Acid–Base System
The acid–base system is the set of physiologic processes that maintains hydrogen ion (\left(\text{H}^+\right)) concentration within a narrow range. Maintenance of (\text{H}^+) is achieved by coordinated buffering, respiratory control of carbon dioxide (\left(\text{CO}_2\right)), and renal control of bicarbonate (\left(\text{HCO}_3^-\right)).
Key Relationships Governing pH
Blood pH reflects the balance between (\text{CO}2) and (\text{HCO}_3^-) through the Henderson–Hasselbalch equation:
[
\text{pH} = 6.1 + \log\left(\frac{\text{HCO}_3^-}{0.03 \times \text{P}2}}\right)
]
A higher (\text{HCO}_3^-) relative to (\text{P}2}) increases pH.
A higher (\text{P}_3^-) decreases pH.}_2}) relative to (\text{HCO
Buffer Systems
Buffers resist rapid pH change by binding or releasing (\text{H}^+). Buffering shifts between protonated and deprotonated forms without eliminating acid or base.
Primary Extracellular Buffers
-
Bicarbonate buffer system (major extracellular buffer):
[ \text{CO}_2 + \text{H}_2\text{O} \rightleftharpoons \text{H}_2\text{CO}_3 \rightleftharpoons \text{H}^+ + \text{HCO}_3^- ] This links pH changes primarily to (\text{CO}_2) handling by the lungs. -
Protein buffers (including hemoglobin):
Proteins accept or donate (\text{H}^+) at specific binding sites, limiting immediate pH shifts. -
Phosphate and other minor buffers:
Intracellular and renal tubular buffering limits pH change during acid handling.
Respiratory Control of Acid–Base Balance
Ventilation determines (\text{CO}_2) elimination, which directly affects (\text{H}^+) because (\text{CO}_2) hydrates to form acid.
- Increased ventilation lowers (\text{P}_{\text{CO}_2}).
- Lower (\text{P}_{\text{CO}_2}) reduces (\text{H}^+) and raises pH.
- Decreased ventilation raises (\text{P}_{\text{CO}_2}).
- Higher (\text{P}_{\text{CO}_2}) increases (\text{H}^+) and lowers pH.
Respiratory compensation is typically faster than renal compensation, occurring over minutes to hours.
Renal Control of Bicarbonate and Hydrogen Ion
The kidneys regulate pH more slowly by changing total body buffer capacity and excreting or regenerating bicarbonate.
Major Renal Mechanisms
-
Reabsorption of filtered bicarbonate:
Near-complete reabsorption of (\text{HCO}_3^-) prevents loss of base. -
Generation of new bicarbonate:
Tubular cells produce new (\text{HCO}_3^-) after buffering secreted (\text{H}^+). -
Excretion of hydrogen ion with urine buffers:
Protons are excreted as: -
Titratable acid (buffering by urinary buffers such as phosphate)
- Ammonium (\left(\text{NH}_4^+\right)\right)), which is formed from glutamine metabolism and enables net acid excretion
Renal compensation typically takes 12–48 hours to become clinically significant and continues over days.
Integrated System Behavior During Disturbances
When an acid load increases (metabolic acidosis), (\text{H}^+) rises and pH falls. The immediate response is buffering, followed by compensatory hyperventilation that lowers (\text{P}_{\text{CO}_2}). Over days, the kidneys increase net acid excretion and regenerate bicarbonate, raising pH toward normal.
When a base load increases (metabolic alkalosis), (\text{H}^+) falls and pH rises. The immediate response is buffering, followed by hypoventilation that raises (\text{P}_{\text{CO}_2}). Over days, the kidneys decrease acid excretion and conserve bicarbonate, which supports the alkalotic state unless corrected by the underlying cause.
Primary vs Compensatory Changes
A primary disorder changes either (\text{P}_{\text{CO}_2}) (respiratory cause) or (\text{HCO}_3^-) (metabolic cause). Compensation then occurs through the other system:
- Respiratory disorders primarily alter (\text{P}_{\text{CO}_2}), with renal (\text{HCO}_3^-) changes following.
- Metabolic disorders primarily alter (\text{HCO}3^-), with respiratory (\text{P}) changes following.}_2
Compensation reduces pH disturbance but does not fully normalize it unless the underlying cause is corrected.