Acid-Base Balance

• What are the primary sources of hydrogen ions (H⁺) in the body?

  1. Carbonic acid (H₂CO₃) formation – From CO₂ and H₂O via carbonic anhydrase.
  2. Metabolism of proteins & amino acids – Sulfuric acid from cysteine/methionine breakdown.
  3. Anaerobic metabolism of glucose – Lactic acid production.
  4. Fat metabolism – Ketone bodies (e.g., acetoacetic acid, β-hydroxybutyric acid).
  5. Ingestion of acids – Certain foods/drugs can contribute.
• How does carbon dioxide (CO₂) contribute to hydrogen ion (H⁺) production?

  CO₂ reacts with water (H₂O) to form carbonic acid (H₂CO₃), which dissociates into H⁺ and bicarbonate (HCO₃⁻): $CO_2\ +$$\ H_2O\ \leftrightarrow\ H_2CO_3\ \leftrightarrow\ H^+$$\ +$$\ HCO_3^-$
•  How does metabolism of proteins generate hydrogen ions?

  The breakdown of sulfur-containing amino acids (e.g., cysteine, methionine) produces sulfuric acid (H₂SO₄), which dissociates into H⁺ and sulfate (SO₄²⁻).
• How does anaerobic respiration contribute to acid production?

  During anaerobic respiration, glucose is metabolized to lactic acid, which releases H⁺ upon dissociation.
• What role do ketone bodies play in acid production?

  Fat metabolism (e.g., during fasting or diabetes) produces ketone bodies (acetoacetic acid, β-hydroxybutyrate), which release H⁺ when dissociated
•  Why is maintaining pH homeostasis important in the body?

  pH affects:

  1. Enzyme activity – Many enzymes function optimally around pH 7.4.
  2. Protein structure & function – Extreme pH can denature proteins.
  3. Membrane stability – pH influences ion channel activity.
  4. Oxygen delivery – pH affects hemoglobin’s oxygen affinity (Bohr effect).
  5. Cellular metabolism – Disrupts biochemical reactions if unbalanced.
• What is the normal physiological pH range of blood?

   7.35 – 7.45
• What happens if blood pH falls below 7.35?

  Acidosis occurs, leading to:

  • Depressed CNS function
  • Respiratory complications
  • Arrhythmias and cardiovascular instability
• What happens if blood pH rises above 7.45?

   Alkalosis occurs, leading to:

  • Over-excitability of nerves & muscles
  • Tetany (muscle spasms)
  • Seizures
• How does pH affect haemoglobin's ability to carry oxygen?

  The Bohr effect states that lower pH (more H⁺) decreases hemoglobin’s oxygen affinity, promoting O₂ release in tissues.
• How does the body regulate pH?

  1. Buffer systems – Bicarbonate, phosphate, and protein buffers.
  2. Respiratory system – Regulates CO₂ levels.
  3. Renal system – Excretes H⁺ and reabsorbs HCO₃⁻.
• What is the main purpose of pH buffering in plasma?

  To maintain a stable pH and prevent acidosis (<7.35) or alkalosis (>7.45), which can disrupt cellular function.
• What is a buffer system?

  A buffer system consists of a weak acid and its conjugate base that resists changes in pH by neutralizing excess H⁺ or OH⁻.
• Name the three main buffer systems in plasma.

  • Bicarbonate (HCO₃⁻/H₂CO₃) buffer system (most important)
  • Protein buffer system (e.g., albumin, hemoglobin)
  • Phosphate buffer system (H₂PO₄⁻/HPO₄²⁻)
• Write the Henderson-Hasselbalch equation for the bicarbonate buffer system.

  pH = pKa + log([HCO₃⁻] / [H₂CO₃])
• What is the normal ratio of bicarbonate (HCO₃⁻) to carbonic acid (H₂CO₃) in plasma?

  20:1 (This maintains a pH of ~7.4)
• What enzyme catalyses the conversion of CO₂ and H₂O to carbonic acid (H₂CO₃)?

  Carbonic anhydrase
• How does the bicarbonate buffer system respond to excess H⁺ ions?

  H⁺ + HCO₃⁻ → H₂CO₃ → CO₂ + H₂O (CO₂ is exhaled via the lungs)
• How does the bicarbonate buffer system respond to excess OH⁻ ions?

  OH⁻ + H₂CO₃ → HCO₃⁻ + H₂O (removing OH⁻ from solution)
• What organ systems regulate the bicarbonate buffer system?

  • Lungs – regulate CO₂ levels through respiration.
  • Kidneys – regulate HCO₃⁻ excretion and reabsorption.
• How do proteins act as buffers in plasma?

  Proteins contain amino acids with ionisable side chains that can accept or donate H⁺ ions.
• What is the most important protein buffer in plasma?

  Albumin
• How does haemoglobin contribute to buffering in blood?

  • Deoxyhaemoglobin binds H⁺ (acting as a buffer).
  • Oxyhaemoglobin releases H⁺, which can combine with HCO₃⁻ to form H₂CO₃.
• What is the main role of the phosphate buffer system in plasma?

  It plays a minor role in plasma but is more important in intracellular and renal buffering.
• Write the chemical equation for the phosphate buffer system.

  H₂PO₄⁻ ⇌ H⁺ + HPO₄²⁻
• Why is the phosphate buffer system less significant in plasma than in cells?

  Plasma has a low phosphate concentration, making it a weaker buffer in extracellular fluid.
• How do the lungs help maintain blood pH?

  • In acidosis: Increase ventilation → more CO₂ exhaled → less H₂CO₃ → pH rises.
  • In alkalosis: Decrease ventilation → more CO₂ retained → more H₂CO₃ → pH lowers.
• How do the kidneys help regulate blood pH?

  • In acidosis: Excrete H⁺ and reabsorb HCO₃⁻.
  • In alkalosis: Excrete HCO₃⁻ and retain H⁺.
• What happens if the bicarbonate buffer system is overwhelmed?

  Blood pH changes significantly, leading to respiratory acidosis/alkalosis or metabolic acidosis/alkalosis.
• What is metabolic acidosis, and how is it compensated?

  A condition where blood pH drops due to excess H⁺ or loss of HCO₃⁻. Compensation: Increased respiratory rate (hyperventilation) to remove CO₂.
• What is metabolic alkalosis, and how is it compensated?

  A condition where blood pH rises due to excess HCO₃⁻ or loss of H⁺. Compensation: Reduced ventilation to retain CO₂.
• Where in the nephron does most hydrogen ion (H⁺) secretion occur?

  Primarily in the proximal tubule, distal tubule, and collecting duct of the nephron.
• What are the two main sources of hydrogen ions (H⁺) in the body that need to be excreted?

  1. Volatile acid (carbonic acid) from CO₂ hydration
  2. Non-volatile acids from metabolism (e.g., lactic acid, sulfuric acid)
• How are hydrogen ions (H⁺) secreted into the tubular lumen in the proximal tubule?

  • H⁺ is secreted via the Na⁺/H⁺ antiporter (NHE3 transporter).
  • Sodium (Na⁺) moves into the tubule cell from the lumen while H⁺ is pumped out.
• What happens to the secreted hydrogen ions (H⁺) in the tubular lumen?

  • Secreted H⁺ combines with filtered bicarbonate (HCO₃⁻) to form carbonic acid (H₂CO₃).
  • Carbonic anhydrase then breaks H₂CO₃ into CO₂ and H₂O, which diffuse back into the tubular cell.
• How is bicarbonate (HCO₃⁻) "reabsorbed" into the blood?

  • Inside the tubule cell, CO₂ + H₂O are converted back into HCO₃⁻ and H⁺.
  • HCO₃⁻ is transported across the basolateral membrane into the peritubular capillary via Na⁺/HCO₃⁻ symporters or Cl⁻/HCO₃⁻ antiporters.
  • The H⁺ is secreted again into the tubule lumen.
• How does the distal tubule and collecting duct contribute to hydrogen ion secretion?

  • Type A intercalated cells actively secrete H⁺ via H⁺-ATPase and H⁺/K⁺ ATPase.
  • These cells are crucial for generating an acidic urine pH.
• What role do intercalated cells in the collecting duct play in bicarbonate balance?

  • Type A intercalated cells: Secrete H⁺ and reabsorb HCO₃⁻ in acidotic states.
  • Type B intercalated cells: Secrete HCO₃⁻ and reabsorb H⁺ in alkalotic states.
• How does ammonia (NH₃) help excrete hydrogen ions in the kidney?

  • Glutamine metabolism in the proximal tubule produces NH₃ and HCO₃⁻.
  • NH₃ binds to H⁺ in the lumen, forming ammonium (NH₄⁺), which is excreted in urine.
  • This process helps regenerate bicarbonate (HCO₃⁻) for buffering in the blood.
• Why is hydrogen ion secretion important for acid-base balance?

  • Prevents metabolic acidosis by excreting excess H⁺.
  • Allows bicarbonate (HCO₃⁻) to be reabsorbed, maintaining blood pH around 7.35–7.45.
  • Helps regulate CO₂ removal in response to respiratory changes.