Sodium, Potassium, Calcium & Magnesium

• Hyponatremia: urgency is driven by symptoms; severe symptoms get 3% saline 100–150 mL boluses, and cap correction at 8–10 mmol/L/24 h.
• ECG changes from hyperkalemia: give calcium gluconate up front, shift potassium next (insulin+dextrose, salbutamol), and finally remove it (diuretics, dialysis).
• Hypercalcemia: volume first, then calcitonin (fast) then zoledronate (durable); symptomatic hypocalcemia gets IV calcium gluconate.
• Replace Mg and PO₄ aggressively in critical illness (refeeding, DKA, alcohol).
• If hyponatremia overcorrects, rescue with DDAVP 1–2 µg IV; vaptans are not for acute correction; K⁺ binders (patiromer, sodium zirconium cyclosilicate) are guideline-recognized for hyperkalemia.

Workup of Hyponatremia

• Hyponatremia (Na <135 mmol/L): check symptoms — severe ones (seizures, coma) → emergent 3% saline treatment (see 52.2)
• Measure serum osmolality
• Serum osmolality below 275 mOsm/kg (hypotonic)?
• Measure urine osmolality
• Is urine osmolality ≤100 mOsm/kg?
• Primary polydipsia, beer potomania, reset osmostat — urine very dilute
• Measure urine sodium
• Urine sodium <20 mmol/L?
• Assess volume: hypovolemic (vomiting, diarrhea, remote diuretics) → normal saline; hypervolemic (CHF, cirrhosis) → water restriction + diuresis
• Euvolemic hypotonic hyponatremia: SIADH, hypothyroidism, adrenal insufficiency, thiazides — restrict fluid ± treat the cause
• Osm 275–295: pseudohyponatremia (severe hyperlipidemia/protein); Osm >295: translocational (hyperglycemia, mannitol) — correct the underlying problem
• Cap the correction rate at ≤8–10 mmol/L per 24 h to avoid osmotic demyelination; during active correction recheck Na frequently; if overcorrection occurs, rescue with DDAVP 1–2 µg IV ± D5W

Workup of Hyperphosphatemia

• Hyperphosphatemia (phosphorus >4.5 mg/dL) — interpret with PTH and serum calcium concentration
• Urine phosphorus?
• INCREASED INTAKE (urine phosphorus >1500 mg/day): vitamin D intoxication (25-OH) · phosphosoda bowel preparation · calcitriol overdose (1,25-OH) · granulomatous disease (1,25-OH) · lymphoma activation (1,25-OH)
• TRANSCELLULAR SHIFTS: tumor lysis syndrome · rhabdomyolysis, hemolysis · relative insulin deficiency · metabolic acidosis
• REDUCED RENAL EXCRETION (urine phosphorus <1500 mg/day): acute or chronic renal insufficiency · secondary hyperparathyroidism · hypoparathyroidism · acromegaly

Workup of Hypomagnesemia

• Hypomagnesemia
• 24-hr urine magnesium vs FEMag?
• RENAL MAGNESIUM WASTING (24-hr urine magnesium >2 mEq OR FEMag >2%): hypercalcemia · osmotic diuresis · polyuric phase of resolving ATN · volume expansion · chronic alcoholism · Gitelman's syndrome (less commonly Bartter's syndrome) · diuretics (loop/thiazide) · aminoglycosides · amphotericin B · platinum-based chemotherapy · pentamidine · cyclosporine A · EGFR blockers (cetuximab)
• REDUCED INTAKE OR EXTRARENAL LOSS (24-hr urine magnesium <2 mEq OR FEMag <2%): starvation · malabsorption · diarrhea · prolonged gastrointestinal drainage (nasogastric suction, intestinal fistulas, biliary drainage) · severe burns
• CHELATION: pancreatitis · alkalemia · hyperphosphatemia (rhabdomyolysis, tumor lysis syndrome, hemolysis, phosphosoda bowel preparation) · citrate-containing infusions (blood products, plasmapheresis, CVVHD) · foscarnet therapy · ethylene glycol toxicity

Workup and Treatment of Hypermagnesemia

• Hypermagnesemia
• ENDOGENOUS SOURCES: tumor lysis syndrome · diabetic ketoacidosis · adrenal insufficiency · theophylline intoxication · occasionally primary hyperparathyroidism
• EXOGENOUS ADMINISTRATION: magnesium-containing laxatives in renal failure · antacids in renal failure · overaggressive IV magnesium (treatment of preeclampsia/eclampsia)
• TREATMENT: stop further magnesium administration · with ECG changes or symptoms, give 1–2 g calcium gluconate IV over 10 min and consider hemodialysis, especially with renal insufficiency that is not easily reversible · if renal function is preserved, IV isotonic saline plus a loop diuretic may enhance magnesium excretion; use hemodialysis for severe or symptomatic hypermagnesemia, especially with renal failure

Treating Hyponatremia

• Hyponatremia (<130 mEq/L)
• Symptomatic? OR acute (<2 days)?
• Severe symptoms: 3% saline 150 mL IV bolus over 20 min, repeat up to 2–3× until symptoms abate, rechecking Na after each bolus
• Calculate fluid rate and composition by the Adrogué–Madias equation (change in serum sodium per 1 L infused): ([infused Na + K] − serum sodium) / (TBW + 1)
• Once symptoms improve, correct serum sodium no faster than 8–10 mEq/L per 24 h
• Vaptans (tolvaptan, conivaptan) are NOT recommended for acute correction — reserve for select chronic SIADH under specialist guidance; demeclocycline 300–600 mg PO bid is an alternative
• Asymptomatic AND chronic (>2 days): mild hyponatremia needs no immediate correction · treat the underlying cause · water restriction
• CORRECT NO FASTER THAN 8–10 mEq/L PER 24 h (≤18 mEq/L per 48 h)

Workup of Hypernatremia

• Hypernatremia
• Volume status?
• Hypervolemic: hyperaldosteronism/Cushing's syndrome OR hypertonic sodium load — treatment: stop the saline infusion, give diuretics to prevent volume overload, consider free water
• Hypovolemic or euvolemic — is ADH present?
• Urine osmolality?
• Urine Osm >300 mOsm/kg (ADH present) — assess total urine osmoles and electrolyte-free water clearance
• Decreased water intake OR increased insensible losses — treatment: replace free water via the Adrogué–Madias equation, correcting no faster than 0.5 mEq/L/hr unless acutely symptomatic (1–2 mEq/L/hr)
• Osmotic diuresis — treatment: replace free water, correcting no faster than 0.5 mEq/L/hr, and address the underlying cause (reduce enteral feed rate)
• Urine Osm <300 mOsm/kg (ADH absent or ineffective) — ddAVP response?
• Response to ddAVP?
• Central DI — ddAVP: 10–40 µg intranasal tid in divided doses OR 1–2 µg SC/IV bid
• Nephrogenic DI — treatment: low-sodium diet with thiazide diuretics, low-protein diet, NSAIDs, plus address the underlying cause if possible (renal tubular disease, chronic loop diuretics, electrolyte abnormalities, lithium toxicity)

Workup of Hypokalemia

• Low serum potassium
• Spurious cause: extreme leukocytosis (WBC >100,000/cm³)
• Transcellular shift: insulin excess · alkalemia · beta₂-adrenergic agonists/stress · hypothermia · theophylline · barium intoxication · thyrotoxicosis · hypokalemic periodic paralysis — consider during alcohol withdrawal, myocardial infarction, asthma attack
• Total body K⁺ decreased: low K⁺ intake OR increased K⁺ losses
• Increased K⁺ losses — extrarenal: nasogastric suction, vomiting, diarrhea (urinary K⁺ <20 mEq/L OR TTKG <3) vs renal (urinary K⁺ >20 mEq/L OR TTKG >3)
• Renal losses plus hypertension — true aldosterone effects: primary hyperaldosteronism · renovascular or malignant hypertension
• Renal losses plus hypertension — aldosterone-like effects: apparent mineralocorticoid excess · Cushing's syndrome · congenital adrenal hyperplasia · Liddle's syndrome
• Renal losses, normotensive — secondarily elevated aldosterone (hypovolemia): Bartter's syndrome · aggressive diuretic use · Gitelman's syndrome

Treating Hypokalemia

• Hypokalemia
• Reverse correctable causes: stop diuretics · correct magnesium deficiency
• Symptoms present (arrhythmia, paralysis, or weakness)?
• IV replacement up to 40 mEq/hr · continuous ECG monitoring · serial serum K⁺ checks
• Acid–base status?
• Metabolic acidosis (diarrhea or renal tubular acidosis) → give K⁺ citrate, K⁺ bicarbonate
• Metabolic alkalosis or normal pH — normotensive: oral KCl · hypertensive: consider K⁺-sparing diuretic

Workup of Hyperkalemia

• High serum potassium
• Spurious cause: ischemic blood draw · leukocytosis (WBC >50,000/cm³) · thrombocytosis (platelet count >1,000,000/cm³)
• Transcellular shift — ICF-ECF exchange: insulin deficiency · hypertonicity · β₂-adrenergic blockade · succinylcholine · fluoride intoxication · digitalis intoxication · inorganic acidosis · hyperkalemic periodic paralysis || Cellular release: rhabdomyolysis · hemolysis · tumor lysis syndrome · intense exercise
• Impaired renal excretion — GFR decreased (<20 mL/min): exogenous administration (potassium-rich foods, K⁺ supplements, blood products) · endogenous retention of metabolic waste || Reduced aldosterone effect: potassium-sparing diuretics · ACE inhibitors · ARBs · type IV renal tubular acidosis (diabetes mellitus, interstitial nephritis, urinary tract obstruction) · NSAIDs · cyclosporine A · papillary necrosis (sickle cell disease, analgesic nephropathy) · heparin · ketoconazole, trimethoprim, pentamidine
• Abbreviations — GFR = glomerular filtration rate · ECF = extracellular fluid · WBC = white blood cell count · ICF = intracellular fluid

Workup of Hypocalcemia

• Hypocalcemia: corrected calcium <8.4 mg/dL OR ionized calcium <4.2 mg/dL
• PTH response?
• PTH appropriately elevated — present but ineffective
• Vitamin D level?
• Vitamin D normal → PTH RESISTANCE: bisphosphonates · uremic environment · CHELATION: hyperphosphatemia (rhabdomyolysis, tumor lysis syndrome, hemolysis, phosphosoda bowel preparation), pancreatitis, alkalemia, foscarnet therapy, citrate-containing infusions (blood products, plasmapheresis, CVVHD), ethylene glycol toxicity
• Vitamin D low → VITAMIN D DEFICIENCY (25-OH vit D <15 ng/mL): severe liver disease · low dietary intake · P450 enzyme inducers (phenytoin, phenobarbital, isoniazid, rifampin)
• Advanced renal disease can reduce activation to the 1,25-form causing hypocalcemia, though 25-OH level may be normal
• PTH low or inappropriately normal → HYPOPARATHYROIDISM: parathyroidectomy ("hungry bone" syndrome) · hypo- or hypermagnesemia · infiltration (hemochromatosis, Wilson's disease, malignant replacement) · autoimmune diseases · radiation-induced parathyroid destruction · HIV infection (can also affect vitamin D activation)

Workup of Hypercalcemia

• Hypercalcemia: corrected calcium >10.3 mg/dL OR ionized calcium >5.2 mg/dL
• PTH response?
• PTH high or inappropriately normal → HYPERPARATHYROID STATE: familial hypocalciuric hypercalcemia — 24-hr urine calcium <200 mg · primary hyperparathyroidism (85% adenomas, 14% hyperplasia, 1% carcinoma) — 24-hr urine calcium >200 mg · lithium use · tertiary hyperparathyroidism (after renal transplantation)
• PTH appropriately low → PTH-independent mechanism; consider vitamin D level testing
• Vitamin D levels abnormally high?
• EXCESS 1,25-OH: granulomatous disease (sarcoidosis) · lymphoma · calcitriol overdose · acromegaly · EXCESS 25-OH: vitamin D intoxication
• PTH-RELATED PEPTIDE: humoral hypercalcemia of malignancy (elevated PTHrP) · DECREASED Ca²⁺ EXCRETION: volume depletion, thiazide diuretics, milk alkali syndrome · BONE RESORPTION: osteolytic malignancy, Paget's disease, immobilization, hyperthyroidism, adrenal insufficiency

Workup of Hypophosphatemia

• Hypophosphatemia (phosphorus <2.8 mg/dL) — interpret with PTH and serum calcium concentration
• FEPhos = (urine phos × serum creatinine) / (serum phos × urine creatinine) — the fractional excretion of phosphorus
• RENAL LOSSES (FEPhos >5% OR urine phos >100 mg/day): chronic alcoholism · hyperparathyroidism · volume expansion · osmotic diuresis · theophylline use · corticosteroid use · Fanconi's syndrome · oncogenic osteomalacia (FGF-23)
• GASTROINTESTINAL LOSSES (FEPhos <5% OR urine phos <100 mg/day): phosphate binders (including antacids) · malabsorption/malnutrition/diarrhea · vitamin D deficiency (reduced absorption)
• TRANSCELLULAR SHIFTS: refeeding syndrome · insulin administration · respiratory alkalosis · catecholamine release, beta-agonist therapy · post-parathyroidectomy ("hungry bone")
• OTHER REMOVAL — intensive continuous dialysis (CVVHD)