Renal physio 4v

• Alkalosis


  pH rises above the optimal value
• Acidosis


  pH drops below optimum value
• Systems that maintain acid base homeostasis


  • Intracellular and extracellular buffers
  • Lungs
  • Kidneys
• How kidneys regulate acid base balance

  Excreting either an acidic or basic urine

  
• Mechanisms by which kidneys regulate ECF H+ ions

  • Tubular secretion of H+
  • Reabsorption of filtered HCO3-
  • Combination of excess H+ ions with phosphate and amino buffers

  
• Tubular secretion of H+ ions

  1. Na+/H+ exchanger (secondary active transport, main route in PCT and thick ascending limb)

  2. H+-ATPase pump (secondary active transport, main route in collecting duct)

  3. H+-K+-ATPase pump (secondary active transport, found in collecting duct)

  
• Reabsorption of filtered bicarbonates

  1. H2CO3 combines with H+ to form CO2 and H2O

  2. CO2 diffuses into tubular cell and combines with H2O to form H2CO3 in presence of carbonic anhydrase, which dissociates to HCO3- and H+

  3. For every H+ formed, a HCO3- is formed and reabsorbed into blood

  
• Combination of excess H+ with phosphate buffer

  Excess H+ combine with HPO42- to form H2PO4- which is excreted as NaH2PO4

  
• Combination of excess H+ with ammonia buffer system

  1. NH4+ is synthesized from glutamine and secreted into tubular lumen

  2. HCO3- moves across basolateral membrane along with reabsorbed Na+ into blood

  3. For each molecule of glutamine metabolized, two NH4+ are secreted and two HCO3- are reabsorbed

  
• Trapping of NH4+


  Non-ionic diffusion or diffusion trapping - membrane is less permeable to NH4+, so it is trapped in tubular lumen and eliminated in urine
• Formation of NH4+ in collecting tubule

  1. NH3 combines with H+ to form NH4+ which is excreted

  2. For each NH4+ excreted, one HCO3- is reabsorbed into blood
• Ways urinary acidification is achieved

  • Na+/H+ counter transport (PCT, thick ascending loop, early DCT)
  • H+ pump (late DCT, collecting ducts)
  • Secretion of H+ with ammonia

  
• Extracellular pH


  Primary physiologic regulator of net acid excretion
• Reabsorption of HCO3-


  1. Reabsorption of 99% of filtered HCO3- (PCT, thick ascending loop, early DCT)

  2. Generate new HCO3- by intercalated cells (late DCT, collecting ducts)

  3. Generate two new HCO3- from glutamine

  
• Titratable acidity


  • Amount of secreted H+ that is buffered by filtered weak acids
  • Measure of acid excreted into urine by kidneys
  • pH of urine will drop from normal
• Quantitative titratable acidity


  • Number of ml of N/10 NaOH required to titrate 1 L of urine to pH 7.4
  • Measure of net acid excretion
• Acid base disturbances


  • Metabolic acidosis
  • Metabolic alkalosis
  • Respiratory acidosis
  • Respiratory alkalosis
• Metabolic acidosis


  • Ketosis
  • Diabetes mellitus
  • Renal acidosis (failure of HCO3- reabsorption and loss in urine)
• Metabolic alkalosis


  • Persistent vomiting
  • K+ deficiency (renal tubules secrete large amount of H+ ions into urine)
  • Injection of HCO3- solutions

  
• Respiratory acidosis


  • Depression of respiratory centres in CNS
  • Abnormality of chest wall or respiratory muscles
  • Obstruction to gas movement in lungs
• Respiratory alkalosis


  • Hyperventilation
• Renal response to metabolic and respiratory acidosis

  1. Excretion of H+

  2. Increased HCO3- production

  
• Renal response to metabolic and respiratory alkalosis

  1. Decreased loss of H+

  2. Increased HCO3- excretion