approach to acid-base disorders

Systematic framework: identify the primary disorder → check compensation → calculate anion gap if metabolic acidosis → delta-delta for mixed disorders. Most bedside acid-base problems reduce to: is this a simple disorder with appropriate compensation, or a mixed picture?

do not miss

severe acidaemia (pH <7.1) → haemodynamic instability and arrhythmia risk; consider NaHCO₃ if pH <7.1 with cardiovascular compromise
toxic alcohol ingestion — early: elevated osmolar gap without AG elevation; late: rising AG as parent compound metabolised. Fomepizole, urgent nephrology/toxicology, consider haemodialysis
lactic acidosis with metformin in acute kidney injury — hold metformin, support haemodynamics, consider RRT

the systematic approach

pH → acidaemia or alkalaemia (or normal pH with mixed disorder)
Primary disorder — pCO₂ and HCO₃⁻ move in the same direction in simple disorders
Compensation — compare measured values against expected (table below); mismatch = additional disorder
If metabolic acidosis → anion gap → if elevated, delta-delta

expected compensation

disorder	expected compensation
metabolic acidosis	Winter’s: expected pCO₂ = 1.5 × [HCO₃⁻] + 8 ± 2 mmHg (× 0.133 for kPa)
metabolic alkalosis	pCO₂ ↑ ~0.09 kPa per 1 mmol/L ↑ HCO₃⁻
acute respiratory acidosis	HCO₃⁻ ↑ 1 per 1.3 kPa ↑ pCO₂
chronic respiratory acidosis	HCO₃⁻ ↑ 3.5–5 per 1.3 kPa ↑ pCO₂ (use midpoint; range avoids false “mixed” calls)
acute respiratory alkalosis	HCO₃⁻ ↓ 2 per 1.3 kPa ↓ pCO₂
chronic respiratory alkalosis	HCO₃⁻ ↓ 5 per 1.3 kPa ↓ pCO₂

anion gap and delta-delta

AG = Na⁺ − Cl⁻ − HCO₃⁻ (normal ~12 mmol/L; method-dependent — modern ion-selective electrodes often 6–12). Correct for albumin: add 2.5 per 10 g/L albumin below 40.

Delta-delta = (AG − 12) / (24 − HCO₃⁻):

1–2 → pure AGMA
>2 → concurrent metabolic alkalosis (or pre-existing elevated HCO₃⁻)
<1 → concurrent NAGMA

Caveat: in lactic acidosis, HCO₃⁻ falls ~0.6× the rise in AG (lower renal lactate clearance) → ratio may exceed 1 without a true concurrent alkalosis. The 1:1 assumption holds better in ketoacidosis.

Osmolar gap = measured − calculated osmolality. Calculated osm = 2 × Na⁺ + glucose + urea + ethanol (all mmol/L). Gap >10 mOsm/kg → consider toxic alcohols (methanol, ethylene glycol), propylene glycol. Omitting ethanol is the most common cause of a spuriously elevated osmolar gap in intoxicated patients — always account for it before invoking toxic alcohols.

toxic alcohol kinetics

Early ingestion: elevated osmolar gap, normal AG (parent osmoles present). Late: AG rises as parent compound converts to organic acids, osmolar gap normalises. A normal osmolar gap does not exclude late-presentation toxic alcohol poisoning.

AGMA — GOLD MARRK

Glycols (ethylene, propylene) · Oxoproline (chronic paracetamol + malnutrition → glutathione depletion) · L-lactate · D-lactate (short bowel syndrome) · Methanol · ASA (salicylates) · Rhabdomyolysis · Renal failure · Ketoacids (DKA, starvation, alcoholic)

NAGMA — urine anion gap and renal tubular acidoses

Urine anion gap (UAG) = urine (Na⁺ + K⁺) − urine Cl⁻:

Negative → appropriate renal NH₄⁺ excretion → GI HCO₃⁻ loss (diarrhoea, fistulae, ureteral diversion)
Positive → impaired renal acid excretion → RTA

	type I (distal)	type II (proximal)	type IV
defect	impaired distal H⁺ secretion	impaired proximal HCO₃⁻ reabsorption	hypoaldosteronism
K⁺	low	low	high
urine pH	>5.5 (cannot acidify)	<5.5 (once threshold passed)	variable
associations	Sjögren, SLE, ifosfamide, amphotericin	Fanconi, myeloma, tenofovir, acetazolamide, topiramate	diabetes, adrenal insufficiency, ACEi/ARBs, MRAs, CNIs, heparin
complications	nephrocalcinosis, CaPO₄ stones	osteomalacia	—
treatment	NaHCO₃, K⁺ citrate	NaHCO₃, K⁺ citrate (high doses)	NaHCO₃, fludrocortisone if AI; K⁺ management

CNIs and type IV RTA

Tacrolimus and ciclosporin activate the WNK-SPAK pathway → ↑ NCC activity in DCT → enhanced Na⁺/Cl⁻ reabsorption → volume expansion, suppressed renin/aldosterone → hyperkalaemia and metabolic acidosis. Thiazides directly block NCC, reversing the mechanism — logical first-line for CNI-induced hyperkalaemia in transplant patients.

metabolic alkalosis

Classify by urine Cl⁻ (not urine Na⁺ — vomiting causes bicarbonaturia with obligatory Na⁺ loss, making urine Na⁺ misleadingly elevated).

saline-responsive (urine Cl⁻ <20 mmol/L)

Vomiting, NG suction, remote diuretic use, post-hypercapnic. Treatment: volume repletion with NaCl.

saline-resistant (urine Cl⁻ >40 mmol/L)

Urine Cl⁻ 20–40 mmol/L is indeterminate — repeat after holding diuretics. Recent diuretic use is the key confounder (actively diuresing patients have high urine Cl⁻ despite a chloride-responsive aetiology).

Normotensive: active diuretics, Bartter, Gitelman
Hypertensive + low renin, low aldo: Liddle, apparent mineralocorticoid excess (liquorice), Cushing
Hypertensive + low renin, high aldo: primary aldosteronism (Conn)
Hypertensive + high renin, high aldo: renovascular disease, reninoma

traps

Forgetting albumin correction — a patient with albumin 20 g/L and an AG of 12 actually has a corrected AG of 17 (AGMA present). Always correct for albumin.
Mixed disorders hide each other — concurrent AGMA + metabolic alkalosis → near-normal pH and HCO₃⁻. The delta-delta exposes it.
Lactic acidosis is not always type A — drug-induced (metformin, linezolid, NRTIs) and D-lactic acidosis (short bowel) are easily missed. Check lactate on every unexplained AGMA.
Saline worsens hyperchloraemic acidosis — large-volume NS (154 mmol/L Cl⁻) causes dilutional NAGMA. Use balanced crystalloids when resuscitating patients with existing metabolic acidosis.

acid-base disorders