Renal Disorders:

Electrolytes & Acid Base

Emily Dornblaser, PharmD, MS, BCPS

UNE School of Pharmacy
Objectives
• Review the buffer systems that regulate pH in the body
• Evaluate Arterial blood gas results and identify potential physiologic
causes of abnormalities
• Identify causes, symptoms, and clinical presentation of Metabolic
Acidosis and Alkylosis
• Review regulation systems of sodium and water in the body
• Classify types of Hyponatremia based on clinical lab values, physical
exam and patient history
• Review clinical presentation and diagnosis of electrolyte disorders
including potassium, magnesium, calcium and phosphorus
Acid Base Outline
• Buffer systems and their regulation
• ABG’s
• Metabolic Acidosis
• Gap vs Non-Gap (hyperchloremic)
• Renal tubule acidosis
• Compensation
• Metabolic Alkalosis
Acid Base Chemistry
• Most important extracellular buffer system:
• CO2 + H2O <--> H2CO3<--> H+ + HCO3-
• HCO3- is regulated by the kidneys (BASE) Bicarb

• pCO2 is regulated by the lungs (ACID) CO2

• pCO2 is the amount of CO2 dissolved in the blood

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Acid Base Balance
• Extracellular Buffering:
• Bicarbonate buffer system regulates pH by eliminating eliminating base through
renal excretion or acid through ventilation
• Renal (Metabolic) regulation:
• Excretion of HCO3-
• Respiratory regulation:
• Increased CO2 elimination with increased breathing
• Decreased CO2 elimination with decreased breathing

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Acid Base Disturbances

Acidosis Alkylosis
pH <7.35 pH > 7.45

HCO3- HCO3-
Metabolic
(no base) (too much base)

Respirato CO2 CO2

ry (too much acid) (no acid)

all your base are belong to us

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Acid Base Compensations

Acidosis Alkylosis
pH <7.35 pH > 7.45

HCO3- HCO3- Can be done

Metabolic CO2 CO2 quickly
(no base) (too much base)

Respirato CO2 - CO2 - Takes a while

HCO3 HCO3 for kidneys to
ry (too much acid) (no acid) respond

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Acid Base Outline
• Buffer systems and their regulation
• ABG’s
• Metabolic Acidosis
• Gap vs Non-Gap (hyperchloremic)
• Renal tubule acidosis
• Compensation
• Metabolic Alkalosis
Measuring Acid Base Status
• Arterial Blood Gas (ABG):
• pH: 7.35-7.45
• PaO2: 80-100mmHg
• PCO2: 35-45
• HCO3: 22-26 (shoot for 24)
• SaO2: >95%
• Written as: pH/pCO2/PO2/HCO3-

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Reading ABG’s
• Step 1: pH
• Is it acidosis or alkalosis?
• Step 2: respiratory or metabolic?
• Is the PCO2 abnormal or is the HCO3- abnormal
• Step 3: Is there compensation occurring?
• Is pH close to normal but the PCO2 and HCO3- are out of whack... (more to
come on this later)
 Practice
pH/pCO2/PO2/HCO3-

• 7.17 / 73 / 69 / 24

• 7.51 / 37 / 120 / 33

• 7.14 / 35 / 140 / 15

• 7.34 / 30 / 100 / 15

• 7.48 / 30 / 78 / 26
Outline
• Buffer systems and their regulation
• ABG’s
• Metabolic Acidosis
• Gap vs Non-Gap (hyperchloremic)
• Renal tubule acidosis
• Compensation
• Metabolic Alkalosis
Metabolic Acidosis
Causes: Low HCO3-

•Consumption of HCO3- for buffering of an exogenous acid or an

accumulated organic acid (lactic acid, ketoacids)
• “GAP Acidosis”
•Renal losses of HCO3- or extra-renal losses of HCO3- (diarrhea)
• “Non-GAP Acidosis”

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Clinical Presentation
• Chronic metabolic acidosis is typically asymptomatic and not severe
• Severe (pH<7.2): typically due to an acute process
• Signs:
• Cardiac- rapid heart rate, wide pulse pressure
• CNS- obtundation or coma
• Respiratory- Hyperventilation, dyspnea
• GI- nausea, vomiting, loss of appetite

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Compensation
• Respiratory buffering- increase respiratory rate to increase PCO 2 elimination
• PCO2 decreases by about 1-1.5mmHg for every 1mEq/L drop in HCO 3- below
24.

• If the PCO2 is not as expected there may superimposed respiratory alkalosis

or acidosis

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Two Types/Causes
Metabolic Non-GAP acidosis Metabolic GAP acidosis
(Hyperchloremic states)
(MUDPILES)
•GI Bicarbonate loss • Methanol ingestion
• Uremia
• Renal Tubular Acidosis
• Diabetic Ketoacidosis

• Type I • Propylene Glycol

• Isoniazid

• Type II • Lactic Acid

• Ethylene glycol

• Type IV • Salicylates
Step 1: Determine if there is acid
accumulation (GAP) or loss of base (Non
Calculating Anion Gap
• Anion Gap: the difference between the anions and the cations in your serum
• If there is a gap in the anions it means there is another anion present that
you are not ‘seeing’ on your basic metabolic panel.

AG = [Na+] - [Cl-] - [HCO3-]

• Normal AG is approximately 9-11

• There is an adjustment factor for Sodium if you have severely elevated glucose
levels in DKA! Rember to do this before calculating the Anion Gap
Non-GAP Acidosis
Renal Tubular Acidosis

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Renal Tubule Acidosis
Proximal: Fail to reabsorb bicarbonate (HCO3-)
• Type 2: hypokalemia
• Can be caused by carbonic anhydrase inhibitors (waste bicarb)
Distal: Fail to excrete acid (H+)
• Type 1: hypokalemia
• Type IV: hyperkalemia

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
GAP Acidosis
(MUDPILES)

Most common two types: • Methanol ingestion

• Lactic Acidosis • Uremia

• Diabetic Ketoacidosis
• Diabetic Ketoacidosis
• Propylene Glycol
• Isoniazid
• Lactic Acid
• Ethylene glycol
• Salicylates

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Lactic Acidosis
• Lactic acid is produced as a byproduct of the anaerobic
metabolism of glucose
• Present when lactate levels are above 4 or 5 mEq/L
• Occurs due to either tissue hypoxia (anaerobic environment) or
impaired oxidative functioning w/in the cell (meds)

Devlin JW et al. Chapter 61: Acid-Base Disorders

In: DiPiro JT et. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 2011
Lactic Acidosis
• Medications are often a culprit!
• Metformin
• NRTI’s (didanosine, stavudine, zidovudine)
• Propofol
• Propylene glycol- solubilizing agent for IV drugs (lorazepam)
• Linezolid
• Cyanide toxicity
• Overdoses of salicylates, isoniazid or iron
• Impaired liver function leads to a decrease in lactate metabolism therefore decreased elimination
Diabetic Ketoacidosis (DKA)
• Typically occurs in type 1 diabetes
• Characterized by ketoacidosis, ketourea
• WHY?
• Goal is to reduce the ion gap by stopping ketosis from occurring
• Physiologically you have a hypertonic state
• What does this do to fluid in the body?
• How does this affect Na+, how does this affect K+, how does this affect HCO3-?
Metabolic Alkalosis
High HCO3-
• Under normal circumstances the kidney is able to readily excrete
excess bicarbonate
• Consider :
1) what caused the alkalosis
2) why are they maintaining alkalosis
 Metabolic Alkalosis:
Causes
• Excessive loss of chloride or hydrogen
• Excessive vomiting or NG suction
• Diuretics- lose Na, K, Cl
• Renal tubule hydrogen loss

• Administration of exogenous bicarbonate

• Milk-alkali syndrome
 Metabolic Alkalosis:
Causes
Impaired Excretion:
Sodium Chloride responsive
• Typically due to volume depletion
• decreased volume means decreased GFR thus
decreased ability to remove bicarb

Sodium Chloride unresponsive

• hyperaldosteronism, hypokalemia, excessive black
licorice intake, mineralocorticoid excess
• typically due to hormonal imbalances
image courtesy of: www.soda-
Clinical Presentation
• Mild-moderate alkalosis is typically asymptomatic (may see signs of
whats causing the alkalosis)

• Severe alkalosis (pH >7.6): cardiac arrythmia’s, mental confusion,

hypoxemia

• Patients tend to be difficult to remove from a ventilator--> have low

drive to breathe
Compensation
HYPOVENTILATION
• Increases pCO2--> try to retain acid

• Increases of 6-7mmHg for each 10mEq increase in bicarbonate

Up Next…. Electrolyte Disorders
• Sodium Disorders
• Potassium
• Magnesium
• Calcium
• Phosphate
Mechanisms of Modulation
Na+ H2O
Tonicity vs Osmolarity
• Osmolarity: the property of a solution that describes how many
particles are dissolved in it.
• Describes the concentration of a solution in terms of the number of particles
it contains.
• 1 osmol= # of particles in 1 mole

• Tonicity: the property of a solution in relationship to a membrane. It is

the number of solutes that can contribute to osmotic pressure
• Osmotic pressure drives osmosis (movement of water across a membrane)
Hypernatremia
(Na+ >145mEq/L)
• Epidemiology:
• Incidence in general medical-surgical patients is 1-7.9%
• Mortality is based on rapidity of development, ranges from 10-70%
• Acute increases >160mEq in adults is associated with a 75% mortality rate

• Commonly associated with those who have an impaired thirst drive or lack ability to
drink on their own
• Newborns and nursing home residents at risk
Hypernatremia
• Always associated with hypertonicity resulting from deficit of water relative to the ECF
• Due to either hypotonic fluid/ water loss or hypertonic fluid administration/ sodium
ingestion
• Causes water to move from ICF to ECF which can cause rupture of cerebral veins
and hemorrhage
•Signs and Symptoms:
• Weakness, lethargy, restlessness & confusion, progressing to twitching, seizures,
coma, death
• Serious symptoms typically occur at >160mEq/L
Hypernatremia Causes
• Do you have too much salt on board?
• You ate too much or you retain too much! (hypervolemic)
•Do you have too little water on board?
• Did you loose just free water?
• Diabetes Insipidus (isovolemic)
•Did you loose more free water than salt?
• Dehydration (hypovolemic)
• Osmotic diuresis
• Caused by solutes: hypovolemic
• Caused by obstruction: isovolemic
Hypervolemic: Sodium Overload
Presentation
• Ingestion of greater than 4 TBSP of salt can result in another form of
osmotic diuresis

• Manifests as polyuria and high Uosm (urine osmoles-> concentrated urine)

• Excess sodium is excreted in the urine in patients with normal renal function
Isovolemic: Diabetes Insipidus
• Central DI: decreased in ADH release
• Causes: Head trauma, CNS malignancy, hypoxic encephalopathy

• Nephrogenic DI: decreased renal response to ADH

• Causes: lithium toxicity, cidofovir, foscarnet, demeclocyline; hyperCa; HypoK,
aquaporin defect
• Results in large volumes (3-20L) of dilute urine daily
• Desmopressin test used to determine if central (response) or nephrogenic (no
response)
Hyponatremia
(Na+<135mEq/L)
• Up to 28% of patients admitted to an acute care hospital have
hyponatremia
• The incidence is 2 fold higher in nursing home residents

• Drug-induced hyponatremia is more common in women than men

• Transient or permanent brain dysfunction results from acute

hypo-osmolality or too rapid a correction of hypo-osmolar
patients
Hyponatremia
• Symptoms are related to magnitude and rapidity of onset.
• Mild: typically asymptomatic
• (Na+ 125-130 mEq/ml)

• Moderate: Nausea, malaise, headache, lethargy, restlessness, disorientation

• (Na+ 115-125 mEq/ml)

• Severe: Seizures, coma, respiratory arrest, brainstem herniation and death

• (Na+ <115 mEq/ml)
Hyponatremia
• Decreases in serum sodium cause water to shift into cells causing them swell
• Brain cells can alter their intracellular osmolarity to minimize cell volume
changes but this takes time
• Maximal compensation takes ~48hrs
• Too rapid a correction of sodium results in rapid brain cell shrinking and may
lead to osmotic demylination syndrome

• Correct sodium by no more than 8-12mEq/24hrs

Hyponatremia work up
• Must determine potential time of onset Is this chronic or acute?
• Acute likely manifests with symptoms  means you can correct quickly
• Chronic allows body time to autoregulate  means fast correction is harmful

• Must determine severity

• Mild-moderate correct slower
• Severe necessitates a faster correction
Determining Type of Hyponatremia

First Step: Determine plasma osmolality

Low Osmolality Elevated Osmolality

(<280mOsm) (>280mOsm)

HYPO tonic HYPERtonic

hyponatremi hyponatremi
a a

NaCl NaCl

290mos 290mos
NaCl m m
H2O H2O
NaCl
 HYPERtonic Hyponatremia

• Hypertonicity indicates increased, non-sodium, effective osmoles

• Typical causative agents: Glucose, mannitol, glycine, sorbitol
• Evaluate past medical history to look for cause:
• Uncontrolled Type 1 DM, recent mannitol tx for elevated ICPs,
sorbitol use as an outpatient
• Treatment is focused on the underlying cause
 NaC Na
NaC NaCl Cl
l
l
Cells
290

HYPOtonic Hyponatremia NaC

l
mos
m H2O
NaCl
NaCl
Swell
(brain
cells) Na
Cl

Step 2: Determine volume status (ECF

status)

Hypovolemic Euvolemic Hypervolemic

Uosm >450
Usom Usom Decreased EABV
(concentrated
>100 <100 Uosm >100mOsm
urine)
 (hypotonic)

Hypovolemic HypoNa+
Hypovolemic
• Renal Losses (UNa >20mEq/L)
• Adrenal insufficiency waste sodium at nephron
Uosm >450
• Thiazides (concentrate
d urine)

• Extra-renal Losses (UNa <20mEq/L)

• Hypotonic loss of fluid (diarrhea, vomiting, sweating)
 (hypotonic)
Euvolemic HypoNa+: (too much
water)
Euvolemic

Concentratin Diluting
g Urine Urine
Reabsorbing Usom Usom Excreting
H2O >100 <100 H2O

Excreting UNa UNa Reabsorbing

Na+ >20mEq/ <20mEq/ Na+

Primary Polydipsia
SIADH Low solute intake
 (hypotonic-euvolemic)
Syndrome of Inappropriate
Antidiuretic Hormone (SIADH)
• Causes of SIADH:
• tumors (lung cancer), head trauma, stroke, meningitis, pulmonary
infections

• Medications causing SIADH:

• Phenothiazines, TCA’s, SSRI’s; Carbamazepine, Cyclophosphamide,
Vincristine
 (hypotonic)

Hypervolemic HoNa+
• Increased ECF volume occurs when renal sodium and water
excretion are impaired
• There is a decreased effective circulating volume (plasma
volume) due to the disease state (low output, low oncotic
pressure)
• Decreased plasma volume triggers increased renal Na+
reabsorption and a non-osmotic ADH release to increase H2O
reabsorption
 (hypotonic)

Hypervolemic HoNa+
Hypervolemic

Decreased EABV
Uosm Reabsorbing
>100mOsm H2O

UNa Reabsorbing
<20mEq/ Na+

CHF
Cirrhosis
Nephrosis
Review of HoNa+
Serum Osm Urine Osm Urine Na+
Normotonic Normal Normal Normal
Hypertonic High (>290) High >20
Hypotonic Hypovolemic
Renal Losses Low (<270) High >450 >20
Extrarenal losses Low (<270) High >450 <20
Hypotonic Euvolemic

SIADH Low (<270) >100 >20

1* Polydipisa Low (<270) <100 <20

Hypotonic Hypervolemic

CHF/Cirrhosis Low (<270) >100 <20

HS Case
• A 66 yr old woman (67” and 60kg) presents w/ nausea, vertigo and
disorientation over the last several days. She was recently started on
carbamazepine for treatment of trigeminal neuralgia. Labs today show a
serum sodium of 108mEq/L

• What is likely causing her hyponatremia?

• What type of hyponatremia is this?
• What would you expect her Uosm and UNa to be?
Disorders of Potassium &
Magnesium

Emily K. Dornblaser, PharmD, MS, BCPS

 Hyperkalemia
(K >5.0mEq/L)
+

• Epidemiology- much less common

• Mild: 5.0-5.9 mEq/L
• Moderate: 6.0-7.0 mEq/L
• Severe: >7.0 mEq/L

• Typically due to CKD or acute renal failure

• Other causes: newly started medications

Hyperkalemia
Clinical Presentation
• Usually asymptomatic- may notice heart palpitations
• Signs:
• Cardiovascular- peaked T waves, widened PR interval, widening of QRS
• Labs: K> 5.0mEq/L
Hyperkalemia
• Initial Work Up:
• Evaluate Labs: Scr, BUN and calculate FeNa to evaluate acute renal failure

• Differential: Review PMHx for CKD or diseases related that may be causing
undiagnosed CKD; review medications that could cause Acute renal failure,
evaluate fluid state for dehydration

• Diagnostics: Obtain EKG to evaluate for cardiac conduction abnormalities

 Causes of Hyperkalemia
• Increased K+ intake
• Typically pts with stage 4 or 5 CKD
• Decreased K+ excretion
• Typically seen in acute renal failure or aldosterone inhibition
• ACE-I; ARB’s; K+ sparing diuretics; NSAIDS; TMP/SMX
• Tubular unresponsiveness to aldosterone
• sickle cell anemia, systemic lupus erythematosus (SLE)
• Redistribution of K+ into ECF
• Metabolic acidosis, DM, lactic acidosis
 Hypokalemia
(K+ <3.5mEq/L)
• Epidemiology- common
• Mild: 3.1-3.5 mEq/L
• Moderate: 2.5-3.0 mEq/L
• Severe: <2.5 mEq/L

• 50% of patients treated with a loop or thiazide diuretic have

hypokalemia
Hypokalemia
Clinical Presentation
•Symptoms: cramping, weakness, malaise, myalgia's
•Signs:
• Cardiovascular- ST segment depression, T-wave inversion
• Heart block, A. flutter, atrial tachycardia, V. Fib, digoxin induced
arrhythmias
•Labs: K< 3.5 mEq/L; may see Mg <1.7mg/dL
Hypokalemia
• Initial Work up:
• Evaluate Labs: Magnesium, Bicarbonate, pH,

• Diagnostics: Obtain EKG to evaluate for cardiac conduction abnormalities

Hypokalemia
Causes:
•Drugs:
• Intracellular shift (Beta receptor agonists, theophylline, caffeine)
• Increased renal loss (diuretics, PCN’s, Mineralocorticoids,
Amphotericin B)
•Loss of K+ rich volume (diarrhea or vomiting)
•HypoMagnesemia- causes renal wasting of K+ and decreased
intracellular amounts

There is no method for storing K+ in the body,

thus maintaining intake is important
Magnesium
• Serum Magnesium: 1.6- 2.4 mEq/L
• Fourth most abundant EC cation, second most abundant IC cation
• Thus serum magnesium concentrations may not accurately reflect total
body content
• Principally found in bone (67%) and muscle (20%)
• Common clinical electrolyte abnormality typically manifests as cardiac
or neuromuscular alterations
 Hypermagnesemia
(Mg >2.4mEq/L)
• Epidemiology: rare, typically in CKD patients or elderly
• Pathophysiology:
• As GFR declines magnesium levels increase
• Causes: decreased excretion (ARF, CKD); excessive intake; Other
(lithium, milk-alkali syndrome)
• Symptoms: lethargy, confusion, muscle weakness
 Hypermagnesemia
Clinical
(Mg >2.4mEq/L)
Manifestations
Aystole 15
Complete Heart
block 14
13
Resp.
12 depression
11 muscle paralysis

10 Coma
9 somnolence
8
7 hyporeflexia
QRS, PR interval
prolongation 6 hypotonia
BBB, Nodal
Rhythms, primary 5 sedation
heart block
Bradycardia; QT
prolongation 4
 Hypomagnesemia
(Mg <1.6 mEq/L)
Clinical Presentation:
•Symptoms: tetany, twiching, convulsions, heart
palpitations
•Signs: cardiac arrythmias (V.fib, torsades), widened
QRS complex, peaked T waves
Hypomagnesemia
Causes:
• Decreased intestinal absorption is most common cause
• Regional enteritis, Ulcerative Colitis, diarrhea
• Renal loss often associated with medications
• Cyclosporine/tacrolimus; AmphoB; Cisplatin; Foscarnet, thiazide
diuretics
• Renal loss associated with tubular defects:
• Renal tubular acidosis, post-obstructive diuresis, acute tubular
necrosis
Disorders of Calcium &
Phosphate
Calcium
• Normal Serum Calcium level: 8.5-10.5mg/dL
• 0.5% of calcium is in the serum, 99% is stored in the bones
• Serum calcium is moderately bound to albumin, the ionized (iCa)
or ‘free’ form is physiologically active
• Measured plasma calcium includes bound and unbound drug
• Corrected SCa = Measured SCa + [0.8 x (4-Albumin)]
• Changes in binding affect iCa
• In patients with truly altered albumin or critically ill patients
measuring an iCa will give better indication of calcium status
Calcium Homeostasis
• Parathyroid hormone (PTH) is increased in response to low calcium or high
phosphorus
• PTH increases osteoclast and blast activity--> increased calcium mobilization from
bone
• PTH increases renal calcium reabsorption and decreases phosphorus reabsorption
at kidney
• PTH increases renal activation of 1,25-OH Vitamin D3 --> increased intestinal
calcium absorption
• Net effect of increased PTH is an increase in serum calcium and calcitonin
Hypercalcemia
Clinical Presentation
•Symptoms: depend on severity and onset
• Severe (>13mg/dL): N/V; anorexia, constipation, polyuria, confusion
• Crisis (>15mg/dL): acute renal insufficiency, obtundation

•Signs:
• Renal- nephrolithiais, decreased concentrating ability, renal insufficiency
• Cardiovascular- shortens QT interval, spontaneous VT’s

•Complications:
• Deposition of calcium-phosphorus complexes in blood vessels, heart valves, kidney stones
 Hypercalcemia
(Ca2+ > 10mg/dL)
Epidemiology:
• Cancers- breast, multiple myeloma, lymphoma, lung (20-40% of
cancer pts)
• many secrete PTH
• Primary hyperparathyroid is the most common cause in general
population
• Occurs due to parathyroid adenomas (85%) and parathyroid
hyperplasia (15%)
Hypercalcemia
• Initial work up:
• Calcium level, Albumin level for correction, Phosphate level, vitamin D level
• Consider an ionized calcium in the setting of altered albumin binding (sepsis, low
albumin, dialysis/Uremia)

• Physical Exam: review for signs of calciphylaxis if CKD, mental status evaluation

• Past Medical History Review: cancer, bone degeneration, severe GERD and
antacid use, vitamin D toxicity

• Diagnostics: KUB if nephrolithiasis concerns, EKG

 Hypocalcemia
(Ca2+ < 8.5mg/dL, iCa<1.0)
• Primary causes:
• Vitamin D deficiency- needed for appropriate absorption of
calcium
• Hypomagnesemia- impairs PTH secretion
• Drug ketoconazoleinduced- furosemide, bisphosphonates,
cinacalcet,
• Phenobarbital and phenytoin increase catabolism of Vit. D
• Acute changes in protein binding (sepsis, alkalosis)
Hypocalcemia
Clinical Presentation
• Symptoms: depend on severity and onset
• Parasthesia, muscle cramps, anxiety, depression

• Signs:
• Neurologic- Tetany (hallmark sign), neuromuscular irritability,
extrapyramidal disorders, dystonias
• Cardiovascular- hypotension, prolonged QT
Phosphorus
• Normal Phosphorus level: 2.5-4.5mg/dL
• Major role in regulating and modulating cellular function,
primarily found intracellularly as organic esters
• Free inorganic phosphate is what is used to make ATP
• Absorption from GI tract mediated by vitamin D
• 85-90% is reabsorbed in the kidney at the proximal tubule
• Reabsorption is decreased by PTH and Vit D
 Hyperphosphotemia
(PO4 > 4.5mg/dL)
• Etiology:
• Occurs frequently in acute renal failure and is a universal finding in CKD
• Tumor lysis syndrome, hemolysis and rhabdomyolysis (endogenous
release)
• Exogenous phosphate loads- fleets enemas, soda/dairy, Vitamin D
increases PO4 absorption
• Acidosis can trigger shift from ICF to ECF
Hyperphosphotemia
Clinical Presentation
•Symptoms: depend on severity and onset
• Acute: GI disturbances, lethargy, seizures
• Chronic: pruritis, “red eye”- deposition of Ca-PO4 crystals

•Signs:
• Calciphylaxis- necrosis of the tissue caused by precipitation of Ca-PO4 crystals
• Results from elevated Calcium-Phosphorus product- Goal ___________(KDOQI
guidelines)
 Hypophosphotemia
(PO4 < 2.4 mg/dL)
Primary causes:
• Decreased GI absorption:
• Phosphate binders, diarrhea, Vit. D deficiency
• Reduced tubular reabsorption:
• Fanconi syndrome, metabolic acidosis, acetazolamide, steroids,
hyperparathyroidism
• Intracellular redistribution: refeeding syndrome, alcoholism, calcitonin,
catecholamines, TPN
Hypophosphotemia
Clinical Presentation
• Symptoms: depend on severity and onset
• Irritability, apprehension, weakness, paresthesia,
confusion, Severe can result in seizures or coma