What is the appropriate work‑up for hypokalemia, hypocalcemia, and hyponatremia?

Work-up for Hypokalemia, Hypocalcemia, and Hyponatremia

Hypokalemia Work-up

Begin by measuring serum potassium, and if <3.5 mEq/L, immediately assess for cardiac arrhythmias with ECG and check serum magnesium, as hypomagnesemia occurs in 42% of hypokalemic patients and must be corrected first to allow potassium repletion. 1

Initial Laboratory Assessment

• Serum potassium level to confirm hypokalemia (<3.5 mEq/L) 2
• Serum magnesium – hypomagnesemia is present in 42% of hypokalemic patients and prevents effective potassium correction 1
• Serum calcium and phosphate – hypocalcemia occurs in 22% and hypophosphatemia in 29% of cases with electrolyte disturbances 1
• Arterial blood gas to identify metabolic alkalosis (suggests renal losses) or acidosis (suggests GI losses or renal tubular acidosis) 3
• ECG to assess for arrhythmias, U waves, T-wave flattening, or ST depression 2

Urine Studies to Determine Etiology

• 24-hour urine potassium or spot urine potassium-to-creatinine ratio 2
  • Urine K <20 mEq/L suggests extrarenal losses (GI losses, inadequate intake) 2
  • Urine K >20 mEq/L indicates renal potassium wasting (diuretics, hyperaldosteronism, renal tubular acidosis) 2

Additional Tests Based on Clinical Context

• Serum glucose – hyperglycemia causes transcellular potassium shifts 2
• Medication review – diuretics, insulin, beta-agonists, cisplatin are common causes 3
• Thyroid function tests if thyrotoxic periodic paralysis suspected 2
• Renin and aldosterone levels if primary hyperaldosteronism suspected with hypertension and metabolic alkalosis 3

Common Pitfall

Do not attempt to correct hypokalemia without first checking and correcting magnesium, as hypomagnesemia causes refractory potassium wasting and prevents normalization of serum potassium. 1, 3

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Hypocalcemia Work-up

Measure serum albumin immediately when hypocalcemia is detected, as each 1 g/dL decrease in albumin lowers total calcium by 0.8 mg/dL; calculate corrected calcium before proceeding with further evaluation. 2

Initial Laboratory Assessment

• Serum total calcium and ionized calcium – ionized calcium is the gold standard and eliminates albumin-related artifacts 4
• Serum albumin – correct total calcium using: Corrected Ca = measured Ca + 0.8 × (4.0 - albumin) 4
• Serum magnesium – hypomagnesemia occurs in 22% of hypocalcemic patients and causes functional hypoparathyroidism 1, 3
• Serum phosphate – elevated in hypoparathyroidism and renal failure; low in vitamin D deficiency 2, 5
• Serum creatinine and BUN to assess renal function 2
• ECG to identify prolonged QT interval, which predisposes to torsades de pointes 2

Hormone and Vitamin Studies

• Intact parathyroid hormone (PTH) 2, 5
  • Low or inappropriately normal PTH with hypocalcemia indicates hypoparathyroidism 5
  • Elevated PTH suggests secondary hyperparathyroidism (vitamin D deficiency, renal failure) 5
• 25-hydroxyvitamin D level – deficiency is a common cause of hypocalcemia 2
• 1,25-dihydroxyvitamin D if vitamin D-dependent rickets or chronic kidney disease suspected 2

Additional Tests Based on Clinical Context

• Serum potassium – hypokalemia coexists in many cases of electrolyte disturbances 1
• Lipase and amylase if acute pancreatitis suspected (calcium sequestration) 2
• Thyroid function tests if hypothyroidism suspected as a cause 5

Common Pitfall

Failing to correct magnesium before treating hypocalcemia leads to refractory hypocalcemia, as hypomagnesemia impairs PTH secretion and creates end-organ resistance to PTH. 1, 3

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Hyponatremia Work-up

Determine volume status through physical examination (orthostatic vital signs, skin turgor, mucous membranes, jugular venous pressure, edema) and measure serum osmolality, urine osmolality, and urine sodium to classify hyponatremia as hypovolemic, euvolemic, or hypervolemic. 6, 7

Initial Laboratory Assessment

• Serum sodium to confirm hyponatremia (<135 mEq/L); full work-up warranted when <131 mEq/L 6
• Serum osmolality to exclude pseudohyponatremia from hyperglycemia or hyperlipidemia 6, 7, 4
  • Calculate: 2 × Na + glucose/18 + BUN/2.8 (normal 275-295 mOsm/kg) 7
• Urine osmolality 6, 7
  • <100 mOsm/kg suggests appropriate ADH suppression (primary polydipsia, beer potomania) 6

  • 100 mOsm/kg indicates impaired water excretion (SIADH, volume depletion, heart failure, cirrhosis) 6

• Urine sodium concentration 6, 7
  • <30 mEq/L suggests hypovolemia from extrarenal losses or hypervolemia (heart failure, cirrhosis) 6

  • 20-40 mEq/L indicates SIADH, cerebral salt wasting, or renal losses 6

Volume Status Assessment

• Hypovolemic signs: orthostatic hypotension, tachycardia, dry mucous membranes, decreased skin turgor, flat neck veins 6
• Euvolemic signs: normal blood pressure, no edema, normal jugular venous pressure 6
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 6
• Point-of-care ultrasound to assess inferior vena cava diameter and collapsibility for volume status 7

Additional Laboratory Tests

• Serum creatinine and BUN to assess renal function and calculate BUN:creatinine ratio 6
• Serum uric acid – <4 mg/dL has 73-100% positive predictive value for SIADH 6
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 6
• Morning cortisol or ACTH stimulation test to exclude adrenal insufficiency 6
• Serum glucose – hyperglycemia causes pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 4
• Serum potassium, magnesium, calcium, phosphate – hyponatremia coexists with other electrolyte abnormalities in 27-42% of cases 1

Neurosurgical Patient Considerations

In patients with CNS pathology, distinguish SIADH from cerebral salt wasting by assessing central venous pressure: CVP 6-10 cm H₂O indicates SIADH (euvolemic), while CVP <6 cm H₂O indicates cerebral salt wasting (hypovolemic). 6

• SIADH: euvolemic, urine Na >20-40 mEq/L, urine osmolality >300 mOsm/kg 6
• Cerebral salt wasting: hypovolemic with orthostatic changes, urine Na >20 mEq/L despite volume depletion 6

Common Pitfalls

• Do not order plasma ADH or natriuretic peptide levels – these tests delay diagnosis without altering management 6
• Physical examination alone is unreliable for volume assessment (sensitivity 41%, specificity 80%); use laboratory parameters 6
• Review all medications – SSRIs, carbamazepine, NSAIDs, opioids, diuretics, chemotherapy agents commonly cause hyponatremia 6
• Hypomagnesemia occurs in 27% of hyponatremic patients and should be checked and corrected 1