Questions: Acid-Base Balance and Respiratory Compensation

Question 1

A patient with severe diarrhea loses large amounts of bicarbonate, dropping their HCO3- from 24 to 14 mEq/L. Their PCO2 is 30 mmHg (normal: 40 mmHg). What is the correct interpretation?

• A. Respiratory acidosis with metabolic compensation — the kidneys have raised bicarbonate in response to high PCO2
• B. Metabolic acidosis with respiratory compensation — bicarbonate loss lowered pH, and hyperventilation is reducing PCO2 to restore the buffer ratio
• C. Metabolic alkalosis with respiratory compensation — bicarbonate loss triggers alkalosis, and slow breathing retains CO2
• D. Mixed disturbance with both lungs and kidneys failing simultaneously

Answer: (B)

Bicarbonate loss is the primary disturbance (metabolic acidosis — the numerator of the HCO3-/CO2 ratio fell). The low PCO2 (30 mmHg) reflects respiratory compensation: the body is hyperventilating to exhale CO2, reducing the denominator of the ratio to partially restore the 20:1 balance. Option C reverses the direction — losing bicarbonate lowers the pH (acidosis), not raises it.

Question 2

According to the Henderson-Hasselbalch equation, which change would directly increase blood pH toward alkalosis?

• A. Increasing PCO2 from 40 to 50 mmHg due to hypoventilation
• B. Decreasing bicarbonate concentration from 24 to 18 mEq/L due to renal bicarbonate loss
• C. Increasing bicarbonate concentration from 24 to 28 mEq/L while PCO2 remains constant
• D. Slowing breathing rate, causing CO2 to accumulate

Answer: (C)

pH = 6.1 + log([HCO3-] / [0.03 × PCO2]). Raising HCO3- increases the numerator of the log ratio, shifting pH upward. Options A and D both increase PCO2, raising the denominator and lowering pH (acidosis). Option B decreases HCO3-, also lowering pH. Only raising bicarbonate (with PCO2 constant) shifts the ratio toward alkalosis.

Question 3

Respiratory compensation for metabolic acidosis works by increasing ventilation to exhale CO2, which directly removes acid from the blood.

• T. True
• F. False

Answer: True

CO2 is in equilibrium with carbonic acid: CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-. By exhaling CO2, the lungs shift this equilibrium to the left, consuming H+ ions and raising pH. Each CO2 exhaled removes one proton from the bicarbonate system. This is the biochemical mechanism of hyperventilation in metabolic acidosis — Kussmaul breathing in diabetic ketoacidosis is the clinical manifestation.

Question 4

Respiratory compensation can fully restore blood pH to 7.4 in cases of metabolic acidosis.

• T. True
• F. False

Answer: False

Respiratory compensation is fast (minutes) but incomplete. As PCO2 falls through hyperventilation, the respiratory drive itself decreases — the stimulus to breathe is reduced — limiting how far this compensation can go. Additionally, extreme hyperventilation is unsustainable. Full correction of metabolic acidosis requires the kidneys to regenerate bicarbonate or excrete hydrogen ions, taking hours to days. Respiratory compensation reduces the severity of the pH deviation but cannot return it to exactly 7.4.

Question 5

Why does the bicarbonate buffer system depend on the ratio of HCO3- to CO2 rather than the absolute concentration of either component alone?

Model answer: The Henderson-Hasselbalch equation shows pH is determined by the logarithm of [HCO3-]/[0.03 × PCO2] — only the ratio matters. This is because buffering is a chemical equilibrium: what determines where CO2 + H2O ⇌ H+ + HCO3- sits is the relative amounts of each component, not their absolute values. This is why the respiratory and renal systems can cooperate: the lungs lower CO2 (shrinking the denominator) and the kidneys raise HCO3- (enlarging the numerator), both shifting the ratio toward the normal 20:1 that yields pH 7.4. A patient could have abnormally high absolute levels of both components, but if the ratio is 20:1, pH is still 7.4.

The ratio-dependence is also why partial compensation can normalize pH even while both components remain abnormal. Recognizing this is the key to reading compensated blood gas results clinically.