Acid-Base Disorders

Introduction

• The kidneys play an important role in regulating the body’s acid-base status via 
  • HCO₃⁻ reabsorption
    • this is the major extracellular buffer and is thus why it is important to conserve HCO₃⁻
      • ~99.9% of filtered HCO₃⁻ is reabsorbed
        • the proximal convoluted tubule is the site where most of the filtered HCO₃⁻ is reabsorbed
    • Na⁺H⁺ exchanger secretes H⁺ into the tubular lumen and combines with filtered HCO₃⁻ to form H₂CO₃
      • H₂CO₃ is converted into CO₂ and H₂O with the aid of brush border carbonic anhydrase
        • CO₂ and H₂O enters the proximal tubular cell to be converted into H₂CO₃ via intracellular carbonic anhydrase
          • H₂CO₃ becomed HCO₃⁻ and H⁺
            • H⁺ gets secreted by the Na⁺-H⁺ exchanger to reabsorb more HCO₃⁻
              • there is no net secretion of H⁺ since it is being recycled
              • angiotensin II stimulates the Na⁺-H⁺ exchanger which subsequently increases HCO₃⁻ reabsorption
                • this explains contraction alkalosis
            • HCO₃⁻ gets transported into the blood via
              • Na⁺-HCO₃⁻ cotransport
              • Cl⁻-HCO₃⁻ exchanger
      • excess of HCO₃⁻ exceeds HCO₃⁻ reabsorption capacity and results in HCO₃⁻ excretion
      • arterial CO₂ and renal compensation
        • not completely understood
        • respiratory acidosis
          • increased CO₂ exposed to renal cells generates more H⁺ to be secreted by the Na⁺-H⁺ exchanger 
            • this increases HCO₃⁻ reabsorption
        • respiratory alkalosis
          • decreased CO₂ exposed to renal cells decrease H⁺ secretion by the the Na⁺-H⁺ exchanger
            • this decreases HCO₃⁻ reabsorption
  • H⁺ excretion
    • H⁺ excretion is accompanied by new HCO₃⁻ synthesis and reabsorption
    • there are two mechanisms involved
      • excretion of titratable acid (e.g., urinary buffers such as inorganic phosphate)
        • this is accomplished by H⁺ATPase (which can be stimulated by aldosterone) and H⁺-K⁺ ATPase on α-intercalated cells of the late distal convoluted tubule and collecting ducts
          • H⁺ binds to HPO₄^-2 to form H₂PO₄⁻ (the titratable acid) 
            • every titratable acid that excreted results in the synthesis of HCO₃⁻
      • excretion of NH₄⁺
        • proximal convoluted tubule
          • NH₄⁺ is secreted via the Na⁺-H⁺ exchanger
            • glutamine is metabolized into glutamate and NH₄⁺ by the enzyme glutaminase in the proximal convoluted tubular cells
            • NH₃ is lipid soluble and diffuses from the tubular cell into the lumen because it is lipid soluble
              • Na⁺-H⁺  exchanger secretes H⁺ which will bind to NH₃ to form NH₄⁺
                • this is diffusion trapping
        • collecting duct
          • H⁺-ATPase and H⁺-K⁺ ATPase on α-intercalated cells secrete H⁺ to bind with NH₃ and form NH₄⁺
• this is diffusion trapping

 Acid-Base Disorders

• Acidosis results in acidemia due to an increased serum H⁺ (decreased pH)
• Alkalosis results in alkalemia due to a decreased serum H⁺ (increased pH)
• These acid base disorders may be due to primary disturbances in HCO₃⁻ (metabolic) or arterial CO₂ (PCO₂) (respiratory) 
  • the Hendersen-Hasselbalch equation shows that changes in HCO₃⁻ or PCO₂ changes pH
    • pH = pKa + log ([HCO₃^–]/(0.03 * PCO₂) 
• Metabolic acidosis
  • due to a decrease in HCO₃⁻
    • either because of increased H⁺ or loss of HCO₃⁻
• Metabolic alkalosis
  • due to an increase in HCO₃⁻
• Respiratory acidosis 
  • due to an increase in CO₂
    • secondary to hypoventilation (which retains CO₂)
• Respiratory alkalosis 
  • due to a decrease in CO₂
    • secondary to hyperventilation
• Winter’s formula
  • determines expected respiratory compensation in response to metabolic acidosis 
  • P_CO2 = 1.5 (HCO₃^–) + 8 +/- 2 
    • if actual PCO₂ is greater than expected PCO₂ → also has a primary respiratory acidosis
    • if actual PCO₂ is less than expected PCO₂ → also has a primary respiratory alkalosis