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Chemistry

Henderson-Hasselbach

Blood gases and pH are vital for homeostasis

Acid-Base Balance

  • Definition of Acids and Bases
    • Acid: A substance that donates protons (\(H^+\))
    • Base: A substance that accepts protons (\(H^+\))
  • pH Scale
    • \(pH = -log[H^+] = -log[H_3O^+]\)
    • Ranges from 0 to 14, with 7 being neutral
    • pH < 7: Acidic
    • pH > 7: Basic (alkaline)
  • Normal Blood pH: 7.35-7.45
  • Importance of Acid-Base Balance
    • Optimal enzyme function
    • Maintenance of cell membrane integrity
    • Appropriate protein structure and function
    • Electrolyte balance
  • Acidemia: Blood pH < 7.35
  • Alkalemia: Blood pH > 7.45
  • Major Buffer Systems in the Body
    • Bicarbonate Buffer System: Primary buffer system in extracellular fluid
    • Hemoglobin Buffer System: Buffers pH changes within red blood cells
    • Phosphate Buffer System: Important in intracellular fluid and urine
    • Protein Buffer System: Buffers pH changes in intracellular and extracellular fluid

Biochemical Theory

  • Sources of Acids and Bases
    • Volatile Acid: Carbon dioxide (\(CO_2\)), produced during metabolism, is converted to carbonic acid (\(H_2CO_3\))
      • \(CO_2\) + \(H_2O\) ↔︎ \(H_2CO_3\) ↔︎ \(H^+\) + \(HCO_3^-\)
      • The lungs regulate \(CO_2\) levels through ventilation
    • Nonvolatile Acids: Produced from the metabolism of proteins and other organic compounds
      • Examples: Sulfuric acid, phosphoric acid, lactic acid, ketoacids
      • The kidneys excrete nonvolatile acids
    • Bases: Generated through metabolic processes, but less significant than acid production

Regulation of Acid-Base Balance

  • Buffer Systems
    • Act immediately to resist pH changes
    • Do not eliminate acids or bases from the body
  • Respiratory System
    • Regulates \(CO_2\) levels through ventilation
    • Responds rapidly (within minutes) to pH changes
  • Renal System
    • Excretes nonvolatile acids and regenerates bicarbonate (\(HCO_3^-\))
    • Responds slowly (over hours to days) to pH changes
  • Compensation Mechanisms
    • Respiratory Compensation: The lungs adjust ventilation to change \(CO_2\) levels in response to metabolic acid-base disturbances
    • Renal Compensation: The kidneys adjust \(HCO_3^-\) excretion and \(H^+\) secretion to compensate for respiratory acid-base disturbances

Respiratory Control

  • Ventilation
    • Increased Ventilation: Blows off \(CO_2\), decreases \(H_2CO_3\), and raises pH
    • Decreased Ventilation: Retains \(CO_2\), increases \(H_2CO_3\), and lowers pH
  • Chemoreceptors
    • Central Chemoreceptors: Located in the medulla oblongata and respond to changes in pH and \(CO_2\) levels in the cerebrospinal fluid (CSF)
    • Peripheral Chemoreceptors: Located in the carotid and aortic bodies and respond to changes in pH, \(CO_2\), and \(O_2\) levels in the blood
  • Response to Acidosis
    • Increased ventilation to blow off \(CO_2\) and raise pH
  • Response to Alkalosis
    • Decreased ventilation to retain \(CO_2\) and lower pH

Renal Control

  • Bicarbonate Reabsorption
    • Most bicarbonate (\(HCO_3^-\)) is reabsorbed in the proximal tubule
    • Involves the enzyme carbonic anhydrase and the secretion of \(H^+\) into the tubular lumen
  • Acid Excretion
    • \(H^+\) is secreted into the tubular lumen
    • \(H^+\) combines with buffers such as phosphate (\(HPO_4^{2-}\)) and ammonia (\(NH_3\)) to form titratable acid (\(H_2PO_4^-\)) and ammonium (\(NH_4^+\))
    • Ammonia is produced from glutamine in the proximal tubule
  • Response to Acidosis
    • Increased \(H^+\) secretion
    • Increased bicarbonate reabsorption
    • Increased ammonia production
  • Response to Alkalosis
    • Decreased \(H^+\) secretion
    • Decreased bicarbonate reabsorption

Acid-Base Imbalances

  • Acidosis: A condition in which the blood pH is below the normal range (< 7.35)
    • Respiratory Acidosis: Caused by increased \(CO_2\) levels (decreased ventilation)
    • Metabolic Acidosis: Caused by decreased \(HCO_3^-\) levels or increased nonvolatile acid production
  • Alkalosis: A condition in which the blood pH is above the normal range (> 7.45)
    • Respiratory Alkalosis: Caused by decreased \(CO_2\) levels (increased ventilation)
    • Metabolic Alkalosis: Caused by increased \(HCO_3^-\) levels or decreased nonvolatile acid levels

Henderson-Hasselbalch Equation

  • Equation
    • \(pH = pKa + \log \left( \frac {[A^-]} {[HA]} \right)\)
      • \(pH\): Measure of acidity or basicity
      • \(pKa\): The negative log of the acid dissociation constant (Ka), indicating the strength of an acid
      • [\(A^-\)]: Concentration of the conjugate base
      • [\(HA\)]: Concentration of the weak acid
  • Application to Bicarbonate Buffer System
    • \(pH = 6.1 + \log \left( {\frac {[HCO_3^-]} {0.03 \times PaCO_2}} \right)\)
      • 6.1 = \(pKa\) of carbonic acid (\(H_2CO_3\))
      • [\(HCO_3^-\)] = Concentration of bicarbonate in mmol/L
      • Pa\(CO_2\) = Partial pressure of carbon dioxide in mmHg
      • 0.03 = Solubility coefficient of \(CO_2\) in blood (converts Pa\(CO_2\) to [\(H_2CO_3\)])
  • Clinical Significance
    • The Henderson-Hasselbalch equation describes the relationship between pH, bicarbonate, and Pa\(CO_2\) in the blood
    • It is used to assess acid-base balance and to determine the cause of acid-base disturbances
    • Changes in bicarbonate and Pa\(CO_2\) affect the pH, and the body uses compensation mechanisms to maintain the pH within the normal range

Key Terms

  • Acid: A substance that donates protons (\(H^+\))
  • Base: A substance that accepts protons (\(H^+\))
  • pH: A measure of the acidity or basicity of a solution
  • Buffer: A solution that resists changes in pH
  • Acidosis: A condition in which the blood pH is below the normal range
  • Alkalosis: A condition in which the blood pH is above the normal range
  • Bicarbonate (\(HCO_3^-\)): A major buffer in the blood
  • Partial Pressure of Carbon Dioxide (Pa\(CO_2\)): A measure of the carbon dioxide level in the blood
  • Ventilation: The process of moving air into and out of the lungs
  • Respiratory Compensation: The adjustment of ventilation to correct metabolic acid-base disturbances
  • Renal Compensation: The adjustment of renal excretion of acid or base to correct respiratory acid-base disturbances
  • Anion Gap: The difference between measured cations and anions in serum, used to assess metabolic acidosis
  • Henderson-Hasselbalch Equation: An equation that describes the relationship between pH, bicarbonate, and Pa\(CO_2\)
  • Hyperventilation: Increased rate and depth of breathing
  • Hypoventilation: Decreased rate and depth of breathing
  • Bohr Effect: The effect of pH and \(CO_2\) on the oxygen-binding affinity of hemoglobin
  • Carbonic Anhydrase: The enzyme that catalyzes the interconversion of carbon dioxide and bicarbonate
  • Normoventilation: The state of normal breathing, with an appropriate balance of oxygen and carbon dioxide
  • Hypoxemia: Deficiency in the saturation of oxygen in arterial blood