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