Acid-Base Disorders

Meet the patient

A 22-year-old woman is brought in agitated, sweating, breathing fast, and complaining of ringing in her ears. The numbers look almost kind: pH 7.39, PaCO2 26 mmHg, HCO3 16, and an anion gap of 20. A tired hand would write "normal pH, no acid-base problem" and move on.[3]

That sentence is the trap the whole topic exists to prevent. A near-normal pH with a PaCO2 and bicarbonate that have both left normal means two disorders are cancelling each other out — here a respiratory alkalosis and a high-gap metabolic acidosis, the fingerprint of salicylate toxicity. Your job at 3am is to run the six-step approach on every gas, calculate the gap, check the delta ratio, and never be reassured by a pH that has no business being normal.[1][3]

What an acid-base disorder is — the two-pan scale

Acid-base is a balance between a kidney arm and a lung arm, and the pH reports who moved first. Homeostasis holds the arterial pH between 7.35 and 7.45 — a free hydrogen-ion concentration of only 35 to 45 nmol/L — because enzyme kinetics, ion channels, electrolyte distribution and drug-protein binding all pivot on it.[1]

Three layers of defence cooperate, and their speed is what sets the compensation rules you will memorise below. Chemical buffers (bicarbonate, phosphate, haemoglobin, proteins) act in seconds; the lungs adjust CO2 in minutes; the kidneys regenerate bicarbonate and excrete acid as ammonium and titratable acid over hours to days. Slow, but the kidney can near-normalise a chronic disturbance completely.[1][2]

A primary disorder is whatever first moves the pH. Compensation is the secondary response that pulls the pH back toward normal — and the two exam-critical rules of the whole topic live here: treat the cause, not the number, and compensation never overcorrects. If the pH is normal or has swung the other way, a mixed disorder is hiding, and salicylate toxicity is the classic place it hides.[1][3]

The four primary disorders — "2 metabolic, 2 respiratory"

Every disturbance is one of four, or a mixture of them, defined by which variable changed and which way the pH tilted. Cluster once and the classification is done: two metabolic (bicarbonate is the driver) and two respiratory (PaCO2 is the driver).[1]

The two metabolic disorders split further, and the splitting rule is the single highest-yield move in the topic. Metabolic acidosis splits by the anion gap, because the gap localises the cause instantly:[5]

• High anion-gap acidosis — an unmeasured acid (lactate, ketones, toxins, sulphates and phosphates of renal failure, oxalate, formate) has accumulated, so the gap widens while chloride stays put. Mnemonic MUDPILES.
• Normal (hyperchloraemic) anion-gap acidosis — bicarbonate has been lost (diarrhoea) or a tubule cannot reclaim it (RTA, acetazolamide); the kidney holds electroneutrality by retaining chloride, so the gap stays normal but chloride climbs. Mnemonic HARDUP.[1]

Metabolic alkalosis splits by the urine chloride, which tells you whether the alkalosis is a chloride-depleted, saline-fixable state or the kidney is autonomously wasting chloride:[34][6]

• Chloride-responsive — a chloride- and volume-depleted state (gastrointestinal hydrogen and chloride loss — vomiting, nasogastric losses — or remote diuretic use). Corrects with sodium chloride (saline) and potassium repletion.[15]
• Chloride-resistant — the archetype is mineralocorticoid excess, assessed through the renin-angiotensin-aldosterone axis. Saline alone will not correct it; treat the cause.[15]

Respiratory disorders split by duration — acute (minutes to hours, chemical buffering only) versus chronic (days, renal compensation developed). The chronic kidney-driven shift is far larger than the acute buffer shift, and this is how you tell a long-standing CO2 retainer from one who has just decompensated.[14]

The six-step approach — read any gas in 60 seconds

The gas only localises; the diagnosis comes from glucose, ketones, lactate, renal function, salicylate, the osmolar gap and the drug chart. The six steps are how you stop missing mixed disorders. Practise them on every blood gas until they are automatic.[1][5]

1. pH — under 7.35 is acidaemia; over 7.45 is alkalaemia.
2. Primary disorder — if HCO3 and PaCO2 moved the same way (both low, or both high), bicarbonate drives it and the disorder is metabolic. If they moved opposite ways, PaCO2 drives it and the disorder is respiratory.
3. Compensation — apply the four formulas below. Incomplete means still evolving; exceeding expectation, or a pH that crosses normal, means a mixed disorder.
4. Anion gap — Na minus (Cl plus HCO3); normal 8 to 12, and correct for albumin.
5. Delta ratio — unmask a second disorder hiding inside a high-gap acidosis.
6. Treat the cause — and correct potassium and chloride while you do.[1]

Compensation never fully normalises — the four rules

Compensation pulls the pH back toward normal but never normalises it. If the pH has crossed normal, a second disorder is present.[13]

The anion gap and the delta ratio — find the hidden disorder

The anion gap tells you the cause is high or normal; the delta ratio tells you a second cause is tagging along. Both are one line of arithmetic, and both are examined directly.[5]

Anion gap = Na minus (Cl plus HCO3) — it measures the unmeasured anions, chiefly albumin in health, and the normal range is 8 to 12 mmol/L (12 to 16 if potassium is kept in the equation). Two corrections that juniors skip and examiners love:[5][12]

• Albumin correction — in hypoalbuminaemia the observed gap underestimates the unmeasured-anion load by 0.25 mmol/L for every 1 g/L the albumin falls (2.5 for every 1 g/dL): adjusted AG = observed AG + 0.25 x (normal albumin minus observed albumin, in g/L). In a hypoalbuminaemic ICU patient, a "normal" gap can hide a real high-gap acidosis. Always correct.[10]
• Delta gap = (the rise in AG) minus (the fall in HCO3). In a pure high-gap acidosis each mmol of bicarbonate consumed generates one mmol of unmeasured anion, so the rise in gap equals the fall in bicarbonate and the delta gap sits near zero.[9]

The delta gap bands to memorise — they are how you diagnose a mixed disorder from a single gas:[9]

• Near zero — a pure high-gap metabolic acidosis: the rise in AG matches the fall in HCO3.
• Over +6 — an additional metabolic alkalosis is present; the rise in AG outstrips the fall in bicarbonate (classic in vomiting on top of DKA).
• Under -6 — an additional hyperchloraemic (nongap) acidosis is present (a high-gap process plus diarrhoea, for example).

Why the balance shifts — mechanism in three lines

The bicarbonate buffer dominates because it is open at both ends: the lungs exhale CO2 and the kidneys regenerate bicarbonate. That lets it buffer acid loads no closed system could manage. Move the ratio and the pH follows.[1]

Metabolic acidosis has only two mechanisms: a gain of acid that consumes bicarbonate (every H+ buffered removes one HCO3, generating CO2 the lungs excrete), or a direct loss of bicarbonate. When the offending acid is hydrochloric — or bicarbonate is lost to diarrhoea — the kidney retains chloride and the gap stays normal. When the offending acid is an organic anion the kidney cannot excrete quickly (lactate, beta-hydroxybutyrate, sulphate, formate, oxalate), chloride does not rise and the gap widens. That single contrast is the basis of the whole gap-based classification.[3][5]

Metabolic alkalosis needs a generator and two maintainers. Generation is a source of alkali or a route for H+ loss — vomiting (gastric HCl), diuretics (electrogenic sodium reabsorption drives H+ secretion in the collecting duct), milk-alkali syndrome, or contraction alkalosis. Maintenance requires the two factors you must correct at the bedside: chloride depletion (the collecting duct cannot reclaim bicarbonate without chloride) and hypokalaemia (which stimulates ammoniagenesis and renal acid excretion). This is why metabolic alkalosis is chloride-responsive in the volume-depleted patient, and why it persists until you fix both potassium and chloride.[6]

Respiratory disorders are simpler — PaCO2 is set by the balance between CO2 production and alveolar ventilation. Anything that lowers ventilation (COPD, opiates, neuromuscular weakness, CNS depression) raises PaCO2 and gives respiratory acidosis; anything that raises ventilation (pain, anxiety, hypoxia via peripheral chemoreceptors, sepsis, progesterone, salicylates, pulmonary embolism, altitude) lowers PaCO2 and gives respiratory alkalosis.[2]

Why bicarbonate can paradoxically worsen acidosis — the buffering reaction is HCO3 plus H+ to carbonic acid to water plus CO2. The CO2 crosses cell membranes and the blood-brain barrier faster than bicarbonate, so if ventilation cannot clear the CO2 load, intracellular and CNS acidosis worsen even as the arterial pH rises. This is the principal reason bicarbonate is restricted, not routine.[1]

[13] [12] [10] [9] [27]

How common, and who gets them. Acid-base disorders are ubiquitous in hospital — almost every critically ill patient has one. The commonest single disorder on the wards is metabolic alkalosis (vomiting, diuretics); in ICU the picture shifts toward lactic acidosis and respiratory failure. The risk factors to run on autopilot map straight onto the cause.[1]

Clinical presentation — read the breathing first

The symptoms are the cause's symptoms, modulated by the pH. Your first bedside clue is the respiratory pattern. Deep, rapid, sighing breathing is Kussmaul (compensating for metabolic acidosis); shallow, slow breathing points to respiratory acidosis (primary hypoventilation); rapid breathing with a high pH points to respiratory alkalosis.[3]

Metabolic acidosis — the patient feels fatigued and dyspnoeic and, as the pH falls, hypotensive and confused. Severe acidosis, with a pH under 7.1, depresses myocardial contractility, blunts catecholamine responsiveness, and causes vasodilation — a vicious spiral in shock in which pressors stop working. Hyperkalaemia may show on the ECG.[3]

Metabolic alkalosis — weakness and fatigue from hypokalaemia, paraesthesia and tetany from ionised hypocalcaemia (alkalaemia drives calcium onto albumin), and arrhythmias. Severe alkalosis shifts the oxyhaemoglobin curve left (less tissue oxygen delivery) and constricts coronary and cerebral vessels.[1]

Respiratory acidosis — headache from cerebral vasodilation, drowsiness, confusion, coarse asterixis (the flap), and at extremes CO2 narcosis with papilloedema and coma. The patient looks hypopnoeic, not hyperpnoeic.[1]

Respiratory alkalosis — light-headedness, perioral and acral paraesthesia from alkalaemia-induced hypocalcaemia, and carpopedal spasm acutely. Chronic cases are often asymptomatic — the kidney has already compensated.[1]

Cause-specific clues at the bedside — a deliberate toxidrome screen beats a vague differential:[1]

• DKA — Kussmaul breathing, fruity ketotic breath, dehydration, abdominal pain that may mimic an acute abdomen, vomiting.
• Toxic alcohol — altered mental state, visual disturbance and optic disc hyperaemia in methanol, flank pain and calcium oxalate crystalluria in ethylene glycol, and a history of alcohol misuse or solvent access.
• Salicylate — tinnitus, hyperpnoea, sweating, vomiting, agitation progressing to seizures and coma; the mixed respiratory alkalosis plus metabolic acidosis gas.
• Uraemia — fetor, pallor, pruritus, pericardial rub, asterixis, oliguria.
• Opiate — pinpoint pupils, hypoventilation, coma.
• COPD — barrel chest, pursed-lip breathing, prolonged expiration, cachexia, cyanosis.[1]

Atypical presentations — the elderly may present with confusion rather than dyspnoea and have a blunted ventilatory response, so Kussmaul is muted and the CO2 climbs quietly. The pregnant patient runs a physiological compensated chronic respiratory alkalosis — progesterone-driven hyperventilation lowers PaCO2, renal compensation lowers the bicarbonate, and the pH drifts mildly alkaline — do not misread her low bicarbonate as metabolic acidosis.[33] The chronic CO2 retainer sits with a near-normal pH and a very high bicarbonate, so a "normal" PaCO2 in that patient may be an acute decompensation. The diabetic on an SGLT2 inhibitor can run euglycaemic DKA — modest glucose, high ketones, high gap.[1][2]

The differential is the differential of the cause

Localise by the anion gap for acidosis, by the urine chloride for alkalosis — then name the cause and its one distinguishing feature. Two comparison tables do almost all of the work.[1]

High anion-gap metabolic acidosis — MUDPILES, with the one feature that names each:[3][5]

Normal anion-gap (hyperchloraemic) metabolic acidosis — HARDUP:[4]

How to tell gut loss (diarrhoea) from renal loss (RTA) in a nongap acidosis — measure the urine anion gap (Na plus K, minus Cl). In diarrhoea the kidney appropriately raises ammonium excretion, the urine chloride rises, and the urine anion gap is negative. In renal tubular acidosis the kidney cannot excrete ammonium, so the urine anion gap is positive. One number decides it.[4][8]

Metabolic alkalosis — chloride-responsive versus resistant:[34][6]

• Chloride-responsive — the chloride- and volume-depleted state: gastrointestinal hydrogen and chloride loss (vomiting, nasogastric suction) or remote diuretic use. Corrects with sodium chloride plus potassium repletion.[15]
• Chloride-resistant — mineralocorticoid excess is the archetype, localised by assessing volume status and the renin-angiotensin-aldosterone axis. Saline will not correct it — treat the cause.[15]

Mixed disorders to recognise — these are the exam favourites, and every one is a near-normal pH waiting to mislead:[1]

• Salicylate toxicity — respiratory alkalosis plus high-gap metabolic acidosis, often with a near-normal pH.
• Cardiac arrest and CPR — respiratory acidosis from apnoea plus a metabolic (lactic) acidosis.
• Vomiting plus uraemia — metabolic alkalosis plus metabolic acidosis.
• Sepsis in a COPD patient — metabolic (lactic) acidosis plus respiratory acidosis.
• DKA with Kussmaul that overshoots — metabolic acidosis plus respiratory alkalosis.
• Pregnancy with sepsis — a chronic respiratory alkalosis plus an acute metabolic acidosis.[1]

Investigations — the gas, the gap, and the gap's delta

The arterial or venous blood gas is the investigation; everything else localises the cause. Modern analysers return pH, PaCO2, PaO2, HCO3, base excess and often lactate in under a minute. Venous gases are acceptable for most metabolic questions — venous pH runs 0.02 to 0.05 lower and venous PCO2 4 to 6 mmHg higher than arterial (values diverge more in severe hypoperfusion) — use arterial when you need oxygenation or a precise PaCO2.[12]

Normal values to memorise: pH 7.35 to 7.45 (acidemia below, alkalemia above); anion gap 8 to 12 mmol/L (12 to 16 with potassium in the equation).[13][12]

The confirmatory tests you send in parallel with the gas, each aimed at one cause:[3]

• Osmolar gap — measured minus calculated osmolality (2 x Na plus glucose plus urea; add 1.2 x ethanol if relevant). Normal is under 10 mOsm/kg. A high anion gap with a high osmolar gap is a toxic alcohol — the parent alcohol is osmotically active before it is metabolised.
• Urine anion gap — Na plus K minus Cl; negative in diarrhoea, positive in RTA.
• Urine chloride — divides metabolic alkalosis into the chloride-depleted (saline-responsive) and the chloride-resistant form.[34]
• Beta-hydroxybutyrate — the dominant ketone in DKA; more sensitive than the nitroprusside test, which catches acetoacetate but misses beta-hydroxybutyrate.
• Lactate — defines lactic acidosis (over 2 high-gap, over 4 severe); a lactate that rises despite resuscitation is an ominous sign.
• Salicylate level — for any unexplained high-gap acidosis with tinnitus, or any mixed gas.
• Renal function, glucose, albumin, calcium — define the uraemic, hyperglycaemic and hypoalbuminaemic contributions.
• ECG — for hyperkalaemia (peaked T, flattened P, prolonged PR, wide QRS, sine wave) and to monitor alkalaemia-induced arrhythmia.[1][4][5]

Resuscitation — treat the cause, correct potassium and chloride

Two cardinal rules govern every acid-base resuscitation, and almost all of the marks live in them. First, treat the underlying cause, not the pH — insulin and fluids fix DKA, fomepizole and dialysis fix toxic alcohol, resuscitation fixes lactic acidosis, naloxone fixes narcotic hypoventilation; the pH follows the cause. Second, correct potassium and chloride throughout — insulin shifts potassium into cells, and fixing alkalosis shifts it back, so hypokalaemia is what kills the patient with DKA or alkalosis; hypochloraemia is what perpetuates alkalosis.[1]

ABCDE first. For the airway and breathing, give oxygen to target SpO2 94 to 98% for most adults but 88 to 92% in the chronic CO2 retainer (COPD) — over-oxygenation worsens hypercapnia through V/Q mismatch and the Haldane effect (oxygen displaces CO2 from haemoglobin). Consider NIV (bilevel) for decompensated respiratory acidosis; intubate if the CO2 is rising with a falling GCS or failing respiratory effort.[2]

For the circulation, take IV access and treat shock. In septic or cardiogenic lactic acidosis run the Surviving Sepsis hour-1 bundle within 1 hour of recognition — lactate measurement, blood cultures before antibiotics, broad-spectrum antibiotics, 30 mL/kg crystalloid for hypotension or a lactate of 4 mmol/L or more, and vasopressors for hypotension during or after fluid resuscitation.[24] Prefer balanced crystalloids (lactated Ringer's, Plasma-Lyte) over saline for large-volume resuscitation — the SMART trial found fewer major adverse kidney events within 30 days with balanced solutions (14.3 vs 15.4%), with less new renal-replacement therapy and persistent renal dysfunction, because the high chloride load in saline itself causes a hyperchloraemic acidosis.[25]

When is sodium bicarbonate considered? Trial evidence is sobering, so the indications are narrow:[26]

• The physiology, not the ritual — at a pH under 7.2 severe acidaemia brings systemic vasodilation, reduced myocardial contractility and mean arterial pressure, diminished catecholamine and vasopressor responsiveness, arrhythmias, hyperkalaemia and altered mental status; restoring a workable pH can restore pressor responsiveness, which is the argument for bicarbonate in the unstable patient.[12]
• Specific indications alongside definitive treatment — hyperkalaemia, tricyclic antidepressant overdose with QRS widening, and severe renal acidosis pending dialysis.[1]
• In every other acidosis — including the vast majority of lactic acidosis — bicarbonate is not routine: BICAR-ICU found no effect on the primary composite outcome in severe acidaemia (pH 7.20 or under), though a prespecified acute-kidney-injury stratum showed better 28-day survival.[26]

Definitive treatment — name the drug, the dose, and the timing

Definitive management is cause-specific, and the examiner wants drug, dose, route, timing and rationale. These are the protocols to reproduce verbatim.[1]

Diabetic ketoacidosis — the prototype

The protocol, with potassium woven through:[16][17]

1. Fluids before insulin — begin fluid resuscitation first; in children give an initial bolus of 10 to 20 mL/kg of 0.9% saline, with the fluid running 1 to 2 hours before the insulin starts. Cerebral oedema is the most common severe complication of paediatric DKA, so avoid over-rapid correction and intervene early with mannitol or hypertonic saline if it develops.[17]
2. Insulin — a weight-based, fixed-rate continuous IV infusion at 0.1 unit/kg/h, continued until the ketosis resolves (0.05 unit/kg/h is an accepted lower-rate alternative in children with comparable 12-hour acid-base recovery). When the blood glucose falls below 14 mmol/L, add 10% glucose so the fixed-rate insulin can continue.[17][16][18]
3. Potassium — insulin and acidosis correction shift potassium into cells, so the net is a fall. Replace potassium early and sufficiently, guided by repeat levels.[17]
4. Bicarbonate is not indicated — its administration is contraindicated in paediatric DKA.[17]
5. Monitor the response with bedside capillary ketones (the method of choice; venous pH and bicarbonate if a ketone meter is unavailable, with venous rather than arterial sampling) and identify and treat the trigger (infection, infarct, non-compliance, new-onset diabetes). Continue any long-acting insulin analogue in usual doses.[16]

Toxic alcohol — methanol and ethylene glycol

Time-critical. The toxic metabolites (formate from methanol; glycolate and oxalate from ethylene glycol) cause the injury, while blocking the parent alcohol's metabolism is the core strategy — start on history and the initial gas while awaiting concentrations:[19][20]

• Fomepizole is the first-line antidote — 15 mg/kg loading dose (intravenous or oral), then 10 mg/kg every 12 hours until the alcohol concentration is under 30 mg/dL; no need to monitor fomepizole levels. If it is unavailable, an ethanol infusion is the alternative alcohol-dehydrogenase blocker. During haemodialysis, give fomepizole as a 1 mg/kg/hour continuous infusion to compensate for its removal.[19]
• Folate or folinic acid is part of methanol treatment and should be continued during extracorporeal treatment.[20]
• Haemodialysis — intermittent, the modality of choice — for severe methanol poisoning: coma, seizures, new visual deficits, metabolic acidosis with pH 7.15 or under, persistent acidosis despite antidotes, anion gap over 24 mmol/L, methanol over 700 mg/L on fomepizole (over 600 on ethanol, over 500 with no antidote), or impaired kidney function; stop when methanol is under 200 mg/L with clinical improvement.[20]
• Supportive care: treat seizures; keep a high index of suspicion in any unexplained high-gap acidosis with an osmolar gap, acute renal failure or neurological disease, so treatment is not delayed.[19]

Salicylate toxicity

Alkalinise the urine and dialyse:[22]

• Urinary alkalinisation is first-line in moderately severe salicylate poisoning that does not meet criteria for haemodialysis — a sodium bicarbonate infusion to hold the urine pH above 7.5 (published cases titrate to a blood pH of about 7.5). Hypokalaemia is the commonest complication and defeats alkalinisation — correct potassium as you alkalinise.[22][23]
• Haemodialysis — intermittent, the preferred modality — for severe poisoning: altered mental status, ARDS requiring supplemental oxygen, or failure of standard therapy, regardless of the level; salicylate over 100 mg/dL acutely (over 90 mg/dL on a weaker grade; over 90 — or 80 on the weaker grade — with impaired kidney function); or severe acidaemia with pH 7.20 or under.[21]

Lactic and uraemic acidosis

Lactic acidosis — resuscitate, restore perfusion, achieve source control and treat sepsis, and reverse any causative drug (stop metformin in AKI and consider dialysis). Bicarbonate does not improve the primary outcome — BICAR-ICU (Lancet, 2018) found no effect on the composite of death or organ failure in severe acidaemia, with a survival signal only in the acute-kidney-injury stratum; mortality tracks the cause.[26]

Uraemic acidosis — treat the renal failure; haemodialysis for severe acidosis (the AEIOU indications). In chronic CKD give oral sodium bicarbonate to keep HCO3 over 22 (the BICRA trial slowed eGFR decline).[1]

Normal-gap acidosis — diarrhoea and the renal tubular acidoses

Treat the gut cause, replace bicarbonate and potassium, and manage the RTA by type:[4][8]

• Type 1 (distal) — hyperchloraemic nongap acidosis with hypokalaemia; complicated by nephrocalcinosis, nephrolithiasis and impaired kidney function. Treat with oral alkali plus potassium supplementation (potassium chloride, or potassium bicarbonate/citrate preparations).[30]
• Type 2 (proximal) — proximal bicarbonate wastage, isolated or as part of Fanconi syndrome (glycosuria, aminoaciduria, phosphaturia, uricaciduria); treat the underlying cause — inherited (cystinosis and others) or acquired, increasingly drug-induced, mainly oncology drugs.[8]
• Type 4 (hypoaldosteronism) — the hyperkalaemic form; treat the hyperkalaemia — fludrocortisone (0.05 mg/day in a reported case) has stabilised refractory hyperkalaemia in presumed type 4 RTA — and withdraw the offending drugs.[31]

Metabolic alkalosis

Chloride-responsive — correct the intravascular volume with sodium chloride and replete potassium — potassium depletion sustains the alkalosis by stimulating renal hydrogen-ion secretion, ammonium production and excretion — and stop the cause (antiemetics, stop the diuretic). Acetazolamide, a carbonic anhydrase inhibitor that blocks proximal sodium-bicarbonate reabsorption and induces bicarbonaturia, is an option for diuretic-induced chloride-depletion alkalosis, including when volume limits further saline.[15][6][32]

Chloride-resistant — saline will not work. Treat the mineralocorticoid excess: spironolactone or eplerenone for hyperaldosteronism; resect an adenoma; address Cushing. In Bartter and Gitelman, use potassium-sparing diuretics (amiloride) and replace magnesium.[1]

Respiratory disorders

Respiratory acidosis — treat the hypoventilation. Reverse the reversible: for opiate toxicity give naloxone — 0.4 mg intramuscularly or 2 to 4 mg intranasally, repeated at the lowest dose needed to restore a normal respiratory rate.[29] Treat a COPD exacerbation with bronchodilators, steroids, antibiotics and controlled oxygen — target saturation 88 to 92%, recommended by both European and British guidance.[27] If PaCO2 is rising with a falling pH, start NIV (bilevel) — the best-evidenced first-line treatment for acute exacerbations of COPD with moderate-to-severe respiratory acidosis, where it prevents endotracheal intubation and reduces mortality; a closely monitored trial is reasonable even in severe acidosis or reduced consciousness, with intubation immediately available.[28] Do not correct chronic hypercapnia rapidly — over-rapid correction of chronic respiratory acidosis has produced life-threatening hypokalaemia from renal potassium wasting.[35]

Respiratory alkalosis — treat the cause. Reassure the anxious patient; manage pain; correct hypoxia (give oxygen for the PE or pneumonia driving the hyperventilation); treat sepsis, fever and salicylate toxicity. Rebreathing (paper bag) is reserved for benign acute hyperventilation syndrome — never use it when hypoxia is the driver, because it worsens hypoxaemia.[1]

The renal tubular acidoses — the three faces of a normal gap

An RTA is a normal-gap acidosis with a potassium that points straight at the type. Memorise the potassium and the urine pH and the differential falls out.[4][8]

[30] [8] [31]

How acid-base patients come to harm

They die of the cause and of the electrolytes, almost never of the pH number itself. This is the preventable list — none of these is funny.[1]

Severe metabolic acidosis is a crisis, not a curiosity. At a pH under 7.2 myocardial contractility and mean arterial pressure fall, arterioles dilate, catecholamine and vasopressor responsiveness is diminished and pressors fail, and arrhythmias, hyperkalaemia and altered mental status follow; respiratory muscle fatigue ends in CO2 retention and arrest. Chronic acidosis dissolves bone (osteoporosis, fractures, growth failure in children) and catabolises muscle. None of this is reversible with a bicarbonate ampoule alone — you must treat the cause.[3][12]

Severe alkalosis (pH over 7.6) is its own emergency: hypokalaemic arrhythmia and digoxin potentiation, ionised hypocalcaemia with tetany, seizures and a prolonged QT, a left-shifted oxyhaemoglobin curve starving tissues of oxygen, cerebral and coronary vasoconstriction, hypoventilatory atelectasis, and — in cirrhosis — hepatic encephalopathy as alkalaemia drives ammonium across into the brain.[1]

Over-rapid correction of chronic respiratory acidosis swings the patient the other way. The kidney has spent days generating bicarbonate; if you suddenly normalise the PaCO2 (intubation and over-ventilation), the high bicarbonate persists and the patient tips into a post-hypercapnic metabolic alkalosis with seizures, arrhythmia and hypokalaemia. Correct chronic hypercapnia slowly.[1]

The classic pitfalls — the mistakes that ship patients:[1][5]

• Treating the number, not the cause — giving bicarbonate for a pH of 7.20 in lactic acidosis without resuscitating the shock.
• Missing a mixed disorder — reading a near-normal pH in salicylate toxicity as "no acid-base problem."
• Using bicarbonate for lactic acidosis — no outcome benefit, possible intracellular worsening.
• Failing to correct potassium in DKA before or with insulin — precipitating dangerous hypokalaemia.
• Not correcting the anion gap for albumin — missing a high-gap acidosis in a hypoalbuminaemic ICU patient.
• Misreading the delta gap — over-reading the anion gap without checking the delta ratio, and missing an additional alkalosis or nongap acidosis.
• Over-oxygenating the chronic CO2 retainer — driving hypercapnia and CO2 narcosis.
• Reading a pregnant woman's gas cold — and mislabelling her physiological low bicarbonate as metabolic acidosis.[1]

Prognosis and disposition

Prognosis tracks the cause, not the pH. In severe acidaemia the trial evidence is sobering — BICAR-ICU found no overall benefit from sodium bicarbonate on the composite of death or organ failure, with a survival signal only in the acute-kidney-injury stratum.[26] In paediatric DKA, cerebral oedema is the most common severe complication and the death to fear; protocolised fluids-insulin-potassium care is the defence.[17] Toxic alcohol mortality is set by the time to fomepizole and dialysis — early treatment is essentially curative; late treatment leaves blindness from methanol or renal failure from ethylene glycol.[19] Salicylate mortality falls with alkalinisation and dialysis but climbs when a patient is intubated without prior alkalinisation — intubation removes the compensatory hyperventilation.[22]

Disposition ladder:[1]

• ICU or HDU — pH under 7.1, failing compensation (rising CO2 with falling GCS), shock on vasopressors, mixed disorders, severe toxin ingestion.
• Nephrology or toxicology referral for the dialysis decision — the AEIOU indications: Acidosis refractory, Electrolytes refractory (hyperkalaemia), Ingestion of a dialysable drug (lithium, salicylate, methanol, ethylene glycol, metformin), Overload (pulmonary oedema), Uraemia (pericarditis, encephalopathy).
• Ward for corrected and stable disorders (DKA resolving, alkalosis corrected).
• Safety-net — recheck gas and electrolytes at defined intervals; mixed disorders and toxins evolve fast.[1]

Chronic metabolic acidosis (CKD, distal RTA) is usually stable, but left untreated it erodes bone and muscle and stunts growth in children. Give oral alkali therapy — the mainstay of treatment in distal RTA, correcting the acidosis and preventing the nephrocalcinosis, kidney stones and kidney-function decline.[30]

Special populations

Pregnancy — the mother runs a physiological compensated respiratory alkalosis: progesterone-driven hyperventilation lowers PaCO2 and the kidney lowers bicarbonate in compensation, leaving a mildly alkalaemic pH. A "normal" PaCO2 in late pregnancy may therefore mean respiratory compromise, and a normal bicarbonate may mask a metabolic alkalosis. The fetus develops acidosis at a maternal pH the mother tolerates, so treat maternal acidosis aggressively.[33]

Elderly — blunted ventilatory and renal responses, an atypical presentation (confusion rather than dyspnoea), polypharmacy (diuretics, ACE inhibitors, salicylates, metformin), and higher mortality at any given pH. Salicylate toxicity is particularly lethal in older people through chronic intoxication; lower your threshold to admit, monitor and treat.[1]

Chronic kidney disease — chronic metabolic acidosis from reduced ammoniagenesis. Treat with oral sodium bicarbonate supplementation, and watch the sodium and volume load.[1]

Chronic CO2 retainers (COPD) — oxygen target 88 to 92%, recommended by both European and British guidance.[27] Start NIV early for decompensated respiratory acidosis — the best-evidenced treatment for AECOPD with moderate-to-severe acidosis, preventing intubation and reducing mortality.[28] Do not over-oxygenate — V/Q mismatch plus the Haldane effect worsens hypercapnia.[1]

Children — DKA is the prototype paediatric disorder: initial fluids of 10 to 20 mL/kg 0.9% saline, a fixed-rate insulin infusion of 0.05 to 0.1 unit/kg/h starting after the fluids, early potassium replacement, no bicarbonate, and a particular fear of cerebral oedema — the most common severe complication, treated with mannitol or hypertonic saline.[17][18]

Diabetic on an SGLT2 inhibitor — at risk of euglycaemic DKA (near-normal glucose with high ketones and a high gap), especially with illness, surgery, or low-carbohydrate intake. Check ketones in any unwell diabetic regardless of the glucose reading.[1]

Evidence, guidelines and the names that score marks

Landmark trials and what they changed:[1]

• BICAR-ICU (Jaber, Lancet 2018) — sodium bicarbonate in critically ill patients with severe metabolic acidaemia did not reduce the primary composite of death or organ failure at 28 days, though the acute-kidney-injury stratum showed a survival benefit. Reinforces that bicarbonate is not routine.[26]
• SMART (Semler, NEJM 2018) — balanced crystalloids versus saline in critically ill adults; balanced solutions reduced Major Adverse Kidney Events at 30 days (14.3 vs 15.4%), including less new renal-replacement therapy and saline-induced hyperchloraemic acidosis.[25]
• JBDS guideline (Savage) — the UK DKA protocol: fixed-rate weight-based insulin infusion, glucose added when the blood glucose falls below 14 mmol/L, bedside ketone monitoring, venous gases.[16]
• Kitabchi and the ADA consensus (Diabetes Care 2009) — the classic three-pillar DKA protocol of fluids first, then insulin, with potassium replacement.[7]

Guidelines — the Adrogue and Madias NEJM 1998 two-part review remains the international reference framework for management.[1][2] Resuscitation bundles follow Surviving Sepsis 2021 (the hour-1 bundle); NICE NG51 and the UK Sepsis Six apply in the UK.

Controversies — the Stewart (strong ion difference) approach gives a deeper mechanistic account (the independent variables are the strong ion difference, total weak acid, and PaCO2) but yields the same clinical answers in most cases and is rarely needed at MBBS level. The role of bicarbonate in severe acidaemia remains debated — BICAR-ICU showed no overall benefit with an acute-kidney-injury subgroup signal — and the value of alkalinisation in salicylate poisoning rests on case-series evidence, but the conservative consensus is stable: treat the cause, reserve bicarbonate for specific indications alongside definitive treatment.[26][22]

The mantra, and the mnemonic

[3] [4]

The gap, the delta gap, Winter's, the urine chloride, and the two rules — said as one breath each:[1]

• Anion gap = Na minus (Cl plus HCO3), normal 8 to 12 mmol/L (12 to 16 with potassium included).[12]
• Albumin correction — the gap falls by 2.5 mmol/L for every 1 g/dL fall in albumin; uncorrected, a hypoalbuminaemic ICU patient hides a high-gap acidosis.[10]
• Winter's formula — expected PaCO2 = 1.5 x HCO3 + 8, for metabolic acidosis.[11]
• Delta gap = (observed AG minus normal AG) minus (normal HCO3 minus observed HCO3): over +6 a coexisting metabolic alkalosis; under minus 6 a coexisting hyperchloraemic acidosis.[9]
• Compensation rarely normalises the pH — if the pH reads normal, suspect two disorders cancelling.[13]
• Respiratory compensation is two-staged — a small acute buffering shift, then the larger chronic renal bicarbonate adjustment.[14]
• Metabolic alkalosis compensates by hypoventilation, and the chloride-depleted form corrects with saline.[15]
• Urine chloride divides metabolic alkalosis into the chloride-depleted (saline-responsive) and the chloride-resistant form.[34]
• Bicarbonate is not routine in severe acidaemia — BICAR-ICU found no overall benefit, an acute-kidney-injury-stratum signal only.[26]
• Pregnancy runs a compensated respiratory alkalosis — low PaCO2, compensated low bicarbonate, mildly alkaline pH; the COPD oxygen target is 88 to 92%.[33][27]

The mantra: read the pH, find the cause, fix the potassium and chloride — bicarbonate is a guest appearance, never the main act.[1]

Ward-round test — three stems, thirty seconds each

Stem 1 — the 22-year-old with tinnitus from the top of the topic (answer)

pH 7.39, PaCO2 26, HCO3 16, anion gap 20, tinnitus and agitation. What is the diagnosis and what is the first thing you do? Model: This is salicylate toxicity — a mixed respiratory alkalosis and high-gap metabolic acidosis, the two cancelling to give a near-normal blood pH (around 7.5 in the classic description, with a urine pH above 7.5). The danger is reading the pH as reassurance. Check a salicylate level immediately, start urinary alkalinisation — first-line in moderately severe poisoning that does not meet dialysis criteria — with sodium bicarbonate to hold the urine pH above 7.5 while correcting potassium (hypokalaemia is the commonest complication and defeats alkalinisation), and arrange intermittent haemodialysis for altered mental status, ARDS requiring oxygen, failure of standard therapy, a level over 100 mg/dL acutely, or severe acidaemia with pH 7.20 or under. Alkalinise before any intubation — intubation removes the compensatory hyperventilation and the acidosis can worsen within minutes.[23][22][21]

Stem 2 — the alcoholic who cannot see (answer)

A 48-year-old man arrives confused and breathless after drinking windscreen washer fluid. pH 7.18, HCO3 12, anion gap 28, osmolar gap 24, and he complains his vision is going. Name the toxin, the antidote with dose, and the dialysis trigger. Model: Methanol — metabolised to formic acid, which causes the high-gap acidosis, the high osmolar gap, and the visual disturbance and optic disc hyperaemia. Give fomepizole 15 mg/kg IV loading, then 10 mg/kg every 12 hours until the methanol concentration is under 30 mg/dL, plus folate or folinic acid, continued through extracorporeal treatment. His new visual deficit is itself an EXTRIP indication for intermittent haemodialysis (as are coma, seizures, pH 7.15 or under, anion gap over 24 mmol/L, methanol over 700 mg/L on fomepizole, or impaired kidney function); during dialysis, convert fomepizole to a 1 mg/kg/hour continuous infusion.[19][20]

Stem 3 — the chronic CO2 retainer who got too much oxygen (answer)

A 70-year-old with COPD, brought in for an exacerbation, was put on a non-rebreather at 100%. He is now drowsy, PaCO2 88 mmHg, pH 7.22. Why did this happen, and what is the immediate management? Model: Over-oxygenation of a chronic CO2 retainer worsened hypercapnia through two mechanisms — V/Q mismatch (oxygen perfuses poorly ventilated units that retain CO2) and the Haldane effect (oxygen displaces CO2 from haemoglobin, increasing the dissolved CO2 load to be excreted). Reduce the oxygen to a controlled target of 88 to 92% — the target recommended by European and British guidance — check the arterial gas, and start NIV (bilevel) for the decompensated respiratory acidosis, the best-evidenced treatment for AECOPD where it prevents intubation and reduces mortality. Intubate only if NIV fails, the airway is unprotected, or the GCS is falling. Do not chase a "normal" PaCO2 — this patient's baseline is high, and over-correcting risks a post-hypercapnic metabolic alkalosis.[27][28]

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