Acid-Base Balance
Blood pH is maintained between 7.35–7.45 (normal = 7.40). This narrow range is critical for enzyme function, oxygen delivery (Bohr effect), and cellular electrolyte balance.
Buffer Systems
- Bicarbonate (pKa 6.1): Primary extracellular buffer. CO₂ (regulated by lungs) + HCO₃⁻ (regulated by kidneys). Henderson-Hasselbalch: pH = 6.1 + log([HCO₃⁻]/[H₂CO₃]). Normal: [HCO₃⁻] = 24 mEq/L, pCO₂ = 40 mmHg.
- Phosphate (pKa 6.8): Important intracellular and urinary buffer.
- Proteins: Histidine residues (pKa ~6). Hemoglobin is major blood buffer — accepts H+ when O₂ is released (Bohr effect).
- Ammonia: Renal ammoniagenesis — NH₃ + H+ → NH₄+ excreted in urine (↑in acidosis).
Primary Acid-Base Disorders
- Metabolic Acidosis (↓pH, ↓HCO₃⁻): - High AG: MUDPILES (Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates) - Normal AG: GI HCO₃⁻ loss (diarrhea), Renal Tubular Acidosis (RTA), NH₄Cl ingestion - Compensation: Hyperventilation (↓pCO₂) — Kussmaul breathing
- Metabolic Alkalosis (↑pH, ↑HCO₃⁻): - Causes: Vomiting (↑HCl loss), diuretics (↑K+ loss), hyperaldosteronism, antacid overuse - Compensation: Hypoventilation (↑pCO₂)
- Respiratory Acidosis (↓pH, ↑pCO₂): - Hypoventilation: COPD, sedation, neuromuscular disease, OSA - Compensation: ↑HCO₃⁻ retention (kidneys — slow, days)
- Respiratory Alkalosis (↑pH, ↓pCO₂): - Hyperventilation: Anxiety, altitude, ↑progesterone (pregnancy), aspirin early, liver failure - Compensation: ↓HCO₃⁻ (kidneys)
Anion Gap (AG)
AG = Na+ − (Cl− + HCO₃⁻). Normal = 8–12 mEq/L (unmeasured anions: albumin, phosphate, sulfate). Elevated AG = unmeasured acids present (lactate, ketone bodies, organic acids). Hypoalbuminemia lowers AG (correct: add 2.5 for each 1 g/dL albumin below normal).
Renal Handling of Acid
- Proximal tubule: 85% of filtered HCO₃⁻ reabsorbed; NH₄+ secretion
- Collecting duct: Intercalated cells secrete H+ (via H+-ATPase and H+/K+-ATPase) → titratable acid + NH₄+
- Aldosterone: ↑H+ secretion and Na+ reabsorption → alkalosis
- Type I RTA: Distal H+ secretion defect → cannot acidify urine (urine pH >5.5), hyperchloremic MAC, nephrocalcinosis
- Type II RTA: Proximal HCO₃⁻ reabsorption defect → HCO₃⁻ wasting, Fanconi syndrome
- Type IV RTA: Hypoaldosteronism (diabetic nephropathy most common) → hyperkalemic MAC
Oxygen-Hemoglobin Dissociation Curve
Shifted RIGHT (↓O₂ affinity, ↑O₂ release) by: ↑Temperature, ↑CO₂, ↑H+ (↓pH = Bohr effect), ↑2,3-BPG (RBC product of glycolysis; ↑in chronic hypoxia). Shifted LEFT (↑O₂ affinity) by: ↓Temp, ↓CO₂, ↓H+, ↓2,3-BPG, CO poisoning, HbF (fetal Hb, lacks β-chains).