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Acid-Base Balance (ABB): Forms, Mechanisms, Disorders, and Correction in Clinical Anaesthesiology

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1. Fundamentals of Acid-Base Balance

Normal Values

• Arterial pH: 7.35-7.45 (H+ = 35-45 nEq/L)
• PaCO2: 35-45 mmHg (4.7-6.0 kPa)
• HCO3-: 22-26 mEq/L
• Base Excess (BE): -2 to +2 mEq/L

The Three Major Determinants of [H+]

• Strong ions dissociate completely and cannot be metabolized
• A decrease in SID (e.g., Cl- gain or Na+ loss) → acidosis
• An increase in SID (e.g., Na+ gain or Cl- loss) → alkalosis
• Organic strong anions include lactate, beta-hydroxybutyrate (BOHB), acetoacetate, citric acid cycle metabolites, and renal acids - these accumulate in metabolic dysfunction

• Principally albumin and phosphate in plasma
• Albumin at physiological pH carries a large negative charge
• Hyperalbuminemia → acidosis; hypoalbuminemia → alkalosis (masks underlying acidosis)
• Hypoalbuminemia is the most common single acid-base disturbance in critically ill patients

• Set by alveolar ventilation
• CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3- (catalyzed by carbonic anhydrase in RBCs)
• CO2 is volatile - buffered acutely by hemoglobin (Haldane effect + chloride shift)
• 65% of extra venous CO2 as HCO3-/H+ bound to Hb, 27% as carbaminohemoglobin, 8% dissolved

Buffer Systems

A buffer ideally has pKa near body pH (6.8-7.2). The HCO3-/CO2 system (pKa 6.1) is highly effective because CO2 is continuously regulated by ventilation - an "open system."

HCO3- as a Dependent Variable

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2. Diagnostic Approaches

A. The Descriptive (Boston) / PaCO2-HCO3- Approach

B. The Anion Gap (AG) Approach

• If AG is elevated: unmeasured anions present (lactate, ketones, uremic acids, toxins)
• If AG is normal and HCO3- low: hyperchloremic acidosis
• Delta ratio = ΔAG / ΔHCO3-: <0.4 = pure hyperchloremic; 1-2 = high-AG acidosis; >2 = mixed disorder

C. The Base Excess (Copenhagen) Approach

• Base Excess (BE) = amount of strong acid/base (mmol/L) to return 1 L of blood to pH 7.4 at 37°C, PaCO2 = 40 mmHg
• Normal: -2 to +2 mEq/L
• Negative BE (base deficit): metabolic acidosis
• Positive BE: metabolic alkalosis
• The BE is corrected stepwise: BE_actual - BE_albumin correction - [Lactate] - BE_NaCl → BE_gap = unmeasured anions

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3. Forms and Mechanisms of ABB Impairment

Respiratory Acidosis

• Perioperative: Excessive sedation/opioids; partial neuromuscular blockade reversal; intraoperative hypoventilation; pneumothorax; CO2 insufflation during laparoscopy; laryngeal mask airway (LMA) use under spontaneous breathing (mild permissive hypercapnia)
• General: COPD, asthma, obesity hypoventilation, neuromuscular disease, spinal cord injury, stroke

• Decreased alveolar ventilation → CO2 accumulates → carbonic anhydrase drives H2CO3 → H+ + HCO3-
• Acute buffering overwhelmed rapidly → pH falls steeply
• Manifestations: cyanosis, vasodilation, narcosis ("CO2 narcosis")

• Acute (minutes-hours): RBC/tissue buffers; HCO3- rises 1 mEq/L per 10 mmHg PaCO2
• Chronic (2-5 days): Renal Cl- excretion via NH4+; HCO3- rises 3-4 mEq/L per 10 mmHg PaCO2 - this is the physiological basis of "post-hypercapnic alkalosis"

• Potentiates nondepolarizing neuromuscular blockade
• Antagonizes neostigmine reversal
• Vasodilation, increased cerebral blood flow
• Catecholamine release (↑HR, ↑BP initially)
• Myocardial depression at severe levels (pH <7.1)

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Respiratory Alkalosis

• Acute: Tissue/plasma buffers; HCO3- falls 2 mEq/L per 10 mmHg fall in PaCO2
• Chronic: Renal HCO3- excretion; HCO3- falls 5 mEq/L per 10 mmHg fall in PaCO2

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Metabolic Acidosis

High-Anion-Gap Metabolic Acidosis (HAGMA) - Unmeasured Anions

• Lactate sources: muscle (25%), brain (25%), skin (25%), RBCs (20%), intestine (10%) - 12,500-15,000 mEq/day normally
• L-lactate (human form, measured by ABG); D-lactate (bacterial fermentation only)
• Each 1 mEq/L rise in lactate → 1 mEq/L fall in HCO3-, equivalent pH fall
• Lactate used as fuel by brain, heart, kidney; processed by liver (Cori cycle)
• Normal plasma lactate <2 mmol/L; lactic acidosis defined as >4-5 mmol/L with pH <7.35

Normal-Anion-Gap (Hyperchloremic) Metabolic Acidosis (NAGMA)

• Myocardial depression (reduced cardiac contractility, ↓response to catecholamines if pH <7.2)
• Vasodilation (peripheral); vasoconstriction (pulmonary) → ↑pulmonary vascular resistance
• Hyperkalemia (H+/K+ exchange across cell membranes: pH ↓0.1 → K+ rises ~0.5 mEq/L)
• Impaired coagulation
• Cerebral dysfunction

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Metabolic Alkalosis

• Urine Cl- <20 mEq/L = chloride-sensitive (vomiting, diuretics, post-hypercapnic) → responds to NaCl/KCl
• Urine Cl- >20 mEq/L = chloride-resistant (primary hyperaldosteronism, Cushing's, Bartter syndrome)

• Chloride-sensitive: 0.9% NaCl + KCl; correct hypovolemia
• Post-hypercapnic: Do NOT over-ventilate COPD patients; allow permissive hypercarbia to normalize gradually
• Severe/refractory: Acetazolamide (inhibits carbonic anhydrase → renal HCO3- loss; increases renal Na/Cl excretion ratio → ↓SID); rarely dilute HCl infusion via central line

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4. Mixed Acid-Base Disorders

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5. ABB Disorders in Specific Pathologies

Perioperative/Anaesthetic States

Critical Illness Patterns

• AKI: Early hyperchloremic acidosis; later unmeasured anion accumulation (50%); late oliguric AKI may cause contraction alkalosis
• Liver failure: Respiratory alkalosis (↑respiratory drive) + metabolic alkalosis (↓lactate clearance, hypoalbuminemia) paradoxically masking acidosis; citric acid cycle metabolite accumulation
• Continuous renal replacement therapy (CRRT/CKRT): Corrects renal acidosis by removing strong ions and phosphate; but in presence of hypoalbuminemia, correcting acidosis may unmask alkalosis
• Nasogastric suction (prolonged): Hypochloremic metabolic alkalosis
• Propylene glycol toxicity (lorazepam diluent): Osmolar gap + high-AG acidosis

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6. Principles of Correction

Respiratory Acidosis

1. Remove the cause: Reverse opioids (naloxone), reverse residual NMB (neostigmine/sugammadex), relieve airway obstruction, drain pneumothorax
2. Support ventilation: Increase respiratory rate or tidal volume; consider NIV (CPAP/BiPAP) for COPD patients
3. Target baseline PaCO2 (not "normal" 40 mmHg) in patients with chronic CO2 retention

Respiratory Alkalosis

1. Treat the underlying cause (analgesia, anxiolysis)
2. Reduce mechanical ventilation settings
3. Rarely, rebreathe CO2

Metabolic Acidosis

1. Treat the cause first - lactate acidosis: restore perfusion; DKA: insulin + glucose; toxins: antidotes/dialysis
2. Sodium bicarbonate: Controversial; generally reserved for pH <7.1 or life-threatening hyperkalemia. Not effective for lactic acidosis or ketoacidosis; may paradoxically worsen intracellular acidosis (CO2 generated crosses cell membranes). NaHCO3 dose (mEq) = 0.3 × Weight (kg) × Base deficit
3. THAM (tromethamine): CO2-neutral buffer; useful when avoiding sodium/CO2 load; used in cardiac surgery and permissive hypercapnia strategies
4. Dialysis/CRRT: For renal acidosis and removal of toxic anions (not effective for lactic/ketoacidosis)
5. Balanced crystalloids over 0.9% NaCl for resuscitation to prevent hyperchloremic acidosis
6. Pre-op: stop SGLT-2 inhibitors 24-48h before surgery; check blood ketones (not just urine) perioperatively

Metabolic Alkalosis

1. Chloride-sensitive: 0.9% NaCl + KCl replacement; correct volume depletion
2. Acetazolamide: 250-500 mg IV; increases renal Cl- retention relative to Na+, ↓SID; useful for post-hypercapnic alkalosis
3. Avoid over-ventilation of COPD patients
4. HCl infusion (0.1-0.2 N HCl via central line): Rarely used; for severe refractory cases (pH >7.6)
5. Treat hypokalemia and hypomagnesemia (coexist with and perpetuate metabolic alkalosis)
6. For iatrogenic bicarbonate excess (post-massive transfusion): Supportive; usually self-limiting as liver clears organic anion load

Permissive Hypercapnia

Permissive Acidosis

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Summary Table: Key ABB Patterns

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