pH < 7.35 (unless compensated).
HCO₃⁻ < 22 mmol/L.
PaCO₂ usually low (<5.3 kPa) due to respiratory compensation (hyperventilation).
PaO₂ often normal.
Base Excess < -2.

⚡ Aetiology

Accumulation of organic or inorganic acids.
Loss of bicarbonate (HCO₃⁻).
Anion Gap (AG) = (Na⁺ + K⁺) – (Cl⁻ + HCO₃⁻). Normal = 8–12 mmol/L.

📊 Causes by Anion Gap

🔺 High Anion Gap	➡️ Normal Anion Gap
💉 Lactic Acidosis – Sepsis, shock, hypoxia, metformin. 🍩 Ketoacidosis – Diabetes, alcohol, starvation. 🩺 Renal Failure – Impaired acid excretion. ☠️ Toxins – Methanol, ethylene glycol, salicylates. 💪 Rhabdomyolysis – Myoglobin → renal damage. 💊 Propylene Glycol – IV drug solvent (lorazepam infusions).	💩 Diarrhoea – GI bicarbonate loss. ⚡ Renal Tubular Acidosis (RTA) – Acid handling defect. 🧂 Hyperchloraemia – Saline overload. 💊 Carbonic Anhydrase Inhibitors – Acetazolamide. 🩹 Ureterosigmoidostomy – Bicarbonate loss. 🩺 Early Renal Failure – Acid retention without AG rise.

🧠 Clinical Features

Hyperventilation (Kussmaul breathing).
Underlying cause often obvious (shock, DKA, diarrhoea etc.).
AG helps narrow differential.

🔎 Key Anion Gap Markers

Anion	Clinical Case
🧪 L-Lactate	Anaerobic metabolism (shock, sepsis).
🍩 Beta-hydroxybutyrate	Diabetic ketoacidosis.
🧴 Hippurate	Toluene poisoning (glue sniffers).
🥛 Glycolate & Oxalate	Methanol/ethylene glycol ingestion.
🌿 D-Lactate	Gut fermentation (e.g., blind loop syndrome).

💊 Management by Cause

Cause	Clinical Features	Diagnostic Tests	Management
💉 Lactic Acidosis	Shock, sepsis, hypoxia, confusion, tachypnoea.	ABG (low pH/HCO₃⁻), serum lactate ↑.	Oxygen, IV fluids, treat cause, inotropes (noradrenaline if septic shock).
🍩 Ketoacidosis	Polyuria, polydipsia, fruity breath, dehydration, confusion.	ABG (low pH, low HCO₃⁻), ketones ↑, glucose ↑ (DKA).	IV fluids, insulin infusion (if DKA), K⁺ replacement, monitor glucose & ketones.
🩺 Renal Failure	Oedema, oliguria, confusion, uremia.	Creatinine ↑, urea ↑, ABG acidosis, electrolytes (hyperkalaemia).	Dialysis if severe, correct underlying cause, treat K⁺ imbalance.
☠️ Toxins	Visual loss (methanol), renal failure (ethylene glycol), tinnitus (salicylates).	ABG: HAGMA, osmolar gap ↑, toxin assays.	Fomepizole, dialysis, bicarbonate (salicylates).
💩 Diarrhoea	Loose stools, dehydration, cramps, lethargy.	ABG: NAGMA, low K⁺, low Na⁺.	Rehydrate (oral/IV), replace electrolytes, treat cause (infection, malabsorption).
⚡ Renal Tubular Acidosis	Polyuria, weakness, bone pain, growth delay (children).	ABG: NAGMA, urine pH pattern, electrolytes.	Oral bicarbonate (NaHCO₃ or K-citrate), treat cause.
🧂 Hyperchloremic Acidosis	Weakness, confusion, oedema if fluid overload.	ABG: NAGMA, Cl⁻ ↑, HCO₃⁻ ↓.	Stop saline infusion, use balanced fluids (Hartmann’s/Ringer’s), correct electrolytes.

🩺 Case 1 — Diabetic Ketoacidosis (DKA)

A 24-year-old woman with type 1 diabetes presents with abdominal pain, vomiting, and drowsiness. Vitals: HR 120, BP 95/60, RR 28 with Kussmaul breathing. Labs: glucose 28 mmol/L, ketones 6 mmol/L, pH 7.15, HCO₃⁻ 10 mmol/L. Management: 💉 Fixed-rate IV insulin infusion, IV fluids (0.9% saline initially), potassium replacement as guided, identify trigger (infection). Avoid: ❌ Bicarbonate therapy unless pH <6.9; avoid rapid fluid shifts in young patients (risk of cerebral oedema).

🩺 Case 2 — Lactic Acidosis in Sepsis

A 68-year-old man presents with fever, hypotension, and confusion. BP 80/50, HR 120, lactate 6.2 mmol/L, pH 7.22, HCO₃⁻ 14 mmol/L. Diagnosis: septic shock with lactic acidosis. Management: 🚑 Sepsis 6 bundle — IV fluids, broad-spectrum antibiotics, oxygen, source control. Consider vasopressors if hypotension persists. Avoid: ❌ Delaying antibiotics; avoid excessive normal saline (can worsen acidosis with hyperchloraemia).

🩺 Case 3 — Renal Failure (Uraemic Acidosis)

A 75-year-old woman with stage 5 chronic kidney disease presents with progressive weakness, nausea, and confusion. Labs: pH 7.28, HCO₃⁻ 16 mmol/L, high urea and creatinine, potassium 6.0 mmol/L. Management: 🩺 Sodium bicarbonate therapy if symptomatic and not fluid overloaded, treat hyperkalaemia, dialysis if severe or refractory. Avoid: ❌ Relying on IV fluids alone; avoid potassium-sparing drugs (e.g. spironolactone, ACEI) in the acute setting.

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Metabolic acidosis

🧪 Analysis of Metabolic Acidosis (ABG)