Acid-Base Balance and pH Regulation

Acid-Base Balance: Maintaining pH

• There are three mechanisms for maintaining pH: buffer systems, ventilation and pH changes, and kidney control of acid/base balance.
• Acid-base disturbances can be respiratory or metabolic.

pH Balance in the Body

• Daily bodily functions involve more acid intake and production than base intake.
• Acid input comes from diet and metabolism.
• The largest source of acid is carbon dioxide (CO2) from aerobic metabolism.
• pH homeostasis relies on buffers, ventilation, and renal regulation of H+ and HCO3.
• Buffers act as the first line of defense.
• Ventilation handles 75% of disturbances.
• Renal regulation of H+ and HCO3- is the slowest of the three mechanisms.

Buffer Systems

• Buffer systems include proteins, phosphate ions, and HCO3-.
• The extracellular buffer system, HCO3-, buffers H+ from non-respiratory sources.

HCO3- Buffering System

• Plasma HCO3- is approximately 600,000 times more concentrated than plasma H+.
• According to the law of mass action, changes in CO2, HCO3, or H+ cause reactions to shift.
• Increased CO2 shifts the equation to the right, creating one H+ and one HCO3-.
• Adding H+ shifts the equation to the left, with HCO3 acting as a buffer to create carbonic acid.

Ventilation

• Ventilation compensates for pH disturbances.
• Peripheral and central chemoreceptors detect changes in plasma PCO2 and/or H+ and signal the respiratory control center to adjust ventilation.
• Alterations in ventilation can correct or cause disturbances in acid-base balance.
• Hypoventilation causes a right shift.
• Hyperventilation causes a left shift.

Kidneys

• Kidneys use ammonia and phosphate buffers and handle the remaining 25% of pH disturbances slowly.
• Directly, by altering the rates of excretion or reabsorption of H+.
• Indirectly, by changing the rate at which HCO3- is reabsorbed or excreted.
• During acidosis, excess H+ is buffered by ammonia within tubule cells or enters the lumen, buffered by phosphate ions.
• H+ is not filtered but enters the tubule via secretion.

Proximal Tubule

• The proximal tubule secretion of H+ and reabsorbs HCO3-.
• HCO3 has no apical transporter, which happen via indirect processes.
• NHE secretes H+.
• H+ in the filtrate combines with filtered HCO3- to form CO2.
• CO2 diffuses into the cell.
• CO2 combines with water to form H+ and HCO3-.
• H+ is secreted again.
• HCO3- is reabsorbed with Na+.
• Glutamine is metabolized to ammonium ion and HCO3-.
• NH4+ is secreted and excreted.

Distal Nephron

• The distal nephron controls acid excretion.
• The collecting duct plays a significant role in regulating acid-base balance.
• Cells contain a high amount of carbonic anhydrase.
• H+ is transported via H+ ATPase or H-K ATPase and HCO3-/Cl- exchanger.
• In acidosis, Type A intercalated cells increase H+ secretion and HCO3- reabsorption, usually with increased K+ reabsorption (hyperkalemia).
• In alkalosis, Type B intercalated cells increase H+ reabsorption and HCO3- secretion, usually with increased K+ secretion (hypokalemia).

Acid-Base Disturbances

• Most variations in plasma pH are handled by buffers, ventilation, and renal excretion.
• Acid-base disturbances are classified by the pH change direction (acidosis or alkalosis) and the underlying cause (metabolic or respiratory).
• In acid-base disturbances, the bodies buffers are ineffective. This leaves respiratory and renal compensation to alleviate the change in pH.

Respiratory Acidosis

• Respiratory induced pH changes must be resolved via renal mechanisms.
• Respiratory acidosis results from alveolar hypoventilation, causing CO2 retention and elevated plasma CO2.
• Compensation must occur via renal mechanisms, excreting H+ and reabsorbing HCO3-.
• Causes of respiratory acidosis include pulmonary fibrosis and skeletal muscle disorders (muscular dystrophy).

Respiratory Alkalosis

• Respiratory induced pH changes must be resolved via renal mechanisms.
• Respiratory alkalosis occurs because of hyperventilation without increased metabolic CO2 production.
• In the clinic, the cause is usually excessive artificial respiration.
• Physiologically, the cause is anxiety-induced hyperventilation.
• Compensation happens via renal HCO3- excretion and H+ reabsorption.

Metabolic Acidosis

• Metabolic acidosis results when dietary and/or metabolic H+ input exceeds H+ excretion.
• Lactic acidosis results from anaerobic metabolism.
• Ketoacidosis results from excessive fat and amino acid breakdown.
• Metabolic acidosis can also occur from excessive HCO3- loss, as with diarrhea.
• Respiratory (increased ventilation) and renal compensation (HCO3- reabsorbed, H+ excreted) usually resolve metabolic acidosis.

Metabolic Alkalosis

• Excessive vomiting of acidic stomach contents or excessive ingestion of bicarbonate-containing antacids are common causes of metabolic alkalosis.
• Ventilation decreases to resolve alkalosis but can cause hypoxia.
• The renal response is to excrete HCO3- and reabsorb H+.