Acid and Base Electrolytes

Question 1

Hyponatremia

• Spurious
• Pseudohyponatremia
• Hyperglycemia
• True hypotonic hyponatremia

Answer 1

Spurious

• blood is drawn proximal to an IV infusion or from a central venous line

Pseudohyponatremia

• May affect any instrument that utilizes “indirect” method of measurement in which sample is prediluted before analysis
• These analyzers calculate the plasma/serum sodium on assumption that water content of plasma is 93%
• The above assumption may be incorrect in the following in which water content in original sample is lower than 93%
  
  • hypertriglyceridemia
  • hypercholetersolemia
  • hyperproteinemia
• Serum osmolarity is normal and an osmolal gap is present
• Direct potentiometry, as performed on blood gas analyzers, not affected

Hyperglycemia

• True physiologic shift in sodium ions into extracellular space, producing hyponatremia that is real but unrelated to an intrinsic defect in sodium homeostasis
• Hypertonic (>295 mOsm/kg) hyponatremia suggests marked hyperglycemia, but can be seen in mannitol administration

​True Hypotonic Hyponatremia (<280 mOsm/kg)

Question 2

Degree of change in sodium concentration attributable to glucose calculated by:

Answer 2

Question 3

True hypotonic hyponatremia

Answer 3

< 280 mOsm/kg

• Patient is hypovolemic
  
  • ​Renal losses
    
    • suggested by increased urine sodium (U_Na > 30 mmol/L)
    • may be caused by
      
      • diuretics
      • renal medullary disease
      • primary adrenal insufficiency (Addison disease)
      • renal tubular acidosis Type I
      • Cerebral salt wasting syndrome
  • Extrarenal sodium losses
    
    • GI tract (vomiting, diarrhea)
    • 3rd spacing (peritonitis, pleuritis)
    • Suggested by low urine sodium (U_Na<30)
• Patient is euvolemic
  
  • ​SIADH
  • Psychogenic polydipsia
  • hypothyroidism
  • primary adrenal insufficiency (Addison)
  • drugs with ADH like effect (vasopressin)
    
    • desmopressin
    • SSRIs
    • TCAs
    • ecstasy
• Patient is hypervolemic
  
  • ​CHF
  • cirrhosis
  • nephrotic syndrome

Question 4

Hypernatremia

Answer 4

• Most commonly seen in people with excess water loss and inability to respond to their thirst: infants, ICU, and debilitated
  
  • extrarenal water loss:
    
    • diarrhea
    • vomiting
    • burns
  • Renal water loss
    
    • osmotic diuretics
    • loop diuretics
    • postobstructive diuresis
    • intrinsic medullary renal disease
• May be iatrogenic: administration of sodium as part of IV fluids, Na HCO3, or other intervention
• Diabetes insipidus
  
  • Central
    
    • damage to the hypothalamus or neurohypopysis related to surgery
    • Space occupying lesions in/near sella
    • head trauma
    • infiltrative lesions such as eosinophilic granuloma and sarcoidosis
  • Nephrogenic
    
    • Medullary diseases (sickle cell and tubulointerstitial nephritis)
    • electrolyte disturbances (hypokalemia and hypercalcemia)
    • renal tubular acidosis
    • Fanconi syndrome
    • drugs (lithium, demeclocycline, colchicine, amphotericin B, gentamicin, furosemide)

Question 5

Hypokalemia

Answer 5

1. Renal loss
   
   1. Elevated urinary potassium (U_K > 30 mEq/day)
   2. Diuretics
   3. hypomagnesemia
   4. antibiotics (carbenicillin, amphotericin B)
   5. mineralcorticoid excess
   6. renal tubular acidosis types I and II
   7. severe Cushing syndrome
   8. congenital adrenal hyperplasia
   9. Bartter syndrome
   10. Liddle syndrome
   11. Gitelmand syndrome
   12. licorice
   13. hyperreninism

• GI loss
  
  • Urinary potassium is low (U_K < 30 mEq/day)
  • Vomiting
  • NG tube suction
  • diarrhea
  • large villous adenoma
• Trancellular shift
  
  • metabolic alkalosis or correction of diabetic ketoacidosis
  • In diabetic ketoacidosis there is an initial hyperK (like most acidotic states), but correction of DKA results in profound hypokalemia unless supplemental potassium is given

Question 6

Pseudohyperkalemia

Answer 6

• Pseudohyperkalemia
  
  • elevated measured potassium in absence of in vivo hyperK
  • Causes
    
    • In vitro cellular leak of potassium from hemolysis
    • in vitro clot formation (release of potassium from platelets especially in patients with hyperkalemia; serum has a higher potassium result than plasma for this reason)
    • leukocytosis
    • Prolonged tourniquet time
    • excessive fist clenching
    • traumatic draw
    • inappropriate order of tubes drawn
    • venipuncture proximal to IV infusion and small gauge needles

Question 7

Hyperkalemia etiology

Answer 7

1. acidosis
   
   • nearly all cases of acidosis have hyperK, exceptions including RTA I and II in which potassium is low
2. renal failure
3. potassium sparing diuretics (SEAT)
   
   1. spironolactone
   2. triameterene
   3. amiloride
   4. eplelrenone
4. adrenal insufficiency
5. iatrogenic
6. rhabdomyolysis

Question 8

Calcium metabolism

Answer 8

• 50% of serum calcium is bound to protein, mainly albumin
• in hypoalbuminemia free (ionized) calcium is normal but total calcium is low
• acidosis decreases binding of calcium to albumin, increasing free calcium
• alkalosis decreases free calcium

Question 9

Hypercalcemia presentation

Answer 9

• nephrolithiasis
• lethargy
• hyporeflexia
• slowed mentation
• nausea
• vomiting
• constipation
• depression
• high peaked T waves on ECG
• increased risk of pancreatitis
• increased risk of peptic ulcer disease
• long term hypercalcemia with concomitant hyperphosphatemia results in metastatic calcification of vessel walls and soft tissue (calciphylaxis)

Question 10

Hypercalcemia etiology

Answer 10

• Primary hyperparathryoidism
  
  • excess PTH results in
    
    • increased serum calcium with decreased serum phosphate
    • increased chloride/phosphate ratio
    • increased urinary cAMP
  • Causes:
    
    • Parathyroid adenoma
    • 4-gland hyperplasia
    • parathyroid carcinoma
• Secondary hyperparathyroidism
  
  • excessive secretion of PTH in response to hypocalcemia of any cause (most often chronic renal failure)
• Tertiary hyperparathyroidism
  
  • after long period of secondary hyperPTH, autonomous parathyroid function may develop
  • post renal transplant
• Malignancy
  
  • mostly from PTH related protein in SCC of lung, head and neck, skin, cervix, esophagus, breast
  • T cell lymphoma
  • small cell carcinoma of ovary
  • paraganglioma
  • renal cell carcinoma
  • islet cell tumors
  • multiple myeloma
  • HCC
• Familial hypocalciuric hypercalcemia: CASR gene on 3q
• Drugs
  
  • thiazides
  • calcium-containing antacids or calcium supplements (milk-alkali syndrome)
  • Hypervitaminosis D: increased calcium and phosphate
• Hyperthyroidism
• Addison
• acromegaly
• Sarcoidosis
• Addison
• Immobilized Paget patient

Question 11

Assays for PTH hormone

Answer 11

• Sensitive to particular portions of the PTH molecule
• N terminal and intact PTH have biological activity and are rapidly cleared from the blood (t_1/2 of 5 minutes)
• PTH-C and PTH-M have t_1/2 of up to 36 hours

Question 12

Forms of parathyroid hormone

Answer 12

• Intact PTH: biologically active, short half-life
• N-terminal PTH: biologically active, short half-life
• Mid-region PTH: not biologically active, long half-life
• C-terminal PTH: not ​biologically active, long half-life

Question 13

Hypocalcemia presentation

Answer 13

• Neurologic excitability
  
  • perioral tingling (parasthesia)
  • muscle spasm
  • hyperreflexia
  • Chvostek sign
  • Trousseau sign
• lengthened QT interval
• low voltage T waves
• dysrhythmias
• laryngeal spasm
• tetany
• respiratory arrest

Question 14

Etiology of hypocalcemia

Answer 14

• Hypoproteinemia
• Low albumin, ionized calcium usually normal
• Chronic renal failure: hyperphosphatemia
• Drugs (HAM LOG)
  
  1. heparin
  2. glucagon
  3. osmotic diuretics
  4. loop diuretics (e.g., furosemide)
  5. aminoglycosides
  6. mithramycin
• Hypoparathyroidism:
  
  • most often iatrogenic
  • post-surgical
  • hypomagnesemia (however, mild transient hypomagnesemia may increase PTH)
  • DiGeorge syndrome
  • autoimmune
• Medullary thyroid carcinoma: rarely affects serum Ca
• Hyperphosphatemia: calcium chelation
• Vitamin D deficiency: Most have normal calcium levels
• Pancreatitis: extensive calcium deposition
• Massive transfusion: citrate

Question 15

Define:

Acidemia

Alkalemia

Answer 15

Acidemia: arterial pH < 7.35

Alkalemia: arterial pH > 7.45

Question 16

Simple acid/base disorder

and

Complex acid/base disorder

Answer 16

• simple: primary acid base disturbance and associated compensation
• complex: more than one primary acid base disturbance

Question 17

Henderson-Hasselbalch equation

Answer 17

pH = pKa + log(base/acid)

pH = 7.4 (normally)

pKa = 6.1

bicarbonate = 24 mol/L

acid (carbonic acid) = 0.03 x PaCO2 = 0.03 x 40 mmHg = 1.2 mol/L

Thus, pH = 6.1 + log(bicarb/[0.03 x PaCO2])

Question 18

Classifying an acid base disorder

Answer 18

1. Determine the primary abnormality
   
   • Metabolic acidosis: bicarb decreased (< 25 mEq/L)
   • Respiratory acidosis: pCO2 usually > 44 mmHg while pH decreases
   • The above are opposite for alkalosis (metabolic alk: bicarb > 25 and for respiratory pCO2 < 40 mmHg)
2. Determine if compensation is appropriate
3. Differentials

Question 19

How to determine if compensation in acid base disorder is appropriate

Answer 19

• Metabolic acidosis: for each 1.3 mEq fall in bicarb, the pCO2 should decrease by 1.0 mmHg
• Metabolic alkalosis: for each 0.6 mEq rise in bicarb, the pCO2 increase by 1 mmHg
• Respiratory alkaloses or acidosis
  
  • Acute: for each 1 mmHg change in pCO2 the bicarb changes by 0.1 in the same direction
  • Chronic: for each 1 mmHg change in pCO2 the bicarb changes by 0.4 in the same direction

Question 20

Calculations and differential for metabolic acidosis

Answer 20

Characterized by presence or absence of anion gap and osmolal gap

• Calculate the anion gap:
  
  • anion gap = [Na] - [Cl] - [HCO3]
  • normal is <12
  • In nonanion gap acidosis the chloride level is often elevated
  • A low anion gap may be caused by hypoalbuminemia and paraproteinemia
• Calculate the osmolal gap:
  
  • osmolal gap = osm_measured - (2[Na] + [glucose]/18 + [BUN]/2.8)
  • [Na] is in mEq/L, [glucose] is in mg/dL, and [BUN] is in mg/dL
  • when international units are used:
    
    • osm_measured - 2[Na] - [glucose] - [BUN]
  • Normal osmolal gap <10
• Increased anion gap (>=12)
  
  • methanol
  • uremia
  • ketoacidosis (diabetes, EtOH, starvation)
  • Paraldehyde
  • Lactic acidosis
  • ethylene glycol
  • salicylate
• Normal anion gap (<12)
  
  • diarrhea
  • recovery phase diabetic ketoacidosis
  • ureterosigmoidostomy
  • NH₄Cl
  • Carbonic anhydrase inhibitors
  • Total parenteral nutrition
  • Renal tubular acidosis
• Increased osmolal gap
  
  • with metabolic acidosis
    
    • methanol
    • propylene glycol
    • paraldehyde
    • ethanol (sometimes)
  • without metabolic acidosis
    
    • isopropanol
    • glycerol
    • sorbitol
    • mannitol
    • acetone
    • ethanol (sometimes)

Question 21

Differential for metabolic alkalosis

Answer 21

Metabolic alkalosis: disorders characterized by chloride responsiveness or resistance

• Chloride responsive (U_Cl < 10)
  
  • diuretic therapy
  • vomiting
  • nasogastric tube suction
  • villous adenoma
  • carbenicillin
  • contraction alkalosis
• Chloride resistant (U_Cl > 10)
  
  • Hyperaldosteronism
  • Cushing syndrome
  • Exogenous steroids
  • Licorice
  • Bartter syndrome
  • Milk-alkali syndrome

Question 22

Differential for respiratory acidosis

Answer 22

• impairment to ventilation
  
  • airway obstruction
  • alveolar infiltrates
  • perfusion defects
  • neuromuscular disease

Question 23

Respiratory alkalosis differential

Answer 23

• hypoxemia in which compensatory hyperventilation leads to hypocapnia
• anxiety
• CNS insults
• pregnancy
• medications