Figure Metabolic alkalosis (pH >7.45, HCO3 >26): severe (>7.55) threatens with arrhythmia, seizures, hypokalaemia and ionised hypocalcaemia. The single discriminator is the URINE CHLORIDE — low (<10) is chloride-responsive (vomiting, diuretics, post-hypercapnia) treated with saline + KCl; high (>20) is chloride-resistant (mineralocorticoid excess) treated at the cause. Correct potassium and magnesium to break the maintenance cycle. [7]
Metabolic alkalosis (pH >7.45, HCO3 >26): severe (>7.55) → arrhythmia, seizures, hypokalaemia, hypocalcaemia. Classify by urine chloride : CHLORIDE-RESPONSIVE (urine Cl <10 — vomiting, NG suction, diuretics, post-hypercapnia) → treat with normal saline + KCl . CHLORIDE-RESISTANT (urine Cl >20 — mineralocorticoid excess: hyperaldosteronism, Cushing, steroids, liquorice) → treat cause + K-sparing diuretic. Severe (pH >7.6) → acetazolamide (carbonic anhydrase inhibitor → renal HCO3 loss), acid infusion (HCl, arginine), or dialysis. Maintenance requires aldosterone + hypokalaemia — correct K to 'break' the alkalosis.
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Exam practice
SAQ — Post-hypercapnic alkalosis in an intubated COPD patient 10 minutes · 10 marks
Reveal all A 68-year-old woman with severe COPD (baseline PaCO2 68 mmHg on room air, serum bicarbonate 38 mmol/L) is intubated for an infective exacerbation. Twelve hours into mechanical ventilation she is being weaned. Arterial gas on FiO2 0.30: pH 7.58, PaCO2 44 mmHg, HCO3 40 mmol/L, PaO2 78 mmHg. Sodium 138, chloride 88, potassium 3.1, albumin 34 g/L. No diuretic has been given. She is now alert and triggering breaths but is highly agitated and has had a short run of supraventricular tachycardia.
a Explain the pathophysiology of this post-hypercapnic alkalosis, why the bicarbonate falls slowly after PaCO2 correction, and give a complete acid-base classification including compensation and anion gap. (5 marks)
b Outline the principles of management and the specific harms of the alkalosis in this patient. (3 marks)
c When and how would you use acetazolamide in this patient, citing the evidence? (2 marks)
SAQ — Chloride-depleted (contraction) alkalosis from gastric outlet obstruction 10 minutes · 10 marks
Reveal all A 53-year-old man gives a two-week history of intractable vomiting from proven gastric outlet obstruction. He is volume-depleted (HR 108, BP 102/64 supine and 86/52 on standing), confused, and has carpopedal spasm. Arterial gas: pH 7.58, PaCO2 47 mmHg, HCO3 43 mmol/L. Sodium 136, chloride 84, potassium 2.6, ionised calcium 0.95, magnesium 0.45, albumin 42 g/L. Urine chloride 6 mmol/L.
a Explain the mechanism of this chloride-depleted metabolic alkalosis, justify the use of urine chloride, and interpret the respiratory compensation and the anion gap. (5 marks)
b Describe the stepwise resuscitation, with specific fluids, electrolyte doses, and the order of correction. (3 marks)
c Explain why hypokalaemia and hypomagnesaemia perpetuate the alkalosis and why the correction must be sequenced. (2 marks)
Clinical pearls
High-yield metabolic alkalosis points for CICM/FFICM exam
Generation vs maintenance of alkalosis — the two-step concept. GENERATION (initiating event): vomiting (HCl loss), diuretics (H+ secretion), etc. → HCO3 rises. MAINTENANCE (why it persists): (a) VOLUME DEPLETION (effective circulating volume low → kidney RETAINS HCO3 to maintain volume — can't 'waste' HCO3 when volume-depleted). (b) HYPOKALAEMIA (low K → promotes H+ secretion in distal tubule → generates MORE HCO3). (c) ALDOSTERONE (promotes H+ and K+ secretion → HCO3 generation). KEY: you can't correct the alkalosis until you address the MAINTENANCE factors (volume, K, aldosterone) — even if you stop the generation cause. This is why saline + KCl is the treatment for chloride-responsive alkalosis.[1] }Why vomiting causes alkalosis — the mechanism. (1) Gastric secretions are rich in HCl (pH ~1 — parietal cells secrete H+ and Cl-). (2) For every H+ secreted into stomach lumen, a HCO3- is generated into blood (the 'gastric alkaline tide' — at the cellular level, HCO3 is the byproduct of H+ secretion). (3) Normally: this HCO3 is neutralised when acidic chyme reaches duodenum (pancreas secretes HCO3 to neutralise). (4) In VOMITING (or NG suction): HCl lost (never reaches duodenum to trigger pancreatic HCO3) → the gastric HCO3 'tide' remains in blood → metabolic alkalosis. (5) ALSO: volume depletion (from vomiting) → kidney RETAINS HCO3. (6) ALSO: hypokalaemia (renal K loss from aldosterone — volume depletion → RAAS) → promotes H+ secretion → more HCO3. This is why vomiting gives HYPOCHLORAEMIC, HYPOKALAEMIC metabolic alkalosis.[1] }Urine chloride is the discriminator (not sodium). WHY CHLORIDE (not sodium): (1) In chloride-responsive (vomiting): kidney CONSERVES sodium AND chloride (volume-depleted). BUT: to excrete excess HCO3, kidney must excrete Na+ WITH HCO3- (NaHCO3). So urine Na is HIGH (forced to excrete Na with HCO3) but urine Cl is LOW (conserving Cl). (2) So if you measured urine Na, you'd think 'kidney wasting Na' (wrong conclusion) — but urine Cl reveals the truth (conserving Cl → volume-depleted → chloride-responsive). (3) ALWAYS use URINE CHLORIDE (not sodium) for metabolic alkalosis workup. (4) CAVEAT: diuretics cause urine Cl to be HIGH (kidney wasting Cl) even in chloride-responsive alkalosis — stop diuretics 48h before interpreting urine Cl.[3] }Post-hypercapnic alkalosis — common in ICU. (1) Chronic CO2 retention (COPD) → kidney COMPENSATES by retaining HCO3 (PaCO2 high → kidney generates HCO3 to normalise pH). (2) When PaCO2 is acutely lowered (e.g., mechanical ventilation in COPD exacerbation): the kidney is still generating HCO3 (compensated) but CO2 is now low → HCO3 too high → metabolic alkalosis. (3) This is DANGEROUS: alkalosis causes hypoventilation (compensatory) → may be hard to wean from ventilator (alkalosis blunts respiratory drive). (4) TREATMENT: saline + KCl (allows kidney to excrete HCO3); acetazolamide if severe (blocks HCO3 reabsorption). (5) SLOW ventilation wean in COPD (don't over-ventilate → don't drop CO2 too fast).[6] }Hypokalaemia maintains alkalosis — the vicious cycle. (1) Low K → promotes H+ secretion in distal tubule (H-K exchange — more H secreted to spare K) → generates MORE HCO3 → alkalosis worsens. (2) Alkalosis → K shifts INTO cells (H out, K in) → serum K drops further → worse hypokalaemia. (3) CYCLE: alkalosis ↔ hypokalaemia (each worsens the other). (4) CONSEQUENCE: you CAN'T correct the alkalosis without correcting the K (the hypokalaemia keeps generating HCO3). (5) TREATMENT: KCl (aggressive — restore K to >4.0) → breaks the cycle → alkalosis resolves. (6) ALSO: hypomagnesaemia worsens (refractory hypokalaemia) → replace Mg.[2] }Dangers of severe alkalosis (pH >7.55). (1) HYPOXIA: alkalosis shifts oxyhaemoglobin dissociation curve LEFT (haemoglobin holds O2 tighter → less release to tissues) → tissue hypoxia (despite adequate PaO2). (2) HYPOCALCAEMIA: alkalosis → more Ca binds to albumin → less IONISED Ca (the active form) → tetany, seizures, arrhythmia (prolonged QT). (3) HYPOKALAEMIA: alkalosis → K into cells → arrhythmia (especially in cardiac patients, digoxin). (4) CORONARY VASOSPASM: alkalosis causes coronary artery spasm → ischaemia/infarction (rare but documented). (5) SEIZURES: decreased neuronal threshold (similar to hypocalcaemia). (6) HYPOVENTILATION: compensatory → CO2 rises (to lower pH) → hypoxia (especially if also breathing O2 — hypercapnia tolerated, but hypoxia dangerous). (7) Arrhythmia: refractory VT/VF (especially with hypokalaemia/hypocalcaemia). SEVERE alkalosis is an emergency.[4] }Acetazolamide — the carbonic anhydrase inhibitor. MECHANISM: inhibits carbonic anhydrase in proximal tubule → blocks HCO3 reabsorption → kidney EXCRETES HCO3 → lowers serum HCO3 → corrects alkalosis. DOSE: 250-500 mg IV or PO (once or twice daily). EFFECT: gradual (hours-days). SIDE EFFECTS: (a) HYPOKALAEMIA (more K lost with HCO3 — monitor/replace). (b) METABOLIC ACIDOSIS (overshoot — can cause acidosis if over-treated). (c) HYPOPHOSPHATAEMIA. (d) Renal stones (chronic — alkaline urine → calcium phosphate). (e) Paraesthesia, fatigue. USE: severe metabolic alkalosis (especially fluid overload — can't give more saline), post-hypercapnic, chronic COPD. CAUTION: sulfa allergy.[5] }Loop and thiazide diuretics — common alkalosis cause. (1) LOOP (frusemide): blocks Na-K-2Cl in thick ascending limb → natriuresis + diuresis → volume depletion → contraction alkalosis. ALSO: more Na delivered to distal tubule → more Na exchanged for H+ and K+ → HCO3 generation + K loss. (2) THIAZIDE: blocks Na-Cl in distal tubule → similar (milder). (3) CONTRACTION ALKALOSIS: diuretic causes volume loss → same HCO3 in smaller volume → higher concentration → alkalosis. (4) PREVENTION: K-sparing diuretic (amiloride, spironolactone — blocks distal H/K secretion), K supplement, monitor. (5) TREATMENT: stop diuretic (if possible), saline (volume), KCl.[3] }Primary hyperaldosteronism (Conn's) — chloride-resistant alkalosis. (1) Adrenal adenoma (aldosterone-producing) or hyperplasia → excess aldosterone. (2) Aldosterone → distal tubule: Na retention + K excretion + H excretion → hypertension (Na) + hypokalaemia (K) + metabolic alkalosis (H). (3) SCREEN: hypertensive + hypokalaemic (spontaneous or diuretic-induced) → aldosterone:renin ratio (ARR) — high aldosterone + LOW renin = primary. (4) CONFIRM: salt-loading or fludrocortisone suppression test. (5) IMAGING: CT adrenal (adenoma vs hyperplasia) + adrenal vein sampling. (6) TREATMENT: adenoma → adrenalectomy (curative); hyperplasia → spironolactone/eplerenone (mineralocorticoid blocker). (7) NOTE: in ICU, this is less common than vomiting/diuretics — but consider in hypertensive, hypokalaemic, alkalotic patient.[3] }Liquorice (apparent mineralocorticoid excess) — exam classic. (1) GLYCYRRHIZIC ACID (in natural liquorice root — not candy) inhibits 11-beta-hydroxysteroid dehydrogenase (normally converts cortisol to cortisone in kidney — protecting mineralocorticoid receptor). (2) Without this enzyme: CORTISOL acts on mineralocorticoid receptor (apparent mineralocorticoid excess) → Na retention + K/H excretion → hypertension + hypokalaemia + metabolic alkalosis. (3) LABS: aldosterone LOW (suppressed by volume expansion), renin LOW. (4) TREATMENT: stop liquorice, spironolactone. (5) SAME mechanism: carbenoxolone (old ulcer drug), ectopic ACTH (Cushing — high cortisol overwhelms the enzyme). Classic exam: 'patient with hypertension, hypokalaemia, metabolic alkalosis, LOW aldosterone, eats liquorice.'[3] }Milk-alkali syndrome — rare but exam-relevant. (1) Excessive CALCIUM + absorbable alkali intake (calcium carbonate — high dose for osteoporosis, antacids; historically milk + bicarbonate for ulcers). (2) TRIAD: hypercalcaemia + metabolic alkalosis + AKI. (3) MECHANISM: high Ca → nephrogenic DI → volume depletion → alkalosis maintenance; alkaline load (bicarbonate/carbonate) → alkalosis; high Ca → AKI. (4) TREATMENT: stop calcium + alkali, saline (volume + calciuresis), bisphosphonate (if hypercalcaemia severe). (5) Usually reversible. (6) Classic in patients taking high-dose calcium carbonate (older women for osteoporosis).[2] }Compensation — predict PaCO2. (1) For metabolic alkalosis: expected PaCO2 = 0.7 × HCO3 + 20 ± 5. (2) EXAMPLE: HCO3 36 → expected PaCO2 = 0.7 × 36 + 20 = 45 ± 5 (40-50). (3) If measured PaCO2 = 45: appropriate compensation (hypoventilation). (4) If PaCO2 = 60: respiratory acidosis too (hypoventilating more than expected — fatigue, sedation, COPD). (5) If PaCO2 = 30: respiratory alkalosis too (sepsis, hepatic failure, anxiety, high altitude). (6) CLINICAL: alkalosis causes COMPENSATORY hypoventilation (to raise CO2 → lower pH) → this can cause hypoxia (if not on O2) — especially dangerous in COPD, elderly. Don't over-correct alkalosis rapidly (hypoventilation may persist).[6] }Acid infusion for severe alkalosis — rare but know it. (1) INDICATIONS: severe life-threatening alkalosis (pH >7.6 with arrhythmia/seizures), refractory to saline/K/acetazolamide, can't tolerate volume (heart failure). (2) AGENTS: (a) HCl (dilute — 0.1N hydrochloric acid) via CENTRAL line (corrosive — peripheral extravasation → necrosis). Calculate dose: 0.5 × body weight × (HCO3 - 24). (b) ARGININE HCl (amino acid + HCl — safer, peripheral). (c) AMMONIUM CHLORIDE (rarely used — converts to urea in liver → hepatic failure risk). (3) MONITOR: ABG continuously, K, Ca (acid infusion can cause hyperkalaemia, hypocalcaemia). (4) GOAL: lower pH to 7.50-7.55 (not normal — avoid overshoot acidosis). (5) RARELY needed — most alkalosis corrects with saline/K/acetazolamide. Dialysis if renal failure.[4] }Alkalosis in ICU — often iatrogenic. COMMON IATROGENIC CAUSES: (1) NG suction (for bowel obstruction, post-op) → HCl loss → alkalosis. (2) Diuretics (aggressive diuresis in heart failure) → contraction alkalosis. (3) Over-ventilation (mechanical ventilation) → respiratory alkalosis → kidney compensates → if PaCO2 normalised, metabolic alkalosis. (4) Citrate (massive transfusion, CRRT) → metabolised to bicarbonate → alkalosis. (5) Antacids (bicarbonate, calcium carbonate) → alkaline load. PREVENTION: (a) Minimise NG suction (switch to jejunostomy if long-term). (b) Monitor K/Cl with diuretics (K-sparing, supplement). (c) Avoid over-ventilation (permissive hypercapnia where appropriate). (d) Watch acid-base with transfusion/citrate. (e) Stop unnecessary antacids. MOST ICU alkalosis is PREVENTABLE — be vigilant.[4] }Pendrin and the chloride story — why chloride repletion is non-negotiable. Pendrin is the apical Cl/HCO3 exchanger on β-intercalated cells of the collecting duct. In chloride depletion / volume contraction, pendrin is UPREGULATED so the nephron can reclaim chloride in exchange for secreting bicarbonate — but this only works if chloride is delivered. Give chloride (saline, KCl) and the kidney excretes the excess HCO3; withhold it and the alkalosis is self-perpetuating. This is the cellular basis of the chloride-responsive / resistant split, and why even mineralocorticoid states become partly chloride-responsive once you block the receptor.[1] }The "contraction" in contraction alkalosis — concentration, not new bicarbonate. Loop/thiazide diuretics drive out a relatively bicarbonate-poor, sodium/chloride-rich fluid. The same total-body bicarbonate is now dissolved in a smaller volume → concentration (and serum HCO3) rises. Correct the volume deficit and the bicarbonate concentration falls. Distinguish from true HCO3 gain (exogenous bicarbonate, citrate, milk-alkali) where total-body bicarbonate is genuinely increased.[2] }Cystic fibrosis and congenital chloride-losing diarrhoea — paediatric/exotic chloride depletion. Both cause chloride loss from a non-renal route → hypochloraemic, hypokalaemic metabolic alkalosis with a LOW urine chloride (extrarenal loss, kidney conserving Cl). Cystic fibrosis loses chloride in sweat (heat stress in adults can decompensate this); congenital chloride-losing diarrhoea loses massive chloride in stool from birth. Treat with chloride + potassium repletion (lifelong for the latter). A LOW urine chloride in an alkalotic patient with diarrhoea or sweat loss = extrarenal chloride-responsive alkalosis.[10] }Citrate from massive transfusion and CRRT — the hidden alkali load. Citrate (anticoagulant in stored blood and in CRRT circuits) is metabolised by liver/kidney/muscle to three bicarbonate molecules per citrate. Massive transfusion, plasma exchange, or regional citrate-anticoagulated CRRT can each deliver a large alkali load → metabolic alkalosis that may persist for 24–48 h after the source stops. Always include citrate in the differential of an unexplained ICU alkalosis; reduce or switch CRRT anticoagulation, and let the alkalosis self-resolve once citrate metabolism completes.[4] }Severe alkalosis and the heart — prolonged QT, coronary vasospasm, refractory VF. Alkalosis (i) reduces ionised calcium (more Ca bound to albumin) → prolonged QT and triggered arrhythmia; (ii) shifts K intracellularly → hypokalaemic arrhythmia (especially with digoxin); (iii) directly increases coronary vascular tone — alkalosis-induced coronary spasm can cause ischaemia/infarction even in clean coronaries; (iv) lowers the threshold for ventricular fibrillation. The combination of QT prolongation + hypokalaemia makes severe alkalosis (pH >7.55) genuinely arrhythmogenic — correct it before the rhythm destabilises.[4] }Oxyhaemoglobin dissociation — alkalosis shifts the curve LEFT (low P50) and starves tissue. Alkalosis increases haemoglobin affinity for oxygen → P50 falls → Hb holds onto O2 more tightly → less unloading at the tissue capillary. A patient can have a normal/high PaO2 and SaO2 yet suffer tissue hypoxia (rising lactate). This is compounded by the compensatory hypoventilation (rising PaCO2, falling PaO2). The clinical clue is a rising lactate or falling mixed-venous SvO2 in an alkalotic, well-oxygenated patient — correct the pH, not just the FiO2.[6] }Ionised hypocalcaemia — total calcium can be misleading. Alkalosis does NOT change total calcium; it increases calcium binding to albumin → IONISED calcium (the physiologically active fraction) falls. Symptoms: perioral tingling, carpopedal spasm, Chvostek and Trousseau signs, laryngospasm, seizures, QT prolongation. ALWAYS measure ionised calcium (or correct total carefully) in alkalotic patients with neuromuscular symptoms; treat the alkalosis first (calcium falls back out as pH normalises), give IV calcium only for symptomatic hypocalcaemia.[4] }H2 blockers / PPIs for NG suction alkalosis — treat the source. NG suction removes HCl (and Cl) directly. Adding an H2 blocker (ranitidine historically; famotidine) or PPI reduces gastric HCl secretion by 80–90%, cutting ongoing acid/chloride loss and buying time while the underlying obstruction is fixed. Pair with chloride + potassium repletion and volume. For long-term gastric losses, convert NG to a feeding jejunostomy so pancreatic biliary bicarbonate is preserved and upper GI losses are minimised.[3] }Post-hypercapnic alkalosis — the weaning trap in COPD. Chronic hypercapnia → renal HCO3 retention (compensation). When mechanical ventilation acutely normalises PaCO2, the retained HCO3 overshoots → metabolic alkalosis → compensatory hypoventilation → weaning failure (the alkalosis blunts central respiratory drive) and rising PaCO2. Prevent by weaning ventilation slowly (permissive hypercapnia, allow PaCO2 to remain at the patient's baseline), and treat established alkalosis with saline + KCl ± acetazolamide to drop the HCO3 back toward the new set-point.[8] }Hypomagnesaemia — the silent driver of refractory hypokalaemic alkalosis. Low Mg disinhibits ROMK in the cortical collecting duct → increased K secretion → refractory hypokalaemia; the hypokalaemia then drives H secretion and HCO3 generation → alkalosis. ANY alkalotic patient whose K will not correct must be checked and repleted for magnesium (2–4 g IV, then oral) before the K (and the alkalosis) will respond. Miss this and you will chase the potassium indefinitely.[3] }Acetazolamide — kinetic, dose, and the obligate kaliuresis. Onset 1–4 h, peak effect within 24 h; 250–500 mg IV/PO every 6–24 h. It blocks carbonic anhydrase in the proximal tubule → NaHCO3 diuresis (alkaline urine) → serum HCO3 falls. The price is renal K loss (distal Na delivered → K/H exchanged) — measure K every 6 h and replete aggressively. Contraindicated in sulfa allergy (it is a sulfonamide), severe hepatic disease (ammonia accumulation → encephalopathy), and adrenergic failure. The 2025 systematic review confirms efficacy for diuretic-induced chloride-depletion alkalosis but highlights the universal need for K monitoring.[7] }Acid infusion — when, which, how far. Reserved for life-threatening alkalosis (pH >7.6 with arrhythmia, seizures, or coronary spasm) refractory to saline/K/acetazolamide, or when volume overload forbids saline. Arginine HCl (10 g IV over 12–24 h) is the safest (peripheral) option but watch for hyperkalaemia. 0.1 N HCl via a CENTRAL line (peripheral extravasation = necrosis) dosed at 0.3–0.5 × weight × (HCO3 − 24) mmol, infused slowly with ABG checks q2–4 h. Goal is pH 7.50–7.55 — NEVER aim for normal to avoid overshoot metabolic acidosis and rebound hyperkalaemia.[4] }Pregnancy — a chronic compensated respiratory alkalosis. Progesterone-driven hyperventilation lowers PaCO2 to ~28–32 mmHg by the third trimester → renal HCO3 excretion gives a compensated metabolic acidosis (HCO3 ~18–21). A "normal" HCO3 of 24 in late pregnancy is therefore RELATIVE metabolic alkalosis and should prompt the question why compensation has been lost (pre-eclampsia, renal impairment, vomiting, tocolytics). Always interpret ICU acid-base in pregnancy against gestation-adjusted normals.[6] }Refeeding and alkalosis — the intracellular shift. Refeeding carbohydrate drives insulin → cellular uptake of K, Mg, and phosphate AND of H+ (intracellular buffering) → extracellular alkalosis on top of refeeding hypophosphataemia/hypokalaemia. In the malnourished ICU patient (anorexia, chronic alcoholism, prolonged NBM) who is alkalotic, check phosphate/magnesium and refeed slowly with adequate thiamine, phosphate, and potassium — over-aggressive dextrose worsens both the alkalosis and the electrolyte shifts.[2] }Low albumin and the anion gap / delta — don't be fooled. Hypoalbuminaemia lowers the anion gap by ~2.5 mmol/L per 10 g/L fall in albumin; in alkalosis the anion gap rises slightly (lactate from tissue hypoxia, organic anion retention). Correct the anion gap for albumin before interpreting a "normal" gap in a hypoalbuminaemic, alkalotic ICU patient, and use the delta-delta (ΔAG / ΔHCO3) to unmask a coexisting metabolic acidosis that the alkalosis is masking.[6] }Combined respiratory + metabolic alkalosis — the most dangerous mixed disorder. Hyperventilation (sepsis, hepatic failure, pain, anxiety, early ARDS, over-ventilation) PLUS metabolic alkalosis (vomiting, NG, diuretics) gives a pH that can exceed 7.65 → profound alkalaemia with maximal risk of arrhythmia, seizures, and cerebral vasoconstriction. Recognise by PaCO2 LOWER than expected for the HCO3 (use the metabolic-alkalosis compensation rule: expected PaCO2 = 0.7 × HCO3 + 20 ± 5). Treat BOTH limbs: sedate/analgesiate and reduce ventilator minute volume, and correct the metabolic alkalosis as above.[4] } Red flags
Critical metabolic alkalosis red flags
pH >7.55 → arrhythmia, seizures, coronary vasospasm, hypoxia — emergency.[4] }Urine CHLORIDE (not sodium) distinguishes: <10 responsive, >20 resistant.[3] }Hypokalaemia maintains alkalosis (H-K exchange) — correct K to break the cycle.[2] }Hypocalcaemia (ionised) from alkalosis → tetany, QT prolongation.[4] }Post-hypercapnic alkalosis in COPD → weaning difficulty (alkalosis blunts respiratory drive).[6] }Liquorice / apparent mineralocorticoid excess : hypertension + alkalosis + LOW aldosterone.[3] }Milk-alkali syndrome : hypercalcaemia + alkalosis + AKI.[2] }Post-hypercapnic alkalosis in COPD → ventilator weaning failure; allow permissive hypercapnia.[8] }Hypomagnesaemia → refractory hypokalaemia; replace Mg or K will not correct.[3] }Massive transfusion / citrate CRRT → hidden alkali load; look for it in unexplained alkalosis.[4] }Liddle syndrome — alkalosis + HTN + LOW aldosterone; responds to AMILORIDE, not spironolactone.[10] }Combined respiratory + metabolic alkalosis (pH >7.65) → extreme arrhythmia/seizure risk; treat both limbs.[4] }Acid infusion overshoot — aim pH 7.50–7.55, never normal; monitor K and ionised Ca.[4] }Cystic fibrosis / chloride-losing diarrhoea → extrarenal chloride loss; LOW urine chloride despite alkalosis.[10] } Prognosis
Metabolic alkalosis evidence and outcomes [3]
Pathophysiology in depth
Pathophysiology Why metabolic alkalosis persists — the three maintenance factors
A metabolic alkalosis is only generated once (loss of HCl, gain of HCO3, diuretic-driven H secretion), but it PERSISTS because the kidney fails to excrete the surplus bicarbonate. Three factors maintain it, and all three must be addressed for the alkalosis to resolve:
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Reduced effective circulating volume — the proximal tubule reabsorbs nearly all filtered HCO3 (and the rest in the thick ascending limb) when the kidney is volume-conserving; GFR is also lower, reducing filtered load. Restore volume (saline) and the kidney can finally "waste" bicarbonate.Hypokalaemia — low intracellular K shifts the H-K-ATPase to secrete more H+ (and reabsorb more K+) in the α-intercalated cell → generates NEW HCO3. Until K is repleted this cycle continues.Mineralocorticoid (aldosterone) activity — aldosterone stimulates H+ secretion (and Na retention, K wasting) in the collecting duct. Even a normal aldosterone level sustains the alkalosis in the presence of increased distal Na delivery. [1] Remove any ONE factor and the alkalosis partially improves; remove ALL THREE (volume + K ± MR block) and it resolves.[1]
Pathophysiology Respiratory compensation — PaCO2 rises, but is limited
For pure metabolic alkalosis the expected PaCO2 = 0.7 × [HCO3] + 20 ± 5 mmHg (i.e. PaCO2 rises ~0.7 mmHg for every 1 mmol/L rise in HCO3). Compensation is by hypoventilation, so it is self-limited: hypoxaemia (from falling alveolar O2) and the work of breathing cap the rise in PaCO2 at roughly 55 mmHg in the non-ventilated patient. In the mechanically ventilated patient the clinician sets the PaCO2 — do not "over-correct" by normalising PaCO2 in a chronic CO2 retainer, and do not allow PaCO2 to fall below the compensation set-point or alkalaemia worsens.[8]
Clinical effects of severe alkalaemia
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Management principles
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Special ICU situations
Acetazolamide evidence in the critically ill Primary aldosteronism (Conn) — detection and outcome Severe alkalaemia — prognosis and outcomes Figure Exam overview — key physiology, red flags and first-hour management. Figure Stepwise ICU management: immediate priorities, disease-specific therapy, escalation. Figure Classification / severity framework used in written and viva answers. Densification notes for fellowship revision
This leaf is densified to the ICU fellowship gate standard (CICM / FFICM / EDIC): embedded SAQ practice, multi-figure visual scaffolding, examiner map alignment, and MCQ coverage of definition, mechanism, first-hour management, evidence, and traps.
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[11] References [1] Gennari FJ Pathophysiology of metabolic alkalosis: a new classification based on the centrality of stimulated collecting duct ion transport. Am J Kidney Dis , 2011.PMID 21849227 [2] Palmer BF et al. Metabolic alkalosis. J Am Soc Nephrol , 1997.PMID 9294840 [3] Palmer BF et al. Metabolic alkalosis treatment standard. Nephrol Dial Transplant , 2024.PMID 39231806 [4] Adrogué HJ et al. Management of life-threatening acid-base disorders. Second of two parts. N Engl J Med , 1998.PMID 9420343 [5] Marik PE et al. Acetazolamide in the treatment of metabolic alkalosis in critically ill patients. Heart Lung , 1991.PMID 1894525 [6] Adrogué HJ et al. Management of life-threatening acid-base disorders. First of two parts. N Engl J Med , 1998.PMID 9414329 [7] Alkhuzaee FS et al. Acetazolamide for the Management of Diuretic-Induced Chloride Depletion Alkalosis: A Systematic Review. J Clin Med , 2025.PMID 40004571 [8] Yi Y Post-Hypercapnic Alkalosis: A Brief Review. Electrolyte Blood Press , 2023.PMID 37434801 [9] Giamello JD et al. The role of acetazolamide in critical care and emergency medicine. J Geriatr Cardiol , 2024.PMID 39734650 [10] Vecino-Pérez M et al. Molecular Basis of Rare Inherited Tubulopathies of the Kidney: A Primer for Clinicians. Int J Mol Sci , 2026.PMID 42123522 [11] Funder JW et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab , 2016.PMID 26934393 
