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• Acid-base homeostasis


  The proper balance between acids and bases, important for maintaining pH
• The body is very sensitive to its pH level, so strong mechanisms exist to maintain it
• Outside the acceptable range of pH, proteins are denatured and digested, enzymes lose their ability to function and death may occur
• Acid-base balance regulation


  1. Buffering agents reversibly bind H+ ions and prevent changes in pH

  2. Extracellular buffers include bicarbonate and ammonia

  3. Intracellular buffers include proteins and phosphate

  4. Bicarbonate buffering system shifts CO2 through carbonic acid to yield H+ ions and bicarbonate
• Compensation for acid-base imbalances

  1. Changing the rate of ventilation

  2. Alters the concentration of CO2 in the blood

  3. Shifts the bicarbonate buffering reaction

  4. Adjusts pH back to normal

  
• Hydrogen ion production


  • Small amounts from oxidation of amino acids and anaerobic metabolism
  • Larger amounts from CO2 release in oxidative metabolism forming carbonic acid
• Carbonic acid formation


  1. CO2 + H2O → H2CO3 → HCO3- + H+

  2. Catalyzed by carbonic anhydrase enzyme

  
• Mechanisms for maintaining pH in normal range

  • Blood and tissue buffering
  • Excretion of CO2 by the lungs
  • Renal excretion of H+ and regeneration of HCO3-

  
• Buffers


  • Limit changes in H+ ion concentration
  • Prevent large quantities of H+ ions from metabolism causing dangerous pH changes
• Bicarbonate buffer system


  Most important buffer system in the body
• Proteins as buffers


  • Plasma and other proteins form important buffering systems
  • Intracellular proteins limit pH changes within cells
• Hemoglobin as a buffer


  Binds both CO2 and H+ ions, providing strong buffering effect
• Carbon dioxide transport and hemoglobin buffering

  1. CO2 passes into red blood cells, combines with H2O to form H2CO3

  2. H2CO3 dissociates into HCO3- and H+

  3. H+ ions bind to hemoglobin

  4. HCO3- passes back into plasma in exchange for Cl-

  5. In lungs, process reverses and H+ recombines with HCO3- to form CO2 which is exhaled

  
• CO2 is responsible for the majority of H+ ions produced by metabolism
• Respiratory system control of H+ ions

  1. Arterial CO2 partial pressure (PaCO2) is inversely proportional to alveolar ventilation

  2. Small ventilation changes affect H+ concentration and pH
• Renal handling of bicarbonate and hydrogen ions

  1. Regeneration of bicarbonate

  2. Excretion of hydrogen ions

  3. Regulation of electrolytes

  
• Bicarbonate regeneration


  1. Filtered HCO3- combines with secreted H+ to form carbonic acid

  2. Carbonic acid dissociates to CO2 and H2O

  3. CO2 crosses into tubular cell, recombines with H2O to form H2CO3

  4. H2CO3 dissociates to HCO3- and H+

  5. HCO3- passes back into bloodstream, H+ passes into tubular fluid in exchange for Na+

  
• Hydrogen ion excretion


  1. H+ ions secreted in proximal and distal tubules, active process requiring ATP

  2. Buffering of H+ ions in urine by HPO4(2-) and NH3

  3. H+ ions secreted in exchange for Na+
• CO2 reabsorption in renal tubular cells

  1. CO2 crosses into tubular cell down concentration gradient

  2. CO2 recombines with H2O to form H2CO3 catalyzed by carbonic anhydrase

  3. Carbonic acid dissociates to HCO3- and H+ ions

  4. HCO3- passes back into blood, H+ passes into tubular fluid in exchange for Na+

  5. All filtered HCO3- is reabsorbed in healthy individual

  
• Excretion of Hydrogen Ions

  1. H+ ions secreted in proximal and distal tubules

  2. H+ ion secretion is active process requiring ATP

  3. Buffering of H+ ions in urine by HPO4(2-) and NH3

  4. HPO4(2-) combines with secreted H+ to form H2PO4-

  5. H+ ions secreted in exchange for Na+, energy from Na-K ATPase

  
• Ammonia buffering in renal tubule

  1. Ammonia produced from glutamine by glutaminase enzyme

  2. NH3 crosses tubule down concentration gradient

  3. NH3 combines with H+ to form NH4+ which is lost in urine

  
• Sodium/Potassium


  • Sodium reabsorption and H+ ion excretion are interlinked
  • Sodium reabsorption controlled by aldosterone and Na+-K+ ATPase in distal tubule
  • Ion exchange proteins exchange Na+ for H+ or K+
  • Changes in aldosterone may result in altered H+ secretion
• Chloride


  • Positive and negative ions in plasma must be balanced
  • Bicarbonate and chloride are most abundant plasma anions
  • Changes in Cl- must be accompanied by opposite change in HCO3- to maintain electrical neutrality
  • Cl- concentration may influence acid-base balance
• Acidosis


  • Physiological condition that increases H+ ion concentration, decreases pH
  • Can be respiratory or metabolic acidosis
  • Respiratory acidosis is increased pCO2
  • Metabolic acidosis is decreased [HCO3-]
• Alkalosis


  • Physiological condition that decreases H+ ion concentration, increases pH
  • Can be respiratory or metabolic alkalosis
  • Respiratory alkalosis is decreased pCO2
  • Metabolic alkalosis is increased [HCO3-]
• Causes of respiratory acidosis

  • Respiratory center depression
  • Neuromuscular disease
  • Restrictive extra-pulmonary disease
  • Intrinsic pulmonary and small airway disease
  • Large airway obstruction
  • Increased CO2 production with impaired alveolar ventilation
• Metabolic acidosis


  • Two types: secretional (direct loss of bicarbonate-rich fluid) and titration (increased exogenous or endogenous acids)
  • Titration-type causes include shock, renal failure, diabetic ketoacidosis
• Respiratory alkalosis


  • Caused by conditions that decrease pCO2 (hypocapnia)
  • Hypocapnia can be caused by hypoxemia, pulmonary disease, activated respiratory center, pain/fear/anxiety
• Metabolic alkalosis


  Caused by loss of chloride-rich fluids or chronic alkali administration