Acid-Base Physiology
Acid-base physiology governs the regulation of hydrogen ion concentration in body fluids. Disorders are classified as metabolic or respiratory acidosis/alkalosis.
Key Facts
Normal arterial blood pH is 7.35–7.45; PaCO2 4.7–6.0 kPa; HCO3⁻ 22–26 mmol/L; base excess ±2 mmol/L The Henderson-Hasselbalch equation: pH = pKa + log([HCO3⁻]/[0.03 × PaCO2]) Three buffer systems: bicarbonate (most important extracellular), phosphate, protein/haemoglobin (intracellular) Respiratory compensation occurs within minutes; renal compensation takes 3–5 days to reach maximum Anion gap = Na⁺ − (Cl⁻ + HCO3⁻); normal 10–18 mmol/L — raised in MUDPILES causes MUDPILES: Methanol, Uraemia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates Type 1 (distal) RTA: cannot secrete H⁺, urine pH >5.3; Type 2 (proximal) RTA: cannot reabsorb HCO3⁻ Metabolic alkalosis is most commonly caused by vomiting (loss of HCl) or diuretic therapy
Overview
Key Facts
Maintaining acid-base balance is critical for enzyme function, protein structure, and cellular processes. The body maintains pH within a narrow range through buffer systems, respiratory regulation, and renal mechanisms.
Epidemiology
Acid-base disturbances are extremely common in hospitalised patients. Metabolic acidosis occurs in approximately 15-25% of ICU admissions. Lactic acidosis is the most common cause of raised anion gap metabolic acidosis in the acute setting.
Aetiology
Metabolic acidosis (low pH, low HCO3⁻):
- Raised anion gap: Lactic acidosis, DKA, uraemia, toxic ingestions (MUDPILES)
- Normal anion gap (hyperchloraemic): Renal tubular acidosis, diarrhoea, Addison's disease, pancreatic fistula
Metabolic alkalosis (high pH, high HCO3⁻): Vomiting, diuretics, Conn's syndrome, Cushing's syndrome
Respiratory acidosis (low pH, high PaCO2): COPD, neuromuscular disease, sedative overdose, chest wall deformity
Respiratory alkalosis (high pH, low PaCO2): Hyperventilation, anxiety, PE, salicylate poisoning (early), high altitude
Pathophysiology
Buffer systems provide immediate defence:
- Bicarbonate system: CO2 + H2O ⇌ H2CO3 ⇌ H⁺ + HCO3⁻ (carbonic anhydrase catalysed)
- Haemoglobin: Binds H⁺ in deoxygenated state (Bohr effect)
- Phosphate: Important intracellular buffer and in urine (titratable acidity)
Respiratory regulation (minutes): Peripheral chemoreceptors (carotid/aortic bodies) sense pH/PaCO2/PaO2; central chemoreceptors (medulla) sense CSF pH via CO2 diffusion
Renal regulation (hours–days): Proximal tubule reabsorbs ~85% filtered HCO3⁻; distal tubule and collecting duct secrete H⁺ via H⁺-ATPase and generate new HCO3⁻ via ammoniagenesis
Clinical Presentation
Metabolic Acidosis
- Kussmaul respiration: Deep, sighing breathing (respiratory compensation)
- Confusion, drowsiness, cardiovascular collapse in severe cases
- Underlying cause symptoms: polyuria/polydipsia (DKA), oliguria (renal failure)
Metabolic Alkalosis
- Muscle cramps, tetany, paraesthesia (reduced ionised calcium)
- Arrhythmias (hypokalaemia often coexists)
- Hypoventilation (respiratory compensation)
Respiratory Acidosis
- Headache, confusion, tremor (CO2 narcosis)
- Bounding pulse, warm peripheries
- Papilloedema in chronic hypercapnia
Respiratory Alkalosis
- Light-headedness, perioral tingling, carpopedal spasm
- Anxiety, chest tightness
Red Flags
- pH <7.1 or >7.6 — life-threatening, urgent intervention required
- Lactate >4 mmol/L with acidosis — consider sepsis, tissue hypoperfusion
- Metabolic acidosis with high anion gap in a young person — consider toxic ingestion
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Diabetic ketoacidosis | Glucose >11, ketones >3, pH <7.3, HCO3 <15 | Blood glucose, ketones, ABG |
| Lactic acidosis | Raised lactate >2 mmol/L, tissue hypoperfusion | Lactate (type A: shock; type B: metformin) |
| Renal tubular acidosis | Normal anion gap, hyperchloraemic | Urine pH, urine anion gap |
| Uraemic acidosis | Raised urea/creatinine, high anion gap | U&Es, eGFR |
| Salicylate poisoning | Mixed respiratory alkalosis and metabolic acidosis | Salicylate level |
| Hyperventilation syndrome | Respiratory alkalosis, anxiety, normal A-a gradient | ABG, clinical diagnosis |
Diagnosis / Investigation
Bedside
- Arterial blood gas (ABG): pH, PaCO2, PaO2, HCO3⁻, base excess, lactate
- Venous blood gas: Adequate for pH and HCO3⁻ screening (pH ~0.03 lower than arterial)
- Urine dipstick: pH, ketones, glucose
- Blood glucose: Capillary — DKA screening
Bloods
- U&Es: Calculate anion gap; assess renal function
- Lactate: Type A (tissue hypoperfusion) vs type B (metabolic)
- Blood ketones: β-hydroxybutyrate >3 mmol/L in DKA
- Toxicology screen: Salicylate, ethanol, methanol levels if ingestion suspected
- Chloride: Assess for hyperchloraemic (normal AG) acidosis
Imaging
- CXR: If respiratory cause suspected (pneumonia, COPD)
- CT head: If CO2 narcosis with reduced consciousness
Special Tests
- Urine anion gap: (Na⁺ + K⁺) − Cl⁻; positive in RTA, negative in GI bicarbonate loss
- Osmolar gap: Measured − calculated osmolality >10 suggests toxic alcohol ingestion
- Urine pH: >5.3 in distal (type 1) RTA despite systemic acidosis
Management
Non-pharmacological
- Identify and treat the underlying cause — this is the priority
- Monitor with serial ABGs to assess response to treatment
- HDU/ICU admission for severe acid-base disturbances
Pharmacological
- DKA protocol: IV 0.9% saline, fixed-rate insulin infusion (0.1 units/kg/hr), potassium replacement per protocol
- Lactic acidosis: Treat underlying cause (fluids, vasopressors for sepsis)
- Sodium bicarbonate 8.4%: Only in severe acidosis (pH <6.9 in DKA, or renal failure) — 50mmol IV over 30-60 min; controversial, can worsen intracellular acidosis
- RTA: Oral sodium bicarbonate 1-2 mmol/kg/day for type 1; higher doses for type 2
- Metabolic alkalosis: Volume resuscitation with 0.9% saline, potassium replacement; acetazolamide 250mg BD if resistant
Surgical
- Renal replacement therapy (haemodialysis) for refractory metabolic acidosis, toxic alcohol ingestion
Referral Criteria
- pH <7.1 or >7.6 — critical care
- Suspected toxic ingestion — toxicology/NPIS
- Recurrent unexplained acidosis — nephrology (RTA workup)
Prognosis
- DKA mortality: <1% in specialist centres; rises to 5% in elderly and those with delayed treatment
- Lactic acidosis: Mortality 50-80% when lactate >10 mmol/L, depending on underlying cause
- Type 1 RTA: Good prognosis with alkali replacement; risk of nephrocalcinosis and renal stones
- Respiratory acidosis in COPD: Acute-on-chronic respiratory acidosis requiring NIV has ~15% in-hospital mortality
- Severe acidosis (pH <7.0) is associated with cardiovascular collapse, reduced myocardial contractility, and resistance to catecholamines
Other Relevant Information
Systematic ABG Interpretation (5-Step Approach)
| Step | Action |
|---|---|
| 1 | Assess oxygenation: PaO2, A-a gradient, P/F ratio |
| 2 | Assess pH: Acidaemia (<7.35) or alkalaemia (>7.45) |
| 3 | Identify primary disorder: Respiratory (PaCO2) or metabolic (HCO3⁻) |
| 4 | Assess compensation: Expected vs actual compensation |
| 5 | Calculate anion gap if metabolic acidosis present |
Expected Compensation
| Primary Disorder | Compensation Rule |
|---|---|
| Metabolic acidosis | PaCO2 = (1.5 × HCO3⁻) + 8 ± 2 (Winter's formula) |
| Metabolic alkalosis | PaCO2 rises 0.7 kPa per 10 mmol/L rise in HCO3⁻ |
| Acute respiratory acidosis | HCO3⁻ rises 1 mmol/L per 1 kPa rise in PaCO2 |
| Chronic respiratory acidosis | HCO3⁻ rises 3.5 mmol/L per 1 kPa rise in PaCO2 |