ACID-BASE BALANCE

Targeting and maintain the blood pH ● Gives

hydrogen
pH 7.35-7.45
ions.
Chloride Shift and Bicarbonate ▪ Contains NH2
(Amino Group)
Compensatory mechanism of the body
● Accepts
when pH increases or decreases.
hydrogen
Regulation ions.
● Lungs – carbon dioxide should be o For eliminating hydrogen
controlled (CO2) ions
o Hypoventilate – deep ● Hemoglobin
breathing (slow): increase o Chloride shift – buffered
CO2 with deoxyhemoglobin
o Hyperventilate – shallow o If pH is too acidic
breating (fast) : decrease
CO2 light breating
o PCO2 (partial pressured
CO2) dissolved CO2:
parameter (potentiometry)
● Kidney – bicarbonate (HCO3)
o Bicarbonate cannot be
excreted through urine
● PO2 (hypoxia)

● Inorganic phosphate
Blood buffers o Tubular secretion (acid
● Bicarbonate – most common base balance:
buffering system bicarbonate, phosphate
o H2O+CO2 (end product of and ammonia)
cellular metabolism) o H2PO4+H🡪 Na2H2PO4
🡪H2CO3 (Carbonic (excreted in urine
Acid)🡪 H+HCO3 (H2PO4), Aldosterone
● Plasma proteins reabsorption (Na2)
o Albumin serves as a buffer o Contributed in the acidity
▪ Contains COOH of urine
(Carboxyl Group) o NH3+H🡪 NH4
ACID-BASE BALANCE

Henderson-Hasselback equation o Metabolic kidney (not

specific, but because of
● Expresses the Acid-base
compensatory organ)
relationship
o Respiratory lungs
● pH=pKa+log HCO3/H2CO3
● Full/partial/ uncompensated
(indirect measurement
o Metabolic; lungs
● pH = pKa + log HCO3 / 0.0307 x
compensated- fast partial
pCO2 (Direct measurement)
compensation (12-24
o pH (variable), pKa
hours of partially
(constant 6.1), PCO2
compensation)
(variable)
o Respiratory; kidney
o looking for HCO3
compensate- slow
● pH = pKa + log conjugated base /
completely compensation
weak acid
(3-5 days for complete
compensation)
Metabolic acidosis - kidney
● Lung is compensated
● Low HCO3=pCO2 drops 1-1.3
mmHg/mEq/L (full in HCO3)
● pH is low, Bicarbonate will also
be low
o Kidney will regulate
Parameters: bicarbonate (HCO3)
● DKA (Diabetic Ketoacidosis)
● pH: 7.35-7.45 o Chloride remains normal
● pCO2: 35-45 mmHg o Chloride shift does not
● HCO3: 22-26 mmol/L often occur
● pCO2: 80-100 mmol/L ● Alcoholism
HCO3 (Bicarbonate):H2CO3 (Carbonic o Prone to lactic acidosis
acid) ratio = 20:1 ● Renal failure
o Accumulation of hydrogen
Oxygen saturation – greater than 95% (due to patients cannot
How to interpret Acid-base? urinate properly anymore)
● Diarrhea
● pH
o Bicarbonate is excreted
o <7.35 acidosis
(bicarbonate should not be
o >7.45 alkalosis
excreted)
● Metabolic/ respiratory
o Dehydration will occur
ACID-BASE BALANCE

● Compensatory mechanism: ● Vomiting

hyperventilate (regulated by o Deep breathing will occur
lungs) during vomiting
o Fast & shallow breathing (hypoventilation)
to avoid the accumulation ▪ Increase in carbon
of carbon dioxide dioxide
o Decrease PCO2 ● Compensation: hypoventilate
● Electrolyte imbalance: o Increase PCO2
hyperkalemia (hydrogen ● Electrolyte imbalance:
concentration) and hypokalemia and hypochloremia
hyperchloremia (chloride shift)
M. alk HCO3 pH pCO2
M. acid HCO3 pH pCO2 Met alk high high
low low Uncomp High High Normal
Uncomp Low Low Normal Partial High High High
Partial Low Low Low Fully High Normal High
Fully Low Normal Low ● For every 10/mmol/L of increased
● pCO3 drops 1-1.3 mmHg/mEq/L Bicarbonate (HCO3), pCO2 will
for every 1 mmol/L HCO3 fall increase by 6 mmHg
● Lungs is Fastest to
Respiratory acidosis
compensate (within 24 hours)
but it is only partially ● Kidney will compensate
compensated (abnormal). ● Compensation: retention of
● Kidney is slower to Bicarbonate, excrete acid;
compensate, but it is hydrogen ions in urine (H2PO4,
completely compensated NH4)
o Hydrogen should be
Metabolic alkalosis
excreted
● Lungs will compensate ● Seen in:
● Less HCO3 o COPD (chronic obstruction
● Least effective compensatory pulmonary disease)
mechanism o Myasthenia gravis
o Hypoxia cannot be o CNS disease
avoided. o Drug overdose
▪ Hypoventillaation o Botulism
occur o Stroke
▪ Hyperventilation will o Myxedemia
occur in response o Pneumonia
to hypoventilation.
HCO3 increase 1 mEq/L for each 10
mmHg rise in pCO2
ACID-BASE BALANCE

R. acid HCO3 pH pCO2 ● Uncompensated – all are

low high abnormal, except HCO3 or
Uncomp Normal Low High pCO2.
Partial High Low High ● Fully compensated – all are
Fully high normal high abnormal, except pH
o pH is normal
Respiratory alkalosis ● Partially compensated – all are
abnormal
● Most effective compensatory ● HCO3 and pCO2 must be on the
mechanism same side, except for
● Kidney will compensate uncompensated.
● Compensation: decreased ● Mixed acid base (co-exist the
reabsorption of Bicarbonate metabolic and respiratory)
(HCO3) without excression ● Follow ROME.
● Electrolyte imbalance
● Metabolic acidosis source should Mixed Acid-Base
be checked ● Normal value
● Occurs due to hyperventilation.
o Excretes carbon dioxide pH pCO2 HCO3
(decreases) Low High Low
● Seen in: ● ROME is applicable.
o Severe pain ● Interpreted as mixed acidosis.
o Anxiety Specimen Collection
▪ Brown bag
● 0.05 mL heparin/mL (inside the
o Aspirin overdose
syringe)
o Hepatic cirrhosis
o Prewashing syringe in
o Gram negative sepsis
0.05 mL heparin
o Salicylate
● Method
o Progesterone drugs
o Gasometer
HCO3 falls 2 mEq/L for each 10 mmHg ▪ Van Slyke
fall on pCO3. ▪ Natelson
o Electrode
R. alk HCO3 pH pCO2
high low ▪ pH –
Uncomp Normal High Low potentiometry
Partial Low High Low ● glass
Fully Low Normal Low membrane
● electrodes:
silver-sliver
Golden Rules in Acid-Base Balance: chloride and
calomel
ACID-BASE BALANCE

▪ pO2 – o pO2 decreased

amperometry ● Glycolysis – decreased pH
● Clark (bacterial infection: sepsis)
electrode ● Excess heparin – decreased pH
▪ pCO2 – ● Low temperature – increased pH
potentiometry
Crucial (atrial blood gas)
● Severingha
us electrode Transportation of the sample to
● Sites for collection: the laboratory
o Radial - 45 degrees
o Brachial – nearby basilic
vein
▪ 45-60 degrees
angle
▪ Do not use 90
degrees
o Femoral tap
▪ 90 degrees angle
for collecting
o Heel and skin puncture
(prewarm-40-45C) in infant
using lancet
● Transported in/on ice.
● Should be read less than 20
minutes
● Liquid heparin usage is limited
o May cause dilution
● Salt heparin is advised
(powdered)

REMEMBER:
● Air – avoid ambient air (anaerobic
collection sample)
o pO2 and pH increased;
pCO2 decreased
● Room temperature
o pO2 and pH decreased;
pCO2 increased
● Leukocytosis
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
CALCIUM HOMEOSTASIS o 25-hydroxycholecalciferol
will catalyzed and become
1,
25-dihydroxycholecalcife
rol (calcitriol) Vitamin D3
to the kidney and become
alpha-dehydroxylate
o Calcitriol
▪ Active form of
Vitamin D
▪ Derived from the
intestines
● Referring to the normalization of ▪ Helps to absorb
the calcium. PTH and Calcitonin calcium
hormone. Vitamin D3 ▪ Receptor inside
● Very important, most especially if enterocyte
you want to maintain the level of (intestinal cells)
calcium. ● Intestinal wall has channels
● Vitamin D – already present in specific to calcium.
the skin. (Inactive Vitamin D) ● In the intestine the surface
o Considered as a hormone composed of enterocyte has
for some researchers receptor of Vitamin D and
(steroid hormone) circulation of Calcium happens
o Important in the absorption o Electrolyte imbalance
of calcium decreases cause difficulty
o Considered as steroid to contract
hormone Parathyroid Hormone (PTH)
o Increases the intestinal
absorption of calcium ● Produced by parathyroid gland
▪ To absorption the inside it there is a
Vitamin D in the o Oxyphil
intestine to o Chief cells (one to produce
absorption calcium PTH)
● Inactive Vitamin D ● Also located in the thyroid gland
o UV from sunlight is ● Regulates calcium level
needed for activation ● Oxyphil, chief cells
o 7-dehydrocholesterol will ● Main stimulus: hypocalcemia (low
become cholecalciferol calcium level, regulates by
o Cholecalciferol will be increasing the absorption of
processed in the liver to calcium in the kidneys
become o Decrease calcium the PTH
25-hydroxycholecalciferol increases to regulates
(Calcidiol) ● Targets the bones and kidneys
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
o Bone – osteoclasts (OC) o Increase PO4 excretion
and osteoblasts (OB) o Increase
▪ Osteoclast – bone alpha-hydroxylase.
resorption (destroy
some part of the
bone which is Calcitonin (C-cells)
regulated by the
hormone) ● C-cells is synthesized by the
● Main target parafollicular cells of thyroid
of PTH ● Lowers the calcium level
● Calcium will ● Calcitonin targets the osteoblast
go to the o High calcium in the
circulation circulation and the blood
since will enter in the bone.
stimulate the o Calcitonin should be
calcium increased to lower the
● First to levels of calcium in the
activates bone.
▪ Osteoblast – bone ● Main stimulus: hypercalcemia
formation (high calcium level)
● Will be ● Pentagastrin stimulation Test:
inhibited by helps to diagnose Medullary
PTH to allow thyroid carcinoma MTC
osteoclast to o If the levels of
release Pentagastrin are not
calcium and decreased – positive for
phosphate MTC (>100ng/L)
o Calcium and phosphate o Normal: <10ng/L
are found in the bone.
▪ Phosphate will be
disposed and GONADAL HORMONES
processed in the Male hormones (Testosterone)
kidneys to not
reabsorb and ● For the development of
excreted. secondary characteristics of men
▪ Occurs in DCT ● Increases libido and metabolism
▪ Calcium and ● Preoptic & Arcuate nucleus:
phosphate is not produces gonadotrophin
secreted at the releasing hormone (male and
same time female)
● Effects on kidneys o Anterior Pituitary
o Increase absorption of o Produced by the GRH
calcium.
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
o Has a receptor in ABP to
gonadotropes transfer.
o Gonadotropes will release ● Testes - Paired organs in men
FSH, LH. o Paired ovoid organ
▪ Responsible for o Enclosed by scrotum
regulation and o Responsible for sperm
monitoring sperm production and for steroid
count hormone production
▪ FSH (Follicle (testosterone)
Stimulating o Contains seminiferous
Hormone) targets tubules and Interstitium,
the seminiferous which contain Leydig
tubules. cells.
● Has a ● Seminiferous tubules – ABP
receptor (Androgen Binding Protein)
specific/ o Contains germ cell (sperm
designed for production) and Sertoli
seminiferous cells (development and
tubules. maturation of sperm)
● Will produce o Sex Hormone binding
a new Globulin (SHBG)
protein to o Site for spermatogenesis
transport ● Leydig cells – contains
called ABP cholesterol.
(Androgen o Where the testosterone
binding created
protein) Sex o LH converts the
hormone cholesterol into
binding testosterone.
globulin. ▪ It will be transported
▪ LH (Luteinizing in the seminiferous
Hormone) targets tubules.
the Leydig cells. ● Inhibin – increases sperm (FSH)
● Inside the o Present in both men and
Leydig cell women
(rich in o To inhibit FSH which is
cholesterol responsible for sperm
for synthesis production
of o Increase sperm count:
testosterone) cause motility and food of
Testosterone the sperm (160million
will bind to normal) inhibit the FSH
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
o Increase inhibin and ▪Complete absent of
decrease FSH sperm
● High testosterone – will inhibit o Signs and symptoms:
LH. ▪ Frontal baldness
o Increase testosterone ▪ Poor beard growth
cause infertility ▪ Fewer chest hairs
o Increase testosterone, ▪ Gynecomastia
decrease LH (enlargement of
o Peak – morning (around breast in male)
6-8am)
o Lowest in 12MN ● Testicular Feminization
● Carrier proteins: Syndrome
o Albumin – major carrier o Also known as Androgen
protein (50%) Insensitivity Syndrome
o ABP / SHBG (45%) o 46, XY karyotype
▪ The remaining 5% o X-linked recessive
are free. disorder
o Androgen receptor
Hypergonadotropic (increase FSH and
resistance 🡪high
LH), Hypogonadism (decrease FSH
testosterone blood level
and LH)
o In peripheral tissue,
● Klinefelter’s syndrome testosterone will be
converted by aromatase
into estradiol 🡪results in
feminization (estradiol)
▪ 5-alpha reductase
should convert
testosterone to
have DHT
(Dehydrotestostero
ne)
o Patients have normal
testes & produce normal
amounts of
Mullerian-inhibiting factor
o Also known as XXY or 47, (MIF)/
XXY Anti-Mullerian-inhibiting
o There is an excess factor, therefore, affected
chromosome. individuals do not have
o Most common human sex fallopian tubes, a uterus,
hormone abnormality or a proximal (upper)
o Azoospermia (semen vagina.
analysis) o Mullerian duct (female)
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
o Wolffian duct (male) ▪ Frontal balding
▪ Increase the level of ▪ Muscle weakness
testosterone and ▪ Atrophy
inhibit Mullerian ▪ Dystonia
duct o 20’s to 30’s
o Externally female o Oligozoospermia (small
o Blind vaginas amount of sperm)
o Testes located inside
o Infertile
o Cannot produce nor ingest
male hormones.
o Formerly known as
Testicular Feminization
Syndrome

● Testicular injury and infection

o Mumps
o Varicocele

● Sertoli cell–only syndrome

o Germ cell aplasia
o For production,
development and
o maturation of sperm
● 5-alpha-reductase Deficiency o Lack of germ cells
o Clinical findings:
▪ Small testes
▪ Azoospermia

o
o 5 alpha reductase is
important for hair growth
o Depend on the
temperature
o Testosterone to DHT
o
● Myotonic Dystrophy
Hypergonadotropic Hypogonadism
o Germ cell compartment
failure ● Kallmann’s syndrome
o Signs and Symptoms: ● Hyperprolactinemia
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
● Type 2 DM
● Age
● Pituitary disease
● Opioid use
● Obstructive sleep apnea

● Kallmann’s syndrome o
o Delayed or absent puberty
(baby face)
o Can be present in both
male and women
o Common in men
o Caused by inability to
produce hormones for
sexual maturation
(increase libido and
metabolism)
o Cleft lip
o Treated by hormonal
replacement therapy

o
● Testosterone Replacement
Therapy
o ▪ Parenteral
▪ Transdermal
● Hyperprolactinemia testosterone patch
o Can also be present in therapy
men ▪ Testosterone gel
o Common in women ▪ Testosterone buccal
o Hypogonadism in both pellet
women and men by ▪ Testosterone pellet
suppressing GnRH o Wolffian and Mullerian
secretion and pulsutility, duct
resulting in low levels of ▪ Wolffian – Male
LH and FSH ▪ Mullerian – Female
● Formation of
Mullerian
duct will be
inhibited by
MIF
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
(Mullerian o High HCG will cause
Inhibiting Ectopic pregnancy
Factor) / o In second and third
AMH trimester the HCG will
(Anti-Mulleria decrease and
n Hormone) progesterone and
o Nitric oxide: estrogen (E3) will
neurotransmitter cause increase (peak)
vasodilator, blood flow🡪 ● Increases the progesterone and
blood pressure. Why the estrogen during pregnancy
testes activated o Will peak at second and
third trimester.
Female Hormones
o It will not decline
● Estrogen and progesterone (continuous increase)
hormone (common) ● HCG should peak at the third
● HCG (Human Chorionic trimester.
Gonadotropin) o After the third trimester,
HCG will decline because
the child is already safe
during pregnancy.
● Types:
o Alpha HCG
o Beta HCG – used in
pregnancy
Estrogen and Progesterone works:
● Starts on the pregnancy of the
HCG (Human Chorionic Gonadotropin) mother
● also secreted by pituitary gland, it o Oocytes will stop the
is not just specifically secreted by production and it will
the placenta become mature.
(syncytiotrophoblastic cells) o During the puberty it will
● Stimulates the production of activate and has 4
progesterone daughter cells where one
● During the pregnancy HCG will survive and the other
stimulates the corpus luteum to will undergo atrophy.
produce progesterone (thicken o During the puberty stage
the endometrium where zygote is the women have a
attached: to be conducive to nocturnal and will
stick) decreases in adult age.
o First trimester (crucial part, o Puberty stage changes in
prone for miscarriage) the body because of
hormones.
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
● Early primary follicle, primary ● Will become corpus albicans if
follicle, secondary follicle fertilization will not occur.
● Graafian follicle containing o Atrophic cells
secondary oocytes (ovulation
Menstruation
process): where oocytes move
out. ● Normal cycle – 28 days (+-3)
o The empty site will o Considered up to 45 days
become corpus luteum in some.
where the progesterone ● A hormonal imbalance
will come out. ● It should last from 2-4 days
o It is rich in cholesterol (common), but it may vary.
(precursor of steroid o 3-7 days is also
hormone). considered.
● If no fertilization occur it will ● Myosis will occur
become corpus albicans o All but one (three out of
● When woman reach the maturity four daughter cells) will
ovulation will occur. have atrophy
● Normal days: 28±3 days (2-4 o Only one daughter cell will
days of menstruation). Normal proceed to become
average 11-13 years old. graafian follicle
Endometrium – where Graafian follicle
the eggs will attach.
● During the luteal phase, the
● Found in the releasing of ovum will occur due
uterus to the surge of LH.
o LH is increased during
FSH and LH will
luteal phase
increase during puberty stage to
o Peaked LH releases
develop changes (maturation of ovaries)
progesterone in women
● LH rises nocturnally ● Luteinization will then occur due
● Ovulation will start to occur after to the production of progesterone
puberty by the corpus luteum
Maturation of egg (follicle) The endometrium will shed off
● Primary follicle ● The shed off endometrium will
● Secondary follicle become menstruation.
● Graafian – contains secondary ● The blood from menstruation will
oocyte. appear dark in color due to the
lack of oxygen.
Corpus luteum – produces sex
hormones. (progesterone) Estrogen
● Rich in cholesterol ● Promotes the breast, uterine
gland, and vaginal development.
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
● Helps to smoothen the skin. ● Follicular phase
● Level of estrogen o Estrogen is dominant
● Inhibits vascular smooth muscles o Starts during Day 1 of
● The way the woman thinks menstruation up to the LH
● Maintain the acidity of vagina surge
(Lactobacillus: estrogen will help ▪ LH surge: it
to survive) happens during the
● In menopausal stage, atrophy will ovulation process
occur due to the lack of estrogen ▪ The Graafian follicle
o No maturation release the ovum
● FSH because of the LH
● Responsible for the follicular o Ovulation process:
phase increase estrogen level
o FSH will stimulate to
Progesterone
increase the estrogen
● If your progesterone is low, it is o Estrogen will stimulate the
impossible to become pregnant uterine epithelial cells,
o Ovum needs to be blood vessel growth, and
attached to the the endometrial glands
endometrium development
● Seen in luteal phase o Estrogen prem the
● Induces the secretory activity of different cells before it
endometrial glands peaks the progesterone
o Progesterone it increases ▪ Readies the uterine
the activity of endometrial epithelial cells,
glands blood vessel
● Can make the endometrium growth, and the
become thick cervical mucus endometrial glands
o Meting of ovum and before the arrival of
sperm. The progesterone progesterone
is responsible in plugging o Progesterone will thicken
to avoid the semen went the endometrium to start
out the implantation
● Has a thermogenic effect (during
ovulation and menstration) ● Luteal phase
● Women will feel hot during o Progesterone is dominant
ovulation o Estrogen peaks 1 day
● There is no implantation in before the ovulation to
progesterone become ready for LH
surge
▪ It overlaps
Menstrual cycle o If no implantation will
occur, the progesterone
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
and estrogen will decrease ● Primary amenorrhea
in production o Absence of menstruation
▪ Shedding of ever since puberty
endometrium will o Total absence of
occur menstruation
● Menstruation ● Secondary amenorrhea
o Discontinued menstruation
for years
o Has menstruation before
Oligomenorrhea – irregular
menstruation pattern

● Endometrium
● Myometrium: crams ● May occur after 40 days, 50
● Inside the uterus there is a spiral days, or up to 5 months interval.
arteries (progesterone) which ● Most common abnormalities
there is a blood involved and if ● May cause infertility.
there is no fertilization the ● Sedentary lifestyle will contribute
arteries cut and have a necrosis in menstruation process
and oxidized (indicates the color ● Pheromones: cause if you have
of the menstration) because of menstruation it will also attacks
progesterone. The slapping of the mindset of other female.
endometrium will become the o Responsible for the
menstrual blood. attractiveness
● Menstruation is counted from the Menopausal stage
1st day through the 7th day
● Prostaglandin helps during ● Lacking estrogen levels
menstruation o Shoots up the FSH and LH
o Responsible for the ● Sign and symptoms:
contraction in the o Decreased estrogen
myometrium ▪ Hot flashes
o Dysmenorrhea ▪ Night sweats
o Erratic levels of estrogen
ABNORMALITIES and progesterone
Amenorrhea – absence of menstruation ▪ Irregular periods
CALCIUM HOMEOSTASIS &
GONADAL HORMONES
o Vaginal acidity will o Height in women can
decrease become normal
▪ Vaginal dryness ● Not in sync for bone maturation
o Atrophic vaginalis: no
normal flora
o Hypergonadotropic
(increase FHS and LH),
hypogonadism lack of
estrogen Polycystic Ovary (PCOS)
Signs Common
symptoms
Decreased Hot flashes
estrogen Night sweats
production by the
ovaries
Low levels of Decreased libido
testosterone
Erratic levels of Irregular periods
estrogen and
progesterone ● Cyst in ovary
Low levels of Mood swings ● Hair growth and abnormal
estrogen menstruation
Thinner vaginal Vaginal dryness ● Metformin
walls o normalizes menstruation in
individuals who have
PCOS
Precocious Puberty o increases fertility
● Premature exposure to the ● Estrogen replacement: cannot
puberty grant to correct
● Precautious puberty (check for o High risk cause of breast
bone age) cancer
● Puberty will become advanced ● Menorrhagia
compared to normal.
● Increase GnRH, FSH, LH,
estrogen and progesterone
● Develops breast as early as 4
years old
● Vagina will become mature
● Menstruation will occur in 7-8
years old
● Height will be mostly affected for
men
ELECTROLYTES
● Ions that capable that carries electrical ▪For water retention (kung
charges nasaan si salt andoon si
● Myocardial rhythm and contractility water)
o Cation – positive ▪ ADH are the target
▪ Always migrates towards (Collecting Ducts: which
cathode (-) reabsorbed) cause
▪ Opposite attracts polyuria
o Anion – negative ▪ Aldosterone targets the
▪ Always migrates towards DCT (final concentration
anode (+) happens)
o Aldosterone – secreted by zona
glomerulosa of the adrenal cortex
FUNCTIONS ▪ Kidneys are the target
(Distal Convoluted Tubule)
● For volume and osmotic regulation
▪ The hormone responsible
(Na, K, Cl)
for the reabsorption of
o Renin (RAAS): stimulus that is
salts (Na, Cl)
responsible to react
● Will help stimulate
o Decrease Blood volume and
ADH production
Blood pressure
o Na (Sodium) – main responsible
● For myocardial rhythm and
in regulating osmolality
contractability (K (muscle), Mg (heart),
▪ Osmolality – moles of
Ca (muscle))
solute divided by
o Pumping of the heart depends on
kilograms of solvent
the electrolytes
o A decrease in blood pressure will
o Difficulty of Breathing (decrease
lead the production of renin
potassium)
o The renin is responsible for the
o Sudden tachycardia (due to
production of angiotensinogen
stress which could result to NCA
o Angiotensinogen will produce
(neurocirculatory asthenia))
Angiotensin 1 (adrenal cortex)
o Thyroid, lipids, electrolytes
o Angiotensin 2 is responsible for
o Potassium – myocardial rhythm
the stimulate the release of
o Main ____ of acid-base balance
aldosterone (hormone secreted
(Bicarbonate)
by zona glomerulosa in the
● Neuromuscular excitability (K, Ca
adrenal cortex; reabsorption of
(important in contraction), Mg)
salts) and the development of
o Electrolytes plays vital role in
vasoconstriction
neuromuscular specially
o Vasoconstriction will result in
potassium (major intracellular
normalized the blood pressure
cation/ fluid)
(constrict the vein)
o Exchange of sodium (inside) and
o ADH/ AVP will help regulate
potassium (outside) in neuron
blood pressure
o Saltatory production: leaping of
sodium and potassium
 ELECTROLYTES
o Calcinuria (calcium in urine) Uncompensated Low High Normal
which affect the muscle Partially High High High
movements. compensated
Fully Normal High High
compensated
● Maintenance of Acid-base balance *pCO2: acid HCO3: alkaline
(HCO3, Cl, K)
Metabolic pH pCO2 HCO
Normal blood ph = 7.35 – 7.45 acidosis: 3
Uncompensated Low Normal Low
Partially Low Low Low
compensated
Fully Normal Low Low
compensated

● 7.47 – alkalosis Respiratory pH pCO2 HCO3

alkalosis:
ROME Uncompensated High Low Normal
● Respiratory - Opposite (Lungs) Partially High Low Low
o pCO2 (partial Carbon dioxide) compensated
▪ to acidify Fully Normal Low Lowfinal
compensated
● Metabolic - Equal (Kidney)
o HCO3 (Bicarbonate)
▪ To convert into alkaline o Uncompensated
● pH (7.35-7.45): acidosis <7.35, alkalosis o Partially compensated
>7.45; pCO2 (35-45 mmHg): o Fully compensated
metabolic(metabolism or kidney), ● Cofactors (Mg, Ca, Zn)
respiratory(lungs); HCO3 (22-26 ● Regulates ATPase pump (Mg, P)
mmol/L): regulated by the kidneys ● Production and utilization of ATP from
o kidney will help the HCO3 to be glucose (Mg, PO4)
normal in pH which result to ● Maintenance of Acid-base balance
Metabolic (HCO3, Cl, K)
● Replication of DNA and the translation
Metabolic pH pCO2 HCO3
of RNA
alkalosis:
Metabolic Increa variable increase
alkalosis se
Uncompensated High Normal High
Partially High High High
compensated
Fully Normal High High
compensated

Respiratory pH pCO2 HCO3

acidosis:
ELECTROLYTES

RAAS (Renin-Angiotensin-Aldosterone
System) Distribution:
● ICF (Intra Cellular fluid): inside the cell
o 2/3 of water distribution
o Inside the cell
● ECF: (Extra cellular fluid)
o 1/3
o Intravascular – refers to the
plasma. (inside the vein)
o Interstitial – in between the fluid
(Water) between cells
Transportation
● Active – requires energy so that the ions
can be transferred from outer to inner
cell
● Diffusion (Passive) – does not require
energy,
Water o Diffusion is based on the size of
molecules/ion
● 40-75% of total body weight
o Water is always passive in
● Universal solvent
diffusion
● Dehydrated cell (decrease weight)
● Functions
o Transport nutrients to cells
(Blood)
o Determines cell volume.
o Removes waste products.
(excretion of water through urine
or sweat)
o Coolant
● Absorbed by the large intestine.
Osmolality
● Molality (moles of solute/kg of solvent)
● Sodium main electrolytes
● Physical property that is based on the
concentration of solutes/kg
ELECTROLYTES
● Normal value: 275-295 mOsm/kg (indication of alcohol intoxication or
o Hyperosmolality poisoning) lactate, BHBA
▪ Thirsty – low H2O (Beta-Hydroxybutyric Acid)
(SOLVENT) o BUN, glucose are also
● ADH (increase) osmotically active
▪ Solute is elevated (High ● Importance of osmolal gap is to
sodium) determine alcohol toxication
o Hypoosmolality ● Osmolal gap greater than 10 mOsm/kg
▪ Low diluted solute suggests a diagnosis of alcohol
▪ High kg of solvent poisoning
▪ Low Sodium
● Diabetes insipidus: pure water release
(Specific gravity decrease): cause salt
retention: increase osmolality
● Osmolal gap: differences of computed
and measured osmolality
● Osmometer – used to measure
osmolality
o It has the principle in changes in
SODIUM
colligative properties
● Specimen: serum, urine
● Formula of osmolality based on
computation: (Computed osmolality)
o 2 (Na) + Glucose + BUN (SI)
o 2 (Na)+ BUN/2.8+Glucose/18
o Osmolal Gap = Measured
Osmalality - Plasma osmolality
(Osmolal Gap)
Anti-Diuretic Hormone (ADH) – for water
retention
● It will dilute the sodium in the body
● Released / secreted by the
● Most abundant cation in the ECF (extra
hypothalamus
cellular fluid)
● Stored in posterior pituitary gland
● Determines osmolality
Osmolal Gap ● Regulated by:
o Water intake
● Test for alcohol poisoning
o Excretion of water
● Difference between the measured
o Blood volume status (RAAS)
osmolality (osmometer) and calculated
● Aldosterone – helps for the excretion of
osmolality
salts
● Indirectly indicates presence of
● Normal value: 135-145 mmol/L
osmotically active substances such as
ethanol, methanol, ethylene glycol SODIUM
 ELECTROLYTES
● NV 135-145 mmol/L o Indirect – sample should be
● Sodium and potassium are inversely diluted
proportional Specimen
o Potassium deficiency: decrease ● Serum
main problem ● Plasma
o Hyponatremia: compensate ● Urine
(sodium will help to reabsorb ● Whole Blood
potassium) ● Sweat
o Before sodium analysis has
Hyponatremia: Hypernatremia (>145
specific specimen of choice.
decrease sodium mmol/L)
decrease potassium Hemolyzed specimen
(<135 mmol/L) ● Slightly hemolyzed specimen – not
*Hypoadrenalism *Diabetes Insipidus significantly affect sodium
(hypoaldosteronism) (DI) Methods:
*Potassium *RTA
● FEP (flame emission photometry
deficiency *Prolonged diarrhea
*Diuretic use *Profuse sweating ● ISE (Iron Selective Electrode)
*Ketonuria (presence *Severe burns o Very convenient to use
of ketones in urine) Older persons o Glass membrane for sodium
*Salt-losing Infants with pH
nephropathy Mentally impaired ▪ pH analysis hypernatremia
*Prolonged vomiting Hyperaldosteronism ● AAS
*Severe burns Excess sodium ● Colorimetry - Albanese Lein
*Renal failure bicarbonate ● Common error:
*Nephrotic syndrome Dialysis fluid excess
o Protein build-up on the
*Hepatic cirrhosis
*CHF membrane through continuous
Excess water intake use
SIADH (Syndrome of POTASSIUM
Inappropriate
Anti-Diuretic POTASSIUM
Hormone): opposite of
DI
Pseudohyponatremia
● *Increase loss of sodium
● *For water retention
● *severe loss of water
● Low water intake

SIADH – low ADH

● Major intracellular cation (ICF)
DI – high ADH
● For contraction of muscle
Pseudohyponatremia – sodium should not be
● Neuromuscular excitability
low; high protein and high lipid level in ISE
● ICF volume regulation
● ISE (Ion selective electrode): for o Major intracellular
electrolytes ● Affects hydrogen concentration
o Direct – the sample is undiluted
ELECTROLYTES
o PIG/KIP (potassium insulin Vomitting Diuretics ARF/CRF
glucose): Diarrhea Nephritis Hypoaldosteronism
Regulation: Gastric RTA Addison’s disease
ction Hyperaldosteronism (low cortisol level)
● Renal function
ntestinal Cushing Diuretics
o Potassium depends on sodium, mor syndrome Acidosis (Sodium
sodium depends on aldosterone. Malabsorption (increase of cortisol with water)
● Inhibited ATPase pump – (associated Cancer level which Muscle injury
with hypomagnesemia, hypoxia) digoxin erapy synthesized by the Chemotherapy
o Ever time that potassium goes arge doses zona fasciculata Leukemia
laxatives (biggest part of the Hemolysis
inside one sodium goes outside
cortex which affect Potassium
(ATPase pump/ Na-K pump) GI loss of aldosterone replacement
● Insulin – increases/stimulates the otassium production) therapy
ATPase pump Hypomagnesemia Prolonged
● Catecholamine – promotes the cellular Acute Leukemia tourniquet
entry/uptake of potassium (pump hearts Alkalosis Excessive fist
Insuline overdose clenching
to delivery in the brain) epinephrine,
Decreased intake
norepinephrine Hyperosmolality
● Propranolol – impairs or inhibits cellular
entry of potassium *Renal loss
o Beta blocker (inhibits/ blocks the Hypokalemia
catecholamine); wherein the ● GastroIntestinal loss will lead to
potassium will not enter the cell hypokalemia
o Vomiting
Factors:
o Diarrhea
● Exercise: arm exercise and fist o Large doses of laxatives
clenching is not okay for potassium ● Renal loss
o To avoid hemoconcentrated o Hyperaldosteronism
sample rest for 2 minutes o Cushing syndrome – increased in
● Cellular breakdown (chemotherapy, cortisol level
leukemia) Hyperkalemia
● Hyperosmolality (sodium level is ● Addison’s disease – decreased in
elevated) cortisol level
Hemolyzed samples are not acceptable
Hypokalemia Hyperkalemia
Zona
● Glomerulosa – aldosterone
● Fasciculata – cortisol
o Largest portion of the cortex
● Reticulata – androgen

Drugs
● Diabetes mellitus – low levels of
insulin, metabolic acidosis
● Captopril – inhibits ACE (important in
the conversion of angio 1 to angio 2)
ELECTROLYTES
● Non-steroidal anti-inflammatory agents ● Blood volume
– inhibits aldosterone. ● Electro-neutrality : limits the
● Spironolactone – potassium sparing reabsorption of sodium
diuretic. ● Almost completely absorbed by the
● Digoxin – inhibits ATPase pump Gastrointestinal tract
● Cyclosporine – inhibits renal response ● Possibly reabsorbed by the Proximal
to aldosterone Convoluted Tubule (PCT)
● Heparin therapy – inhibit aldosterone o Due to sodium, aldosterone
secretion o But the chloride will limit the
Normal value of potassium: 3.5 – 5.0 mmol/L reabsorption of sodium
Methods for potassium: o Excessive sweating (stimulates
● FEP the production of aldosterone):
● ISE (Iron Selective Electrode) Sodium and chloride
o Very convenient to use ● Functions:
o Valinomycin gel: potassium o Maintains osmolality.
● AAS o Activator of enzymes
● Colorimetry – Lockhead and Purcell o Regulates Blood volume (RAAS)
● KCl: emersion of electrodes o Electro-neutrality
● Specimen: serum, plasma, urine, ▪ Limits the reabsorption of
heparin sodium, HCO3
o Most ideal/best specimen/sample ▪ Sodium exits, potassium
for electrolytes is heparinized enters
plasma ▪ Chloride shift – water and
o Most commonly used is serum. carbon dioxide will
● NV for potassium: 3.5-5.0 mmol/L become carbonic acid
● Increase potassium: decrease muscle ▪ Bicarbonate: buffering
excitability system
● Decrease potassium: increase ● Ones the
excitability bicarbonate
● Resting membrane potential is higher releases outside,
than action potential Chloride will be take
o Result in lactate acidosis place

CHLORIDE (Sodium and Chloride relationship

directly proportional) ● Specimen:
o Excreted in Urine, serum, plasma
● Major extracellular anion
(heparinized plasma), white blood
● Maintains osmolality
cells, sweat
● Activator
ELECTROLYTES
o Sweat chloride is elevated – for ● Probe is
cystic fibrosis (high chloride in the necessary to use
sweat)
o Method of collection (Sweat) –
Pilocarpine Iontophoresis (role
out cystic fibrosis)
● Excessive sweating – aldosterone
levels will increase (due to water that is
excreted)
● Normal value of Chloride: 98-107
mmol/L CF: 1mEq/L
● Methods
o Mercuric Titration (Principle) MAGNESIUM
(Schales and Schales)
▪ Indicator: ● Second most abundant cation in ICF
diphenylcarbazone ● Dependent on our diet
▪ End Product: Mercury ● Serves as a co-factor in Enzymes
chloride ● Secreted by kidney (Magnesium
o Spectrophotometric ammonium phosphate: crystal)
▪ Mercuric Thiocyanate ● Has something to do with myocardial
(indicator) (Whitehorn rhythm.
Titration Method) o Imbalance in magnesium
▪ Ferric perchlorate (end o Source of magnesium: nuts
product) vegetables, fruits, fish
o Coulometric Amperometric ● Forms:
(principle) o Ionized (55%) – free forms of
▪ Cotlove Chloridometer specific analyte.
(for sodium) o Bound (30%) – with albumin.
o ISE (Ion Selective Electrode) o Complex with ions (15%): bind
▪ One analyzer (Na, K, Ca, with citrate, phosphate
pH or Na, K, Cl, pH) ● Factors affecting Magnesium levels:
▪ Tri-N-octylprpylammoniu o PTH (Parathyroid Hormone)
m chloride decanol* ▪ Secreted by the
▪ Calcium and chloride parathyroid gland
should be separated in Ion ▪ Increase of Renal
selective electrode (will abruption and GI
result in build-up / absorption
precipitation of salts and ▪ Regulates (elevates) the
inaccuracy of the results) calcium level through bone
▪ Calcium and Chloride: resorption (increasing the
precipitation happens calcium)
▪ To prevent precipitation, it ● High PTH- high
must have washer calcium
(solvent) ● Decrease calcium,
PTH must
ELECTROLYTES
increases goes o 46% in the muscle and other
through the organs
circulation (calcium) o <1% in the serum
o PO4 and Mg
goes in
kidney and
excreted by
urine
● Calcitonin will also
increase
● Calcitonin helps to
lower the calcium.
o Secreted by ● Hyperparathyroidism: high PTH
the o Parathyroid glands are found in
parafollicular typhoid
cells of the ● Bone (Ca, PO4, Mg):
thyroid gland ● Bone cancer and Bone metastases
▪ May increase the ● Methods:
reabsorption of o ISE
magnesium in the o AAS
gastrointestinal tract o Dye-Lake-Titan yellow dye
▪ increase the reabsorption (Clayton yellow / Thiazole yellow
in the kidneys o Colorimetric
o Aldosterone: inhibits the ▪ Calmagite
absorption in magnesium ▪ Formazan
o T4 (Thyroxine) ▪ Methyl thymol blue /
▪ Secreted by the follicular Magnesium thymol blue
cells of the thyroid gland ● Specimen: best specimen:
▪ Lowers the absorption of heparinized plasma (inhibit the thrombin
the magnesium activity)
● Normal value of Magnesium: 0.63-1.0 o Usual specimen serum
mmol/L CALCIUM
o Conversion factor Convert to
● 99% is found in the bone; 1% in
mEq/L = mmol/L / 0.5
circulation
● 50-60% of magnesium is reabsorbed in
● Coagulation
the Ascending loop of Henle (ALH)
● Enzyme activity
● Renal threshold for magnesium:
● Excitability of muscle – for contraction
0.60-0.85 mmol/L
● Maintains Blood pressure
o Magnesium is filtered by
● Regulated by:
glomerulus to regulate
o PTH
myocardial rhythm
▪ PTH is connected by
● Distribution of Magnesium:
Vitamin D
o 53% in the bone (highest
▪ Stimulates the Vitamin D
percentage)
production by the kidneys
ELECTROLYTES
o Vitamin D ▪ Magnesium inhibitor: 8
▪ Increases the absorption hydroxyquinoline
of calcium ▪ Dye used in
▪ GI absorption Ortho-Cresolphthalein
o Calcitonin complexone (Calcium):
▪ Produced by parafollicular Arsenzo III
cells produced by thyroid o Precipitation and Redox Titration
to lower the calcium level ▪ Clark Collip Precipitaion:
▪ If calcium is low, calcitonin ● End product:
should also be low, and Oxalic acid
PTH will increase. ▪ Ferro Ham Chloranilic
● Hypocalcemia (increase PTH, decrease Acid Precipitation:
Calcitonin): ones to normalized ● End product:
decrease PTH to be equal Chloranilic acid
● Normal value of Calcium: 2.15-2.50 o Specimen ideal for electrolytes –
mmol/L Heparinized plasma
o Convert to mEq/L = mmol/L / 0.5 ▪ Anti-thrombin activity,
● Forms: (common to ask) rather than binding with
o Ionized – 45% (50% in some calcium
sources) o Most common specimen in
▪ Free calcium electrolytes – serum
▪ Low ionized calcium –
Diseases associated with calcium
impairs myocardial/
cardiac function
● Thyroid function:
FT3, FT4, TSH,
Ionized calcium
(regulated by
thyroid and
calcitonin): Primary to Renal, Multiple myeloma, hyper
hyperthyroidism (note high light)
(tachycardia)
▪ Collection should be PHOSPHOROUS
anaerobic ● 80% (majority) of the phosphorus in the
o Bound – 40% bones
o Complex – 15% ● Majority are in the bone (phosphate)
● Methods: ● Predominant intracellular anion
o EDTA titration (Bachra, Dawer, ● Absorption occurs in the intestine
Sobel) ● Regulated by:
o ISE o Vitamin D
o AAS o Calcitonin (control)
o FEP o Growth hormone (increases the
o Ortho-Cresolphthalein absorption of phosphorus)
Complexone o PTH (regulates the calcium)
ELECTROLYTES
● Most phosphate in serum is in organic o Lactic acidosis
form o Hypernatremia
● High calcium, increase calcitonin to o Instrument error
lower ● Low anion gap (Very rare)
● Calcitonin: main purpose is to move the o Hypoalbuminemia
calcium inside the bone o Severe hypercalcemia
o Calcinuria: increase calcium
Malabsoprtion: fecalysis, Electrolytes
● Forms:
Na decrease
o Free (Ionized) – 55%
K decrease
o Complexed – 35%
Ca decrease
o Protein-bound – 10%
TP slightly decreases
● Method:
Albumin
o Fiske-Subbarow – read at
600-700nm (Colorimetric)
▪ End product: Molybdenum
blue
Glucose increase
● Normal value of Phosphorous: 0.87-1.45 Cholesterol decrease
mmol/L Magnesium decrease
o Conversion factor in mEq/L: Calcium increase
0.3229 T3 increase
T4 increase
TSH decrease
Diagnosis Grave’s Disease

*GI Inflammatory, anorexia, alcoholism

[A/G is Albumin to Globulin ratio]
Anion Gap (AG)
● Difference between the unmeasured
anions and unmeasured cations
● Depends on the given.
o AG = Na – (Cl + HCO3)
▪ Normal value: 7-16
mmol/L
o AG = (Na + K) – (Cl + HCO3)
▪ Normal value: 10-20
mmol/L
● High anion gap
o Uremia
o Ketoacidosis
o Salicylate poisoning
CLINICAL CHEMISTRY 2
COMPILED TRANSES
§ Stimulate ACTH
production if
positive
o ACTH – produced by
Anterior Pituitary
§ Stimulate ACTH
production if
positive
o Cortisol – produced by the
adrenal gland
§ Decreased cortisol
if positive feedback
mechanism
• Negative feedback
o Increased cortisol if
negative (due to stress)
o Decreased / absence of
ACTH production due to
CRH
o Inhibits the hypothalamus
to secrete CRH
• The study of hormones (decreased)
o Hormones - the o More common compared
biochemical messengers to positive feedback due to
of the body its ability to control and
§ Secreted by regulate the
ductless glands. mechanism/secretion
§ Blood is very
important for Classification
transportation of • Amines – the simplest form of
hormones to distant hormones
glands o PIF (prolactin inhibiting
Feedback Mechanism hormone)
o T3, T4
TRH (hypothalamic hormone) -> TSH o Serotonin
(anterior pituitary) -> T3, T4 (thyroid) o Melatonin
- If T3, T4 is normal = TRH & TSH o Catecholamine
shutdown (negative feedback o Epinephrine
mechanism) o Norepinephrine
• Peptides/Proteins
• Positive feedback o Glycoproteins
o CRH – produced by the § FSH
hypothalamus. § TSH
CLINICAL CHEMISTRY 2
COMPILED TRANSES
§ HCG From Anterior pituitary
§ EPO Hormone Stimulate To Target
§ LH produce Organ
o Polypeptides – many CRH Corticotropes ACTH Adrenal
peptide chains gland
§ Oxytocin TRH Thyrotropes TSH Thyroid
§ ADH gland
§ ACTH GnRH Gonadotropes FSH, LH Gonads
§ CRH (Ovary,
§ GHRH Testes)
§ GH GHRH Somatotropes GH Bone
§ Prolactin PIF - Lactotropes PRL Mammary
§ GNRH (inhibits gland
§ MSH prolactin) (Breast)
§ VIP o Estrogen isoforms:
§ Gastrin § E1 (Estrone) - Most
§ Secretin predominant
§ Cholecystokinin isoform of estrogen
§ HPL among
§ Calcitonin postmenopausal
§ PTH women
§ Insulin § E2 (Estradiol) -
§ Somatostatin Most predominant
§ Glucagon isoform of estrogen
§ TRH among
§ And many more… premenopausal
women
• Steroids
§ Most potent (active)
o Aldosterone
form of estrogen
o Cortisol
§ E3 (Estriol) - Most
o Estrogen
predominant
o Progesterone
isoform of estrogen
o Testosterone
among pregnant
HYPOTHALAMUS woman
• Testes
o Testosterone – for libido
GnRH -> FSH, LH -> Gonads -> and secondary
characteristic of men
• Ovary (voice, shoulder, body
o Progesterone – regulates mass)
menstrual cycle
o Estrogen – for secondary GHRH -> GH -> Bone ->
characteristic of women
• Cannot secrete hormone
(hips, breast, sex, libido)
CLINICAL CHEMISTRY 2
COMPILED TRANSES
• Cannot store hormone § Epinephrine – most
• Receives hormone (GH) potent
• Fight or flight
CRH -> ACTH -> Adrenal
response/hor
gland/suprarenal glands ->
mone
• Adrenal Cortex (adrenaline)
o Zona glomerulosa (G • Coffee can
zone) boost
§ Outer most layer epinephrine.
§ Synthesize § Norepinephrine
mineralocorticoid • Increases
(salt) blood
• Aldosterone pressure.
– most TRH -> TSH -> Thryroid gland
potent
(active) Principal cells:
• Aldosterone
• Follicular cells – secretes t3, t4
is for the
o T3, and T4 is for brain
reabsorption
development (developing
of salts
fetus)
o Zona fasciculata (F zone)
o If not = mental retardation
§ Middle layer
o Increases metabolism
§ Thickest later
because It is important in
§ Secretes
different metabolic
glucocorticoids.
processes
• Cortisol –
• Parafollicular cells – secretes
most potent
calcitonin
• For
o Calcitonin – lowers
metabolism
calcium level
of lipids,
proteins & PIF -> inhibits PRL -> Mammary
carbohydrate gland/breast
s
• To maintain lactation process
o Zona reticularis
§ Innermost layer From posterior pituitary
§ Produces Hormone
androgens. Oxytocin
• Testosterone ADH
– most
potent
Oxytocin – contraction of gravid uterus
• Medulla
o Synthesize catecholamine. • Known as the love hormone.
CLINICAL CHEMISTRY 2
COMPILED TRANSES
• Oxytocin level will rise due to o Relays information within
feeling of love. the cell
• The adenylyl cyclase enzyme
ADH – water retention
will be activated
Other hormones • Requires ATP (adenosine
triphosphate) in this reaction
• Pancreatic hormones
• There will be an activation of
o Glucagon – secreted by
CAMP (Cyclic Adenosine
alpha cells of the islets of
Monophosphate)
Langerhans.
o Serves as the second
§ Hyperglycemic
messenger.
agent
• CAMP is activated if the first
o Insulin – secreted by beta
messenger binds to the hormone
cells of the islets of
• Carrier protein is not required
Langerhans.
except for some
§ Hypoglycemic agent
o Somatostatin – secreted • It will create a new protein after
by delta cells of the islets all of the reaction occurs
of Langerhans. • Not all non-steroid hormones has
§ Also produced by this mechanism (it may vary)
the hypothalamus Steroid
• Parathyroid hormones –
regulates calcium levels (which is • Precursor - cholesterol
then regulated by calcitonin) o Does not repel to protein
• Melatonin so It needs a carrier
o Secreted by pineal gland protein
o Responsible for biological • Protein is required.
clock • It has a receptor inside the
o Also known as the third nucleus
eye • There will be a reaction in the
o Increases If dark cytoplasm or directly inside the
nucleus
Other note: If glucose is increased – o Synthesis of protein occurs
insulin will compensate here (But non-steroid can
MECHANISMS OF HORMONES do this too)
• There is no need for a mediator,
Non-steroid unlike non-steroidal
• (amine, glycoprotein, polypeptide) • It will create a new protein after
• Requires first messenger – binds the reaction occurs
in G-protein receptor. • Not all steroid hormones has this
• In the cell membrane, there is a mechanism (it may vary)
receptor (G-protein receptor)
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o Bone and breast do not
secrete hormones, thus
making them exocrine
organs

Pituitary gland – the master gland

• Controls the different endocrine
glands
• Also known as hypophysis
(“lying under” glands position on
the underside of the brain)
o Adenohypophysis –
anterior pituitary Oxytocin
o Neurohypophysis –
• Main mechanism is
posterior pituitary
to contract
Anterior Pituitary Principal cells • Fergusson reflex
Hormones o It the stretching
GH Somatotropes of the cervix,
PRL Lactotropes uterus, and
ACTH Corticotropes vagina during
FSH, LH Gonadotropes labor
TSH Thyrotropes (increased
oxytocin)
Anterior pituitary groups: o Neuroendocrine reflex
o Positive feedback
• Tropic hormones • A love hormone
o Target organ – endocrine • Intimacy
gland • Important in the contraction of
o ACTH gravid uterus
o FSH, LH • Target of oxytocin is the
o TSH myometrium
• Myometrium - a muscular layer
• Direct effector found in the uterus and will
o Target organ – non- stimulate prostaglandin
endocrine gland o Prostaglandin contracts
o GH the smooth muscles in the
o PRL cervix.
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o Induces pain (especially • Cervix needs to be relaxed;
during labor) therefore oxytocin levels will
• There is a hemostasis (to avoid decrease.
bleeding) o Oxytocin will increase
• Myoepithelial cells of again due to milk letdown.
mammary gland/breast – • Oxytocin is also present in men,
another target of oxytocin but it is more prominent in
o For milk ejection women. (the reason why women
o Milk letdown reflex are more emotional/empathetic)
o Breast crawl o Men will produce oxytocin
• Oxytocin secretion will burst once during sexual activity and
you hear the baby cry. ejaculation process.
• Stress will inhibit the secretion of o Prostaglandin is
the oxytocin. responsible for stimulating
o Therefore, there will be no ejaculation. (vas deferens)
milk ejection from the • Hypersecretion of oxytocin
mother and the breast will o Not common
harden o It is common if we use
o Increased cortisol will Pitocin.
decrease oxytocin, vice § Pitocin is a
versa. synthetic oxytocin,
o Stress can be passed on a which is induced in
baby when breastfeeding women who lacks
(autism) (autism may also oxytocin. Can be
be from vaccination) used for better
• Has a half-life of 3-5 minutes. delivery/labor
o Because of the rapid
Mechanism of oxytocin
degradation
§ Because of the • From the hypothalamus, the PVN
enzyme (paraventricular nucleus) will
oxytocinase – produce oxytocin
degrades oxytocin. • It will be then stored
§ Important in labor in the posterior
• Contraction occurs due to pituitary gland
calcium. (faster release of
o Therefore, high calcium oxytocin If
levels result in high stored)
contraction.
Other note: Postpartum syndrome
o Helps the prostaglandin for
contraction (in labor) • Moodswings after birth
o PTH and other hormones • Prolactin is mainly the problem
also helps in this • Make sure there is no
mechanism. hemorrhage
CLINICAL CHEMISTRY 2
COMPILED TRANSES
• Increase anterior pituitary • 1-2% increase in osmolality will
• Has an effect on oxytocin increase the ADH secretion
because they are connected (involved in RAAS)
o Normal osmolality: 275-
ADH (Anti-Diuretic Hormone)
295 mOsm/kg
• Also known as Vasopressin or o It will dilute sodium to also
Arginine Vasopressin maintain blood pressure.
• For water retention • 5-10% decrease in blood volume
• Produced by the will increase the ADH secretion
hypothalamus, (involved in RAAS)
specifically the • Nicotine stimulates the release of
Supraoptic ADH.
nucleus. o Water retention is present.
• Stored in the • Alcohol (beer) will lower the ADH.
Posterior pituitary gland after the • Diabetes Insipidus – lacks ADH
supraoptic nucleus is stimulated. in general. (but DI with normal
• Maintains osmotic homeostasis ADH is also possible)
(sodium & H20 needs ADH to o True DI/Neurogenic – ADH
regulate) is totally absent or has a
• It is a potent/active pressor that low secretion.
results vasoconstriction. § The synthetization
o Where the “vasopressin” is defective.
comes from o Nephrogenic DI – normal
• Target – kidney (collecting duct) ADH
• Stimulates the secretion of ACTH § There is a
(high ACTH) resistance of ADH
o cortisol will also be in the kidney,
increased from cortex results in polyuria.
(adrenal gland) § Kidney is the target
o cortisol is osmotically of ADH
active -> increases • SIADH (Syndrome of
glucose Inappropriate Antidiuretic
o aldosterone will also be Hormone) – there is an excess
increased. ADH.
• The thirst will stimulate ADH o Edema
secretion o Increased blood pressure
o Thirst is also involved in o Electrolyte imbalance
RAAS and osmolality. o Euvolemic – normal blood
• Hypovolemia (low blood volume) volume (non-measurable)
will increase ADH secretion. o Hypo osmolarity – water
retention and salts are
diluted.
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o Hyperosmolar urine – high • For maintaining the lactation
solute in urine process
o Hyponatremia • Produced by
• Tests: the anterior
o ADH stimulation pituitary
§ Also known as • Arcuate
Water deprivation nucleus
test – the preferred produces PIH(prolactin inhibiting
test hormone)/PIF(prolactin inhibiting
§ Requires 12 hours factor)/dopamine
Non per orem • Major inhibitor: dopamine (PIF,
(NPO) fasting. PIH)
§ Requires o Inhibits the lactotrophs
administering 1 • PVN from hypothalamus will
microgram of release TRH and will stimulate
desmopressin. lactotrophs to produce prolactin
§ Desmopressin • Estrogen – if estrogen is
stimulates ADH increase, it will also stimulate
production. lactotroph but it will inhibit
o Overnight Water Retention dopamine/PIF/PIH (positive
test feedback)
§ Urine output is • Breastfeeding – positive for
observed. lactotroph
§ Fasting 10pm (8-10 • 3 to 4 hours after the individual
hours) has awakened.
• Peak: 4:00-8:00am / 8:00-
10:00pm
• Half-life of prolactin is 26-47
minutes.
• Circadian rhythm/fashion
o 24-hour interval
o Highest during sleep
o Ideal for breast feeding
o Lowest levels of prolactin
occur at 10am and noon.
Prolactin (PRL) • Pulsatile fashion
o Burst-like secretion of
prolactin.
o Pregnancy
o Exercise
o Healthy stressor/eustress
CLINICAL CHEMISTRY 2
COMPILED TRANSES
§ Normal/beneficial o May be abnormal/irregulat
stress menstruation (other factors
§ Prefix –eu means may effect this too such as
“normal” prostaglandin, FSH, LH,
genetics)
Other note: Spotting
• Fertilized egg attached to the
lining of uterus
• May also be a sign of miscarriage
Impregnation bleeding – color
orange/brown

• Prolactin inhibits GnRH Growth Hormone (GH)

o FSH, LH will decrease if
prolactin is high.
• GnRH stimulates the release of
gonadotropin:
o FSH – for ovulation (that’s
why women who gave
birth doesn’t ovulate
immediately) and sperm
formation
o LH
o Other note: other factor
affects this (such as B- • It is inhibited by somatostatin.
HCG) o Released / synthesized by
• Normal value of Prolactin (in the pancreas (targets only
gut) and hypothalamus.
Women): 1-2 ng/mL
o Paraventricular nucleus
o Low prolactin level
§ Pituitary necrosis and Arcuate nucleus can
§ Menstrual disorder also produce somatostatin
§ Infertile (targets GH)
o High prolactin level o Somatostatin that is
§ Infertile produced from the
§ Sexual dysfunction hypothalamus inhibits GH
§ Amenorrhea and TSH (targets glucose)
o Somatostatin that is
• decreased
produced from the
libido
pancreas inhibits the gut
§ Impotent
• Also known as somatotropin
• Increased prolactin
• Pulsatile fashion (increases in):
o Infertility
o Onset – puberty age
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o During sleep specially § It will stimulate the
dreaming Growth Hormone
o 2-3 hours of sleep and GHRH
• Metabolize fat stored. production
• Increases level of glucose § Pulsatile rhyhm
• Hypothalamus -> Arcuate o Increased ghrelin =
nucleus – secretes GHRH decrease glucose
o Targets somatotrophs and • Leptin – fat controller
releases growth hormone o Hormone that makes you
and binds to GH receptor satisfied (whether if you’re
§ Has receptors found full or not)
on liver o Controls the craving
(hepatocyte) o Antagonizes the Ghrelin
o GHRH secretes o Synergistic effect with
somatostatin too CCK (but leptin can stand
o Stimulants: alone too)
§ Increased amino
Other note: There are a lot of happy
acid
hormone but It is mostly endorphine
§ Increased GH
§ Increased IgF-1 TARGET
§ Exercise (for IGF-1 Growth Hormone
metabolism) (synchronous)
§ Healthy stressors Muscle – to Liver – for IGF-1
§ Decrease glucose increase amino synthesis and
§ Decrease fatty acid acids and protein gluconeogenesis
synthesis
• Liver plays a significant role
(specially skeletal
o Growth hormone is
muscle)
responsible for the Bone Adipose –
synthesis of new protein possible lipolysis
(IgF-1) which will then
§ Insulin-like Growth result in
Factor gluconeogenesis
(Somatomedin C) Cartillage – Muscle – to
§ If increased = responsible for increase amino
inhibits somatotrope the elongation of acids and protein
from releasing GH bone synthesis (this is
• Increases the level of IgF-1 why the creatinine
level of children to
• Ghrelin – hunger hormone
old age is
o Responsible for hunger
different)
o It binds with the Growth
• These are responsible for the
Hormone receptor
growth and development of an
(happens in liver)
individual
CLINICAL CHEMISTRY 2
COMPILED TRANSES
closure of epiphysis
of the bone.
Disorders
o Acromegaly
• Low growth hormones § Adult onset
o Dwarfism § Normal growth in
§ Either idiopathic newborn
• Most § There is coarsening
common of the facial
among features. (wider
children than usual) as an
§ Or due to pituitary individual ages in
adenoma time.
• Common § Change in width of
among adults bone
§ “Little people” is no o Oral Glucose Tolerance
longer used as the Test (OGTT) – standard
term method for acromegaly
§ Decreases § Confirmatory test
metabolism for the presence of
o Insulin tolerance test IGF-1
(ITT) is the gold standard § <1 ng/mL
method for diagnosing low § Not the same with
growth hormone levels. the setup for OGTT
o Insulin-like Growth Factor of diabetes
(IGF) – not preferred. § OGTT for growth
o Exercise test – particular in hormones, blood
children will be extracted
o Gold standard/tests: every 30 minutes
§ Insulin within 2 hours
tolerance/arginine • It is observed
stimulation to be low
§ Exercise test § If glucose fails to
• High growth hormones become lower, it is
o Giantism / Gigantism positive for
§ A juvenile onset acromegaly
(prominent in FBS
children) DM Acromegaly
§ Abnormal growth 30 min 30 min
such as tallness 1hr 1hr
§ Increased length 2hr 1hr 30min
§ Enlarged organ 3hr 2hr
§ A condition that • Positive for DI If the results are
develops before the decreasing
CLINICAL CHEMISTRY 2
COMPILED TRANSES
• Normal: <1ng/mL o Thyroglobulin – new
protein that is synthesized
from the follicular cells.
§ A chain that is filled
with tyrosine amino
acid.
§ Exits in the colloid
(glue-like structure)
§ Binds to the iodine
after it is converted
from iodide.
• In blood, iodide and electrolytes
Thyroid Gland (sodium) is present for thyroid
hormone synthesis
• PVN -> TRH -> thyrotropes -> o Iodide is negatively
TSH -> Thyroid gland -> T3 & T4 charged.
• Very important for the brain § Needs to enter the
development follicular cell to
• Increases B1 receptors produce T3 and T4
• Increases the basal metabolic o Sodium
rate. § NIS (Na Iodide
• Increases metabolism Symporter)
(glycogenesis, lipolysis, protein § Goes along with
synthesis, gluconeogenesis) Iodide in entering
• Lowers lipid (cholesterol, follicular cells
triglycerides) • A form of 2nd
• Thyroid follicle active
o Simple cuboidal epithelial transportatio
tissues n
o Made up of principal • Pendrin – needed to pump iodide
cells: from follicular cells to the lumen
o Parafollicular cells • Thyroid peroxidase (TPO) –
surrounds the thyroid important for the oxidation of
follicle. iodide
§ Secretes calcitonin o Responsible for the
o Follicular cell. conversion of iodide to
§ Synthesizes the T3 iodine (I2) that binds
and T4. tyrosine
• PVN stimulates thyrotropes to
release TSH.
o TSH has a receptor from
the thyroid / follicular cell
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o MIT + DIT = T3
§ Triiodothyronine
o DIT + DIT = T4
§ Tetraiodothyronine /
thyroxine
o T3 & T4 will then go to the
blood vessel
T4 vs T3
• 100% of T4 comes from the
thyroid
• T4 can become T3
o Due to 5’deiodinase (or
5’monodeiodinase)
enzyme converts T4 to T3.
o Non-thyroidal T3
o Known as the Reverse T3
(rT3)
• T3 can be derived from T4 (80%)
or from the thyroid (20%)
• Approximately 110 nmol of T4 is
produced daily.
• 10 nmol of T3 is produced daily
Carrier proteins of Thyroid gland
• Amine
o A Non-steroid hormone
(does not need carrier
protein, an exception)
o It acts like a steroid
hormone.
• 2 iodine + 1 tyrosine = • TBG (Thyroxine binding globulin)
Diiodotyrosine (DIT) o 70% of T4 is bound to
• 1 iodine + 1 tyrosine = TBG
Monoiodotyrosine (MIT) o Most important protein
• Endocytosis will occur in the carrier
follicular cell after binding of • TBPA (Transthyretin binding
tyrosine & iodine prealbumin)
• Lysosomal enzymes (for o 20% of T4 is bound to
digestion, metabolism, “suicide TBPA.
bag”) – cuts the thyroglobin inside • Albumin
the follicular cell, which results in
T3 and T4 outcome
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o 10% of T4 is bound to • Can cause
Albumin. hyperthyroidi
sm.
Pathophysiology of Thyroid Gland
• Increases
• Hyperthyroidism (Increased T3, iodine,
T4) therefore T3
o Grave’s disease (diffuse and T4 will
thyrotoxicosis) accumulate
§ Aka Toxic diffused in
goiter thyroglobulin.
§ It is an autoimmune § Destroys organ
disorder. o Toxic multinodular
• Due to the adenoma
presence of § Increased radio
autoantibody. iodine uptake
§ It has an (RAIU)
autoantibody of • Used only in
TSH hyperthyroidi
immunoglobulin sm.
antibody and TSH § Presence of lumps
receptor antibody. in the thyroid
§ A form of primary § FNAB (fine needle
hyperthyroidism (1’ aspiration biopsy) –
hyperthyroidism) to know If malignant
or benign
o Exophthalmos

§Neck is elongated.
§Eyes are bulging.
o Toxic adenoma §Immunoglobulin
o The use of amiodarone deposits/stored on
§ An anti-arrhythmic eye socket
drug § Push eyeball
o Tremors
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o Rapid weight loss o Amiodarone intake –
destroys organ
o Cretinism
§ Congenital
hypothyroidism
§ Has severe mental
retardation.
§ Has a dwarf
appearance.
o Myxedema – severely
Other note: hyperthyroidism = increased advance hypothyroidism
sweat, increased glucose, decrease § Gain in weight
lipid, decrease TAG (the reason why
Other note:
lipid, glucose etc are included in thyroid
profile) • Hypothyroidism – decrease
sweat, bilog mukha
• Hypothyroidism • Pregnant – increase thyroid for
o Hashimoto’s thyroiditis the development of baby
• Seafood is high in iodine
• Goitrogen – any root crops is bad
for hyperthyroidism
Treatment
• Hyperthyroidism
o Propythiouracil /
methimasole
§ Inhibits the coupling
§A Primary of monoiodotyrosine
hypothyroidism and diiodotyrosine
§ Autoimmune (T3, T4)
disorder o Propranolol
§ Autoimmune § No direct action for
antibody present is T3, T4 production
TPO antibody and § Treatment for
Thyroglobulin tachycardia &
antibody. palpitation
o Surgery § Affect the glucose
o Lithium intake of the patient (beta-
§ A medication for blocker)
bipolar patients § This may also be
(monitoring too) used for treatment
§ Can cause of AMI
hypothyroidism. o Radio ablation Therapy
CLINICAL CHEMISTRY 2
COMPILED TRANSES
§ Destroys the TSH T3, T4
hypersecretion Tertiary Decreased Decreased
tissue (Hypothalamus) (increases
§ Patient is exposed in TRH
to radioactive stimulation)
material Secondary Decreased Decreased
o Levothyroxine (anterior (remains
§ Maintenance after Pituitary) low in TRH
stimulation)
surgery (post-
Primary Increased Decreased
surgery) (thyroid)
§ If not taken = there
may be a problem
in the heart
(glucose)
• Hypothyroidism
o Thyroxine / Levothyroxine
o Fine needle aspiration
biopsy

TRH stimulation test • Primary hyperthyroidism

• Commonly used in hypothyroid hypothyroidism – problem in
target organ thyroid that releases
• Can be used to differentiate
T3, T4
hyperthyroid from hypothyroid.
o stimulates the • Secondary hyperthyroidism
hypothalamus. hypothyroidism – problem in
target organ anterior pituitary that
• The stimulation reflects in TSH.
releases TSH
• Only for secondary and tertiary
• Tertiary hyperthyroidism
hypothyroidism differentiation
hypothyroidism – problem in
• Not a direct measurement
target organ hypothalamus that
Hyperthyroid: releases TRH
TSH T3, T4 ACTH
Tertiary Increased Increased
(Hypothalamus) • The
Secondary Increased Increased hypothalamus
(anterior has a
Pituitary) paraventricular
Primary Decreased Increased nucleus which
(thyroid) has a receptor
to the anterior
pituitary.
Hypothyroid:
CLINICAL CHEMISTRY 2
COMPILED TRANSES
• The receptor is bound to § DHEA will be
corticotropes. sulfated (sulfate will
• CRH binds to the receptors. attach to the DHEA)
• Will create ACTH • DHFA sulfate
• Peak: 6:00-8:00 AM • Medulla – inner layer
• Lowest: 6:00-11:00 PM o Di ko nasundan si maam
• A diurnal variation dito
• ACTH has a target organ
o Adrenal gland – also
known as suprarenal G-zone – secretes aldosterone.
gland. Aldosterone is stimulated by these
§ above the kidneys carrier proteins:
§ Very important in
regulating blood • Binds with CBG
pressure. o BP, BV, electrolytes,
§ Electrolyte balance stress
§ Volume of blood • Binds with albumin
• Low BP =
If the BP and BV is low, it will stimulate
Low BV
renin.
§ Major source of
steroid hormones • Increased Renin will trigger the
liver to release angiotensinogen.
Layers of the adrenal gland:
• Angiotensinogen will secrete
• Cortex – outer layer angiotensin 1 (inactive)
o Zona glomerulosa (G- • Angiotensin converting
zone) enzyme (ACE) (from the lungs) is
§ 10% needed to convert angiotensin 1
§ Most potent to its active form (Angiotensin 2)
mineralocorticoid o Angiotensin 2 – a strong
(aldosterone) stimulus of aldosterone
o Zona fasciculata (F-zone) secretion
§ 75%
The aldosterone targets the nephron,
§ Cortisol
particularly the DCT (Distal Convoluted
§ DHEA
Tubule).
(Dehydroepiandrost
erne) • Low sodium, High potassium –
• Initially electrolyte imbalance
comes from o Aldosterone will help for
fasciculata. the increase of the sodium
o Zona reticularis (R-zone) • To have a normal osmolality:
§ 15% o retention of salt to DCT
CLINICAL CHEMISTRY 2
COMPILED TRANSES
o Potassium is excreted to • Targets the adipocyte
the urine o Triglycerides (found in the
• DCT and collecting duct – final adipocytes) will be
concentration of urine metabolized by cortisol
(lipolysis)
• Amino acid formed by cortisol will
stimulate the liver to produce
gluconeo, glycogenesis

F-zone (Cortisol) • Peak: 8:00-10:00AM

• Lowest: 10:00-12:00MN
• Stress hormone
• Stimulus of F-zone comes from
• Pro-opiomelanocortin (POMC)
the ACTH.
o The precursor of the
• Involved in metabolism of protein. endorphin
• Involved of lipolysis (breakdown o Endorphin – one of the
of fats), gluconeogenesis, happy hormones
glycogenesis. § Gives a euphoric
• Produces glucocorticoids. feeling.
• Affect your Blood pressure, as § A pain reliever
well as Glucose. § A stress reliever
o Therefore, BV will also hormone
increase due to stress. § A neurotransmitter
o Glucose will increase due (released in the
to stress. pituitary gland)
• It is lipid soluble. o Endorphin is needed to be
• Bound with CBG and albumin increased to balance
o CBG is the major protein stress.
carrier (75%) § Eating chocolates
o Albumin (25%) stimulates
• Cortisol will stimulate the endorphin
protease enzymes to the muscle. production.
o To metabolize proteins
§ Will form amino
acids.
CLINICAL CHEMISTRY 2
COMPILED TRANSES
Urine metabolites of glucocorticoids: appearance
of the patient
• 17-hydroxycorticosteroid
§ Hypoaldosteronism
o Porter-Silber method for
• There is an
measuring
electrolyte
§ End color is yellow.
imbalance
§ Reagent used is
• No
phenylhydrazine in
abnormalities
sulfuric acid
seen in
(H2SO4)
appearance
• 17-ketogenic steroids
of the patient
(Ketosteroid)
o Cortisol
o Zimmermann method for
§ Cushing
measuring
syndrome
§ End color is
• Hypercortisol
reddish purple.
ism
§ Reagent used is
• Increase in
sodium
cortisol.
bismuthate.
R-zone (Androgens)
• Responsible for the virility of an
individual
o Femininity
o Masculinity
• DHEA – precursor of androgen
hormones
o Testosterone come from
the DHEA.
• Pathophysiology:
o Aldosterone • Buffalo hump
§ Conn syndrome • Osteoporosis
• A primary • Unexplained
hyperaldoste hyperglycemi
ronism a
• Main • Changes in
problem is weight
found in the • Amenorrhea
adrenal • Obesity
gland.
• No
abnormalities
seen in
CLINICAL CHEMISTRY 2
COMPILED TRANSES
§ Cushing disease § Will be the start of
• Secondary dopamine
hyperadrenal production.
ism • HVA
• Increase in secretion
ACTH. • Norepinephri
§ Addison’s disease ne
• Low cortisol o Will
level becom
• Hypocortisoli e
sm epinep
• Affects lipid hrine.
metabolism. • Norepinephrine and Epinephrine
• Lipid o Will produce catechol-O-
increased. methyltransferase.
• No § With MAO
abnormalities (Monoamine
seen in oxidase), it
appearance Converts
of the metanephrine and
patient. normetanephrine.
§ metanephrine and
Catecholamine normetanephrine
• Secreted by the adrenal medulla. will be oxidized by
• Three different hormones MAO to become
secreted by the AM. Vanillylmandelic
o Norepinephrine acid (VMA)
§ More on being a • 3-methoxy-4-hydroxyphenylglycol
neurotransmitter o Metabolite of ME
(similar to • HVA
dopamine) • VMA
o Epinephrine
§ Adrenaline rush
§ Fight or flight Abnormalities in catecholamines:
o Dopamine
• Pheochromocytoma
§ Higher secretion in
o Adults
the brain
• Neuroblastoma
§ A neurotransmitter
o In children
• Derived from tyrosine
• Hirsutism
o Becomes L-dopamine
o Androgen of female is too
high.
o Excessive hair growth
CLINICAL CHEMISTRY 2
COMPILED TRANSES
ENZYMOLOGY

Discusses the clinically important o Vitamins (B)

enzymes. o All coenzymes are
cofactor.
Terminologies:
● Proenzyme – also known as
● Enzymes – the biological protein zymogen.
catalysts, they are also protein o Zymogen – inactive
which are responsible for enzymes.
biochemical reactions. Prone in o Much bigger than the
denaturation (folding). active enzyme
o Simple – it is composed
Proteolytic Enzyme and Zymogen
primarily of proteins.
o Conjugated – it has a
non-protein portion +
protein portion.
● Apoenzyme – the protein portion
of conjugated enzyme
● Holoenzymes – the
biochemically active conjugated
enzyme
o It is a coenzyme
(non-protein) +
apoenzyme (protein) =
holoenzyme
● Isoenzyme – the multiple forms
of genetic origin. ● Substrate – substance upon
o CK1 (CK BB- brain), CK2 which the enzyme “acts”
(CK MB- heart), CK3 (CK o Binds to the active site
MM- muscle) o Ones the proteolytic
o LD1, LD2, LD3, LD4, LD5 cleavage remove the
● Cofactor – non-protein part of substrate bind into active
conjugated enzyme (activator or site
coenzyme) Classifications
o Not all cofactors are
coenzymes. ● EC 1 Oxidoreductase – an
● Activator – inorganic cofactors enzyme that catalyzes an
o Calcium oxidation-reduction reaction
o Chloride o Subclasses: Oxidase,
o magnessium reductase, dehydrogenase
● Coenzymes – an organic o LD, G6PD – clinically
cofactors important enzymes
o NAD
ENZYMOLOGY

to a double bond or the removal

of a group to form a double bond
in a manner that does not involve
hydrolysis or oxidation
o Subclasses: dehydratase,
decarboxylase,
● EC 2 Transferase – an enzyme deaminase, hydratase
that catalyzes the transfer of a o ALD (Aldolase)
functional group from one
molecule to another.
o ALT, AST, GGT, CK
o Subclasses:
transaminase, kinase

● EC 5 Isomerase – an enzyme
that catalyzes the isomerization
(interconversion) of a substrate in
a reaction, converting it into a
molecule isomeric itself.
● EC 3 Hydrolase – an enzyme
● Occurs rearrangement.
that catalyzes a hydrolysis
o Subclasses: racemase,
reaction in which the addition of a
mutase
water molecule to a bond causes
the bond to break
o Subclasses: Lipase,
protease, nuclease,
carbohydrase,
phosphatase
o AMS (amylase), LPS
(lipase), ACP (Acid ● EC 6 Ligase – an enzyme that
phosphatase), ALP catalyzes the bonding together of
(Alkaline Phosphatase), two molecules into one with the
5’NT (5 nucleotidase) participation of ATP
o Subclasses: Synthetase,
carboxylase

● EC 4 Lyase – an enzyme that

catalyzes the addition of a group
ENZYMOLOGY

Enzyme + Substrate =
Enzyme-Substrate complex
● Enzymatic method: indirect
method (measure the product)
● Enzyme (gluconic measurement),
substrate (Glucose oxidase)
product(gluconic acid + H2O2)
● Will produce enzymes + product.
● Enzyme is proportional to
enzymatic activity.
● Product is the most significant
part. (measure using
spectrophotometer)
o Without the product, it
cannot be read.
MODELS OF ENZYME ACTION o Wavelength 340nm (UV
● Active site – very important for light)
substrate (must be compatible all o Enzymatic colorimetric:
the time) binding site of substrate wavelength (visible light)
(without substrate no reaction) Enzyme Reaction
● Zero order kinetics – reaction
rate depends only on the enzyme
concentration.
● First order kinetics – the rate is
directly proportional/ depends to
the substrate concentration.
(usually remedy)
Factors that Influence Enzymatic
Reactions
● Substrate concentration –
o (ie. Enzyme is constant,
Substrate is high)
o (constant enzyme and
substrate increase):
achieve the maturation
concentration
● Enzyme concentration
ENZYMOLOGY

o (ie. Substrate is constant, the active site. (find other

enzyme is high) active site)
o (substrate constant, ▪ Remedy is to lower/
enzyme (increase)): decrease the
increases (peak) to inhibitor but may be
achieve the maximum difficult to
saturation detect/identify the
▪ Increased reaction inhibitors present in
● pH: general optimum pH is 7.0 – an individual
8.0 (but It depends on the patient.
enzyme) o Uncompetitive – binds to
o ACP: acidic pH is needed Enzyme-Substrate
to activate (5.0 optimum) complex (it will inactivation
o ALP: alkaline pH is of the enzyme, which is
needed to activate (9.0 - needed for the product
10.0 optimum) reading)
● Temperature – 25, 30, 37 degree ▪ No remedy (if the
Celsius substrate will be
o Optimum temp for increase, the and
maximum reaction (37 ES complex
degree Celsius) inhibitors will also
o 40-50 degree Celsius – be increased, and
increased rate of vice versa.)
denaturation ● Hemolysis – red blood cells
o 60-65 degree Celsius – consist of enzymes.
there will be an o Will increase enzyme
inactivation of enzymes. concentration. (RBC has
● Cofactors – a non-protein large amount of enzyme
portion of unconjugated enzymes which could burst out)
● Inhibitors – it will stop the ● Lactescence / Turbidity / Milky
catalytic reaction specimens (chylomicron
o Competitive – competes increases) – the color that will be
with substrate to inhibit the read from the spectrophotometer
active site. Binds with the will be altered. (due to the white/
active site. milky appearance)
▪ Usual remedy is to o May uses serum blank or
increase the dilute
substrate
Regulation of Enzyme Activity
concentration.
o Non-competitive – binds ● A cell that continually produces
to the other site other than large amount of enzyme for
ENZYMOLOGY

which substrate concentration is ● Negative – the regulator will bind

always very low is wasting to the allosteric site to avoid the
energy. The production of the substrate from entering the active
enzyme must be “turned off”. site. Inhibit the substrate to not
(increases when there is a tissue bind in the active site.
injury) ● Positive – the regulator will bind
● A product of an to the allosteric site to allow the
enzyme-catalyzed reaction that is substrate to bind to the active
present in plentiful amounts in a site.
cell, is a waste of energy if the
Feedback Control
enzyme continues to catalyze the
reaction that produces the
product. The enzyme needs to be
“turned off”
Allosteric Enzymes
● Has a substrate (active site) and
regulator (allosteric site) (positive
or negative) Positive (increase product) negative
(decrease the enzyme)
Examples:
● Enzyme 1: Glucose + ATP 🡨HK🡪
GGP + ADP
● Enzyme 2: G6P + NADP
<-G6PD-> NADPH +
Phosphogluconolactone

LIVER ENZYMES

● Enzyme that has a substrate and LD / LDH, LD, ALT, AST, GGT, ALP,
a regulator 5’NT
Coenzyme Tissue Methods Norma
/ Cofactor Sources l Value

Allosteric regulator
 ENZYMOLOGY

NAD Heart [Link] 1 o Catalyzes alcohol to

Liver [Link]-La 0 become acetaldehyde.
Muscles Due o Associated with some
Kidney [Link] cardiovascular diseases.
RBC Cabaud ▪ Arteriosclerotic
Brain [Link] Broida
cardiovascular
failure (increased
*Temperature 37oC LD6)
● LD5 - cold labile (sensitive to low
ISOENZYMES
temperature)
Subunits (H= heart)(M=muscle) ● LD1 – second to the highest
● LD2 – will increase if there is
Subunits
Megaloblastic anemia
LD1 HHHH (specific to the heart /
(Pernicious anemia) and if the
cardiac muscle and RBC)
● Fastest specimen is hemolyzed.
LD2 > LD1 > LD3 > LD4 > LD5 (normal
LD2 HHHM (RBCs)
● Most predominant in terms of predominance)
isoenzyme of LD LD1 > LD2 – flipped pattern.
LD3 HHMM (Lungs) ● LD1 > LD2 > LD 3> LD4 > LD5
LD4 HMMM (Liver) ● If LD1 is increased (flipped
LD5 MMMM (specific to the skeletal pattern), it may be associated to:
muscle) o Acute myocardial
● Slowest infarction (AMI)
● Cold labile ▪ Oxygen present to
● LD2>LD1>LD3>LD4>LD5 the heart is not
(normal pattern) enough or properly
● LD1>LD2>LD3>LD4>LD5 circulated.
(flipped pattern Acute myocardial ▪ Chest pain (angina
infraction) pectoris)
● LD1: predominant in heart: ▪ LD is increased
increase in hemolytic anemia within 12-24 hours.
● LD2: predominant in RBC: ● Peak is
megaloblastic anemia to support 48-72 hours
the findings PBS and indices (2-3 days)
● LD6 – a variant of LD5 ● Maintains up/
o Also known as the alcohol elevated to
dehydrogenase 10-14 days.
(metabolism of alcohol) ▪ Myoglobin is
o Not specific increased (sensitive
 ENZYMOLOGY

protein, but it is not Pyridoxal Liver Reitman- 7-45

ideal for PO4 Frankel u/L
determining AMI) (active
▪ Troponin is form of Karmen
increased (specific Vitamin
B6)
protein for AMI)
● Karmen method – it has a
o Hemolytic anemia
coupling enzyme.
● LD only is indicated – represents
o Not colorimetric
the totality of Lactate
dehydrogenase. *Alanine + alpha-ketoglutarate –ALT🡪
● LD is a cardiac marker oxaloacetate + glutamate
LACTATE DEHYDROGENASE: *Pyrivate+ NADH+ H--LD🡪 Lactate+
NAD
● Wacker – direct / forward
reaction/ method ● Reitman-Frankel – color
o 8.3 – 8.9 pH developer is
o Lactate + NAD 🡪 Pyruvate dinitrophenylhydrazine (DNPH)
+ NADH + H o Color intensifier: Sodium
Alpha hydroxybutyrate Hydroxide
(alpha-HBD) – the substrate o Colorimetric method
which is very specific for LD1 o Colorimetric, should be
activity. read within the visible
● Wroblewski – La Due – reverse range of light
reaction: faster (disadvantage:
exhaustion of substrate
o 7.1 – 7.4 pH
o Pyruvate + NADH + H 🡪
Lactate + NAD
o Alpha hydroxybutyrate: as
substrate for LD1 activity

ALT (Alanine Aminotransferase) AST normal ALT increase: not properly

● Most specific for the liver corelated
● Also known as serum glutamic AST (Aspartate Aminotransferase)
pyruvic transaminase (SGPT)
● Also known as serum glutamic
● OT/PT
oxaloacetic transaminase
● Not present in RBC
(SGOT)
Coenzyme Tissue Methods Norma ● AST (new name), SGOT (old
Sources l Value name)
 ENZYMOLOGY

● Not specific Oxaloacetate + NADH + H –MDH

(Malate dehydrogenase🡪 Malate + NAD
Coenzyme Tissue Methods Nor
Sources Val
Pyridoxal Cardiac Karmen 5-3
PO4 (active Liver GGT (Gamma-Glutamyl Transferase)
form of Skeletal e Clinical Methods NV
Vitamin B6) muscle ces Significance
Pancreas
RBC y *Hepatobiliary Szasz M: 6-55
● Used as cardiac marker and it will disorders u/L
raise to 6-8 hours ate *Drugs Rosalki
● AST will increase/ rise in 6 – 8 eas *Chronic & Tarrow F:
hours after angina (chest pain) alcoholism 5-38 u/L
*Acute Orlowski
o Peak is within 24 hours.
pancreatitis (at 37C)
o Becomes normal after 5 *Diabetes
days. mellitus
● Viral hepatitis – 100 times higher (HBA1c)
than the upper limit of increased *Acute
AST myocardial
o Viral hepatitis (highest infarction
level of AST observed (Trop)
100x the upper limit) ● Chronic alcoholism – GGT is
o 4-8 times upper limit increased (first to increase), ALT
● AST Isoenzymes: is normal.
o Cytoplasmic AST – most ● Biliary tract obstruction – Total
predominant bilirubin will be increased.
o Mitochondrial AST – if it ● Increased GGT: Biliary tract
is present in the blood, it obstruction and chronic
indicates the presence of alcoholism
cell necrosis. Szasz – most common for measuring
● Karmen method – it has a GGT
coupling enzyme
o Requires Vitamin B6 ● Gamma glutamyl p-nitroanilide +
o pH 7.3-7.8 glycylglycine ---GGT🡪
o also present in RBC para-nitroaniline
(hemolyzed) ● Both ALT and GGT not affected
in hemolysis (absent in RBC)
Aspartate + alpha-ketoglutarate –AST🡪
oxaloacetate + glutamate
 ENZYMOLOGY

ALP (Alkaline Phosphatase) increase, LDH increase: Liver

disease
Activator Tissue Methods Normal
Sources Value ● ALP increase, ALT normal
Magnesium Intestine *Bessey M: ● Carcinoplacental isoenzymes
Liver Lowry & 53-128 ● Regan – inhibited by
Bone Brock u/L
Spleen *Bower-Mc F: 42-98 phenylalanine.
Placenta Comb u/L ● Nagao – inhibited by
Kidney (more
specific) phenylalanine and leucine.
*King-Arm o Leucine – for isolation
strong
*Sinowara of Regan
Jones &
Reinhart Inhibitors
*Huggins &
Talalay ● Phenylalanine – inhibits intestinal
*Moss
and placental isoenzyme.
● Similar with GGT if there is ● 3M urea – only inhibits the bone
obstruction ● Levimasole – inhibits liver &
● Increased in obstruction bone.
● pH= optimum 5
● LBPI – isoenzymes for ALP 5’NT (5’Nucleotidase)
o Liver isoenzyme
o Bone isoenzyme ● Liver enzyme used differentiate
o Placenta isoenzyme liver disease to the other
o Intestine isoenzyme diseased based o ALP
● Bower-McComb – most specific ● Can be used to differentiate ALP.
and common method for ALP (LBPI isoenzymes)

P-nitrophenylphosphate ---ALP🡪 ALP 5’NT

p-nitrophenol + phosphate ion Increased Normal Non-live
r
● 90-100 to achieve maximum Normal Increased
Increased Increased Liver
Stability
L Stable (not sensitive) at 56C for
10 mins GGT ALP
B Labile (not sensitive) at 56C for Increased Normal Chronic
10 mins Alcoholism*
P Most Stable at 65C for 30 Increased Increased Liver
mins (pregnant) Normal Increased Bone,
I Labile and sensitive at 65C for placenta,
30 mins intestine
● Example: ALP increase, GGT
increase AST increase, ALT
ENZYMOLOGY

Diagnosis: Vigorous exercises

Clinical chemistry
LDH normal
AST normal G6PD (Glucose-6-phosphate dehydrogenase)
ALT normal Tissue Clinical Significance NV
ALP normal Sources
GGT increase
Total Bilirubin normal *Adrenal *G6PD deficiency 7.9-16.3
BUA increase cortex *Hemolytic anemia u/g of
*Spleen *Acute myocardial Hemogl
Glucose decrease *Thymus infarction obin
(hypoglycemic) *Lymph *Primaquine
Indices nodes *Megaloblastic
*Lactating anemia
MCV-120fL mammary
MCH-29 gland.
MCHC32 *RBC
Urinalysis
CHO/CHON-neg
● G6PD deficiency (decrease in G6PD) –
PC-0-2 may lead to hemolytic anemia
Bacteria few o Test for hemolysate
AU-few ● Not a diagnostic test for AMI
Diagnosis: Chronic alcoholism ● Increase in G6PD – test for serum.

G6P + NADP –---G6PD--🡪

phosphogluconolactone + NADPH + H
LD increase
Creatine Kinase (CK)
ALT normal
ALP normal Tissue Clinical Methods NV
Sources Significance
GGT normal
Skeletal *Acute Tanzer-Gil M: 46-171 u/L
AST increase muscle myocardial varg
Glucose normal Heart muscle infarction F:
BUN N Brain tissue *Rhabdomyol Oliver-Ros 34-145 u/L
Bladder ysis alki
Creatinine increase Placenta *Muscular
Urinalysis GIT dystrophy
Color red Thyroid *Stroke
Uterus *Seizures
RC 6-10 Kidney *Nerve
PC 0-2 Lung degeneration
HC 2-3 Prostate *CNS shock
Spleen *Hypothyroid
Protein- trace Liver
Glucose- negative Pancreas
ENZYMOLOGY

● Forward / direct reaction with a pH of

● CK1 – fastest 9.0
o CK-BB ● Coupling enzymes are PK and LD
o Specific for the brain 1. Creatine + ATP ---CK--🡪 Creatine PO4
● CK2 + ADP
o CK-MB (hybrid) 2. ADP + Phosphoenolpyruvate (PEP)
o Used as a marker for cardiac –PK--🡪 Pyruvate + ATP
abnormality (heart muscle) 3. Pyruvate + NADH + H ---LD--🡪 Lactate
● CK3 – slowest + NAD
o CK-MM
Oliver-Rosalki
o Specific for the skeletal muscles
● Highest level of CK is found in ● Reverse reaction with a pH of 6.8
Muscular dystrophy. ● Three times faster than the forward
● CK is light sensitive / photosensitive reaction
analyte. ● The main disadvantage is it is prone to
o It becomes inactivated if substrate exhaustion
exposed to light ● Coupling enzymes are HK and G6PD
● CK is very sensitive to pH 1. Creatine PO4 + ADP ---CK--🡪 Creatine
● Imidazole – serves as a buffer for CK + ATP
(due to CK being pH sensitive) 2. ATP + Glucose ---Hexokinase--🡪 ADP +
● CK is absent in RBCs, but very much G6P
affected in hemolysis. 3. G6P + NADP –-G6PD--🡪 NADPH +
● Adenylate Kinase (AK) – high value in phosphogluconate
RBCs.
o Can react to ATP, which will Inhibitors of CK:
affect CK reaction (falsely
● Urate
elevated)
● Cystine
● Acute Myocardial Infarction – sensitive
to CK but it is not in the highest level. ACP (Acid Phosphatase)
● CK is the most sensitive cardiac
enzyme for AMI. ● It is not a cardiac enzyme.
o Rise: 4-8 hours ● Most commonly used tumor marker for
o Peak: 12-24 hours prostate cancer
o Normalization: 48-72 hours ● Isoenzymes
(2-3 days) o RBC
o Myoglobin will increase faster o Prostate (rich in ACP): tumor
than CK, then AST marker in Prostate cancer
● Advantage: for rape cases, medico
Inhibitors of CK: legal
o Vaginal washing is the initial
● Urate
sample to detect the presence
● Cystine
of semen containing ACP
● Disadvantage: Will only increase in the
Subunits of CK critical level of prostate cancer, not a
sensitive marker for prostate
● Muscle isoenzyme o Prostate normally increases in
● Brain isoenzyme size (due to lack of sexual
activity)
Tanzer-Gilvarg
ENZYMOLOGY

o PSA (Prostate Specific o Gallstones

Antigen): test done for the age
of 50 (annual) Activator Tissue Clinical Method NV
▪ Better tumor marker Sources Significanc s
e
for ACP (due to its
Calcium Pancrea Pancreatiti *Amyloc 28-100
sensitivity for prostate
and s s (not lastic ng/mL
cancer)
Chloride Salivary specific) *Saccha
Tissue Clinical Methods NV gland rogenic
Sources Significance pH 5.0 Skeletal Mumps Chromo
Prostate Prostate Hudson 0-3.5 muscle genic
Bone carcinoma Babson & ng/mL SI (color
Liver Reed Fallopia intensity)
Spleen Rape Roy (Prostate n tubes Continuo
Kidney Bodansky ACP) us
RBC Paget’s Gutman, (couplin
Platelet disease King & g
Armstrong enzymes
)
Isoenzymes of ACP

● RBC
● Prostate – isoenzyme that cannot be
found in women. Isoenzymes:
Inhibitors of ACP: ● Pancreatic amylase (P-AMS)
o Slower isoenzyme
● Tartrate – will only inhibit prostate
● Salivary amylase (S-AMS)
isoenzyme.
o Faster isoenzyme
● Cupric sulfate – will inhibit the RBC
isoenzyme. Amyloclastic – measure the amylase activity.
● 2% Formaldehyde – will inhibit the RBC
isoenzyme. Saccharogenic – measures the amount of
reducing sugars.
Source of Error in ACP:
Amylase is responsible of the breakdown of
● Loss of carbon dioxide starch
o CO2 (can decrease the pH) –
very important to maintain the Substrate of Amylase –starch
acidity.
Inhibitors of AMS:
Medico legal (Rape): death (vaginal washing of
● Triglyceride
the vagina of the victim (rape victim)) specimen
● Heparin
of choice, 2-4 days active ACP
● Lectin – it inhibits the salivary amylase.
Amylase (AMS)
Continuous monitoring (coupling enzymes)
● More specific
1. Maltopentose ----AMS-🡪 maltotriose +
● Smallest enzymes
maltose
● It is a pancreatic enzyme.
● Very important in the breakdown of Rise Peak Normalize
starch LPS (mas 4-8 24 hours 8-14 days
● Sensitive to Acute pancreatitis matagal to hours
o Alcoholism elevate)
o Fatty foods
 ENZYMOLOGY

AMS 5-8 24 hours 3-5 days LD 12-24 48-72 hours 10 days

hours hours (last
2. maltotriose + maltose ---Glucosidase🡪 to elevate
glucose
3. Glucose + ATP ---HK-🡪 ADP + G6P
PANCREATIC ENZYMES
4. G6P + NADP ---G6PD-🡪
phosphogluconate + NADPH
Bangungut: acute hemorrhagic pancreatitis
Source of Error:
CAA: Carcino antigenic antigen colon cancer
● Drug abuse (Morphine / Opiates)
o Will result to falsely elevated/
positive amylase.

Lipase (LPS)

● The specific marker for acute

pancreatitis (AMS and LPS is
elevated)
● Important for the breakdown of
triglycerides

Tissue Clinical Methods NV

Sources Significance
Pancreas Pancreatitis Cherry-Cr <38 u/L
Small andall
intestine
Stomach Tietz &
Fierck
● Substrate for Lipase – olive oil
● Inhibitor for Lipase – Hemoglobin
o Hemolyzed sample is not
allowed.

CARDIAC ENZYMES

Rise Peak Normalize

CK 4-8 hours 12-24 hours 48-72 hours
(first to
elevate-
sensitive)
AST 6-8 hours 24 hours 5 days
ALD 6-8 hours 3-4 days ---------------
(card
iac
mark
er)
LIVER FUNCTION TEST ▪ Bilirubin should be excreted, or else your
body may result to jaundice.
● Enzymes (ALT AST GGT LD ALP 5’NT)
o The body can produce 3 liters of bile, but only 1
● Protein (Albumin)
liter can be excreted
● Urea (synthesized in the liver)
o Bile is made up of bile acids or salts, bile
● Uric acid (synthesized in the liver)
pigments, cholesterol, and other substances
● Ammonia (end product of amino acid deamination)
extracted from the blood.
Ornithine cycle ▪ For emulsification of fats
o Bilirubin synthesis:
● Protein - once it metabolizes, it will develop into amino
▪ Biochemical hepatocyte system
acid then becomes ammonia due to deamination.
● Hepatocyte – handles all hepatocyte
Anatomy of the Liver process
● Weighs 1.2 – 1.5kg ▪ REC (Macrophages)
● Vascularogram (hepatic artery and portal vein) ● Engulfs the unnecessary substances
● Has falciform ligament (divides the liver into two lobes) ● Kupffer cells
o Connected to the heart. ▪ Hepatobiliary system
o Right lobe is six times larger than the left lobe. ● Bilirubin synthesis – excretes
● Hepatic artery – delivers oxygenated blood from the heart bilirubin
to the liver (25% blood flow) o Bilirubin synthesis
● Portal vein – the blood coming from the intestine is rich in ▪ RBC (120 days)
nutrients, then it will be transported into the liver (75% ▪ Spleen – heme, globin, iron
blood flow) ● Iron is stored into the liver, bone
● The liver can regenerate itself, however if it is abused marrow, which binds to transferrin
due to alcohol and lack of sleep, it can affect negatively. and forms ferritin.
● Globin – protein portion of
Liver Physiology hemoglobiin
● Excretory and secretory o Amino acid should be reused
o Excretion of endogenous and exogenous to develop protein
substances into the bile or urine such as bilirubin o Aminoaciduria (AA in the
o Bilirubin is the end product of hemoglobin urine)
degradation. ● Heme – will eventually converted
▪ Principal bile pigment into B1 from biliverdin
o Biliverdin – yellowish-green
o Biliverdin reductase – recycled to the liver
important for the development and may enter into the
of B1 circulation
o B1 forms from biliverdin and ▪ A quarter of the blood
binds with albumin from the heart will be
o B1 + albumin (complex) received to the kidney
▪ Dissociation will occur and will be filtered and
and albumin will be excreted into the form
replaced with ligandin of urobilin
o Ligandin – will transport B1 in o 200 – 300 mg of bilirubin
the Endoplasmic Reticulum produced per day
o ER – important for protein o Feces – 50 to 250 mg of
synthesis urobilinogen excreted per day
o B1 + Uridyl diphosphate o Urine – 1 to 4 mg of
glucoronyl trtansferase urobilinogen excreted per day
▪ Forms Bilirubin o
diglucuronide (B2)
o B2 will be excreted from the
liver to the intestine ● Metabolism
▪ Good bacteria and B2 o Carbohydrates, lipids, and proteins
will form mesobilirubin ▪ Carbohydrates – glycogen
▪ Reduction of ▪ Lipids – lipogenesis (formation of fats in the
mesobilirubin will form liver)
mesobilirubinogen ▪ Proteins – Krebs cycle (the highest ATP
▪ Eventually will become that can be produced inn the liver)
urobilinogen. o Liver is the accessory organ of the digestive
o Urobilinogen – colorless system
substance ● Detoxification and drug metabolism
▪ A.k.a. Stercobilinogen o Binds the material reversibly
▪ Oxidized into urobilin / o Chemically modify the compound
stercobilin, which gives o Drug metabolism:
pigment into stool. ▪ First pass – liver
▪ Urobilin that was not ● Circulation and REC may be the
converted will be future passage
 o Detoxification process – bilirubin should be Icteric sample – the serum is dark yellow
eliminated
Overt jaundice – yellow pigment is prominently seen in the
▪ Ammonia
naked eye.
Liver function alterations during disease
● 3-5 mg/dL
● Jaundice – yellow (laboratory diagnosis of ● Normal bilirubin – 1mg/dL
hyperbilirubinemia) ● Conversion factor of bilirubin (CI to SI) – 17.1 umol/L
o Pre-hepatic - spleen
Pre-Hepatic jaundice (Hemolytic Anemia)
o Hepatic
o Post-hepatic ● According to Bishop, the total bilirubin is greater than 5
mg/dl
● According to Henry, the total bilirubin is 1.5 to 3.0 mg/dl
● Unconjugated hyperbilirubinemia
HEPATIC JAUNDICE
● Unconjugated Hyperbilirubinemia (B1 / Indirect bilirubin /
Insoluble)
o Gilbert’s syndrome
o Criggler-Najjar syndrome
o Physiologic jaundice
● Conjugated Hyperbilirubinemia (B2 / Direct bilirubin /
Soluble)
o Dubin-Johnson
o Rotor syndrome
Gilbert’s syndrome
● Common in 20-30 y/o
● Mild unconjugated (2-3 mg/dL)
● Has genetic lesions
● UGT1A1 (Chromosome 2) – gene that encodes UDPGT,
which is involved in the conjugated process
● B1 is elevated due to the deficiency of UDPGT
● A.k.a Bilirubin transport deficit
 o The liver is black in color due to accumulation of
lipofuscin.
● Rotor syndrome:
o Viral origin (80% probability to be developed into
rotor syndrome)
Physiological jaundice
● Appears after 24 hrs
● Occurs in babies
● Total bilirubin rises by less than 5mg/dL per day
● Maximum immunity by 4th-5th day in term & 7th day in
preterm
● Serum level less than 15 mg/dl
● Clinically not detectable after 14 days
Pathological jaundice
Criggler-Najjar syndrome
● Appears within 24 hours of age
● B1 may be elevated higher than 5mg/dL ● Increase of bilirubin greater than 5 mg/dL per day
● B1 – Kernicterus (greater than 20 mg/dl) which goes to ● Serum bilirubin is greater than 15 mg/dL
the brain ● Jaundice days Jaundice persisting after 14 days
● Has two types ● Stool clay / white colored and urine staining
o Type 1 – the complete absence of UDPGT ● Yellow staining clothes
o Type 2 – deficiency in UDPGT ● Direct bilirubin is greater than 2mg/dL
Lucey-Discroll
Dubin-Johnson and Rotor syndrome ● Deficiency in UDPGT
● Obstructive in origin ● Similar to Criggler Najjar type 2 and Gilbert’s syndrome
o Results a problem in excretion (Excretion Deficit), o But is very common only in neonates.
which B2 will be elevated
● Dubin-Johnson:
POST-HEPATIC JAUNDICE
o Mild hyperbilirubinemia (2-5 mg/dl total bilirubin)
o Delta bilirubin – B2 that is bound to albumin ● Usually in the gallbladder (cholelithiasis / gallstones)
(abnormal) ● Clay colored stool (Gray)
Cirrhosis o Some with leukopenia and thrombocytopenia due
to hypersplenism (absorbed large amounts of
● Scarred tissue
acanthocytes)
Causes o Hyperbilirubinemia, ALP
o De Ritis (>2)
● Chronic alcoholism (30g of alcohol/day)
▪ AST:ALT ratio
o Most common cause of liver cirrhosis
● Hepatitis infection Tumors
● Autoimmune hepatitis
● Alpha-I antitrypsin deficiency
● Wilson disease
● Hemochromatosis
● Galactosemia
● Non-alcoholic steatohepatitis
● Bile duct obstruction
● Drugs
● Toxin
● Infections
Treatment
● May depend on the cause.
● Poor prognosis
● Primary liver (origin) vs metastatic liver cancer
Lab Findings ● metastatic liver cancer (Colon, lung and breast)
● CBC (normal) ● Benign (hepatocellular adenoma / hemangiomas)
● AST (slightly elevated) o Hemangiomas – most common benign tumor
● Bilirubin and ALP (occasionally elevated) ● Malignant
● Advanced alcoholic cirrhosis o Hepatocellular carcinoma (HCC) – the most
o Anemia common malignant
o Hemolytic anemia due to hypercholesterolemia ▪ Diagnosed with the help of
(acanthocytosis) Alpha-Fetoprotein (AFP)
o Leukocytosis o Hepatoma
o Bile duct carcinoma
● Hepatoblastoma
o Malignancy that is common in children
 ● Hepatitis ● Metabolic acidosis
● Poor prognosis ● Ammonia
● CSF, glutamine
Lab Findings
● Treatment: Glucose or Mannitol to reduce cerebral
● AFP edema
● Hyperbilirubinemia
● Anemia
● ALP Drug Related and Alcohol Related disorders
o Not specific to liver, but also present in bone,
● Acetaminophen
intestine, placenta
● Ethanol
Reye’s syndrome
● Alcohol fatty liver – moderate high AST, ALT, GGT, ALP
(>5mg/dL total bilirubin)

● AST is more than twice the upper limit

● ALT lower than AST (0-40 u/L) 80 (90 u/L)
● De Ritis is >2
● Decreased albumin

Hepatitis
● Hepatitis is a general
term referring to
● Fatty liver with encephalopathy inflammation of the
● Encountered exclusively in children below 15 yrs old liver.
● Progressive CNS damage ● Causes:
● Hepatic injury o Infectious
● Hypoglycemia ▪ Viral
● Aspirin ▪ Bacterial
● Influenza / chickenpox ▪ Fungal
● Minimal / absent jaundice ▪ Parasitic
● Aminotransferase o Non-infectious
● PT ▪ Alcohol
 ▪ Drugs Reactive Non-Re Non-Re Non-Re Non-Re Non-Re
▪ Autoimmune active active active active active
▪ Metabolic diseases Reactive Non-Re Reactive Non-Re Non-Re Non-Re
active active active active
Hepatitis A Virus (HAV) Reactive Non-Re Reactive Non-Re Reactive Non-Re
● HAV IgM – earliest to elevate when antigen enters the active active / active
body Non-Re
active
o Will not last for lifetime
Reactive Non-Re Reactive Non-Re Non-Re Reactive
o Positive IgM – present for infection active active active
● HAV IgG – have a history Reactive Non-Re Non-Re Reactive Non-Re Reactive
o Exists for a lifetime. active active active
HAV IgM Reactive IgM Non-reactive IgG Non-Re Reactive Non-Re Reactive Non-Re Reactive
HAV IgG Non-reactive IgM Reactive IgG active active active
PRESENT PAST Negative Reactive Negative Negative Negative Negative
EIA – mostly for screening
Hepatitis B Virus Rapid test kit –
● MOT:
o Parenteral
Methods
o Sexual intercourse
o Saliva ● Ehrlich – earliest method for urine bilirubin
o Perinatal o Can detect diazotized sulfanilic acid (DSA)
● Hepatitis Profile ● Van den Bergh – uses an accelerator (alcohol)
o HBsAg (Surface) – to increase HBsAg o Earliest method for blood (serum)
o AHBs (Anti) o Accelerator – serves as a solubilizer
o HBcIgM (Core) – if positive, Acute Hepa B ▪ Solubilize B1 (due to B1 being insoluble) to
infection read total bilirubin
o HBcIgG (Core) ▪ Total bilirubin – B2 = B1
o HBeAg (Envelope) – if reactive; (highly ● Evelyn Malloy – most commonly used for bilirubin
contagious) o 50% methanol is used as an accelerator to make
o A-HBe (Anti) – if recovering from disease, this will B1 soluble
be the first to elevate ● Jendrassik-Grof – reference method (gold standard)
HBsAg A-HBs HBcIgM HBcIgG HBeAg A-HBe
 o Caffeine-benzoate-acetate (Caffeine) is used as
an accelerator to make B1 soluble
Remember:
● Fasting
● Lipemia-increase
● Hemolyzed
● Avoid light – 30-50%/hour (photosensitive)
● Stable for 2 days at Room Temperature (in amber bottle);
1 week at 4C; -20C indefinitely
Other tests
● Enzymes
● Albumin
● Prothrombin Time (PT)
TOXIC METALS

ARSENIC – odor of garlic and metallic o Fatal dose

taste
Laboratory Diagnosis of Arsenic
● Inorganic arsenicals Sodium
● Using of ion emission
arsenate, lead or copper arsenide
spectroscopy, the analysis of
● Organic arsenicals carbarsone,
urine, hair, and nails is used to
tryparsamide, and arsine gas
diagnose the chronic arsenic
● It is produced as a by-product
poisoning
from gold, copper, and lead
● Atomic absorption
smelters.
spectrophotometry (AAS)

Health effects of Arsenic

Treatment for Arsenic
● Burning and dryness of the
● Administration of sulfhydryl
mouth and throat
containing compounds
● Difficulty swallowing
● Removal of residue arsenic by
● Vomiting
gastric lavage or emesis
● Watery or bloody diarrhea
● Dimercaprol
contains intestinal mucus
● Hemodialysis
● Odor of garlic on the breath
● Metallic taste in the mouth
● Cyanosis
Trivia on Arsenic:
● Hypotension
● Tachycardia ● Arsenic is commonly used in
● Ventricular arrhythmias homicide and suicide agent
● Acute renal tubular necrosis
● Hyperpigmentation of the skin
● Keratosis LEAD – basophilic stippling
● Anemia ● Highly toxic
● Hemolysis ● Component of household paints
● Pulmonary edema ● Serious effects occur in central
and peripheral nervous systems
● Lead is a by product or
Dosage for Arsenic component of many industrial
● 120 mg of arsenic trioxide processes, which has contributed
o Acute fatal dosage to its widespread presence in the
● Less than 30 ppm of arsenic gas environment
o Poisoning ● IQ of children is less than 80
● 0.1 to 0.5 g/kg of organic when exposed to lead.
arsenicals
TOXIC METALS

● Lead in pencils is actually ● Reinsch test – to determine the

graphite. presence of heavy metals.

Dosage for Lead Health Effects of Mercury

● >0.5 mg/day lead accumulation ● CNS effect
● 0.5 g lead Fatal dose ● GI symptoms
● Severe pulmonary reactions
● Severe renal tubular damage
Laboratory evaluation and specimen ● Pheochromocytoma
● ALAD activity
● Vivo x ray fluorescent
Laboratory Evaluation and specimen for
● Assay for Zinc
Mercury
● Heinsch
● Hair analysis
● 24-hour urine determination
Treatment for Lead:
● BAL (British Anti-Lewisite)
Treatment for Mercury
● Gastric lavage
● Dilute magnesium sulfate or ● Gastric lavage or emesis
sodium sulfate solutions ● Use of dimercaprol succorer
● Usage of chelating agents

Trivia on Mercury:
MERCURY
● In china and tibet, the use of
● 4 different forms: Element or mercury was thought to prolong
metallic (Hg o), mercurous (Hg life, heal fractures, and maintain
++), mercuric (Hg 2+2+), and generally good health.
alkyl mercury.
● It reacts with sulfhydryl group
leading to enzyme inhibition and ALUMINUM
alteration of cellular membrane.
● Aluminum is the most heavily
● Consumption of contaminated
consumed non ferrous metal in
foods is the major source of
the world
exposure in the general
● population.
● For chronic toxicity, 24-hour urine Health Effects of Aluminum
is used.
TOXIC METALS

● Damage to the central nervous ZINC – good for tissue repair

system
● A bluish white, lustrous metal
● Dementia
● Covered with a white coating.
● Loss of memory
● Fourth most used metal
● Listlessness
● Alloys, especially in brass,
● Severe trembling
galvanizing steel, paints, skin
lotions, and in treatment of
Wilson’s disease.
Absorption and Secretion of Aluminum
● Lungs
● Digestive tract Health Effects of Zinc
● A small amount of the aluminum
● Second only to iron in importance
found in antacids will be
as a trace element
absorbed
● Structure, regulation and catalytic
action of enzymes
● Glycolysis and cholesterol
Deficiency in Aluminum - Alzheimer’s
metabolism, maintains
disease, Parkinson’s disease and
membrane structures, and effects
multiple sclerosis.
functions of insulin

Toxicity of Aluminum
Absorption, Transport and Excretion of
● Chronic renal disease Zinc
● Desquamative interstitial
● The normal zinc body content of
pneumonia, pulmonary alveolar
an individual is about 2.5g
proteinosis, Crohn’s disease,
● Highest concentrations in eyes,
dementia and infertility.
prostate and hair.
● Small intestine and especially in
the jejunum.
Laboratory Evaluation of Aluminum
● In blood, the absorbed zinc is
● Inductively Coupled plasma and distributed in whole blood.
Mass Spectrometry (ICP/MS) ● Presence of animal proteins and
amino acids in a meal, intake of
calcium, and unsaturated fatty
Reference Intervals for Aluminum acids
● Aluminum in Serum/Plasma: <6
ng/mL
Deficiency of Zinc
TOXIC METALS

● Growth retardation, slows ● An enzyme activator

skeletal maturation, causes ● Arginase, pyruvate carboxylase
testicular atrophy and reduces and manganese superoxide
taste perception. dismutase in mitochondria
● Acrodermatitis ● Hydrolases, kinases,
● Diarrhea and impaired T cell decarboxylases and transferases.
immunity, insufficient wound
healing, delayed testicular
development in adolescence. Absorption of Manganese
● Dietary manganese is poorly
absorbed.
Toxicity of Zinc
● Iron, calcium, phosphates and
● Relatively nontoxic fiber
● 100mg/day
● Zinc fume fever
Deficiency of Manganese
● Epilepsy
Laboratory Evaluation of Zinc Status
● Hip abnormalities, joint disease
● Flame AAS, ICP AES, and ICP and congenital malformation.
MS ● Blood clotting defects,
● Low urine zinc levels in presence hypocholesterolemia, dermatitis,
of low serum zinc levels elevated serum calcium and
● Zinc concentration in red blood phosphorous
cells is approximately 10 times
that in serum
Toxicity of Manganese
● Nausea, vomiting, headache,
MANGANESE
disorientation, memory loss,
● Ferromanganese anxiety and compulsive laughing
● Scavenger during steel or crying
production ● Parkinson’s disease
● Fertilizers, animal feeds, ● Locura manganica (Manganese
pharmaceutical products, dyes, madness)
catalysts and wood preservatives
and production of glass and
ceramics Laboratory Evaluation of Manganese
● ICP MS, GFAAS, and NAA.
● Urine manganese is used in
Health Effects of Manganese
conjunction with serum
TOXIC METALS

manganese to evaluate possible ● 3% of dietary intake.

toxicity or deficiency.

Deficiency of Copper
Reference Intervals for Aluminum
● premature infants
● Manganese in serum: 0.43 0.76 ● Neutropenia and hypochromic
ug/L anemia in early stages,
● Manganese in whole blood: 10 11 osteoporosis, decreased.
ug/L ● pigmentation of the skin, possible
● Manganese in urine: <2.0 ug/L neurologic abnormalities
● coronary heart disease.
● Menkes disease.
COPPER
● Excellent electrical and heat
Toxicity of Copper
conducting properties.
● Copper forms alloys with zinc ● Wilson’s disease
(brass), and nickel (cupronickel, ● Neurologic disorders, liver
widely used in coins) dysfunction and Kayser Fleischer
rings.

Health Effects of Copper

Laboratory Evaluation of Copper
● 5 - 120 mg.
● highest concentrations found in ● Flame AAS, ICP MS, ICP AES,
the liver, brain, heart and kidneys. and ASV.
● Hepatic copper ● Wilson’s disease, Indian
● Cornea, spleen, intestine and childhood cirrhosis.
lung
● Ceruloplasmin.
Reference Intervals for Aluminum
● Copper in Serum: 700 1500 ug/L
Absorption, Transport and Excretion of
● Copper in serum (pregnancy at
Copper
term): 118 320 ug/L
● 10 mg or more of copper. ● Copper in urine: 15 60 ug/24
● 50 80% of ingested copper. hours
● About half of dietary copper is ● Copper in RBCs: 90 150 ug/L
excreted in feces.
● Severe diffuse diseases of small
bowel, lymph sarcoma, and CADMIUM
scleroderma.
● Soft, Bluish white metal
TOXIC METALS

● Pigments and batteries, metal

plating and plastic industries.
Absorption, Transport and Excretion of
● Released in burning of fossil fuels
Cadmium
● Smokers
Health Effects of Cadmium ● Ingested food
● The absorption is 10-50%
● protein Cd adducts.
● Gastrointestinal absorption
● Newborn babies
● higher than females than in
● Cadmium concentrations
males
● Smoking
● feces 90%
● Placenta
● In blood

Absorption, Transport and Excretion of

Toxicity of Cadmium
Cadmium
● Renal dysfunction
● Smokers
● Nasal epithelial and lung damage
● Ingested food
similar to emphysema.
● The absorption is 10 50%
● Respiratory distress
● Gastrointestinal absorption
● higher than females than in
males
Laboratory Evaluation of Cadmium
● feces 90%
● In blood ● Usually quantified by GFAAS,
ICP MS; and ICP AES.
Reference Intervals for Cadmium
Toxicity of Cadmium
● Cadmium in urine: <2.6 ug/L
● Soft, Bluish white metal
● Cadmium in blood: less than 5.0
● Pigments and batteries, metal
ug/L
plating and plastic industries.
● Released in burning of fossil fuels
CHROMIUM
Health Effects of Cadmium ● Greek word “CHROMA”
● Make rubies red & emeralds
● protein Cd adducts.
green.
● Newborn babies
● 21st most abundant element in
● Cadmium concentrations
the earth’s crust
● Smoking
● Used for manufacturing stainless
● Placenta
steel.
TOXIC METALS

● Two types: ● Transferrin and albumin involved

o Hexavalent - more toxic in absorption and transport.
o Trivalent - less toxic o Transferrin binds to the
Chromium absorbed.
o Albumin accepts and
Health Effects of Chromium transports Chromium if the
transferrin sites are
● Trivalent chromium
saturated.
o Enhances insulin action.
● Excreted through the Urine.
o A dietary element
o Maintains the metabolism Toxicity of Chromium
of glucose, fat, &
● Cr (3+) protein complex
cholesterol
o Allergic dermatitis with
▪ Adequate daily
eczema
intake of chromium
● Cr (6+) Powerful oxidizing agent
(50 200ug/day) in
● Skin ulcer, renal & hepatic
adults
necrosis
● Hexavalent chromium
● Severe dermatitis & skin ulcers
o Considered as a
o Hexavalent chromium
carcinogen
salts
o Lung cancer may develop
if exposed to Cr(6+)
● Hexavalent:
▪ Workers in wood
o Carcinogenic
treatment,
o Airway irritant, airway
▪ stainless steel
obstruction, & possibly
welding,
lung cancer
▪ chrome plating,
o Nasal septum ulcers or
▪ the leather tanning
perforations
industry,
o Bronchitis or asthma
▪ and the use of lead
o Target organ: Lung
chromate or
▪ May also target
strontium chromate
kidneys, liver, skin,
paints are at risk.
& immune system

Absorption, Transport and Excretion of

Laboratory Evaluation of Chromium
Chromium
● GFAAS (Graphite furnace atomic
● Lungs, Skin and GI tract
absorption spectroscopy)
o Hexavalent chromium is
● NAA (Neutron activation analysis)
absorbed better than
trivalent chromium.
TOXIC METALS

● ICP MS (Inductively Coupled ▪ severe

Plasma Mass Spectrometry) gastroenteritis,
● Plasma, serum, and urine melena, abdominal
o do not indicate the total pain, and
body status of the hematemesis
individual (vomiting of blood)
o whereas urine levels may ▪ occurs up to 6
be useful for metabolic hours after
studies ingestion
● Acute iron poisoning - common in
young children
Treatment for Chromium o Usually caused by
ingesting products that
● For the skin:
contain iron.
o Antibiotic creams are
● Large doses of iron are thought
prescribed
to cause acute mucosal cell
o Topical chelating agents
damage
(EDTA)
● If it is inhaled:
● IRON OVERLOAD:
o Breathing aid
o Hemosiderosis - iron
● If it is severe: (Cancer)
overload that does not
o Chemotherapy
cause damage in tissues,
o Surgery
(Mild)
IRON o Hemochromatosis -
● 4th most abundant element excess iron that induces
● Most abundant transition metal tissue damage, (Rare)
● Classified as a trace element in ▪ Acquired caused by
the body overingestion of
● Oxygen transport in the blood iron, leakage of iron
● Participates in redox chemistry from red blood
(Both ferrous and cells.
● ferric states) ▪ Inherited
● Agent in redox & electron transfer (Hereditary
reactions hemochromatosis)
Primary iron
overload.
Health effects & Toxicity of Iron ● Systemic toxicity may occur (due
to iron poisoning): >30 mg/kg
● Iron intoxication o Cyanosis
o Vomiting - early o Convulsions
manifestation o Shock
TOXIC METALS

o Coagulopathy o Saturating concentrations

o Renal failure of iron are added to a
o Hepatic failure serum sample.
o Excess iron is removed.
● PERCENT SATURATION
Absorption, Transport and Excretion of o The percent saturation,
Iron also called the transferrin
saturation, is the ratio of
● Intestine
serum iron to TIBC.
o Iron must be in the ferrous
o Approximately 20% to
oxidation state
50%, but it varies with age
● Transported by transferrin
and sex.
o Iron is oxidized to ferric
state
● FERRITIN
o Measured in serum
● Excess iron that is not absorbed
▪ Various
is excreted in the feces
immunochemical
● Shedding of intestinal cells and
methods
bleeding normal losses of iron
o Iron deficiency anemia
● Excessive absorbed iron is
(low)
excreted in the urine
o Iron overload &
hemochromatosis (high)
Laboratory Evaluation of Iron o Chronic infections,
malignancy, and viral
● TOTAL IRON CONTENT (Serum hepatitis (often high)
Iron)
o Fe (3+) bound to ● TRANSFERIN
transferrin o Measured by
o Serum or heparinized immunochemical methods
plasma such as nephelometry.
o Oxalate citrate and EDTA o Iron deficiency (high)
▪ Cannot be used as o Iron overload &
they will bind with hemochromatosis (low)
iron and interfere o Chronic infections &
with the assay malignancy (low)
o Early morning sampling ● AAS
o Specimen with visible ● ICP ms (Inductively Coupled
hemolysis should be Plasma Mass Spectrometry)
avoided o Liver biopsy, a follow up to
abnormal blood results,
● TIBC especially with HH
TOXIC METALS

● Ferrozine colorimetric indicator, ● Involved in the enzymes:

used in modern clinical o Xanthine oxidase,
laboratory. aldehyde oxidase, and
● Iron quantification in liver is not sulfite oxidase
used for the evaluation of acute “Molybdopterin”
iron toxicity. ● Toxic doses of molybdenum may
● Hepcidin testing has not yet been cause anemia and copper
shown to be clinically useful. deficiency.
● Acute molybdenum toxicity Rare,
may be acquired through
industrial mining and
metalworking exposure
o Loss of appetite
o Loss of weight and hair
o Diarrhea
o Muscular incoordination
Treatment for Iron
● Chronic molybdenum toxicity
● Gastric lavage or Emesis o Loss of appetite
o Prevents iron absorption. o Unenergetic
● Chelation therapy with o Diarrhea
deferoxamine o Reduced growth rate.
o Severe acute intoxication

Absorption, Transport and Excretion of

MOLYBDENUM Molybdenum
● Hard, silvery white metal ● Well absorbed in the GI tract,
● Molybdenite, wulfenite, & (stomach and small intestines)
powellite ● Transported through the kidney,
● Used for the production of alloys liver, bones, and pancreas in its
o Corrosion inhibitors highest concentration.
o Flame retardants ● Excreted through the urine.
o Smoke suppressants o Some are excreted
o Lubricants through bile & sweat.
o Molybdenum blue
pigments
● Highest food levels are in leafy Laboratory Evaluation of Molybdenum
vegetables and legumes
● ICP Ms (Inductively Coupled
Plasma Mass Spectrometry)
● GFAAS
Health effects & Toxicity of Molybdenum
TOXIC METALS

● Blood levels are less than 60 o Thioredoxin reductase

μg/L
Toxicity of Selenium
● Acute oral exposure
Treatment for Molybdenum o Nausea, vomiting, and
diarrhea
● Limit the consumption of foods
o Tachycardia
that are high in levels of
● Chronic exposure
molybdenum.
o Nail diseases
o Skin and hair loss
o Neurologic problems
SELENIUM – soil is rich in selenium.
o Unsteady gait
● Naturally occurring metalloid o Paralysis
● Similar to sulfur (chemical &
Absorption, Transport and Excretion of
physical)
Selenium
● Essential trace elements
● Major constituent of 40 minerals ● Well absorbed in the GI tract and
& minor constituent of 37 others orally
● Used in the electronics industry ● Transported to the liver and
(Photocell) kidneys
● Other uses: ● Less in the heart, lung, spleen,
o Nutritional supplements pancreas and adrenals
o Pigments ● Also less in muscles and brain
o Pesticides ● Excreted through the urine and
o Rubber production feces
o Anti-dandruff shampoos
Laboratory Evaluation of Selenium
o Fungicides
● ICP Ms (Inductively Coupled
Health Effects of Selenium
Plasma Mass Spectrometry)
● 1930s selenium was considered ● GFAAS
a toxic element. ● Determination of urinary and
● 1940s considered as a blood selenium
carcinogen. o useful measure of
● 1950s it was declared as an selenium status.
essential element.
Treatment for Selenium
● 1960s & 1970s it has been
viewed as an anticarcinogen. ● Limit the consumption of foods
that are high in levels of
● Involved in the metabolism of Selenium.
thyroid hormones.
o Deiodinase enzymes
TOXIC METALS

● Highest concentration of a drug

obtained in the dosing interval.
THERAPEUTIC DRUG MONITORING
Trough conc.
● To establish maximum benefits
with minimal toxic effects for ● Lowest concentration of a drug
drugs whose correlations with obtained in the dosing interval.
dosage, effect, or toxicity is not
clear.
● Common routes of drug In general, drugs are eliminated from
administration: the circulation
o Oral
Prozam – treatment for obsessive
o IV (Intravenous)
compulsive disorder (OCD)
o IM (intramuscular)
o SC (subcutaneous)
Parameters: ROUTES OF ADMINISTRATION IN
TDM
● Liberation
● Absorption ● Intravenous
● Distribution o Most direct and effective
● Metabolism delivery to their site of
● Excretion action
● Oral administration
Remember:
o Least invasive
● Drugs are absorbed in the GI ● Intramuscular
tract. ● Subcutaneous
● Liquid is absorbed quickly than ● Inhaled
tablets. ● Absorbed through skin
● Drugs absorbed from the GI goes (transdermal patch)
through the liver. ● Rectal delivery
● Acidic drugs – bind to albumin. o Used in infants/ Oral
● Basic drugs – bind to alpha-acid delivery not possible.
glycoprotein (AAG)
● Some drug binds to both albumin
and AAG DRUG ABSORPTION
● Only free drugs can interact with In Oral Administration
target sites and produce a
response. Factors:

Peak conc. ● Dissociation from its administered

form
TOXIC METALS

o In Absorption, Tablets and o Standard dose, Total

capsule < Liquid plasma drug may be within
● Solubility in gastrointestinal fluids therapeutic range
o Stomach, weak acids are o High free fraction
efficiently absorbed ▪ Has toxic effects
o Intestine, weak bases are o Low free fraction
efficiently absorbed ▪ Less / non
● Diffusion across gastrointestinal therapeutic effect
membranes o Factors:
o Passive diffusion (From ▪ Inflammation
GIT into Bloodstream) ▪ Malignancies
o Hydrophobic / Nonionized ▪ Pregnancy
state ▪ Hepatic disease
▪ Nephrotic syndrome
Absorption factors:
▪ Malnutrition
● Intestinal motility ▪ Acid base
● pH disturbances
● Inflammation o Fraction of free drugs is
● Presence of foods/ Drugs affected by the
o Morphine concentration of
▪ May slow substances that compete
gastrointestinal for binding sites.
motility ▪ Other drugs
o Antacids, Kaolin, ▪ Endogenous
Sucralfate, substances: Urea,
Cholestyramine, antiulcer Bilirubin, Hormones
medication
● Age ● Bound, Drug protein complexes
● Pregnancy o Albumin, majority of
● Pathologic conditions protein constituents in
plasma
Predicting the final circulating
▪ Change in
concentration in blood from standard
concentration
oral overdose can be difficult.
affects Free vs
● TDM is used for effective oral Bound status of
dosage regimens. drugs
FREE VS BOUND DRUGS o Alpha 1 acid
glycoprotein increase,
● Free drug fraction, Active during acute phase
▪ Increased binding
of drugs such as:
TOXIC METALS

● Propranolol, Hepatic mixed function oxidase

● Quinidine, system (MFO system)
● Chlorpromazi
● MFO system is Non specific
ne
● Hydrophobic substances ->
● Cocaine,
Enzymatic reactions -> water
● Benzodiazep
soluble products -> Bile/general
ines
circulation -> (Elimination) Renal
o Measurement of free drug
filtration
fraction should be
● Phase I -> Phase II -> Water
considered for drugs that
soluble drugs -> Elimination
are highly protein bound.
Phase I reactions
● Produce reactive intermediates
DRUG METABOLISM
Phase II reactions
● All substances absorbed from the
intestine enter hepatic portal ● Conjugate functional groups
system.
(Glutathione, glycine, phosphate, and
First pass metabolism sulfate) -> Reactive sites on the
intermediates = Water soluble
● GIT -> Liver (Liver uptake) ->
products
Circulation
o Liver metabolism may be ● Example
influenced by genetics, o Acetaminophen
Pharmacogenomics. o Glutathione
o Impaired liver function, ● During overdose, Phase I >
decreased capacity to Phase II
metabolize drugs o Depleted conjugating
groups
Most drugs are xenobiotics,
o Accumulation of Phase I
exogenous substances capable of
products
entering biochemical pathways intended
o Leading to Toxic effects
for endogenous substances.
▪ Irreversible damage
to hepatocytes
Biotransformation MFO system can be induced
● Enzymatic process that produces Xenobiotics, inducers of MFO system
a therapeutically active (MFO substrates)
metabolite from the drugs.
● Certain drugs may affect their
● Patients with liver disorder
own rate of elimination
may require reduced dosages
TOXIC METALS

o Competitive and non ● Digoxin and amiodarone are

competitive drug frequently ordered therapeutic
▪ drug interaction drug levels.
o Drug food interaction
CLASS OF CARDIOACTIVE DRUGS
Acetaminophen + Alcohol
● Class I - Rapid Na+ channel
● More toxic blockers
● Results to accelerated clearance ● Class II - Beta receptor blockers
and shorter drug half life ● Class III – potassium channel
blocker
Hepatic disease, loss of functional
● Class IV - calcium channel
tissue
blockers
● slower rate of clearance, longer
drug half life.
Cardioactive Drugs
● Digoxin
DRUG ELIMINATION
o Foxglove
● Drugs not secreted or subject to o Sodium Potassium pump
reabsorption o 0.8-2 ng/mL
o Elimination of free drugs o Treatment for CHF
directly related GFR ● Quinidine
● Decreased GFR o Treatment of rapid
o Increased drug half life irregular heartbeats
and elevated plasma o Antimalarial, antipyretic
concentration and oxytocic effects
o 2 Formulation:
Aminoglycoside antibiotics
▪ Quinidine Sulfate
● Cyclosporine ▪ Quinidine gluconate
o Not secreted or ● Procainamide (Pronestyl)
reabsorbed by the renal o NAPA
tubules (N-acetylprocainamide)
o Drug induced lupus
● Disopyramide
CLASSIFICATION OF THERAPEUTIC o Substitute for quinidine
DRUG o Anticholinergic effects
Cardioactive / Antiarrhythmic Drug
● Used to treat arrhythmias Antiarrhythmic Drugs
● Lidocaine (Xylocaine)
TOXIC METALS

o Local anesthetic and o “Red man syndrome”

antiarrhythmic o Nephrotoxic and ototoxic
o 1’ product of hepatic
metabolism:
▪ MEGX ANTIEPILEPTIC DRUGS
(monoethylglycinex
● Anticonvulsants
ylidide)
● Phenytoin, carbamazepine and
● Propanolol
valproic acid are commonly
o Treatment for angina
available on either clinical
pectoris
chemistry or immunoassay
● Amiodarone (Cordarone)
analyzers
o blocks potassium channels
in the cardiac muscle Types of Antiepileptic Drugs
o Iodine containing drugs ● Phenobarbital
o Hyperthyroidism o Slow acting barbiturate
● Verapamil o Enhances bilirubin
o Treatment for angina, metabolism
hypertension, o Primidone
supraventricular ● Phenytoin (Dilantin)
arrhythmias o Used treatment for seizure
ANTIBIOTICS disorders
● Valproic Acid (Depakene)
● Bacteriostatic vs Bactericidal
o Used treatment for seizure
● Broad Spectrum vs Narrow
disorders
spectrum
o Treatment for Petit mal
Types of Antibiotics (Absence seizures) and
grand mal (tonic-clonic)
● Aminoglycoside
● Carbamazepine (Tegretol)
o Treatment for Gram
o Treatment for grand mal
negative bacterial
(tonic-clonic)
infections
● Ethosuximide
o Nephrotoxic and ototoxic
o Drug of choice for
o Amikacin, Gentamycin,
controlling petit mal
Tobramycin, Kanamycin
seizure
● Chloramphenicol
● Felbamate
o Treatment of infection
o Known for its toxicity and
caused by gram negative
is primarily indicated in
bacteria.
severe epilepsies such
● Vancomycin
as in children with the
o Treatment for Gram (+)
mixed seizure disorder
cocci and bacilli
TOXIC METALS

Lennox Gastaut o Treatment for bipolar

syndrome. disorder (manic
● Gabapentin depression)
o Similar to neurotransmitter ● Tricyclic Antidepressant
GABA o a class of drugs used to
● Lamotrigrine (Lamictal) treat depression,
o use is indicated in patients insomnia,
with partial and o extreme apathy, and loss
generalized seizures of libido.
● Levetiracetam o Amitriptyline, Nortriptyline,
o use is indicated in patients Desipramine, Imipramine,
with partial and Diazepam
generalized seizures ● Clozapine
● Oxcarbazepine o used to treat otherwise
o It is indicated for the treatment refractory
monotherapy of partial schizophrenia
seizures and in ● Olanzapine
secondarily generalized o treats schizophrenia, acute
tonic clonic seizures. manic episodes, and the
● Tiagabine recurrence of bipolar
o It is indicated in treating disorders
partial seizures.
IMMUNOSUPPRESIVE DRUG
● Topiramate
o Indicated in partial and ● Medications that suppress
generalized seizures. immune response
● Zonisamide ● Treat organ transplant rejection
o Implicated in the therapy
Types of Immunosuppressive Drugs
of partial and generalized
seizures. ● Cyclosporine
o Suppression of host
PSYCHOACTIVE DRUGS
versus allograft rejection of
● According to WHO, these are heterotopic transplanted
substances that, when taken in or organs.
administered into one's system, ● Tacrolimus
affect mental processes, e g o 100 times more potent
perception, consciousness, than cyclosporine
cognition or mood and emotions ● Sirolimus (Rapamycin)
o It is U.S. Food and Drug
Types of Psychoactive Drugs
Administration approved
● Lithium for patients receiving
kidney transplants.
TOXIC METALS

● Mycophenolic Acid o inhibits the thromboxane,

o used most commonly as which affects the bleeding
supplemental therapy with / coagulation of the blood
cyclosporine and and platelet function
tacrolimus in renal o A blood thinner
transplant patients. ● Common cause of adverse
effect in children
ANTINEOPLASTIC DRUG
o Trinder’s Spot test -
● Chemotherapeutic Agents determinesthe presence of
● Assessment of the therapeutic salicylates
benefit and toxicity of most
Acetaminophen (Tylenol)
antineoplastic drugs is not aided
by TDM ● An analgesic anti pyretic drug,
similar to salicylate
Types of Antineoplastic Drug
● Main problem is it is hepatotoxic
● Methotrexate drug
o Inhibition of proliferation of o Destroys the liver
malignant cells and benign
cells
o Other medications same RA 9165 (Comprehensive Dangerous
as methotrexate: Cisplatin, Drug Act of 2001)
Cyclophosphamide
● Busulfan
o treat a certain type of Drug Testing
chronic myelogenous
● 45 ml – required amount.
leukemia (CML)
o In strasinger, 30-45 mL
BRONCHODILATORS ● 60 mL
o Single collection – 45-60
● Theophylline
mL is allowed
o Treatment for Asthma and
▪ The problem is in
other COPD
collection of 45 mL,
Salicylates only 30 mL is given
in DOH,
● Most commonly associated anti
● there should
pyretic analgesic drugs
be a backup
o Lowers fever.
specimen
o Pain killer
▪ If positive in DTL
● MOA – inhibits the thromboxane
(Drug Testing
and prostaglandin
Laboratory), it will
● Disadvantage –
TOXIC METALS

alarm the DOH for ● Shabu

confirmation
Different forms of Meth
o Split collection – 30mL in
one container, and 30 mL
in the second container
▪ Two containers with
the same control
number
▪ Ideal for DOH
specimen MDMA
● Observed / Unobserved – ways
of collection. ● Methylenedioxymethamphetamin
o Observed – watches the e (MDMA) is an illicit
patient during collection. amphetamine derivative
o Unobserved – does not ● “Ecstasy”
watch the patient during ● Designer drugs
collection. How methamphetamine affects the brain
METHAMPHETAMINE ● Effects on dopaminergic
● Stimulant pathways
● Found in sleeping pills ● Increased mental alertness
● White saliva (Like milk) ● Competitive inhibitors of the
● Methamphetamine is a variant of enzyme monoamine oxidase
amphetamine, was first Routes of Administration
synthesized in Japan in 1893
● Methamphetamine went into wide ● Injection
use during World War II ● Smoked
● In the 1950s, methamphetamine ● Orally
was prescribed as a diet aid and ● Inhalation
to fight depression Desired effects of Meth
● In 1970, the US government
made it illegal for most uses ● hallucinations
● euphoria (extreme happiness)
Street Names of Meth ● empathic and emotional
● Crank responses
● Crystal meth ● increased visual and tactile
● Speed sensitivity
● Glass Adverse effects of Meth
● Ice
● Chalk ● headaches
● nausea
TOXIC METALS

● vomiting ● Bloody shot eyes

● anxiety ● Schizophrenia
● agitation
COCAINE
● impaired memory
● violent behavior ● Derived from the coca plant
● tachycardia ● Crack – potent form of cocaine
● hypertension ● Also known as Coke, Coca, Cola
● respiratory depression o Coca Cola used cocaine
● seizures as part of the ingredient
● hyperthermia ● Clearance varies
● cardiac toxicity o For drug testing, it is
● liver toxicity questioned if you take
● renal failure medication
● Ecgonine – derivative for cocaine
Treatment for Meth overdose
● Benzoylecgonine – major
● No specific antidote for metabolite of cocaine
amphetamine or
methamphetamine overdose is
known OPIATES
● Propranolol for cardiovascular
● Commonly used pain killers in the
symptoms
hospital
Therapeutic value for Meth ● Has pinpoint pupils
● Oxycontin – more potent than
● Narcolepsy
● Derived from the opium poppy
● Attention deficit disorder
plant
AMPHETAMINE - stimulant
PHENCYCLIDINE
● Bennies
PCP (Phenylcyclohexylpiperidine)
● Uppers
● Dixies ● Angel dust / Angel hair
● A hallucinogen that was originally
used as an anesthetic, which can
MARIJUANA provide the user a wide variety of
physical and behavioral effects.
● Hashish
● Ingested, injected, or inhalation
● Derived from Cannabis sativa –
with the use of tobacco or
cannabinoid
marijuana.
o Hallucinogen
● All subjects show cognitive
● THC (Tetrahydrocannabinol)
disorganization:
o Metabolite of marijuana
o Difficulty in focus
● Makes you hungry
TOXIC METALS

o Deficiencies with abstract o Ingestion of high dosage

thinking of LSD
o Halting speech o Agonistic effect of LSD
● PCP effects are often compared o Parasympathetic CNS is
with symptoms of having affected
Schizophrenia. ● enhanced sense of clarity but
● reduced ability to control what is
experienced
● changes in the sense of time,
hallucinations, blurred vision, and
synesthesias
Street Names of LSD
● Acid
● Dots
● Blotter
● Window pane
● Battery acid

LSD (Lysergic acid diethylamide)

● one of the most potent SEDATIVE-HYPNOTICS
pharmacologic materials ● Sedative
● have both agonistic and o reduces excitement, calms
antagonistic effects on the patients (without
dopaminergic pathways. inducing sleep)
● Mind bending effects o Most sedatives in larger
● Most powerful mind-altering doses produce hypnosis
chemicals o Tranquilizers
● Not known to be addicting ▪ Used in animals if
o But can lead to tolerance they misbehave
when used frequently ● Hypnotics
● Can lead to PTSD, insomnia o A drug which produces
● Primarily affects the sympathetic sleep resembling natural
and parasympathetic nervous sleep
system.
o Sympathetic – voluntary Anxiolytic - Anxiety is a feeling of
o Parasympathetic - tension, anxiety, or uneasiness by the
involuntary known or unknown cause.
● Bad trip – caused by panic
reaction by LSD.
TOXIC METALS

Barbiturates
● Condensation products of urea
and malonic acid
● Barbitals
Benzodiazepines
● Benzodiazepam
● Diazepam (Valium)
TOXICOLOGY

● STUDY OF TOXINS extensive periods greater than 3

● Deals with the adverse effects of months
toxins. o Alcohol
Routes of Administration
● Ingestion – can be intentional. ALCOHOL
● Inhalation
Ethanol
● Transdermal – pesticides
● Not just specifically found in
Dose-Response relationship
alcoholic beverages
● Can also be found in cosmetic
and cleaning products.
● Additive in food coloring
● Fuel
● Most common substance of
abuse
● Interfere with iron transportation
Mechanism of Action
● ED50 – dose of the drug, in ● A CNS depressant
which 50% of the population out o Such as Beer
of a hundred individuals had ● NAD+ Pyruvate will be converted
therapeutic effect. (Effective into lactate + NADH
dose) o Lactic acidosis – formed
● TD50 – dose of the drug, in which due to accumulation of
50% of the population out of a lactate
hundred individuals had adverse
Anesthesia will not be given to patients
effect.
who are ethanol intoxicated.
● LD50 - dose of the drug, in which
50% of the population out of a ● It will not work, patient is already
hundred individuals have died sedated due to ethanol
(little effect, causes mortality) ● Similar mechanism as ethanol
o Suppresses level of
Exposure
glucose
● Acute exposure – single
Synapse – found in the end of neurons
exposure, yet your body had
responded immediately (adverse ● Releases neurotransmitters –
effect.) norepinephrine, nitric oxide
o Carbon monoxide ● Muscles for response
● Chronic exposure – multiple
exposures, repeated exposure,
TOXICOLOGY

● Na-K (ATPase) pump will be o Ocular toxicity – lead to

transported into the cell due to optic neuropathy
ethanol (blindness)
ETHANOL
● Alcohol dehydrogenase - ISOPROPYL ALCOHOL
Oxidizes alcohol
Metabolism of Isopropyl alcohol:
● Acetic acid – final product of
alcohol ● Alcohol Dehydrogenase –
● Alcohol also increases blood flow produces Acetone –
to the skin =Turned pink o Major metabolite of
● Dehydration – due to polyuria isopropanol
● Carbon dioxide
● Water
Gastric lavage - treatment
ETHYLENE GLYCOL
● Calcium oxalate – seen in
patients with ethylene glycol
intoxication.
● 0.03 – 0.12% - Most common
● Most common alcohol that is
percentage (in vehicular
ingested in children.
accidents)
o Due to impairment of
motor skills
CARBON MONOXIDE
● 0.09 – 0.25 – loss of critical
judgement, memory impairment ● Cherry red color of the face
● 0.18 – 0.30 – staggering, slurred ● Shift to the left
speech ● Binds with skeletal and
● 0.27 – 0.40 – unable to stand, myocardial muscle
walk / vomiting ● Cerebral vasodilation
● If exceeds 0.5% - it can lead to ● Cannot be detected by the
coma and death senses.
o Colorless
o Odorless
METHANOL o Tasteless
● Silent killer
● Final product of methanol –
● Source:
formic acid
o Gasoline engines
● Methanol – a wood alcohol
o Improperly ventilated
● Formic acid
furnaces
TOXICOLOGY

● Lethal carbon monoxide Severe headaches, fatigue,

o Can occur in a closed 30
impairment of judgment
garage within 10 minutes.
● Higher affinity of carbon 40-50 Confusion, fainting on exertion
monoxide for hemoglobin is
200-225 times greater than for Unconsciousness, respiratory
oxygen 60-70 failure, death with continuous
● High carboxyhemoglobin exposure
o Half life – 60-90 minutes
o Carboxyhemoglobinemia - 80 Immediately fatal
Inspired air contained
0.1% carbon monoxide by
volume = 50%
Two quantitative assays for COHb
carboxyhemoglobinemia at
equilibrium ● Spectrophotometry
● Too much exposure to carbon ● Gas chromatography
monoxide can lead to cerebral
DNS (Delayed Neurological Sequelae)
edema.
o Due to lack of oxygen and ● Due to oxidative damage to the
nutrition brain
Methods for Carbon Monoxide MBP (Myelin Basic Protein)
● Spot test - Persistence of a pink ● Causes immunologic reaction.
solution is consistent with a
Treatment for Carbon Monoxide
COHb level of 20% or greater
● 100% oxygen (from oxygen tank)
COH
Symptoms and Comments
b (%)
CYANIDE
0.5 Typical in nonsmokers
● Silver cleaners
● Bitter almond odor
5-15 Range of values seen in smokers
● Musty old sneakers smell
o Sometimes Odorless
Shortness of breath with
10 ● Super toxic substance
vigorous exercise
o Tasteless
o Colorless
Shortness of breath with
20 ● Sources
moderate exercise
o Tapioca
o Almonds
TOXICOLOGY

● Core of the apple contains

cyanide.
● Sodium thiosulfate – dilutes the
cyanide
● Commonly used in suicidal
attempts
● Trivia: Sodium nitrite is injected
into meats, but it is advertised as
no preservatives
o Sodium nitrite is
carcinogenic.
o Found in canned goods as
well.
 TOXICOLOGY

A. TOXICOLOGY
➢ The study of poisonous substances
➢ Exposure to toxins may be due to suicide attempt, accidental exposure, occupational
exposure.
➢ GIT absorption= passive diffusion
➢ NOT all toxins can be absorbed by the GIT but may produce local effects
➢ WORK-UP FOR DRUG OVERDOSE:
o CBC
o Serum electrolytes
o BUN
o Glucose
o Urinalysis
o ABG
➢ Routes of exposure could be through ingestion, inhalation, and transdermal absorption.
➢ Confirmatory Test: GC-MS
➢ TD50: Dose that would be predicted to produce a toxic response in 50% of the
population
➢ LD50: Predicts death in 50% of the population
➢ ED50: predicted to be effective in 50% of the population

TOXIC AGENTS

A. ALCOHOL
➢ ETHANOL/ grain alcohol
➢ Most common abused drug
➢ Inhibits Vasopressin
➢ May result to ketoacidosis and lactic acidosis
➢ It increases osmolality of the blood
➢ ETHANOL ACETALDEHYDE ACETYL COENZYME A (Uses Alcohol
Dehydrogenase)
➢ ANTIDOTE: Diazepam
➢ Sampling
o Anaerobic collection
o Alcohol-free skin cleaner for disinfection
o Serum: capillary blood and arterial blood are preferred
o Methods: GLC, Enzymatic (Alcohol Dehydrogenase)- PREFFERED,
Electrochemical oxidation
o RESULTS: High liver enzymes (ALT, AST, GGT)
0.01-0.05 No obvious impairment
0.03-0.12 Impaired motor skills
0.09-0.25 Loss of critical judgment, memory impairment
0.18-0.30 Staggering, slurred speech
0.27-0.40 Unable to stand, walk, vomit
0.35-0.50 Death
>/=0.10 Causes VA

➢ Methanol/ Wood alcohol

➢ Commonly used solvent
➢ Formaldehyde is converted to Formic acid through alcohol dehydrogenase
➢ May cause blindness and metabolic acidosis
➢ Isopropanol/ rubbing alcohol
➢ Acetone is the metabolite of isopropanol
➢ May result to high acetone in the blood and urine
➢ ANTIDOTE: activated charcoal
➢ Ethylene glycol
➢ An anti-freeze
➢ Metabolites: oxalic acid and glycolic acid
➢ May result to metabolic acidosis
➢ Caox in urine
➢ HPLC is the preferred method
Alcohol Fatal Dose
Ethanol 300-400 mL
Methanol 60-250 mL
Isopropanol 250 mL
Ethylene Glycol 100 rams

B. METALS
1. Lead
➢ inhibits enzymes and Vitamin D metabolism; results to decreased 25-Hydroxylase and
increase in ALA
➢ Inhibits pyrimidine-5’-nucleotidase and Na-K ATPase resulting to diminished integrity of
RBC membrane
➢ Rapidly eliminated from plasma, hence serum and plasma specimens should not be used
➢ Indication of toxicity: urinary ALA, free protoporphyrin, + basophilic stipplings
➢ Removed by therapeutic chelators: EDTA and Dimercaptosuccinic acid (DMSA)
➢ Toxic dose: >0.5 mg/day; fatal dose: 0.5g
➢ Specimen: WB (preferred); urine (for recent exposure)
➢ Methods: Zinc Protoporphyrin Test, Delta-ALA test, AAS, X-ray Fluorescence of bones,
Anodic Stripping Voltammetry, Inductively Coupled Plasma Emission Spectrophotometry
 [Link]/ Quick Silver
➢ Binds with Sulfhydryl protein
➢ Inhibits COMT- enzyme essential in the metabolism of catecholamines
➢ Major toxic effect: Pink disease (acrodynia) and erethism
➢ Specimen: WB and 24-hr urine
➢ Method: Reinsch test
[Link]
➢ Inhibits sulfhydryl groups
➢ Common agent of heavy metal poisoning
➢ It can cross the placenta
➢ Chronic exposure: Mees lines- nail specimen
➢ Odor of garlic breath and metallic taste
➢ ANTIDOTE: Bristish Anti-Lewisite (“arsenic-rescue”)
➢ Methods: Reinsch Test, AAS
➢ Fatal dose: 120 mg (arsenic trioxide); 30 ppm (arsenic gas)
4. Cadmium
➢ + GGT in urine
➢ Toxicity may result to destruction of Type 1 Epithelial cells in the lungs and decreased
resistance to bacterial infections.
➢ It may accumulate in renal tubules causing tubular damage
C. CARBON MONOXIDE
➢ Colorless, odorless and tasteless
➢ Silent killer
➢ Binds with heme proteins like cytochromes, hemoglobin and myoglobin
➢ Has higher affinity for hemoglobin (200x more than Oxygen)
➢ Shift to the left
➢ Toxic level: 20%
➢ Affects brain and heart
➢ “Cherry-red” color of the face
➢ Uses WB (EDTA)
 D. Cyanide
➢ Bitter almond odor/ musty old sneaker smell
➢ Super toxic substance
➢ Binds to iron
➢ Inhibits Electron transport chain resulting to cell death
➢ Alters mental status
➢ ANTIDOTE: Sodium thiosulfate, amyl and sodium nitrite
➢ Toxic level: >2 ug/mL
E. Pesticide
➢ Affects the neurotransmitter Acetylcholine
➢ Confirmatory Tests: Erythrocytic acetylcholinesterase, pseudocholinesterase

B. THERAPEUTIC DRUG MONITORING

1. Cardiotropics- used to treat Congestive Heart Failure and arrhythmias
➢ Classes:
o I- blocks sodium influx
o II- Beta receptor blockers
o III- blocks repolarizing potassium currents
o IV- slows Calcium influx

➢ TOXIC SIDE EFFECTS: gastric disturbances, nausea, vomiting, atrial and ventricular
arrythmias
• Digitalis glycosides- inhibits Na-K ATPase pump
• Digoxin- causes release of Calcium in myocardium
1. Effect: 1-2 hours (oral)
2. Short half-life: 35-40 hours
3. Excreted unchanged in urine- 50-75%
4. Therapeutic level: 0.5-2 ng/mL
5. Toxic level: >3 ng/mL
• Digitoxin
1. Long half-life: 4-6 days (oral)
2. Effect: 1-4 hours (maximum of 8 hours)
3. Absorbed: 90-100%
4. Therapeutic level: 9-25 ng/mL
• Procainamide (Pronestyl)- anti-arrhythmic drug and used to treat supraventricular or
ventricular arrhythmias; causes decreased myocardial excitability
TOXIC SIDE EFFECTS: reversible lupus-like syndromes by binding of NAPA to monocyte
and macrophage membrane proteins to stimulate production of autoantibodies
• Half-life: 3-5 hours
 • Therapeutic level: 4-10 ug/mL
• Toxic level: >12 ug/mL
• 50-60% excreted in urine unchanged
• Metabolite: N-ACETYL PROCAINAMIDE (NAPA)
• Quinidine- treat supraventricular and ventricular arrhythmias and tachyarrythmias;
causes decreased myocardial contractility
TOXIC SIDE EFFECTS: Cinchonism, vertigo, tinnitus, death
• 60-85% metabolized by the liver
• 20% excreted in urine
• Half-life: 5-12 hours
• Therapeutic level: 2.3-5 ng/mL
• Effect: 1-3 hours
• Lidocaine (Xylocaine)- anti-arrhythmic drug and local anaesthetic; prevents arrhythmia
after MI; decrease rate of ventricular diastolic depolarization
TOXIC SIDE EFFECTS: convulsion, bradycardia, and hypotension
• IV: 50-100 mg
• Half-life: 2 hours
• Therapeutic level: 1.2-5.5 ug/mL
• Effect: 5-8 hours
• 10% excreted in urine
• Metabolized by the liver via dealkylation
• End-product: Monoethylglycinexylidide (MEGX)
• Propranolol- treat angina pectoris, hypertension after MI, CAD, arrhythmias; has
antagonizing effects of epinephrine
TOXIC SIDE EFFECT: Thrombotic cytopenic purpura
• Half-life: 3 hours
• Therapeutic level: 50-100 ng/mL
• Effect: 6 hours
• 0.5% excreted in urine unchanged

2. Anti-convulsant- treats seizure

• Phenobarbital- for seizure, anxiety, insomnia; given to infants with mothers that addict
to barbiturates; enhances metabolism of bilirubin
• Half-life: 4-6 days
• Completely absorbed
• Brain is the main site for storage
• Contraindicated in porphyria, partial porphobilinogen, deaminase deficiency
• Phenytoin (Dilantin)- for tonic-clonic, simple partial or complex seizure; blocks sodium
and calcium influx
TOXIC SIDE EFFECTS: nystagmus, ataxia, stupor, arrhythmia
 • Half-life: 24 hours
• Stored in brain
• Primidone (Mysoline)- for tonic seizure
TOXIC SIDE EFFECTS: sedation, same with phenytoin
• Complete absorption
• Half-life: 12 hours
• Metabolites: PHENOBARBITAL, PHENYLETHYLMALONAMIDE (PEMA)
• Ethosuximide (Zarontin)- for petit mal, not bound to protein
TOXIC SIDE EFFECTS: drowsiness, ataxia, SLE, Aplastic anemia, pancytopenia
• Metabolite: DESMETHYLMETHSUXIMIDE
• Carbamazepine (Tegretol)- anti-epileptic drug; for treating tic douloureux; reduce of
excitatory synaptic transmission; decreases sodium and calcium influx
TOXIC SIDE EFFECTS: light headedness, drowsiness, aplastic anemia, agranulocytosis,
thrombocytopenia
• Metabolite: 10,11 EPOXIDE FORM, 10,11 DIHYDROXYFORM
• Valproic acid (Depakene)- for seizure; enhance GABA
TOXIC SIDE EFFECTS: sedation, somnolence, pancreatitis

3. Anti-asthma
• Theophylline
• Bronchodilator
• Prevents attack
• Emphysema
• Increases relaxation of the smooth muscle of the bronchial airways and pulmonary
blood vessel
• Toxic effects: tachycardia, arrhythmia, seizure, GI bleeding

4. Anti-inflammatory
• Acetaminophen ( Tylenol)
• Analgesic and anti-pyretic
• Metabolite: GLUCORONIDE, SULFATE CONJUGATES, DEACETYLATED DERIVATIVES,
HYDROXYLATED DERIVATIVES
 • Inhibits prostaglandin
• Toxic side effect: anemia
• Acetylsalicylic acid (aspirin)
• Antipyretic and anti-inflammatory
• Inhibits prostaglandin
• SI absorption
• Cause of FATAL DRUG POISONING IN CHILDREN

5. Psychoactive Drugs
• Lithium- for manic-depressive illness (bipolar)
• TCA- treat depression, insomnia
• Fluoxetine/ Prozac- blocks re-uptake of serotonin

6. Antibiotics

7. Immunosuppressive Drugs

8. Anti-Neoplastic Drugs
• Methotrexate- Inhibits DNA synthesis in all cells (blocking dihydrofolate reductase)
9. Busulfan
• Leukemia and lymphoma prior to BM transplant
TUMOR MARKERS

The laboratory test that can be used to ● Stage 4 – malignant tumor

assess if a patient has cancer or not.
Enzymes
CANCER
● ACP – can be used to diagnose
● Uncontrolled growth of cells for prostate cancer, but it is not
which forms a solid mass or specific.
tumor (neoplasm) o RBC
● Eventually, it will spead into other o Prostate
organs of the body (metastasis) o PSA (Prostate specific
antigen) – ideal (50 and
above)
● LD – for hematologic
malignancies
o Not specific
o Peripheral blood smear –
ideal for hematologic
malignancies
● ALP – normally used to detect
liver and bone diseases
(metastatic carcinoma of the
bone, Hepatocellular CA,
osteocarcinoma, lymphoma,
leukemia)
Stages of Cancer
o Not specific
o In situ hybridization - ideal
● NSE (Neuron-specific enolase) –
used for neuroendocrine tumors
(malignant glands that secrete
hormones)
o Not specific
Protein
● M-protein – plasma cell
dyscrasia (multiple myeloma,
Waldenstroms
macroglobulinemia)
● Free-light chains – plasma cell
● Stage 1 – hyperplasia dyscrasia (multiple myeloma,
● Stage 2 – dysplasia Waldenstroms
● Stage 3 – in situ cancer macroglobulinemia)
TUMOR MARKERS

● Beta 2-microglobulin – for hormone secretion) is

hematologic malignancies ideal for ADH
(lymphoproliferative disorders, ● C-peptide – needed for the
multiple myeloma) production of insulin
o PBS is more preferred to o Can be used for insulin
use secreting tumor
● AFP (Alpha Feto Protein) – a (insulinoma), but
protein that is secreted by the C-peptide cannot be used
yolk sac alone.
o Can be used to detect ● Calcitonin – a hormone that
hepatocellular carcinoma lowers the calcium level
o Secreted by the
Endocrine (hormones/metabolites)
parafollicular cells of the
● ACTH (adenocorticotropic thyroid
hormone) – can be used for o For MTC (Medullary
pituitary adenoma (benign tumor) Thyroid Carcinoma)
o Comes from anterior o For Neuroendocrine
pituitary (corticotrope) Tumor
o Ectopic ACTH producing ● Chromogranin A – can be used
tumor for pheochromocytoma (high
o Not specific for pituitary epinephrine, common in elderly),
adenoma neuroblastoma (common in
● ADH (Anti-Diuretic children), carcinoid tumors, small
hormone/Vasopressin) – posterior cell lung cancer.
pituitary tumor o Not specific for
o Secreted by the pheochromocytoma
hypothalamus and goes to ● Cortisol – for adrenal tumors
the storage site, which is o Secreted by adrenal gland
the posterior pituitary. through adrenal cortex
o Not specific for posterior (zona fasciculata)
pituitary tumor o Not specific
▪ Oxytocin is also o Cushing syndrome (high
secreted, but it cortisol) and Addison
cannot be used disease (low cortisol)
because it is heavily should be correlated with
affected by ACTH to confirm
emotions (it ● Gastrin – used for detecting
fluctuates) Zollinger-Ellison syndrome
o SIADH (syndrome of (hyper secretion of gastrin,
inappropriate antidiuretic results in too much acid),
TUMOR MARKERS

Neuroendocrine tumor, o To diagnose

Gastrinoma neuroblastoma,
o Not specific pheochromocytoma,
● GH (Growth Hormone) – used paraganglioma
for diagnosing pituitary adenoma o Not specific
o Secreted by anterior ● B-HCG (Beta-Human Chorionic
pituitary (somatotropes) Gonadotropin) – for pregnancy
o Ectopic growth hormone testing
producing tumor o Used for diagnosing
o Acromegaly – excessive choriocarcinoma.
production of growth
Carbohydrate / Cancer Antigen
hormone in adults
▪ OGTT – for ● CA 19-9 – can be used for
confirmation pancreatic cancer
● HVA (Homovanillic acid) – a ● CA 15-3 – can be used for breast
metabolite of dopamine cancer
o To diagnose o ELISA immunoassay
neuroblastoma, ● CA 27-29 – can be used for
pheochromocytoma, breast cancer
paraganglioma o ELISA immunoassay
o Not specific ● CA 125 – can be used for ovarian
o Urine can be used as a cancer
specimen
Other antigens
● Metanephrine – metabolite of
epinephrine ● CEA (Carcinoembryonic antigen)
o can be used for o Not specific for colorectal
pheochromocytoma, cancer, but has a high
paraganglioma, percentage rate that it is
neuroblastoma colorectal cancer
● 5-HIAA (Hydroxyindole acetic ● PSA
acid) – metabolite of serotonin o PSA level is directly
o For detecting carcinoid related to the size of gland
tumors Hormone Receptors
● Parathyroid Hormone – for
parathyroid adenoma ● Estrogen receptors – can be
● PRL (Prolactin) – for pituitary used for breast cancer
adenoma, prolactinoma o Immunohistochemistry
o Secreted by the anterior method
pituitary (lactotropes) ● Progesterone receptors – can be
● VMA (Vanillyl Mandelic Acid) – used for breast cancer
urine metabolite of catecholamine
TUMOR MARKERS

o Immunohistochemistry ● Her2/neu – used for breast,

method ovarian, and Gastrointestinal
Tract cancer
Growth Factors
● Transforming Growth Factors
alpha and beta Breast Cancer
o Alpha-TGF – for epithelial
cell tumor
▪ Breast, stomach,
colon, liver
▪ Excellent marker for
malignancies, but it
is not specific
o Beta-TGF – found in liver
and bladder carcinoma.
▪ Not tumor specific
● Platelet-derived Growth Factor –
derived from platelets Colorectal Cancer
o Sarcoma, carcinoma
● Basic Fibroblast Growth Factor –
can be used for epithelial cell
tumors and other (lung cancer,
lymphoma)
o Primarily ____
o Not tumor specific
● Epidermal Growth Factor – can
be used for stomach and tongue
cancer
● Hepatocyte Growth Factor – for
non-malignant liver disease
Growth Factor Receptors ● Fecal Occult-Blood test or CEA
(Carcinoembryonic antigen)
● EGF-receptor (Epidermal Growth
Factor receptor) – used for head,
neck, ovarian, and cervical Ovarian Cancer
cancer
o An excellent marker for
asbestos tumors (but
asbestos is obsolete
already)
TUMOR MARKERS

● PSA, ACP

● CA-125 (most helpful and

available)

Pancreatic Cancer

● CA 19-9
Prostate Cancer