Renal Pharmacology  ·  Module 5 of 5

Fluid, Acid-Base, and Electrolyte Emergencies

Hyperkalemia three-phase management · Hyponatremia correction limits · Acid-base bicarbonate therapy · Drug-induced tubular disorders

• Hyperkalemia emergency management proceeds in three mechanistically distinct sequential phases — not interchangeable. Phase 1 (membrane stabilization — onset minutes): calcium gluconate IV raises cardiac myocyte threshold potential (widens gap between resting potential and threshold → reduces peaked T waves, wide QRS, sine-wave pattern); does NOT lower serum K⁺; lasts 30–60 min; calcium chloride delivers 3× elemental calcium but causes tissue necrosis if extravasated — requires central access. Phase 2 (redistribution — 15–30 min): insulin drives K⁺ into cells via Na⁺/K⁺-ATPase (↓ serum K⁺ 0.5–1.5 mEq/L; effect lasts 4–6 h; monitor glucose q30–60 min); high-dose nebulized albuterol (10–20 mg; 4–8× bronchodilator dose) → β2 → cAMP → Na⁺/K⁺-ATPase activation (additive to insulin, −0.5–1.0 mEq/L; tachycardia limits use in ischemic heart disease); sodium bicarbonate useful mainly in concurrent metabolic acidosis (H⁺-K⁺ exchange). Phase 3 (elimination — definitive): loop diuretics (if urine output present); patiromer (distal GI cation exchanger) or sodium zirconium cyclosilicate (SZC, throughout GI); avoid sodium polystyrene sulfonate (Kayexalate) — intestinal necrosis risk especially with sorbitol; hemodialysis — fastest, most effective; treatment of choice if refractory or anuric.
• Hyponatremia (Na⁺ <135 mEq/L): volume status determines etiology; correction rate is the dominant safety variable. Maximum correction: 6–8 mEq/L in first 24 h; never exceed 10–12 mEq/L in any 24-h period. Chronic severe hyponatremia (Na⁺ <120 for >48 h): brain extrudes osmoles to adapt; rapid correction exposes brain to rising osmolality before osmoles can be restored → myelin disruption in pons and extrapontine regions → osmotic demyelination syndrome (dysarthria, dysphagia, quadriplegia, locked-in syndrome — largely irreversible). Treatment: symptomatic (seizure, obtundation, herniation) → 3% NaCl 100–150 mL IV over 10–20 min → raises Na⁺ ~2–3 mEq/L; recheck q2h; slow immediately when symptoms resolve. If overcorrected: D5W 3–6 mL/kg/h ± desmopressin to relow Na⁺ back within limit. Vaptans: aquaresis for euvolemic (SIADH) or hypervolemic hyponatremia (HF, cirrhosis); contraindicated in hypovolemic hyponatremia (water loss would worsen volume depletion); not first-line.
• Metabolic acidosis — bicarbonate therapy: anion gap = Na⁺ − (Cl⁻ + HCO₃⁻). High AG (lactic acidosis, DKA, toxin, renal failure): IV bicarbonate buffering reaction generates CO₂ that freely crosses cell membranes and BBB → paradoxical intracellular and CSF acidosis even as extracellular pH rises; also reduces hyperventilatory drive → ↑ PaCO₂. Reserve bicarbonate for pH <6.9 when cardiac contractility and catecholamine responsiveness critically impaired. Definitive treatment: address the cause (lactate source, insulin deficiency). Non-AG (RTA, diarrhea, HCO₃⁻ loss): bicarbonate is the indicated treatment. Type 1 RTA: collecting duct cannot acidify urine below pH 5.5 → alkali corrects acidosis, prevents nephrocalcinosis, reduces osteomalacia from bone buffering. Type 2 RTA: proximal HCO₃⁻ wasting → large supplemental doses required; promptly filtered and lost. CKD metabolic acidosis: bicarbonate supplementation slows CKD progression (bicarbonate supplementation study).
• Metabolic alkalosis — urine chloride is the pivotal diagnostic test. Urine Cl⁻ <20 mEq/L → chloride-responsive: kidney avid for Na⁺/Cl⁻ due to volume depletion or chloride deficit; causes: vomiting (HCl loss), NG suction, prior diuretics; treatment: isotonic saline restores volume → kidney excretes excess HCO₃⁻; replete K⁺ (hypokalemia perpetuates alkalosis via H⁺-K⁺ exchange). Urine Cl⁻ >20 mEq/L → chloride-resistant: ongoing mineralocorticoid activity drives H⁺ + K⁺ secretion independently of volume; causes: primary hyperaldosteronism, Cushing's, Bartter/Gitelman syndromes; saline cannot correct; treat underlying mineralocorticoid excess (spironolactone/eplerenone; surgical resection of aldosterone-producing adenoma). Volume-overloaded patients with diuretic-induced alkalosis who cannot receive saline: acetazolamide (PCT CA inhibition → HCO₃⁻ excretion corrects alkalosis without adding volume; ADVOR trial: acetazolamide + IV furosemide → faster, more complete decongestion in acute HF).
• Drug-induced electrolyte disorders — four predictable nephrotoxic patterns. Amphotericin B: inserts into tubular cell membranes → distal tubular pores → type 1 RTA + K⁺ wasting (hypokalemia) + Mg²⁺ wasting (hypomagnesemia) + afferent arteriolar vasoconstriction → ↓ GFR; liposomal formulation limits free drug delivery to renal tubule → preferred formulation. Cisplatin: platinum accumulates in distal tubule → permanently downregulates TRPM6 → renal Mg²⁺ wasting persisting months to years after discontinuation; hypokalemia follows (Mg²⁺ depletion keeps ROMK open — same mechanism as Module 1); proximal tubular injury → Fanconi syndrome; prevent with aggressive IV hydration before and after infusion. Lithium: enters principal cells via ENaC → inhibits adenylate cyclase → ↓ cAMP → impairs AQP2 insertion in response to ADH → nephrogenic DI (vasopressin-resistant polyuria/polydipsia → hypernatremia if fluids restricted); chronic exposure → irreversible interstitial fibrosis; amiloride (blocks ENaC → ↓ Li⁺ entry) is preferred treatment. Tenofovir disoproxil fumarate (TDF): accumulates in PCT mitochondria via OAT secretion → inhibits mitochondrial DNA polymerase gamma → energy failure → impairs all energy-dependent PCT reabsorption → Fanconi syndrome (hypophosphatemia + glycosuria + aminoaciduria + proximal RTA); persistent hypophosphatemia → osteomalacia + fractures; switch to tenofovir alafenamide (TAF) — less renal accumulation, maintains antiviral efficacy.