic Herbicides (vineyard workers), metal smelting, wood preservation Liver Lung Skin Hepatic angiosarcoma Lung cancer Squamous cell
carcinoma
Asbestos Old roofng material, shipyard workers Lung Bronchogenic carcinoma > mesothelioma
Tobacco smoke Bladder Cervix Esophagus Kidney Larynx Lung Oropharynx Pancreas Transitional cell carcinoma Squamous cell carcinoma
Squamous cell carcinoma/ adenocarcinoma Renal cell carcinoma Squamous cell carcinoma Squamous cell and small cell carcinoma Oropharyngeal
cancer Pancreatic adenocarcinoma
Ethanol Esophagus Liver Breast Squamous cell carcinoma Hepatocellular carcinoma Breast cancer
Ionizing radiation Thyroid Papillary thyroid carcinoma, leukemias
Nickel, chromium, beryllium, silica Occupational exposure Lung Lung cancer
Nitrosamines Smoked foods Stomach Gastric cancer (intestinal type)
Radon Byproduct of uranium decay, accumulates in basements Lung Lung cancer (2nd leading cause after tobacco smoke)
Vinyl chloride Used to make PVC pipes (plumbers) LiVer Hepatic angiosarcoma
Oncogenic microbes
Microbe - Associated cancer
EBV Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, 1° CNS lymphoma (in immunocompromised patients) HBV, HCV
Hepatocellular carcinoma
HHV-8 Kaposi sarcoma
HPV (usually types 16, 18) Cervical and penile/anal carcinoma, head and neck cancer
H pylori Gastric adenocarcinoma and MALT lymphoma
HTLV-1 Adult T-cell Leukemia/Lymphoma
Liver fluke (Clonorchis sinensis) Cholangiocarcinoma
Schistosoma haematobium Squamous cell bladder cancer
Serum tumor markers - Tumor markers should not be used as the 1° tool for cancer diagnosis or screening. They may be used to monitor tumor
recurrence and response to therapy, but defnitive diagnosis is made via biopsy. Some can be associated with non-neoplastic conditions.
MARKER IMPORTANT ASSOCIATIONS NOTES
Alkaline phosphatase Metastases to bone or liver, Paget disease of bone, seminoma (placental ALP). Exclude hepatic origin by checking LFTs and
GGT levels.
α-fetoprotein Hepatocellular carcinoma, endodermal sinus (yolk sac) tumor, mixed germ cell tumor, ataxia-telangiectasia, neural tube defects.
Normally made by fetus. Transiently elevated in pregnancy. High levels associated with neural tube and abdominal wall defects, low levels associated
with Down syndrome.
hCG Hydatidiform moles and Choriocarcinomas (Gestational trophoblastic disease), testicular cancer, mixed germ cell tumor. Produced by
syncytiotrophoblasts of the placenta. CA15-3/CA27-29 Breast cancer.

CA 19-9 Pancreatic adenocarcinoma.

CA 125 Ovarian cancer.
Calcitonin Medullary thyroid carcinoma (alone and in MEN2A, MEN2B). Calci2nin.
CEA Colorectal and pancreatic cancers. Minor associations: gastric, breast, and medullary thyroid carcinomas. CarcinoEmbryonic Antigen. Very
nonspecifc.
Chromogranin Neuroendocrine tumors.
LDH Testicular germ cell tumors, ovarian dysgerminoma, other cancers. Can be used as an indicator of tumor burden.
Neuron-specifc enolase Neuroendocrine tumors (eg, small cell lung cancer, carcinoid tumor, neuroblastoma).
PSA Prostate cancer. Prostate-Specifc Antigen. Also elevated in BPH and prostatitis. Questionable risk/beneft for screening. Marker for recurrence
after treatment.
Important immunohistochemical stains - Determine primary site of origin for metastatic tumors and characterize tumors that are diffcult to classify. Can
have prognostic and predictive value. STAIN TARGET TUMORS IDENTIFIED
Chromogranin and synaptophysin Neuroendocrine cells Small cell carcinoma of the lung, carcinoid tumor, neuroblastoma
Cytokeratin Epithelial cells Epithelial tumors (eg, squamous cell carcinoma)
Desmin Muscle Muscle tumors (eg, rhabdomyosarcoma)
GFAP NeuroGlia (eg, astrocytes, Schwann cells, oligodendrocytes) Astrocytoma, Glioblastoma Neuroflament Neurons Neuronal tumors (eg,
neuroblastoma)

PSA Prostatic epithelium Prostate cancer

S-100 Neural crest cells Melanoma, schwannoma, Langerhans cell histiocytosis
TRAP Tartrate-resistant acid phosphatase Hairy cell leukemia
Vimentin Mesenchymal tissue (eg, fibroblasts, endothelial cells, macrophages) Mesenchymal tumors (eg, sarcoma), but also many other tumors (eg,
endometrial carcinoma, renal cell carcinoma, meningioma).
Paraneoplastic syndromes
MANIFESTATION DESCRIPTION/MECHANISM MOST COMMONLY ASSOCIATED TUMOR(S)
Musculoskeletal and cutaneous-
Dermatomyositis Progressive proximal muscle weakness, Gottron papules, heliotrope rash Adenocarcinomas, especially ovarian Acanthosis nigricans
Hyperpigmented velvety plaques in axilla and neck Gastric adenocarcinoma and other visceral malignancies
Sign of Leser-Trélat Sudden onset of multiple seborrheic keratoses GI adenocarcinomas and other visceral malignancies
Hypertrophic osteoarthropathy Abnormal proliferation of skin and bone at distal extremities > clubbing, arthralgia, joint effusions, periostosis of
tubular bones. Adenocarcinoma of the lung. Endocrine-
Hypercalcemia - PTHrP - SCa2+mous cell carcinomas of lung, head, and neck; renal, bladder, breast, and ovarian carcinomas. Inc 1,25- (OH)2 vitamin
D3 (calcitriol) - Lymphoma.
Cushing syndrome inc ACTH Small cell lung cancer
Hyponatremia (SIADH) inc ADH Small cell lung cancer
Hematologic-
Polycythemia inc Erythropoietin Paraneoplastic rise to High hematocrit levels Pheochromocytoma, renal cell carcinoma, HCC, hemangioblastoma,
leiomyoma
Pure red cell aplasia Anemia with low reticulocytes Thymoma
Good syndrome Hypogammaglobulinemia Thymoma
Trousseau syndrome - Migratory superfcial thrombophlebitis Adenocarcinomas, especially pancreatic.
Nonbacterial thrombotic (marantic) endocarditis - Deposition of sterile platelet thrombi on heart valves - Adenocarcinomas, especially pancreatic
Neuromuscular-
Anti-NMDA receptor encephalitis Psychiatric disturbance, memory defcits, seizures, dyskinesias, autonomic instability, language dysfunction Ovarian
teratoma
Opsoclonusmyoclonus ataxia syndrome “Dancing eyes, dancing feet” Neuroblastoma (children), small cell lung cancer (adults) Paraneoplastic
cerebellar degeneration Antibodies against antigens in Purkinje cells Small cell lung cancer (anti-Hu), gynecologic and breast cancers (anti-Yo), and
Hodgkin lymphoma (anti-Tr)
Paraneoplastic encephalomyelitis Antibodies against Hu antigens in neurons Small cell lung cancer
Lambert-Eaton myasthenic syndrome Antibodies against presynaptic (P/Q-type) Ca2+ channels at NMJ
Myasthenia gravis Antibodies against postsynaptic ACh receptors at NMJ Thymoma

MM >10%
Waldenstrom >10%
MGUS <10%
MDS <20%
AML >20%
Polycythemia vera-
RBCs inc. WBCs inc. PLATELETS inc. PHILADELPHIA CHROMOSOME ⊖. JAK2 MUTATIONS ⊕

Essential thrombocythemia-
PLATELETS inc. PHILADELPHIA CHROMOSOME ⊖. JAK2 MUTATIONS ⊕ (30–50%)

Myelofbrosis (megakaryocytes)-
RBCs dec. WBCs Variable. PLATELETS Variable. PHILADELPHIA CHROMOSOME ⊖. JAK2 MUTATIONS ⊕ (30–50%)

CML-
RBCs dec. WBCs inc. PLATELETS inc. PHILADELPHIA CHROMOSOME ⊕. JAK2 MUTATIONS ⊖ Alemtuzumab - CD52 (Aalam house no 52)
Bevacizumab - VEGF (inhibits blood vessel formation)
Cetuximab, panitumumab - EGFR (ram setu in pani to bring back eGFr)
Rituximab - CD20 (Ritu house no 20)
Trastuzumab - HER2 (“trust HER”)
(PNC) (Pembrolizumab, nivolumab, cemiplimab - PD-1)

(ADA Laila) (Atezolizumab, durvalumab, avelumab - PD-L1) (Ipilimumab - CTLA-4) (ipill kha aur cut le)
Alectinib - ALK (sounds similar)
(EGF) Erlotinib, Gefitinib, aFatinib - EGFR

(DIN) Imatinib, dasatinib, nilotinib - BCR-ABL (nice din in philadelphia) Ruxolitinib - JAK1/2 (Ruxar and jack got married)
Bortezomib, ixazomib, carfilzomib - Proteasome
(DEV) Vemurafenib, encorafenib, dabrafenib - BRAF (dev removes bra) MEK inhibitors (eg, trametinib) (trams make in india)

Palbociclib - Cyclin-dependent kinase 4/6

Olaparib - Poly(ADP-ribose) polymerase (dec DNA repair) Chromosomal translocations
TRANSLOCATION ASSOCIATED DISORDER NOTES
t(8;14) Burkitt (Burk-8) lymphoma (c-myc activation) t(11;14) Mantle cell lymphoma (cyclin D1 activation)

t(11;18) Marginal zone lymphoma

t(14;18) Follicular lymphoma (BCL-2 activation)
t(15;17) APL (formerly M3 type of AML)
t(9;22) (Philadelphia chromosome) CML (BCR-ABL hybrid), ALL (less common); Philadelphia CreaML cheese
The Ig heavy chain genes on chromosome 14 are constitutively expressed. When other genes (eg, c-myc and BCL-2) are translocated next to this heavy
chain gene region, they are overexpressed. Arm abduction DEGREE MUSCLE NERVE 0°–15° Supraspinatus Suprascapular 15°–90° Deltoid Axillary
> 90° Trapezius Accessory
> 90° Serratus Anterior Long Thoracic (SALT)
Rotator cuf muscles - Shoulder muscles that form the rotator cuff:
Supraspinatus (suprascapular nerve)— abducts arm initially (before the action of the deltoid); most common rotator cuff injury (trauma or degeneration
and impingement tendinopathy or tear [arrow in A ]), assessed by “empty/full can” test
Infraspinatus (suprascapular nerve)— externally rotates arm; pitching injury
teres minor (axillary nerve)—adducts and externally rotates arm
Subscapularis (upper and lower subscapular nerves)—internally rotates and adducts arm Innervated primarily by C5-C6. SItS (small t is for teres
minor).
For both ulnar and median nerve -
loss of flexors with proximal lesion;
loss of extensors with distal lesion.
(ED-PF)
(check distal lesion with extension.
check proximal lesion with flexion.)

distal median - claw

distal ulnar - claw
proximal median - hand of benediction proximal ulnar - ok gesture/ape hand (check distal lesion with extension. check proximal lesion with flexion.)

Clawing more pronounced with distal lesions, less with proximal lesions Erb palsy (“waiter’s tip”) - upper trunk
Klumpke palsy (claw hand / total claw hand) - lower trunk
Wrist drop - posterior cord, radial nerve

Winged scapula - SALT

Deltoid paralysis - axillary nerve
“Saturday night palsy” (wrist drop) - radial nerve, posterior cord
Difficulty flexing elbow, variable C8 sensory loss - musculocutaneous N
Decreased thumb function “hand of benediction” - median nerve
Intrinsic muscles of hand, claw hand (ulnar claw) - ulnar nerve
Thoracic outlet syndrome - Compression of lower trunk and subclavian vessels, most commonly within the scalene triangle.
Carpal tunnel contents-
FDP tendon
FDS tendon
FPL tendon
Median nerve
Complications of proximal scaphoid fractures include avascular necrosis and nonunion due to retrograde blood supply from a branch of the radial
artery. Iliohypogastric (T12-L1) - IT
Genitofemoral nerve (L1-L2) - cremaster
Lateral femoral cutaneous (L2-L3)
Obturator (L2-L4) - AAA-GOP
Femoral (L2-L4) - SQIP
Sciatic (L4-S3) - BASS
Common (fibular) peroneal (L4-S2) - PPT
(superficial peroneal - PP; deep peroneal - T)
Tibial (L4-S3) - TB-PPF
Superior gluteal (L4-S1) - GGT
Inferior gluteal (L5-S2) - G maximus
Pudendal (S2-S4) - ext sphincters of urethra and anus
Thenar muscles (OAF) - opposition, abduction and flexion of thumb.

Erb palsy (“waiter’s tip”)- DIBs Iliohypogastric (T12-L1) - IT Genitofemoral nerve (L1-L2) - cremaster Lateral femoral cutaneous (L2-L3) Obturator
(L2-L4) - AAA-GOP

Femoral (L2-L4) - SQIP

Sciatic (L4-S3) - BASS
Common (fibular) peroneal (L4-S2) - PPT
(superficial peroneal - PP; deep peroneal - T)
Tibial (L4-S3) - TB-PPF
Superior gluteal (L4-S1) - GGT
Inferior gluteal (L5-S2) - G maximus
Pudendal (S2-S4) - ext sphincters of urethra and anus
Erb palsy (“waiter’s tip”) - upper trunk
Klumpke palsy (claw hand / total claw hand) - lower trunk
Wrist drop - posterior cord, radial nerve
Winged scapula - SALT
Deltoid paralysis - axillary nerve
“Saturday night palsy” (wrist drop) - radial nerve, posterior cord Difficulty flexing elbow, variable C8 sensory loss - musculocutaneous N Decreased
thumb function “hand of benediction” - median nerve Intrinsic muscles of hand, claw hand (ulnar claw) - ulnar nerve

For both ulnar and median nerve -

loss of flexors with proximal lesion;

loss of extensors with distal lesion.
(ED-PF)
(check distal lesion with extension.
check proximal lesion with flexion.)
Abductors Gluteus medius, gluteus minimus
Adductors Adductor magnus, adductor longus, adductor brevis
Extensors (SSG) Gluteus maximus, semitendinosus, semimembranosus
Flexors (TRIPS) Iliopsoas, rectus femoris, tensor fascia lata, pectineus, sartorius Internal rotation (GGT) Gluteus medius, gluteus minimus, tensor
fascia latae External rotation (GOPI) Iliopsoas, gluteus maximus, piriformis, obturator

Osgood-schlatter ds - avulsion of secondary ossification centre of proximal tibial tubercle. Legg-calve-perthes ds - Idiopathic avascular necrosis of
femoral head.
SCFE - Displaced epiphysis relative to femur neck due to axial force on femoral head. Developmental dysplasia of the hip - Abnormal acetabulum;
ortolani and barlow maneuver. Nursemaid’s elbow - radial head subluxation.

Medial tibial stress syndrome - shin splints.

Iliotibial band syndrome - lateral femoral epicondyle.
De Quervain tenosynovitis - AbPL and EPB tendons; + Finkelstein test - tender radial styloid with stretch of thumb tendons.

IECN
epidermis - impetigo
upper dermis - erysipelas
deeper dermis - cellulitis
deeper tissue - necrotizing fascitis Anterior drawer/Lachman - ACL Posterior drawer - PCL
AP abduction (valgus stress test) - MCL AP adduction (varus stress test) - LCL McMurray test (LIME) - menisci Surgical neck of humerus -
Axillary NERVE.
Posterior circumflex ARTERY.

Surgical neck of humerus - POSTERIOR circumflex artery.

Femoral head - MEDIAL circumfex femoral artery.
Muscle stretch receptors - Body of muscle/type Ia and II sensory axons. Golgi tendon organ - Tendons/type Ib sensory axons.

Muscle stretch receptors-

PATHWAY inc stretch > via dorsal root ganglion (DRG) > activation of inhibitory interneuron and α motor neuron > simultaneous inhibition of
antagonist muscle (prevents overstretching) and activation of agonist muscle (contraction). LOCATION/INNERVATION Body of muscle/type Ia and II
sensory axons. ACTIVATION BY inc muscle stretch. Responsible for deep tendon refexes.

Golgi tendon organ-

PATHWAY Inc tension > via DRG > activation of inhibitory interneuron > inhibition of agonist muscle (reduced tension within muscle and tendon).
LOCATION/INNERVATION Tendons/type Ib sensory axons. ACTIVATION BY Inc muscle tension.
Endochondral ossifcation - Cartilaginous model of bone is frst made by chondrocytes. Osteoclasts and osteoblasts later replace with woven bone and
then remodel to lamellar bone. Membranous ossifcation - Woven bone formed directly without cartilage. Later remodeled to lamellar bone.

Osteoblastic activity measured by bone ALP, osteocalcin, propeptides of type I procollagen.

Estrogen - Inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing osteoclasts.

Unhappy triad (MMA) - Consists of damage to the ACL, MCL, and medial meniscus (attached to MCL). Osgood-schlatter ds - avulsion of secondary
ossification centre of proximal tibial tubercle. Legg-calve-perthes ds - Idiopathic avascular necrosis of femoral head.
SCFE - Displaced epiphysis relative to femur neck due to axial force on femoral head.

Developmental dysplasia of the hip - Abnormal acetabulum; ortolani and barlow maneuver. Nursemaid’s elbow - radial head subluxation.
Medial tibial stress syndrome - shin splints.
Iliotibial band syndrome - lateral femoral epicondyle.

De Quervain tenosynovitis - AbPL and EPB tendons; + Finkelstein test - tender radial styloid with stretch of thumb tendons. OA - 1st CMC, DIP, PIP;
not MCP
RA - MCP, PIP, wrist; not DIP or 1st CMC.
POLYMYOSITIS - characterized by endomysial inflammation with CD8+ T cells.

DERMATOMYOSITIS - Perimysial inflammation and atrophy with CD4+ T cells. Polymyalgia rheumatica - normal CK
Polymyositis/dermatomyositis - inc CK
Neuromuscular junction diseases

Myasthenia gravis-
FREQUENCY Most common NMJ disorder
PATHOPHYSIOLOGY Autoantibodies to postsynaptic ACh receptor.
CLINICAL Fatigable muscle weakness—ptosis; diplopia; proximal weakness; respiratory muscle involvement dyspnea; bulbar muscle involvement
dysphagia, diffculty chewing Spared refexes Worsens with muscle use.
ASSOCIATED WITH Thymoma, thymic hyperplasia
AChEINHIBITOR ADMINISTRATION Reverses symptoms (pyridostigmine for treatment)
Lambert-Eaton myasthenic syndrome
FREQUENCY Uncommon
PATHOPHYSIOLOGY Autoantibodies to presynaptic Ca2+ channel > dec ACh release
CLINICAL Proximal muscle weakness, autonomic symptoms (dry mouth, constipation, impotence); Hyporefexia; Improves with muscle use
ASSOCIATED WITH Small cell lung cancer
AChEINHIBITOR ADMINISTRATION Minimal effect

Tight jn - zonula occludens

Adherens jn - zonula adherens, belt desmosome Desmosome - macula adherens, spot desmosome
Dermatologic macroscopic terms
LESION CHARACTERISTICS EXAMPLES
Macule Flat lesion with well-circumscribed change in skin color < 1 cm Freckle (ephelide), labial macule A Patch Macule > 1 cm Large birthmark
(congenital nevus) B
Papule Elevated solid skin lesion < 1 cm Mole (nevus) C , acne
Plaque Papule > 1 cm Psoriasis D
Vesicle Small fuid-containing blister < 1 cm Chickenpox (varicella), shingles (zoster) E
Bulla Large fuid-containing blister > 1 cm Bullous pemphigoid F
Pustule Vesicle containing pus Pustular psoriasis G
Wheal Transient smooth papule or plaque Hives (urticaria) H
Scale Flaking off of stratum corneum Eczema, psoriasis, SCC I
Crust Dry exudate Impetigo J
Dermatologic microscopic terms
LESION CHARACTERISTICS EXAMPLES
Dyskeratosis Abnormal premature keratinization Squamous cell carcinoma
Hyperkeratosis inc thickness of stratum corneum Psoriasis, calluses
Parakeratosis Retention of nuclei in stratum corneum Psoriasis, actinic keratosis
Hypergranulosis inc thickness of stratum granulosum Lichen planus
Spongiosis Epidermal accumulation of edematous fuid in intercellular spaces Eczematous dermatitis Acantholysis Separation of epidermal cells
Pemphigus vulgaris
Acanthosis Epidermal hyperplasia (inc spinosum) Acanthosis nigricans, psoriasis
parakeratosis (retention of nuclei) - psoriasis, actinic keratosis
hypergranulosis - lichen planus
psoriasis - hyperkeratosis(inc stratum corneum) , parakeratosis(retention of nuclei) , acanthosis(inc spinosum)
Spongiosis - eczema
Hyperkeratosis inc thickness of stratum corneum Psoriasis, calluses
Hypergranulosis inc thickness of stratum granulosum Lichen planus
Acanthosis Epidermal hyperplasia (inc spinosum) Acanthosis nigricans, psoriasis
Venous ulcer-
ETIOLOGY Chronic venous insuffciency; most common ulcer type
LOCATION Gaiter area (ankle to midcalf), typically over malleoli
APPEARANCE Irregular border, shallow, exudative
PAIN Mild to moderate
ASSOCIATED SIGNS Telangiectasias, varicose veins, edema, stasis dermatitis (erythematous eczematous patches)
Arterial ulcer-
ETIOLOGY Peripheral artery disease (eg, atherosclerotic stenosis)
LOCATION Distal toes, anterior shin, pressure points
APPEARANCE Symmetric with well-defned punched out appearance
PAIN Severe
ASSOCIATED SIGNS Signs of arterial insuffciency including cold, pale, atrophic skin with hair loss and nail dystrophy, absent pulses.
Neuropathic ulcer-
ETIOLOGY Peripheral neuropathy (eg, diabetic foot) LOCATION Bony prominences (eg, metatarsal heads, heel) APPEARANCE Hyperkeratotic
edge with undermined borders PAIN Absent ASSOCIATED SIGNS Claw toes, Charcot joints, absent refexes

Burn classification-
Superficial burn - Epidermis only. Similar to sunburn; localized, dry, blanching redness with no blisters. Painful.
Superficial partial-thickness burn - Epidermis and papillary dermis. Blisters, blanches with pressure, swollen, warm. Painful to temperature and air.
Deep partial-thickness burn - Epidermis and reticular dermis. Blisters (easily unroofed), does not blanch with pressure. Painless; perception of pressure
only.
Full-thickness burn - Epidermis and full-thickness dermis. White, waxy, dry, inelastic, leathery, does not blanch with pressure. Painless; perception of
deep pressure only.
Deeper injury burn - Epidermis, dermis, and involvement of underlying tissue (eg, fascia, muscle). White, dry, inelastic, does not blanch with pressure.
Painless; some perception of deep pressure. Rule of 9s - Entire head 9%, Entire torso 18%, Entire arm (L) 9% , Entire arm (R) 9%, Entire abdomen
18%, Perineum 1%, Entire leg (L) 18%, Entire leg (R) 18%, Total 100%.

Posterior cerebral artery - Occipital lobe. Contralateral hemianopia with macular sparing; alexia without agraphia (dominant hemisphere, extending to
splenium of corpus callosum); prosopagnosia (nondominant hemisphere).

Basilar artery (think lower midbrain and upper pons) - Pons, medulla, lower midbrain - Reticular activating system (RAS). Corticospinal and
corticobulbar tracts. Ocular cranial nerve nuclei, paramedian pontine reticular formation. Locked-in syndrome.

Anterior inferior cerebellar artery - Facial nucleus. Vestibular nuclei. Spinothalamic tract, spinal trigeminal nucleus. Sympathetic fbers. Middle and
inferior cerebellar peduncles. Labyrinthine artery. Lateral pontine syndrome.

Posterior inferior cerebellar artery - Nucleus ambiguus (CN IX, X, XI). Vestibular nuclei. Lateral spinothalamic tract, spinal trigeminal nucleus.
Sympathetic fbers. Inferior cerebellar peduncle. Lateral medullary (Wallenberg) syndrome.

Anterior spinal artery - Corticospinal tract. Medial lemniscus. Caudal medulla—hypoglossal nerve (tongue deviates ipsilaterally - pushing effect).
Medial Medullary syndrome— caused by infarct of paramedian branches of ASA and/or vertebral arteries.
Alar plate (dorsal): sensory; regulated by TGF-β (including bone morphogenetic protein [BMP])
Basal plate (ventral): motor; regulated by sonic hedgehog gene (SHH)

Three primary vesicles- Forebrain (prosencephalon) Midbrain (mesencephalon) Hindbrain (rhombencephalon)

Five secondary vesicles
Telencephalon - Cerebral hemispheres, Basal ganglia; Lateral ventricles
Diencephalon - Thalamus, Hypothalamus, Retina; Third ventricle Mesencephalon - Midbrain; Cerebral aqueduct Metencephalon - Pons Cerebellum;
Upper part of fourth ventricle Myelencephalon - Medulla; Lower part of fourth ventricle Neuroepithelia in neural tube—CNS neurons, CNS glial cells
(astrocytes, oligodendrocytes, ependymal cells).

Neural crest—PNS neurons (dorsal root ganglia, autonomic ganglia [sympathetic, parasympathetic, enteric]), PNS glial cells (Schwann cells, satellite
cells), adrenal medulla, melanocytes, face/ branchial arch mesenchyme.
Mesoderm—microglia (like macrophages).
Neural tube defects - Neuropores fail to fuse by the 4th week of development > persistent connection between amniotic cavity and spinal canal.
Associated with diabetes and folate defciency during pregnancy. Inc -fetoprotein (AFP) in amniotic fuid and serum (except spina bifda occulta =
normal AFP). Inc acetylcholinesterase (AChE) in amniotic fuid is a helpful confrmatory test.

Posterior fossa malformations -

Chiari I malformation Ectopia of cerebellar tonsils inferior to foramen magnum (1 structure). Congenital, usually asymptomatic in childhood, manifests
in adulthood with headaches and cerebellar symptoms. Associated with spinal cavitations (eg, syringomyelia).

Chiari II malformation Herniation of cerebellum (vermis and tonsils) and medulla (2 structures) through foramen magnum > noncommunicating
hydrocephalus. Usually associated with aqueductal stenosis, lumbosacral myelomeningocele (may present as paralysis/sensory loss at and below the
level of the lesion). More severe than Chiari I, usually presents early in life.
Dandy-Walker malformation Agenesis of cerebellar vermis > cystic enlargement of 4th ventricle (arrow in B ) that fills the enlarged posterior fossa.
Associated with noncommunicating hydrocephalus, spina bifda.

Tongue development-
1st pharyngeal arch forms anterior 2/3 of tongue (sensation via CN V3 , taste via CN VII). 3rd and 4th pharyngeal arches form posterior 1/3 of tongue
(sensation and taste mainly via CN IX, extreme posterior via CN X). Motor innervation is via CN XII to hyoglossus (retracts and depresses tongue),
genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing). Motor innervation is via CN X to
palatoglossus (elevates posterior tongue during swallowing).
Taste—CN VII, IX, X (solitary nucleus). Pain—CN V3 , IX, X.
Motor—CN X, XII.
Neuron action potential -
[Link] membrane potential: membrane is more permeable to K+ than Na+ at rest. Voltage-gated Na+ and K+ channels are closed. [Link]
depolarization: Na+ activation gate opens > Na+ flows inward.
[Link] repolarization: Na+ inactivation gate closes at peak potential, thus stopping Na+ infow. K+ activation gate gate opens > K+ flows
outward.
[Link] hyperpolarization: K+ activation gates are slow to close > excess K+ effux and brief period of hyperpolarization. Voltage- gated Na+
channels switch back to resting state. Na+/K+ pump restores ions concentration.
(RMP-MF)
R - JS
Mer (Mr) - DP
P - PH
Meis (Miss)- D-PILL
F - PT
(RMP-MF)
R - JS - Finger tips, joints
Mer (Mr) - DP - Finger tips, superficial skin
P - PH - Deep skin layers, ligaments, joints
Meis (Miss)- D-PILL - Glabrous (hairless) skin
F - PT - All tissues except cartilage and eye lens
P and Meis(Miss) - adapt quickly
Mer(Mr) and R - adapt slowly
(PMs adapt quickly, MRs adapt slowly)
Peripheral nerve -
Endoneurium—thin, supportive connective tissue that ensheathes and supports individual myelinated nerve fbers. May be affected in Guillain-Barré
syndrome.
Perineurium (blood-nerve permeability barrier)—surrounds a fascicle of nerve fibers.
Epineurium—dense connective tissue that surrounds entire nerve (fascicles and blood vessels).
Endo = inner Peri = around Epi = outer.
Chromatolysis - Reaction of neuronal cell body to axonal injury. Changes refect inc protein synthesis in effort to repair the damaged axon.
Characterized by:
Round cellular swelling
Displacement of the nucleus to the periphery Dispersion of Nissl substance throughout cytoplasm.
Wallerian degeneration—disintegration of the axon and myelin sheath distal to site of axonal injury with macrophages removing debris. Proximal to the
injury, the axon retracts, and the cell body sprouts new protrusions that grow toward other neurons for potential reinnervation. Serves as a preparation
for axonal regeneration and functional recovery.
Acetylcholine - Basal nucleus of Meynert (forebrain) Dopamine - Ventral tegmentum, SNc (midbrain) GABA - Nucleus accumbens (basal ganglia)
Norepinephrine - Locus ceruleus (pons)
Serotonin - Raphe nuclei (brain stem)
Neurotransmitter changes with disease-
ANXIETY - GABA dec; Norepinephrine inc; Serotonin dec.
DEPRESSION - Dopamine dec; Norepinephrine dec; Serotonin dec.
SCHIZOPHRENIA - Dopamine inc.
ALZHEIMER DISEASE - Acetylcholine dec.
HUNTINGTON DISEASE - Acetylcholine dec; Dopamine inc; GABA dec. PARKINSON DISEASE - Acetylcholine inc; Dopamine dec; Serotonin
dec.
Circumventricular organs with fenestrated capillaries and no blood-brain barrier allow molecules in blood to affect brain function (eg, area postrema—
vomiting after chemotherapy; OVLT [organum vasculosum lamina terminalis]—osmoreceptors) or neurosecretory products to enter circulation (eg,
neurohypophysis—ADH release).
CTZ and adjacent vomiting center nuclei receive input from 5 major receptors: muscarinic (M1 ), dopamine (D2 ), histamine (H1 ), serotonin (5-HT3 ),
and neurokinin (NK-1) receptors.
5-HT3 , D2 , and NK-1 antagonists used to treat chemotherapy-induced vomiting.
H1 and M1 antagonists treat motion sickness; H1 antagonists treat hyperemesis gravidarum.
RENAL PHARMACOLOGY
Mannitol - ADVERSE EFFECTS Dehydration, hypo- or hypernatremia, pulmonary edema. Contraindicated in anuria, HF.
Acetazolamide - ADVERSE EFFECTS Proximal renal tubular acidosis (type 2 RTA), paresthesias, NH3 toxicity, sulfa allergy, hypokalemia. Promotes
calcium phosphate stone formation (insoluble at high pH). “Acid”azolamide causes acidosis. Acetazolamide alkalinizes urine.
Loop diuretics -
Furosemide, bumetanide, torsemide - MECHANISM Sulfonamide loop diuretics. ADVERSE EFFECTS Ototoxicity, Hypokalemia, Hypomagnesemia,
Dehydration, Allergy (sulfa), metabolic Alkalosis, Nephritis (interstitial), Gout. OHH DAANG
Ethacrynic acid - MECHANISM Nonsulfonamide inhibitor of cotransport system (Na+/K+/2Cl ). ADVERSE EFFECTS Similar to furosemide, but
more ototoxic. Loop earrings hurt your ears.
Thiazide diuretics ADVERSE EFFECTS (Hypergluc.) Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia,
hyperuricemia, hypercalcemia. Sulfa allergy.
Potassium-sparing diuretics - ADVERSE EFFECTS Hyperkalemia (can lead to arrhythmias), endocrine effects with spironolactone (eg, gynecomastia,
antiandrogen effects).
Diuretics: electrolyte changes
Urine NaCl - Inc with all diuretics (concentration varies based on potency of diuretic effect). Serum NaCl may decrease as a result.
Urine K+ - Inc especially with loop and thiazide diuretics, excluding K+-sparing diuretics.
Blood pH- Dec (acidemia): carbonic anhydrase inhibitors: dec HCO3 reabsorption. K+ sparing: aldosterone blockade prevents K+ secretion and H+
secretion. Additionally, hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.
Inc (alkalemia): loop diuretics and thiazides cause alkalemia through several mechanisms: Volume contraction > inc AT II > inc Na+/H+ exchange in
PCT > inc HCO3 reabsorption (“contraction alkalosis”). K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells.
In low K+ state, H+ (rather than K+) is exchanged for Na+ in cortical collecting tubule > alkalosis and “paradoxical aciduria”.
Urine Ca2+ - Inc with loop diuretics: Dec paracellular Ca2+ reabsorption > hypocalcemia. Dec with thiazides: enhanced Ca2+ reabsorption.
Angiotensin-converting enzyme inhibitors - ADVERSE EFFECTS Cough, Angioedema (both due to inc bradykinin; contraindicated in C1 esterase
inhibitor defciency), Teratogen (fetal renal malformations), inc Creatinine (dec GFR), Hyperkalemia, and Hypotension. Used with caution in bilateral
renal artery stenosis because ACE inhibitors will further dec GFR > renal failure. (Captopril’s CATCHH.)
Angiotensin II receptor blockers - ADVERSE EFFECTS Hyperkalemia, dec GFR, hypotension; teratogen.
Aliskiren - ADVERSE EFFECTS Hyperkalemia, dec GFR, hypotension, angioedema. Relatively contraindicated in patients already taking ACE
inhibitors or ARBs and contraindicated in pregnancy.

REPRODUCTIVE PHARMACOLOGY
Gonadotropin-releasing hormone analogs - ADVERSE EFFECTS Hypogonadism, dec libido, erectile dysfunction, nausea, vomiting.
Degarelix MECHANISM GnRH antagonist. ADVERSE EFFECTS Hot fashes, liver toxicity.
Estrogens - Ethinyl estradiol, DES, mestranol. ADVERSE EFFECTS inc risk of endometrial cancer (when given without progesterone), bleeding in
postmenopausal patients, clear cell adenocarcinoma

of vagina in females exposed to DES in utero, inc risk of thrombi. Contraindications—ER ⊕ breast cancer, history of DVTs, tobacco use in females >
35 years old.
Selective estrogen receptor modulators-
Clomiphene - May cause hot fashes, ovarian enlargement, multiple simultaneous pregnancies, visual disturbances.
Tamoxifen - Hot fashes, inc risk of thromboembolic events (especially with tobacco smoking), and endometrial cancer. Used to treat and prevent
recurrence of ER/PR breast cancer and to prevent gynecomastia in patients undergoing prostate cancer therapy.

Raloxifene - hot fashes, inc risk of thromboembolic events (especially with tobacco smoking), but no increased risk of endometrial cancer (vs
tamoxifen, so you can “relax”); used primarily to treat osteoporosis.
Hormone replacement therapy - Unopposed estrogen replacement therapy inc risk of endometrial cancer, progesterone/progestin is added. Possible
increased cardiovascular risk.
Combined contraception - Adverse effects: breakthrough menstrual bleeding, breast tenderness, VTE, hepatic adenomas. Contraindications: people >
35 years old who smoke tobacco (inc risk of cardiovascular events), patients with inc risk of cardiovascular disease (including history of venous
thromboembolism, coronary artery disease, stroke), migraine (especially with aura), breast cancer, liver disease.

Copper intrauterine device ADVERSE EFFECTS Heavier or longer menses, dysmenorrhea. Insertion contraindicated in active PID (IUD may impede
PID resolution).
Danazol - ADVERSE EFFECTS Weight gain, edema, acne, hirsutism, masculinization, dec HDL levels, hepatotoxicity, idiopathic intracranial
hypertension.
Testosterone, methyltestosterone - ADVERSE EFFECTS Masculinization in females; dec intratesticular testosterone in males by inhibiting release of
LH (via negative feedback) > gonadal atrophy. Premature closure of epiphyseal plates. inc LDL, dec HDL.
Antiandrogens-
Abiraterone - 17 -hydroxylase/17,20-lyase inhibitor (dec steroid synthesis) - Prostate cancer. ADVERSE EFFECTS - Hypertension, hypokalemia (inc
mineralocorticoids)
Finasteride - 5 -reductase inhibitor (dec conversion of testosterone to DHT) - BPH, male-pattern baldness. ADVERSE EFFECTS - Gynecomastia,
sexual dysfunction.
Flutamide, bicalutamide - Nonsteroidal competitive inhibitors at androgen receptor (dec steroid binding) - Prostate cancer. ADVERSE EFFECTS -
Gynecomastia, sexual dysfunction.
Ketoconazole - 17 -hydroxylase/17,20-lyase inhibitor - Prostate cancer. ADVERSE EFFECTS - Gynecomastia.
Spironolactone - Androgen receptor and 17 -hydroxylase/17,20-lyase inhibitor - PCOS. ADVERSE EFFECTS - Amenorrhea.

RESPIRATORY PHARMACOLOGY
H1-blockers - ADVERSE EFFECTS Sedation, antimuscarinic, anti- -adrenergic. Second generation - Loratadine, fexofenadine, desloratadine,
cetirizine. Names usually end in “- adine.” Setirizine (cetirizine) is second- generation agent. CLINICAL USE Allergy. ADVERSE EFFECTS Far less
sedating than 1st generation because of dec entry into CNS.
Dextromethorphan - Antitussive (antagonizes NMDA glutamate receptors). May cause serotonin syndrome if combined with other serotonergic agents.
Pseudoephedrine, phenylephrine - ADVERSE EFFECTS Hypertension. Rebound congestion (rhinitis medicamentosa) if used more than 4–6 days.
Associated with tachyphylaxis. Can also cause CNS stimulation/anxiety (pseudoephedrine).
Pulmonary hypertension drugs-
Endothelin receptor antagonists - Hepatotoxic (monitor LFTs). Example: bosentan.
PDE-5 inhibitors - Contraindicated when taking nitroglycerin or other nitrates (due to risk of severe hypotension). Example: sildenafl.
Prostacyclin analogs - Side effects: fushing, jaw pain. Examples: epoprostenol, iloprost.
Asthma drugs -
Inhaled 2-agonists - Albuterol—Can cause tremor, arrhythmia.
Salmeterol, formoterol—Can cause tremor, arrhythmia.
Zileuton—Hepatotoxic.
Methylxanthines - Theophylline— Limited use due to narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by cytochrome P-450.
Blocks actions of adenosine.
Hemoglobin development - Embryonic globins: ζ and ε. Fetal hemoglobin (HbF) = α2 γ2 . Adult hemoglobin (HbA1 ) = α2 β 2 . HbF has higher
affnity for O2 due to less avid binding of 2,3-BPG, allowing HbF to extract O2 from maternal hemoglobin (HbA1 and HbA2 ) across the placenta.
HbA2 (α2 δ2 ) is a form of adult hemoglobin present in small amounts.
Fetal erythropoiesis - Fetal erythropoiesis occurs in: Yolk sac (3–8 weeks), Liver (6 weeks–birth), Spleen (10–28 weeks), Bone marrow (18 weeks to
adult). YLSB
A: normal hemoglobin β chain (HbA, adult)
F: normal hemoglobin y chain (HbF, fetal)
S: sickle cell hemoglobin β chain (HbS)
C: hemoglobin C β chain (HbC)
Coombs test - Also called antiglobulin test. Detects the presence of antibodies against circulating RBCs.
Direct Coombs test—anti-Ig antibody (Coombs reagent) added to patient’s RBCs. RBCs agglutinate if RBCs are coated with Ig. Used for AIHA
diagnosis.
Indirect Coombs test—normal RBCs added to patient’s serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent is added.
Used for pretransfusion testing.
Coombs reagent - anti human globulin.
Direct coombs - Only anti-IgG is added. Tests antibody coated RBCs.
Indirect coombs - Both anti-IgG and test RBCs are added. Tests antibodies in serum.

Aspirin irreversibly inhibits cyclooxygenase, thereby inhibiting TXA2 synthesis. Clopidogrel, prasugrel, ticagrelor, and ticlopidine inhibit ADP-
induced expression of GpIIb/IIIa by blocking P2Y12 receptor. Abciximab, eptifbatide, and tirofban inhibit GpIIb/IIIa directly. Ristocetin activates vWF
to bind GpIb. Failure of aggregation with ristocetin assay occurs in von Willebrand disease and Bernard-Soulier syndrome. Desmopressin promotes the
release of vWF and factor VIII from endothelial cells. vWF carries/protects factor VIII; volksWagen Factories make gr8 cars.
Clopidogrel, prasugrel, ticagrelor, ticlopidine (PTCT) - blocks P2Y12(ADP) receptor Abciximab, eptifibatide, tirofiban (TEA) - inhibits Gp2b/3a
directly

Ristocetin - activates vWF

Ristocetin failure - von Williebrand ds and bernard-soulier synd
Desmopressin - releases vWF and F8 from endothelium
Gp1b def - bernard-soulier
Gp2b/3a def - glanzmann thrombasthenia vWF def - von Willebrand ds.
Acanthocytes (“spur cells”) - (ALE) Liver disease, abetalipoproteinemia, vitamin E defciency.
Echinocytes (“burr cells”) - (EPL) Liver disease, ESRD, pyruvate kinase defciency.
Dacrocytes (“teardrop cells”)
Degmacytes (“bite cells”)
Target cells (HALT) - HbC disease, Asplenia, Liver disease, Thalassemia.
Howell-jolly bodies - Basophilic nuclear remnants (do not contain iron).
Heinz bodies - Denatured and precipitated hemoglobin (contain iron).
Basophilic stippling - Basophilic ribosomal precipitates (do not contain iron).
Pappenheimer bodies - Basophilic granules (contain iron).
Iron granules - Sideroblastic anemias (eg, lead poisoning, myelodysplastic syndromes, chronic alcohol overuse). Contain iron - Heinz bodies,
Pappenheimer bodies
Do not contain iron - Howell-jolly bodies, Basophilic stippling
HEINZ - Hb ppts
BASOPHILIC STIPPLING - RIBOSOMAL PPTS
HOWELL-JOLLY - NUCLEAR REMNANTS
Sideroblastic anemia - ringed sideroblasts (iron granules), basophilic stippling, pappenheimer bodies. Microcytic (MCV < 80 fL) -
Hemoglobin affected (TAIL) -
Defective globin chain: •Thalassemias
Defective heme synthesis: •Anemia of chronic disease •Iron deficiency (late) •Lead poisoning.

Normocytic (MCV 80–100 fL) -

Nonhemolytic (low reticulocyte index) -
•Iron deficiency (early) •Anemia of chronic disease •Aplastic anemia •Chronic kidney disease.

Hemolytic (high reticulocyte index) -

Intrinsic -
Membrane defects •Hereditary spherocytosis •Paroxysmal nocturnal hemoglobinuria. Enzyme deficiencies •G6PD deficiency •Pyruvate kinase
deficiency. Hemoglobinopathies •Sickle cell anemia •HbC disease.
Extrinsic -
•Autoimmune •Microangiopathic •Macroangiopathic •Infections.

Macrocytic (MCV > 100 fL) -

Megaloblastic - DNA affected-
Defective DNA synthesis •Folate deficiency •Vitamin B12 deficiency •Orotic aciduria.
Defective DNA repair •Fanconi anemia.
Nonmegaloblastic -
•Diamond-Blackfan anemia •Liver disease •Chronic alcohol overuse.
1 (α α/α –) - α-thalassemia minima.
2 (α –/α –; trans) or (α α/– –; cis) - α-thalassemia minor.
3 (– –/– α) - Hemoglobin H disease (HbH); excess β -globin forms β4.
4 (– –/– –) - Hemoglobin Barts disease; no α-globin, excess γ-globin forms γ4 - Hydrops fetalis; incompatible with life. Interpretation of iron studies-
Iron defciency-
Serum iron dec. Transferrin or TIBC inc. Ferritin dec. % transferrin saturation (serum iron/TIBC) dec dec.
Chronic disease-
Serum iron dec. Transferrin or TIBC dec*. Ferritin inc. % transferrin saturation (serum iron/TIBC) -/dec. Hemochromatosis-
Serum iron inc. Transferrin or TIBC dec. Ferritin inc. % transferrin saturation (serum iron/TIBC) inc inc.
Pregnancy/ OCP use-
Serum iron -. Transferrin or TIBC inc. Ferritin -. % transferrin saturation (serum iron/TIBC) dec.

Autoimmune hemolytic anemia - A normocytic anemia that is usually idiopathic and Coombs . Two types:
Warm AIHA–chronic anemia in which primarily IgG causes extravascular hemolysis. Seen in SLE and CLL and with certain drugs (eg, -
lactams, -methyldopa). “Warm weather is Good.”
Cold AIHA–acute anemia in which primarily IgM + complement cause RBC agglutination and extravascular hemolysis upon exposure to cold >
painful, blue fngers and toes. Seen in CLL, Mycoplasma pneumoniae infections, infectious mononucleosis.
Spherocytes and agglutinated RBCs A on peripheral blood smear. Warm AIHA treatment: steroids, rituximab, splenectomy (if refractory). Cold AIHA
treatment: cold avoidance, rituximab. Leukopenias
CELL TYPE CELLCOUNT CAUSES
Neutropenia - Absolute neutrophil count < 1500 cells/mm3 Severe infections typical when < 500 cells/mm3 Sepsis/postinfection, drugs (including
chemotherapy), aplastic anemia, SLE, radiation Lymphopenia - Absolute lymphocyte count < 1500 cells/mm3 (< 3000 cells/mm in children) HIV,
DiGeorge syndrome, SCID, SLE, corticosteroidsa , radiation, sepsis, postoperative
Eosinopenia - Absolute eosinophil count < 30 cells/mm3 Cushing syndrome, corticosteroids.
Corticosteroids cause neutrophilia, despite causing eosinopenia and lymphopenia. Corticosteroids activation of neutrophil adhesion molecules,
impairing migration out of the vasculature to sites of infammation. In contrast, corticosteroids sequester eosinophils in lymph nodes and cause
apoptosis of lymphocytes.
Acute intermittent porphyria - Porphobilinogen deaminase, previously called uroporphyrinogen I synthase (autosomal dominant mutation) -
Porphobilinogen, ALA - Symptoms (5 P’s):
Painful abdomen
Port wine–colored Pee
Polyneuropathy
Psychological disturbances
Precipitated by factors that inc ALA synthase (eg, drugs [CYP450 inducers], alcohol, starvation). Treatment: hemin and glucose.
Porphyria cutanea tarda - Uroporphyrinogen decarboxylase - Uroporphyrin (tea-colored urine) - Blistering cutaneous photosensitivity and
hyperpigmentation. Most common porphyria. Exacerbated with alcohol consumption. Causes: familial, hepatitis C. Treatment: phlebotomy, sun
avoidance, antimalarials (eg, hydroxychloroquine).
Blood transfusion therapy
COMPONENT DOSAGE EFFECT CLINICAL USE
Packed RBCs - inc Hb and O2 carrying capacity. Acute blood loss, severe anemia.
Platelets - inc platelet count (inc 5000/mm3 /unit). Stop signifcant bleeding (thrombocytopenia, qualitative platelet defects).
Fresh frozen plasma/ prothrombin complex concentrate - inc coagulation factor levels; FFP contains all coagulation factors and plasma proteins; PCC
generally contains factors II, VII, IX, and X, as well as protein C and S. Cirrhosis, immediate anticoagulation reversal. Cryoprecipitate - Contains
fbrinogen, factor VIII, factor XIII, vWF, and fbronectin. Coagulation factor defciencies involving fbrinogen and factor VIII.
Blood transfusion risks include infection transmission (low), transfusion reactions, iron overload (may lead to 2° hemochromatosis), hypocalcemia
(citrate is a Ca2+ chelator), and hyperkalemia (RBCs may lyse in old blood units).

Zone I—periportal zone: Affected 1st by viral hepatitis. Best oxygenated, most resistant to circulatory compromise. Ingested toxins (eg, cocaine).
Zone II—intermediate zone: Yellow fever.
Zone III—pericentral (centrilobular) zone: Affected 1st by ischemia (least oxygenated). High concentration of cytochrome P-450. Most sensitive to
metabolic toxins (eg, ethanol, CCl4 , halothane, rifampin, acetaminophen). Site of alcoholic hepatitis.
Molecular pathogenesis of colorectal cancer -
Chromosomal instability pathway: mutations in APC cause FAP and most sporadic cases of CRC via adenoma-carcinoma sequence.
Microsatellite instability pathway: mutations or methylation of mismatch repair genes (eg, MLH1) cause Lynch syndrome and some sporadic CRC via
serrated polyp pathway. Usually leads to rightsided CRC.
Adenomatous polyps - Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS. Tubular histology has less malignant
potential than villous (“villous histology is villainous”); tubulovillous has intermediate malignant potential. Usually asymptomatic; may present with
occult bleeding.
Serrated polyps - Neoplastic. Characterized by CpG island methylator phenotype (CIMP; cytosine base followed by guanine, linked by a
phosphodiester bond). Defect may silence MMR gene (DNA mismatch repair) expression. Mutations lead to microsatellite instability and mutations in
BRAF. “Sawtooth” pattern of crypts on biopsy. Up to 20% of cases of sporadic CRC.
Normal colon > Loss of APC gene - dec Intercellular adhesion - inc proliferation > Colon at risk > KRAS mutation - Unregulated intracellular
signaling > Adenoma > Loss of tumor suppressor gene(s) (TP53, DCC) - inc Tumorigenesis > Carcinoma.
(AKT)
1. APC
2. K-RAS
3. Tumor suppressor gene(s) (TP53, DCC)
Ascending colon CRC—exophytic mass, iron defciency anemia, weight loss.
Descending colon CRC—infiltrating mass, partial obstruction, colicky pain, hematochezia.
Rigler triad of gallstone ileus: radiographic fndings of pneumobilia, small bowel obstruction, gallstone (usually in iliac fossa).
Charcot triad of cholangitis includes jaundice, fever, RUQ pain.
Reynolds pentad of cholangitis is Charcot triad plus altered mental status and shock (hypotension).
Acute pancreatitis - Diagnosis by 2 of 3 criteria: acute epigastric pain often radiating to the back, inc serum amylase or lipase (more specific) to 3x
upper limit of normal, or characteristic imaging

findings.
H2-blockers ADVERSE EFFECTS Cimetidine is a potent inhibitor of cytochrome P- 450 (multiple drug interactions); it also has antiandrogenic effects
(prolactin release, gynecomastia, impotence, dec libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta.
Cimetidine dec renal excretion of creatinine. Other H2 blockers are relatively free of these effects. Proton pump inhibitors ADVERSE EFFECTS inc
risk of C diffcile infection, pneumonia, acute interstitial nephritis. Vitamin B12 malabsorption; dec serum Mg2+ and dec Ca2+ absorption (potentially
leading to increased fracture risk in elderly).
Antacids - Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying.
All can cause hypokalemia. Overuse can also cause the following problems:
Aluminum hydroxide - Constipation, Hypophosphatemia, Osteodystrophy, Proximal muscle weakness, Seizures (CHOPS)
Calcium carbonate - Hypercalcemia (milk-alkali syndrome), rebound acid inc. Can chelate and dec effectiveness of other drugs (eg, tetracycline).
Magnesium hydroxide - Diarrhea, hyporefexia, hypotension, cardiac arrest (Mg2+ = Must go 2 the bathroom)
Misoprostol ADVERSE EFFECTS Diarrhea. Contraindicated in patients of childbearing potential (abortifacient).
Octreotide ADVERSE EFFECTS Nausea, cramps, steatorrhea. Inc risk of cholelithiasis due to CCK inhibition.
Sulfasalazine ADVERSE EFFECTS Malaise, nausea, sulfonamide toxicity, reversible oligospermia.
Loperamide ADVERSE EFFECTS Constipation, nausea.
Ondansetron ADVERSE EFFECTS Headache, constipation, QT interval prolongation, serotonin syndrome.
Metoclopramide ADVERSE EFFECTS - Inc parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea. Drug
interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction, Parkinson disease (due to D2-receptor
blockade), dec seizure threshold.
Orlistat ADVERSE EFFECTS Abdominal pain, fatulence, bowel urgency/frequent bowel movements, steatorrhea; dec absorption of fat-soluble
vitamins.
Laxatives - Indicated for constipation or patients on opiates requiring a bowel regimen.
Bulk-forming laxatives - (PM) ADVERSE EFFECTS Bloating.
Osmotic laxatives - (PMLM) ADVERSE EFFECTS Diarrhea, dehydration; may be misused by patients with bulimia nervosa; overuse may cause
metabolic alkalosis.
Stimulants - (BS) ADVERSE EFFECTS Diarrhea, melanosis coli; overuse may cause metabolic alkalosis.
Emollients - Docusate ADVERSE EFFECTS Diarrhea; overuse may cause metabolic alkalosis.
B-PM
O-PMLM
S-BS
E-D
Aortic arch derivatives Develop into arterial system.
1st Part of maxillary artery (branch of external carotid). 1st arch is maximal.
2nd Stapedial artery and hyoid artery. Second = stapedial.
3rd Common carotid artery and proximal part of internal carotid artery. C is 3rd letter of alphabet.
4th On left, aortic arch; on right, proximal part of right subclavian artery. 4th arch (4 limbs) = systemic.
6th Proximal part of pulmonary arteries and (on left only) ductus arteriosus. 6th arch = pulmonary and the pulmonary-to-systemic shunt (ductus
arteriosus).
Right recurrent laryngeal nerve loops around product of 4th arch (subclavian artery).
Left recurrent laryngeal nerve loops around product of 6th arch (ductus arteriosus).
Acetaminophen - SE - Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts
in liver. N-acetylcysteine is antidote — regenerates glutathione.
Aspirin - SE - Gastric ulceration, tinnitus (CN VIII), allergic reactions (especially in patients with asthma or nasal polyps). Chronic use can lead to
acute kidney injury, interstitial nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Toxic doses cause
respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis. Treatment of overdose: NaHCO3.
Celecoxib - SE - Inc risk of thrombosis, sulfa allergy.
NSAIDS - SE - Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia (prostaglandins vasodilate afferent arteriole),
aplastic anemia.
Leflunomide - SE - Diarrhea, hypertension, hepatotoxicity, teratogenicity.
Teriparatide - SE - Inc risk of osteosarcoma (avoid use in patients with Paget disease of the bone or unexplained elevation of alkaline phosphatase).
Avoid in patients who have had prior cancers or radiation therapy. Transient hypercalcemia.
Bisphosphonates - SE - Esophagitis (if taken orally, patients are advised to take with water and remain upright for 30 minutes), osteonecrosis of jaw,
atypical femoral stress fractures.
Probenicid - Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin). Can precipitate uric acid calculi.
NSAIDs - Any NSAID. Use salicylates with caution (may decrease uric acid excretion, particularly at low doses).
Colchicine - GI, neuromyopathic side effects. Can also cause myelosupression, nephrotoxicity.
TNF- inhibitors - Etanercept - SE - Predisposition to infection, including reactivation of latent TB, since TNF is important in granuloma formation and
stabilization. Can also lead to drug-induced lupus.
TNF- inhibitors - Infliximab, adalimumab, certolizumab, golimumab - SE - Predisposition to infection, including reactivation of latent TB, since TNF
is important in granuloma formation and stabilization. Can also lead to drug-induced lupus.

Epilepsy therapy -
Benzodiazepines - SE - Sedation, tolerance, dependence, respiratory depression.
Carbamazepine - SE - Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis (cleft lip/palate, spina bifida),
induction of cytochrome P-450, SIADH, SJS. Ethosuximide - SIDE EFFECTS - EFGHIJ—Ethosuximide causes Fatigue, GI distress, Headache,
Itching (and urticaria), SJS.
Gabapentin - SE - Sedation, ataxia. Also used for peripheral neuropathy, postherpetic neuralgia.
Lamotrigine - SE - SJS (must be titrated slowly), hemophagocytic lymphohistiocytosis (black box warning).
Levetiracetam - SE - Neuropsychiatric symptoms (eg, personality change), fatigue, drowsiness, headache.
Phenobarbital - SE - Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression. 1st line in neonates
(“phenobabytal”).
Phenytoin, fosphenytoin - SE - PPHENYTOIN: cytochrome P-450 induction, Pseudolymphoma, Hirsutism, Enlarged gums, Nystagmus, Yellow-brown
skin, Teratogenicity (fetal hydantoin syndrome), Osteopenia, Inhibited folate absorption, Neuropathy. Rare: SJS, DRESS syndrome, drug-induced
lupus. Toxicity leads to diplopia, ataxia, sedation.
Topiramate - SE - Sedation, slow cognition, kidney stones, skinny (weight loss), sight threatened (glaucoma), speech (word- finding) difficulties.
Valproic acid - SE - VALPPROaTTE: Vomiting, Alopecia, Liver damage (hepatotoxic), Pancreatitis, P-450 inhibition, Rash, Obesity (weight gain),
Tremor, Teratogenesis (neural tube defects). Epigastric pain (GI distress).
Vigabatrin - SE - Permanent visual loss (black box warning). Vision loss with GABA transaminase inhibitor.
Barbiturates - SE - Respiratory and cardiovascular depression (can be fatal); CNS depression (can be exacerbated by alcohol use); dependence; drug
interactions (induces cytochrome P-450). Overdose treatment is supportive (assist respiration and maintain BP). Contraindicated in porphyria.
BZDs - Dec REM sleep. Most have long half-lives and active metabolites (exceptions [ATOM]: Alprazolam, Triazolam, Oxazepam, and Midazolam
are short acting > higher addictive potential). SE - Dependence, additive CNS depression effects with alcohol and barbiturates (all bind the GABAA
receptor). Less risk of respiratory depression and coma than with barbiturates. Treat overdose with flumazenil (competitive antagonist at GABA
benzodiazepine receptor). Can precipitate seizures by causing acute benzodiazepine withdrawal.
Nonbenzodiazepine hypnotics - Examples: Zolpidem, Zaleplon, esZopiclone. SE - Ataxia, headaches, confusion Cause only modest day-after
psychomotor depression and few amnestic effects (vs older sedative-hypnotics). Dec dependency risk and dec sleep cycle disturbance (vs
benzodiazepine hypnotics).
Suvorexant - Orexin (hypocretin) receptor antagonist. SE - CNS depression (somnolence), headache, abnormal sleep- related activities.
Contraindications: narcolepsy, combination with strong CYP3A4 inhibitors. Not recommended in patients with liver disease. Limited risk of
dependency.
Ramelteon - SE - Dizziness, nausea, fatigue, headache. No known risk of dependency.
Triptans - Sumatriptan. 5-HT1B/1D agonists. SE - Coronary vasospasm (contraindicated in patients with CAD or vasospastic angina), mild paresthesia,
serotonin syndrome (in combination with other 5-HT agonists).
Dopamine agonists - Non-ergot (preferred)—pramipexole, ropinirole; toxicity includes nausea, impulse control disorder (eg, gambling), postural
hypotension, hallucinations, confusion. Ergot— bromocriptine rarely used due to toxicity.

Inc dopamine availability - Amantadine (inc dopamine release and dec dopamine reuptake); toxicity = peripheral edema, livedo reticularis, ataxia.
Carbidopa/Levodopa - SE - Nausea, hallucinations, postural hypotension. With progressive disease, L-DOPA can lead to “on- off” phenomenon with
improved mobility during “on” periods, then impaired motor function during “off” periods when patient responds poorly to L-DOPA or medication
wears off.
Alzheimer ds- 1. Donepezil, rivastigmine, galantamine - AChE inhibitor. 1st-line treatment. Adverse effects: nausea, dizziness, insomnia.
Contraindicated in patients with cardiac conduction abnormalities.
2. Memantine - NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+ ). Used for moderate to advanced dementia. Adverse
effects: dizziness, confusion, hallucinations.
Inhaled anesthetics - Myocardial depression, respiratory depression, postoperative nausea/vomiting, inc cerebral blood flow and ICP, dec cerebral
metabolic demand. SE - Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane, epileptogenic), expansion of trapped
gas in a body cavity (N2O). Malignant hyperthermia—rare, life-threatening condition in which inhaled anesthetics or succinylcholine induce severe
muscle contractions and hyperthermia. Susceptibility is often inherited as autosomal dominant with variable penetrance. Mutations in ryanodine
receptor (RYR1) cause inc Ca2+ release from sarcoplasmic reticulum. Treatment: dantrolene (a ryanodine receptor antagonist).
Thiopental - Dec cerebral blood flow. High lipid solubility. Effect terminated by rapid redistribution into tissue, fat.
Midazolam - May cause severe postoperative respiratory depression, dec BP, anterograde amnesia.
Propofol - May cause respiratory depression, dec BP.
Ketamine - NMDA receptor antagonist. Dissociative anesthesia, Sympathomimetic. Inc cerebral blood flow. Emergence reaction possible with
disorientation, hallucination, vivid dreams.
Local anesthetics - SE - CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, arrhythmias (cocaine),
methemoglobinemia (benzocaine, prilocaine).
Depolarizing neuromuscular blocking drugs - Succinylcholine—Complications include hypercalcemia, hyperkalemia, malignant hyperthermia. Inc risk
of prolonged muscle paralysis in patients with pseudocholinesterase deficiency.
Cyclobenzaprine - Acts within CNS, mainly at the brain stem. Muscle spasticity. Centrally acting. Structurally related to TCAs May cause
anticholinergic side effects, sedation.
Opioid analgesics - Full agonist: morphine, heroin, meperidine (long acting), methadone, codeine (prodrug; activated by CYP2D6), fentanyl. Partial
agonist: buprenorphine. Mixed agonist/antagonist: nalbuphine, pentazocine, butorphanol. Antagonist: naloxone, naltrexone, methylnaltrexone. SE -
Nausea, vomiting, pruritus (histamine release), opiate use disorder, respiratory depression, constipation, sphincter of Oddi spasm, miosis (except
meperidine > mydriasis), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Treat toxicity with
naloxone (competitive opioid receptor antagonist) and prevent relapse with naltrexone once detoxified.
Pentazocine - κ-opioid receptor agonist and μ-opioid receptor weak antagonist or partial agonist. Can cause opioid withdrawal symptoms if patient is
also taking full opioid agonist (due to competition for opioid receptors).
Butorphanol - κ-opioid receptor agonist and μ-opioid receptor partial agonist. Causes less respiratory depression than full opioid agonists. Use with full
opioid agonist can precipitate withdrawal. Not easily reversed with naloxone.
Tramadol - SE - Similar to opioids; decreases seizure threshold; serotonin syndrome.
α-agonists - Mydriasis (α1); do not use in closed-angle glaucoma. Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions,
ocular pruritus.
Prostaglandins - Darkens color of iris (browning), eyelash growth.
Cholinomimetics (M3) - Direct: pilocarpine, carbachol Indirect: physostigmine, echothiophate. Miosis (contraction of pupillary sphincter muscles) and
cyclospasm (contraction of ciliary muscle).
CNS stimulants - SE - Nervousness, agitation, anxiety, insomnia, anorexia, tachycardia, hypertension, weight loss, tics, bruxism.
Antipsychotics - Typical (1st-generation) antipsychotics—haloperidol, pimozide, trifluoperazine, fluphenazine, thioridazine, chlorpromazine. Atypical
(2nd-generation) antipsychotics—aripiprazole, asenapine, clozapine, olanzapine, quetiapine, iloperidone, paliperidone, risperidone, lurasidone,
ziprasidone. SE - Antihistaminic (sedation), anti- 1-adrenergic (orthostatic hypotension), antimuscarinic (dry mouth, constipation) (anti-HAM). Use
with caution in dementia. Metabolic: weight gain, hyperglycemia, dyslipidemia. Highest risk with clozapine and olanzapine (obesity). Endocrine:
hyperprolactinemia > galactorrhea, oligomenorrhea, gynecomastia. Cardiac: QT prolongation. Neurologic: neuroleptic malignant syndrome.
Ophthalmologic: chlorpromazine— corneal deposits; thioridazine—retinal deposits. Clozapine—agranulocytosis (monitor WBCs clozely), seizures
(dose related), myocarditis. Extrapyramidal symptoms—ADAPT: Hours to days: Acute Dystonia (muscle spasm, stiffness, oculogyric crisis).
Treatment: benztropine, diphenhydramine. Days to months: Akathisia (restlessness). Treatment: B-blockers, benztropine, benzodiazepines.
Parkinsonism (bradykinesia). Treatment: benztropine, amantadine. Months to years: Tardive dyskinesia (chorea, especially orofacial). Treatment:
benzodiazepines, botulinum toxin injections, valbenazine, deutetrabenazine. NOTES - Lipid soluble > stored in body fat > slow to be removed from
body. Typical antipsychotics have greater affinity for D2 receptor than atypical antipsychotics > inc risk for hyperprolactinemia, extrapyramidal
symptoms, neuroleptic malignant syndrome. High- potency typical antipsychotics: haloperidol, trifluoperazine, pimozide, fluphenazine (Hal tries pie to
fly high)— more neurologic side effects (eg, extrapyramidal symptoms). Low-potency typical antipsychotics: chlorpromazine, thioridazine (cheating
thieves are low)— more antihistaminic, anti- 1-adrenergic, antimuscarinic effects.
Lithium - SE - Tremor, hypothyroidism, hyperthyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis (causes Ebstein anomaly).
Narrow therapeutic window requires close monitoring of serum levels. Almost exclusively excreted by kidneys; most is reabsorbed at PCT via Na+
channels. Thiazides, NSAIDs, and other drugs affecting clearance are implicated in lithium toxicity. *LiTHIUM: Low Thyroid (hypothyroidism) Heart
(Ebstein anomaly) Insipidus (nephrogenic diabetes insipidus) Unwanted Movements (tremor)*
Buspirone - Partial 5-HT1A receptor agonist. Does not cause sedation, addiction, or tolerance. Begins to take effect after 1–2 weeks. Does not interact
with alcohol (vs barbiturates, benzodiazepines).
SSRis - Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram. SE - Fewer than TCAs. Serotonin syndrome, GI distress, SIADH,
sexual dysfunction (anorgasmia, dec libido), mania precipitation if underlying bipolar disorder. It normally takes 4–8 weeks for antidepressants to show
appreciable effect.
SNRIs - Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran. SE - inc BP, stimulant effects, sedation, nausea.
TCAs - Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, doxepin, amoxapine. SE - Sedation, a1- blocking effects including
postural hypotension, and atropine-like (anticholinergic) side effects (tachycardia, urinary retention, dry mouth). 3° TCAs (amitriptyline) have more
anticholinergic effects than 2° TCAs (nortriptyline). Can prolong QT interval. Tri- CyCliC’s: Convulsions, Coma, Cardiotoxicity (arrhythmia due to
Na+ channel inhibition); also respiratory depression, hyperpyrexia. Confusion and hallucinations are more common in the elderly due to
anticholinergic side effects (2° amines [eg, nortriptyline] better tolerated). Treatment: NaHCO3 to prevent arrhythmia.
MAO inh - SE - CNS stimulation; hypertensive crisis, most notably with ingestion of tyramine. Contraindicated with SSRIs, TCAs, St. John’s wort,
meperidine, dextromethorphan, pseudoephedrine, linezolid (to avoid precipitating serotonin syndrome). Wait 2 weeks after stopping MAOIs before
starting serotonergic drugs or stopping dietary restrictions.
Bupropion - Toxicity: stimulant effects (tachycardia, insomnia), headache, seizures in patients with bulimia and anorexia nervosa. dec risk of sexual
side effects and weight gain compared to other antidepressants.
Mirtazapine - Toxicity: sedation (which may be desirable in depressed patients with insomnia), inc appetite, weight gain (which may be desirable in
underweight patients), dry mouth.
Trazodone - Toxicity: sedation, nausea, priapism, postural hypotension. Think traZZZobone due to sedative and male- specific side effects.
Varenicline - Toxicity: sleep disturbance. Varenicline helps nicotine cravings decline.
Vilazodone - Toxicity: headache, diarrhea, nausea, anticholinergic effects. May cause SEROTONIN SYNDROME if taken with other serotonergic
agents.
Vortioxetine - Toxicity: nausea, sexual dysfunction, sleep disturbances, anticholinergic effects. May cause SEROTONIN SYNDROME if taken with
other serotonergic agents.
Buprenorphine - Sublingual form (partial agonist) used to prevent relapse. Can precipitate withdrawal symptoms when combined with full agonist.