Acid-base balance

The core idea

Henderson–Hasselbalch: pH = 6.1 + log (HCO₃⁻ ÷ (0.03 × PaCO₂ in mmHg)). pH depends on the ratio of bicarbonate (set by the kidneys) to CO₂ (set by the lungs). Normal: pH 7.35–7.45, PaCO₂ 4.7–6.0 kPa (35–45 mmHg), HCO₃⁻ 22–26 mmol/L.

Lines of defence

1. Buffers (seconds): bicarbonate is the main ECF and plasma buffer (including in DKA), because its CO₂ can be blown off; haemoglobin is the main buffer of CO₂ in red cells; proteins and phosphate buffer inside cells; phosphate (titratable acid) and ammonia buffer urine. 2. Lungs (minutes): ventilation changes PaCO₂. 3. Kidneys (hours to days): they reclaim filtered bicarbonate and make new bicarbonate.

• Reabsorb filtered bicarbonate, about 80% in the proximal tubule (Na⁺/H⁺ exchange and carbonic anhydrase), the rest distally.
• Make new bicarbonate by excreting H⁺ as titratable acid and as ammonium. Proximal cells make NH₄⁺ from glutamine; ammonium excretion is the main adjustable route and rises in chronic acidosis. In chronic respiratory acidosis (COPD, PaCO₂ 62 mmHg, HCO₃⁻ 32), the raised bicarbonate comes from increased renal ammonium production and excretion.

The four primary disorders and expected compensation

Compensation never fully corrects pH and never overshoots. Values outside the expected range mean a mixed disorder. A high bicarbonate in COPD is compensation unless it exceeds the expected value.

Reading a blood gas

1. pH: acidaemia or alkalaemia? 2. Which of PaCO₂ or HCO₃⁻ explains the direction (primary disorder)? 3. Is the other value compensating by the expected amount? 4. In metabolic acidosis, calculate the anion gap. 5. Check oxygenation separately.

Anion gap

Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻), normally about 8–12 mmol/L. It represents unmeasured anions, mainly albumin (each 10 g/L fall in albumin lowers it by about 2.5).

• Euglycaemic DKA: an SGLT2 inhibitor (empagliflozin) lowers glucose by glycosuria, so after surgery or fasting a patient can have severe ketoacidosis (pH 7.15) with glucose only about 11 mmol/L.
• D-lactic acidosis: in short bowel syndrome, carbohydrate reaches the colon, where bacteria ferment it to D-lactate, causing confusion, slurred speech and ataxia with a high anion gap. Routine lactate assays measure only L-lactate, so they are normal.
• Ureterosigmoidostomy: colonic mucosa exchanges urinary chloride for bicarbonate (and absorbs ammonium), giving hypokalaemic hyperchloraemic acidosis (Cl⁻ 115, HCO₃⁻ 16, gap 7).
• CKD: with too few nephrons, ammonium excretion is inadequate; urine pH is appropriately low (5.3). Early CKD gives a normal gap; advanced CKD adds retained anions. Oral bicarbonate is considered when HCO₃⁻ stays below about 20.
• Methanol and ethylene glycol also raise the osmolar gap: methanol causes blindness (formic acid), ethylene glycol renal failure with oxalate crystals. Treat with fomepizole and dialysis.
• Salicylate poisoning: mixed respiratory alkalosis (direct respiratory centre stimulation) and high anion gap metabolic acidosis.

Renal tubular acidosis (all normal anion gap)

A low urine pH does not exclude RTA: in proximal RTA the intact distal tubule acidifies the urine once bicarbonate has fallen.

Metabolic alkalosis

• Chloride-responsive (urine Cl⁻ below 20): vomiting or nasogastric suction (including hyperemesis gravidarum and self-induced vomiting with eroded dental enamel and knuckle calluses), previous diuretic use. Treat with 0.9% saline and potassium. Early in vomiting urine sodium may be high because bicarbonaturia carries Na⁺, so urine chloride is the better guide.
• Chloride-resistant (urine Cl⁻ high): Conn syndrome, Cushing syndrome, Bartter, Gitelman, Liddle, current diuretics; often with hypertension, raised sodium and low potassium.
• Massive transfusion: the citrate anticoagulant is converted by the liver to bicarbonate, so an early acidosis turns into alkalosis a day or two later.
• Post-hypercapnic alkalosis: a chronic CO₂ retainer has a compensatory HCO₃⁻ of 33. If ventilation drops PaCO₂ quickly to 38 mmHg, the bicarbonate remains and pH jumps to 7.56, with risk of seizures and arrhythmias. Ventilate COPD patients to their usual PaCO₂, not to normal.
• Pyloric stenosis and paradoxical aciduria: vomiting loses HCl and volume. To conserve volume, aldosterone drives Na⁺ reabsorption in the collecting duct in exchange for H⁺ and K⁺, and once K⁺ is depleted H⁺ is secreted preferentially, so urine is acidic despite alkalaemia. Correct fluids, chloride and potassium before pyloromyotomy.

Acid–base and potassium

• Acidosis shifts K⁺ out of cells as H⁺ is buffered inside; correcting it with bicarbonate makes cells take up K⁺ as they release H⁺, lowering serum K⁺. In DKA total body K⁺ is low despite a high serum level (insulin lack and hyperosmolality).
• Acute acidosis reduces renal K⁺ secretion; alkalosis increases it.

Hazards of bicarbonate therapy

Bicarbonate generates CO₂, which crosses the blood–brain barrier faster than HCO₃⁻, causing a paradoxical CSF and intracellular acidosis and worsening confusion. It also lowers K⁺ and ionised calcium and causes sodium overload. In trauma, acidosis with hypothermia and coagulopathy (the lethal triad) is treated by damage-control surgery and warmed resuscitation, not bicarbonate.

Remember Ratio rules pH: kidneys set HCO₃⁻, lungs set CO₂; calculate the gap whenever bicarbonate is low.

Exam trap Diarrhoea gives a normal anion gap acidosis; DKA, lactate and advanced renal failure raise the gap.

Exam trap Correcting a chronic retainer's PaCO₂ to normal unmasks the compensatory bicarbonate as metabolic alkalosis.

How FCPS asks about this

• Main plasma buffer in DKA: bicarbonate; main urinary buffers: phosphate and ammonia.
• Most filtered bicarbonate reabsorbed: proximal tubule; type 2 RTA is a low proximal threshold.
• Urine pH that never falls below 5.5 with stones: type 1 (distal) RTA, low urinary citrate.
• Acidic urine with alkalosis in pyloric stenosis: aldosterone-driven Na⁺ reabsorption in exchange for H⁺ (paradoxical aciduria).
• Normal anion gap acidosis: diarrhoea, RTA, acetazolamide, ureterosigmoidostomy, saline excess.
• Alkalosis after massive transfusion: citrate converted to bicarbonate by the liver.
• Raised HCO₃⁻ in chronic COPD: increased renal ammonium excretion (compensation).