26.5 Disorders of Acid-Base Balance

Disorders of Acid-Base Balance

Acid-base balance keeps blood pH within a narrow range that cells need to function properly. When pH drifts too far in either direction, enzyme activity, oxygen delivery, and electrolyte balance all suffer. The lungs and kidneys are the two main organs responsible for correcting these shifts, and understanding how they do it is the key to diagnosing acid-base disorders.

Blood Variables for Acid-Base Diagnosis

Three lab values form the foundation of acid-base diagnosis. Each one tells you something different about what's going wrong and where the problem originates.

Blood pH reflects the overall acid-base status.

• Normal range: 7.35–7.45
• Below 7.35 = acidosis (too much $H^+$)
• Above 7.45 = alkalosis (too little $H^+$)

Partial pressure of carbon dioxide ($PaCO_2$) reflects the respiratory component. $CO_2$ is an acid in the blood because it combines with water to form carbonic acid ($H_2CO_3$).

• Normal range: 35–45 mmHg
• Above 45 mmHg = respiratory acidosis (the lungs aren't blowing off enough $CO_2$, usually from hypoventilation)
• Below 35 mmHg = respiratory alkalosis (the lungs are blowing off too much $CO_2$, usually from hyperventilation)

Bicarbonate ($HCO_3^-$) reflects the metabolic component. The kidneys control how much bicarbonate is reabsorbed or excreted.

• Normal range: 22–26 mEq/L
• Below 22 mEq/L = metabolic acidosis (either excess acid is being produced or $HCO_3^-$ is being lost)
• Above 26 mEq/L = metabolic alkalosis (either $HCO_3^-$ is being retained or $H^+$ is being lost)

Anion Gap

The anion gap helps you figure out the cause of a metabolic acidosis. It's calculated as:

$\text{Anion Gap} = Na^+ - (Cl^- + HCO_3^-)$

• Normal range: 8–16 mEq/L (this represents unmeasured anions like albumin and phosphate)
• High anion gap means new acids are accumulating in the blood. Think lactic acidosis, diabetic ketoacidosis, or toxin ingestion. The extra acid anions (lactate, ketoacids) replace $HCO_3^-$ but aren't measured in the basic panel, so the gap widens.
• Normal anion gap means $HCO_3^-$ is being lost directly (e.g., from diarrhea or renal tubular acidosis). Chloride rises to replace the lost bicarbonate, keeping the gap unchanged.

Compensation for Respiratory Imbalances

When the problem starts in the lungs, the kidneys step in to compensate. Renal compensation is effective but slow, taking hours to days to reach full effect.

Respiratory acidosis ($PaCO_2$ > 45 mmHg):

1. Excess $CO_2$ drives the reaction $CO_2 + H_2O \rightarrow H_2CO_3 \rightarrow H^+ + HCO_3^-$, pushing pH down.
2. The kidneys respond by excreting more $H^+$ and reabsorbing more $HCO_3^-$.
3. Blood $HCO_3^-$ rises, which buffers the excess acid and pulls pH back toward normal.
4. Hemoglobin and plasma proteins also buffer $H^+$ immediately, but their capacity is limited.

Respiratory alkalosis ($PaCO_2$ < 35 mmHg):

1. Too little $CO_2$ means less carbonic acid is formed, so pH rises.
2. The kidneys respond by excreting more $HCO_3^-$ and retaining more $H^+$.
3. Blood $HCO_3^-$ falls, which brings pH back down toward normal.
4. Hemoglobin and plasma proteins release $H^+$ as an immediate but limited buffer response.

Compensation for Metabolic Imbalances

When the problem starts with metabolism or the kidneys, the lungs compensate first because they can adjust ventilation within minutes.

Metabolic acidosis ($HCO_3^-$ < 22 mEq/L):

1. Falling pH stimulates peripheral chemoreceptors.
2. The respiratory center increases ventilation rate and depth (hyperventilation).
3. More $CO_2$ is exhaled, lowering $PaCO_2$ and reducing carbonic acid formation.
4. The kidneys also ramp up $H^+$ secretion into the tubular fluid and generate new $HCO_3^-$ from $CO_2$ in tubular cells.

Metabolic alkalosis ($HCO_3^-$ > 26 mEq/L):

1. Rising pH suppresses the respiratory drive.
2. Ventilation slows (hypoventilation), retaining more $CO_2$.
3. The retained $CO_2$ forms more carbonic acid, which releases $H^+$ and pulls pH back down.
4. The kidneys excrete excess $HCO_3^-$ and reduce $H^+$ secretion.

Acid-Base Homeostasis Mechanisms

Three lines of defense maintain acid-base balance, each operating on a different timescale.

1. Chemical buffer systems (seconds)

These are the first responders. They immediately bind or release $H^+$ to resist pH changes.

• Bicarbonate buffer system ($H_2CO_3 / HCO_3^-$): The most important extracellular buffer. It works because the lungs can regulate $CO_2$ and the kidneys can regulate $HCO_3^-$, giving the body control over both sides of the equation.
• Protein buffers, including hemoglobin: The most abundant intracellular buffers. Amino acid side chains accept or donate $H^+$ depending on pH.
• Phosphate buffer system ($H_2PO_4^- / HPO_4^{2-}$): Especially important inside cells and in renal tubular fluid, where phosphate concentrations are higher than in plasma.

2. Respiratory regulation (minutes)

The lungs adjust how much $CO_2$ is retained or exhaled. Since $CO_2$ is the acid-forming side of the bicarbonate equation, changing ventilation rate directly shifts blood pH.

3. Renal regulation (hours to days)

The kidneys provide the most powerful and precise correction by:

• Reabsorbing or excreting $HCO_3^-$
• Secreting $H^+$ into the tubular fluid
• Generating new $HCO_3^-$ when needed (from $CO_2$ and water in tubular cells)

The Henderson-Hasselbalch Equation

This equation ties the three key variables together:

$pH = 6.1 + \log \frac{[HCO_3^-]}{0.03 \times PaCO_2}$

The 6.1 is the $pK_a$ of carbonic acid, and 0.03 is the solubility coefficient of $CO_2$ in blood. You don't need to calculate this by hand for most clinical scenarios, but the equation shows you why pH depends on the ratio of bicarbonate to dissolved $CO_2$. If the ratio stays at about 20:1, pH stays near 7.4. Any compensation strategy is really about restoring that ratio.