Renal Physiology – Acid-Base Regulation (Part 4)

Basic Definitions

• Acid: Molecule that can release a hydrogen ion (HCl, H₂CO₃).

• Base: Molecule that can accept a hydrogen ion (HCO₃⁻, phosphate, hemoglobin).

• Normal arterial blood pH: 7.4
  → corresponds to [H⁺] = 40 nEq/L.

Acid-Base Regulation

• The body maintains precise pH via three mechanisms:

  1. Buffer systems – act within seconds.

  2. Lungs – act within minutes, eliminate CO₂ (carbonic acid).

  3. Kidneys – act within hours to days, excrete acid and regulate bicarbonate.

Bicarbonate Buffer System

• Equation:
  CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

• Excess acid → buffered by HCO₃⁻ → forms H₂CO₃ → breaks into CO₂ + H₂O → CO₂ exhaled.

• Excess base (e.g., NaOH) → reacts with H₂CO₃ → forms Na⁺ + HCO₃⁻ + H₂O.

Henderson-Hasselbalch Equation

• pH depends on:

  • Directly proportional to [HCO₃⁻]

  • Inversely proportional to PCO₂

• Clinical principle:

  • Lungs control PCO₂ → respiratory disorders.

  • Kidneys control [HCO₃⁻] → metabolic disorders.

Phosphate Buffer System

• Components: H₂PO₄⁻ / HPO₄²⁻.

• pKa ~ 6.8 (less effective at plasma pH 7.4).

• Works mainly in:

  • Renal tubules

  • Intracellular fluid (more acidic environment, higher phosphate concentration).

Respiratory Regulation

• Normal PCO₂ = 40 mmHg (≈ 1.2 mmol/L CO₂).

• Ventilation ↔ pH relationship:

  • ↑ Ventilation → ↓ PCO₂ → ↑ pH (alkalosis).

  • ↓ Ventilation → ↑ PCO₂ → ↓ pH (acidosis).

• Negative feedback:

  • Acidosis (↑ H⁺) → ↑ ventilation.

  • Alkalosis (↓ H⁺) → ↓ ventilation.

• Dysfunction → respiratory acidosis (CO₂ retention).

Renal Regulation

Bicarbonate Handling

• Normal serum HCO₃⁻: 24 mEq/L.

• Daily filtered load:

  • GFR = 180 L/day → 4320 mEq HCO₃⁻ filtered daily.

• To prevent loss:

  • Each HCO₃⁻ must pair with an H⁺ → forms H₂CO₃ → CO₂ + H₂O.

  • Requires 4320 mEq H⁺ secretion/day.

Non-Volatile Acids

• Produced from metabolism (cannot be exhaled as CO₂).

• Must be excreted by kidneys.

• CTotal H⁺ excretion ≈ 4400 mEq/day.

Renal Response to Disorders

• Acidosis:

  • ↑ H⁺ secretion.

  • ↑ HCO₃⁻ reabsorption.

  • Additional HCO₃⁻ generation.

  • Na⁺/H⁺ exchange & ATP-dependent H⁺ secretion.

• Alkalosis:

  • ↓ H⁺ secretion.

  • ↓ HCO₃⁻ reabsorption → more bicarbonate excreted in urine.

Limits of Urine Acidification

• Lowest urine pH ≈ 4.5.

• This corresponds to only 0.03 mEq/L free H⁺ → insufficient.

• Most H⁺ excreted is buffered by:

  • Phosphate

  • Ammonia (NH₃/NH₄⁺)

Factors Affecting Renal H⁺ Secretion & HCO₃⁻ Reabsorption

• ↑ PCO₂ → ↑ H⁺ secretion, ↑ HCO₃⁻ retention.

• ↑ H⁺ or ↓ HCO₃⁻ → same response.

• ↓ ECF volume → ↑ H⁺ secretion (to retain Na⁺/water).

• ↑ Angiotensin II / Aldosterone → ↑ H⁺ secretion.

• Hypokalemia → promotes H⁺ secretion and HCO₃⁻ retention.

• Opposite conditions → opposite effects.

Key Takeaway:

• Lungs regulate CO₂ → respiratory component.

• Kidneys regulate HCO₃⁻ → metabolic component.

• Acid-base balance depends on tight coordination of both systems with buffer support.