Acid-Base Balance

Acid-base homeostasis keeps arterial blood pH within the narrow range of 7.35–7.45, defended by buffers, the lungs (rapid, minutes) and the kidneys (slow, hours–days). For NEET PG this is a perennial favourite: arterial blood gas (ABG) interpretation links pure physiology to medicine, nephrology, toxicology and critical care, so a stepwise approach plus a handful of formulae will reliably bag marks.

Core concepts and the Henderson–Hasselbalch equation

pH is the negative logarithm of hydrogen ion concentration. At a normal pH of 7.4, [H⁺] is 40 nmol/L. A useful clinical rule: for every 0.01 change in pH away from 7.4, [H⁺] changes by ~1 nmol/L in the opposite direction (so pH 7.3 ≈ 50 nmol/L, pH 7.5 ≈ 32 nmol/L).

The bicarbonate–carbonic acid system is the body's principal extracellular buffer because both components are independently regulated (HCO₃⁻ by kidney, CO₂ by lung). The Henderson–Hasselbalch equation is:

pH = 6.1 + log ([HCO₃⁻] / (0.03 × PaCO₂))

• 6.1 = pKa of the bicarbonate buffer system
• 0.03 = solubility coefficient of CO₂ (mmol/L/mmHg)
• Normal ratio HCO₃⁻ : (0.03 × PaCO₂) = 24 : 1.2 = 20 : 1, which gives pH 7.4

The simplified Henderson equation is exam-friendly:

[H⁺] (nmol/L) = 24 × (PaCO₂ / [HCO₃⁻])

High-yield: It is the ratio of HCO₃⁻ to PaCO₂ — not the absolute values — that sets the pH. As long as the 20:1 ratio is preserved, pH stays at 7.4. This is the conceptual basis of compensation.

Normal ABG values

Parameter	Normal value
pH	7.35–7.45
PaCO₂	35–45 mmHg (avg 40)
HCO₃⁻	22–26 mmol/L (avg 24)
PaO₂	80–100 mmHg
Base excess	−2 to +2 mmol/L
Anion gap	8–12 mmol/L
[H⁺]	35–45 nmol/L

The four primary disturbances

Disturbances are named by the primary change. Acidaemia (pH < 7.35) or alkalaemia (pH > 7.45) is the measured blood result; acidosis/alkalosis is the underlying process.

• Metabolic acidosis → primary ↓HCO₃⁻
• Metabolic alkalosis → primary ↑HCO₃⁻
• Respiratory acidosis → primary ↑PaCO₂
• Respiratory alkalosis → primary ↓PaCO₂

High-yield: In a simple disorder, the primary change and the compensatory change move in the same direction. e.g. metabolic acidosis: HCO₃⁻ ↓ (primary) and PaCO₂ ↓ (compensation). If they move in opposite directions, suspect a mixed disorder.

Compensation rules — the formulae you must memorise

Compensation never fully corrects pH back to exactly 7.4 (over-correction implies a second primary process). The expected compensation tells you whether the response is appropriate.

Primary disorder	Expected compensation	Formula
Metabolic acidosis	↓ PaCO₂	Winter's formula: PaCO₂ = 1.5 × HCO₃⁻ + 8 (±2)
Metabolic alkalosis	↑ PaCO₂	PaCO₂ = 0.7 × HCO₃⁻ + 21 (±2), or ↑PaCO₂ ≈ 0.7 per 1 ↑HCO₃⁻
Acute respiratory acidosis	↑ HCO₃⁻	HCO₃⁻ ↑ 1 per 10 ↑PaCO₂
Chronic respiratory acidosis	↑ HCO₃⁻	HCO₃⁻ ↑ 3.5–4 per 10 ↑PaCO₂
Acute respiratory alkalosis	↓ HCO₃⁻	HCO₃⁻ ↓ 2 per 10 ↓PaCO₂
Chronic respiratory alkalosis	↓ HCO₃⁻	HCO₃⁻ ↓ 4–5 per 10 ↓PaCO₂

High-yield (most-tested): Winter's formula — Expected PaCO₂ = 1.5 × [HCO₃⁻] + 8 ± 2. If measured PaCO₂ is higher than predicted → superimposed respiratory acidosis; if lower than predicted → superimposed respiratory alkalosis. This single line answers most "mixed disorder" stems.

A quick metabolic-acidosis check: the last two digits of the pH should approximate the PaCO₂ (e.g. pH 7.25 → PaCO₂ ≈ 25 mmHg). Compensation respiratory limit: PaCO₂ rarely falls below ~10–12 mmHg.

Stepwise approach to an ABG

A disciplined sequence prevents errors in the exam:

1. Check pH → acidaemia (<7.35) or alkalaemia (>7.45)?
2. Identify the primary disorder → look at PaCO₂ and HCO₃⁻; which one explains the pH? (e.g. low pH + low HCO₃⁻ = metabolic acidosis)
3. Is compensation appropriate? → apply the relevant formula (Winter's, etc.).
4. Calculate the anion gap (always, even in alkalosis) → AG = Na⁺ − (Cl⁻ + HCO₃⁻).
5. If high AG metabolic acidosis, calculate the delta ratio / delta-delta → uncovers a coexisting normal-AG acidosis or metabolic alkalosis.
6. Check oxygenation (PaO₂, A–a gradient) where relevant.

Stepwise (flow): pH → primary process → expected compensation → anion gap → delta-delta → clinical correlation.

Metabolic acidosis and the anion gap

The anion gap reflects unmeasured anions: AG = Na⁺ − (Cl⁻ + HCO₃⁻), normal 8–12 mmol/L (~12 with older analysers). Always correct for albumin: AG falls by ~2.5 mmol/L for every 1 g/dL drop in albumin (a hypoalbuminaemic patient with a "normal" AG may actually have a raised gap).

High anion gap metabolic acidosis (HAGMA) — mnemonics

Classic MUDPILES:

• M — Methanol
• U — Uraemia
• D — Diabetic (and other) ketoacidosis
• P — Paraldehyde / Propylene glycol
• I — Iron, Isoniazid (INH), Inborn errors
• L — Lactic acidosis
• E — Ethylene glycol
• S — Salicylates

Modern preferred mnemonic GOLD MARK: Glycols (ethylene, propylene), Oxoproline (pyroglutamic acid, chronic paracetamol), L-lactate, D-lactate, Methanol, Aspirin, Renal failure, Ketoacidosis.

Normal anion gap (hyperchloraemic) metabolic acidosis — USED CARP / HARDUPS

Due to GI or renal bicarbonate loss. USED CARP: Ureteroenterostomy, Small-bowel fistula, Extra chloride, Diarrhoea (commonest cause overall), Carbonic anhydrase inhibitors (acetazolamide), Adrenal insufficiency, Renal tubular acidosis, Pancreatic fistula.

High-yield: Diarrhoea = normal AG acidosis with low/normal urinary anion gap (negative UAG) because the kidney appropriately excretes NH₄Cl. Renal tubular acidosis = normal AG acidosis with positive urinary anion gap. Urinary AG = (Urine Na⁺ + K⁺) − Urine Cl⁻; "NeGUTive = GUT" loss (diarrhoea), positive = renal (RTA).

Renal tubular acidosis snapshot

Feature	Type 1 (Distal)	Type 2 (Proximal)	Type 4 (Hyperkalaemic)
Defect	↓ distal H⁺ secretion	↓ proximal HCO₃⁻ reabsorption	Aldosterone deficiency/resistance
Serum K⁺	Low	Low	High
Urine pH	> 5.5 (high)	Variable (<5.5 once HCO₃⁻ low)	< 5.5
Nephrocalcinosis / stones	Yes	No	No
Classic cause	Sjögren, amphotericin	Fanconi, acetazolamide, myeloma	Diabetic nephropathy, ACE inhibitors

Delta ratio (delta-delta)

Delta ratio = (Measured AG − 12) / (24 − Measured HCO₃⁻)

• < 0.4 → coexisting normal AG metabolic acidosis
• 0.4–1 → mixed high-AG and normal-AG metabolic acidosis
• 1–2 → pure high anion gap metabolic acidosis (DKA, lactic acidosis)
• > 2 → coexisting metabolic alkalosis or pre-existing high HCO₃⁻ (chronic respiratory acidosis)

Osmolar gap — the toxic-alcohol clue

Calculated osmolality = 2 × Na⁺ + (glucose/18) + (urea/2.8) (mg/dL units) — or in SI use glucose and urea directly in mmol/L.

Osmolar gap = measured osmolality − calculated osmolality (normal < 10–15 mOsm/kg).

High-yield: A raised osmolar gap plus a high anion gap metabolic acidosis strongly suggests methanol or ethylene glycol poisoning. Methanol → optic disc hyperaemia / blindness; ethylene glycol → calcium oxalate crystals in urine and acute kidney injury. Antidote for both = fomepizole (or ethanol), which inhibits alcohol dehydrogenase.

Metabolic alkalosis

Primary ↑HCO₃⁻; maintained only if the kidney cannot excrete the excess bicarbonate (volume depletion, chloride depletion, hypokalaemia, hyperaldosteronism). Divided by urinary chloride:

• Chloride-responsive (urine Cl⁻ < 20 mmol/L): vomiting/NG suction (loss of HCl), diuretics (late), villous adenoma, post-hypercapnia. Treated with normal saline + KCl.
• Chloride-resistant (urine Cl⁻ > 20 mmol/L): primary hyperaldosteronism (Conn's), Cushing's, Bartter syndrome, Gitelman syndrome, severe K⁺ depletion. Saline does not correct.

High-yield: Vomiting / pyloric stenosis causes hypochloraemic, hypokalaemic metabolic alkalosis with paradoxical aciduria (acidic urine despite alkalaemia, because volume/K⁺ depletion drives distal H⁺ secretion in exchange for Na⁺). A classic infant exam stem.

Respiratory disturbances

Respiratory acidosis = alveolar hypoventilation → CO₂ retention.

• Acute: airway obstruction, opioid/sedative overdose, acute neuromuscular weakness (Guillain–Barré, myasthenic crisis), pneumothorax.
• Chronic: COPD, obesity hypoventilation, kyphoscoliosis. Renal compensation raises HCO₃⁻ over days.

Respiratory alkalosis = alveolar hyperventilation → CO₂ washout. Causes — CHAMPS: CNS disease, Hypoxia/High altitude, Anxiety/pain, Mechanical over-ventilation, Pregnancy/Progesterone, Salicylates/Sepsis.

High-yield: Salicylate (aspirin) poisoning in adults classically gives a mixed primary respiratory alkalosis + high anion gap metabolic acidosis — the respiratory centre is directly stimulated and uncoupled oxidative phosphorylation produces acids. Early phase: respiratory alkalosis predominates.

Acute vs chronic respiratory acidosis

Feature	Acute	Chronic
HCO₃⁻ rise per 10 ↑PaCO₂	+1	+3.5–4
pH change per 10 ↑PaCO₂	−0.08	−0.03
Mechanism	Tissue buffering	Renal HCO₃⁻ retention
Time course	Minutes	3–5 days

Clinical features of acid-base derangements

• Acidaemia: depressed myocardial contractility, arrhythmias, vasodilatation, hyperkalaemia, Kussmaul breathing (deep sighing respiration in metabolic acidosis, e.g. DKA), insulin resistance, decreased catecholamine responsiveness.
• Alkalaemia: tetany, paraesthesiae, carpopedal spasm (due to fall in ionised calcium), arrhythmias, hypokalaemia, cerebral vasoconstriction (dizziness, syncope in hyperventilation).

High-yield: Alkalosis lowers ionised calcium (more Ca²⁺ binds albumin) → tetany and a positive Chvostek/Trousseau sign even when total calcium is normal. This is why hyperventilating patients feel tingling and cramps.

Investigations / investigation of choice

• Arterial blood gas is the gold standard for diagnosing the disorder; venous gas approximates pH and HCO₃⁻ but not oxygenation.
• Serum electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻) for anion gap.
• Serum osmolality (measured) for osmolar gap when toxic ingestion suspected.
• Urinary anion gap / urine pH to separate diarrhoea from RTA.
• Urinary chloride to classify metabolic alkalosis.
• Lactate, ketones, glucose, renal function, salicylate level as directed by the gap.

Management / drug of choice principles

The cornerstone is treat the underlying cause.

• DKA: fluids + insulin + potassium; bicarbonate only if pH < 6.9.
• Lactic acidosis: restore tissue perfusion; treat sepsis.
• Methanol/ethylene glycol: fomepizole, supportive bicarbonate, haemodialysis.
• Salicylate poisoning: urinary alkalinisation with sodium bicarbonate (target urine pH 7.5–8), haemodialysis if severe.
• Chloride-responsive metabolic alkalosis: normal saline + KCl; acetazolamide if volume-overloaded.
• Respiratory acidosis: ventilatory support, reverse the cause (naloxone for opioids).
• Bicarbonate therapy is generally reserved for severe acidaemia (pH < 7.1–7.2) or specific intoxications, as over-aggressive correction risks overshoot alkalosis, hypokalaemia and paradoxical CNS acidosis.

Complications

• Severe acidaemia: refractory shock, ventricular arrhythmias, cardiac arrest.
• Severe alkalaemia: seizures, tetany, arrhythmias, reduced cerebral and coronary perfusion.
• Iatrogenic: overshoot alkalosis after bicarbonate, hypokalaemia, hypocalcaemia, volume overload, hypernatraemia (from sodium bicarbonate).

Key differentials and the mixed-disorder traps

• High AG acidosis vs normal AG acidosis → distinguished by anion gap and delta ratio.
• Diarrhoea vs RTA (both normal AG) → urinary anion gap.
• Metabolic alkalosis subtypes → urinary chloride.
• A "normal" pH with grossly abnormal PaCO₂ and HCO₃⁻ → suspect a mixed disorder (e.g. metabolic acidosis + metabolic alkalosis cancelling out, as in a vomiting patient who also has lactic acidosis).
• Triple disorder example: chronic alcoholic with vomiting, alcoholic ketoacidosis and lactic acidosis.

Recently asked / exam angle

• Winter's formula numerical: given HCO₃⁻, calculate expected PaCO₂ and decide if compensation is adequate — the single most repeated calculation.
• Identify the disorder from a given ABG (commonest stem type) — practise the 6-step approach.
• Salicylate poisoning = mixed respiratory alkalosis + HAGMA: a recurrent favourite.
• RTA typing by serum K⁺ and urine pH; Type 4 with hyperkalaemia in diabetics.
• Urinary anion gap to differentiate diarrhoea (negative) from RTA (positive).
• Osmolar gap + HAGMA → toxic alcohol; antidote fomepizole.
• Paradoxical aciduria in pyloric stenosis / persistent vomiting.
• The 20:1 HCO₃⁻:CO₂ ratio and the pKa 6.1 of bicarbonate buffer (pure-physiology one-liner).
• Kussmaul breathing as a sign of metabolic acidosis.
• Effect of alkalosis on ionised calcium → tetany.

Rapid revision

1. Normal pH 7.35–7.45; [H⁺] 40 nmol/L at pH 7.4; HCO₃⁻:CO₂ ratio = 20:1.
2. Henderson–Hasselbalch: pH = 6.1 + log(HCO₃⁻ / 0.03 × PaCO₂); pKa = 6.1.
3. Winter's formula: expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2 (metabolic acidosis).
4. Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻); normal 8–12; correct for albumin (+2.5 per 1 g/dL fall).
5. HAGMA = GOLD MARK / MUDPILES; commonest normal-AG cause = diarrhoea.
6. Urinary AG negative = GI (diarrhoea), positive = RTA.
7. RTA: Type 1 distal (hypoK⁺, urine pH >5.5, stones); Type 2 proximal; Type 4 hyperkalaemic.
8. Metabolic alkalosis split by urine Cl⁻: <20 chloride-responsive (saline-corrects), >20 resistant.
9. Vomiting → hypochloraemic hypokalaemic metabolic alkalosis with paradoxical aciduria.
10. Salicylate poisoning (adult) = respiratory alkalosis + high-AG metabolic acidosis.
11. High osmolar gap + HAGMA = methanol/ethylene glycol → fomepizole; ethylene glycol → oxalate crystals.
12. Alkalosis ↓ ionised calcium → tetany; acidosis → hyperkalaemia and Kussmaul breathing.