A patient with chronic obstructive pulmonary disease (COPD) has persistently elevated arterial PCO₂. After 5 days, a blood gas shows elevated plasma [HCO₃⁻] alongside the high PCO₂. What explains the elevated bicarbonate?
AThe lungs are retaining bicarbonate to compensate for the elevated CO₂
BThe kidneys have increased H⁺ secretion and ammoniagenesis, generating new HCO₃⁻ to compensate for the respiratory acidosis
CThe elevated bicarbonate is a primary metabolic alkalosis occurring simultaneously with the respiratory acidosis
DBicarbonate spontaneously rises when CO₂ is high because of the equilibrium CO₂ + H₂O ⇌ H⁺ + HCO₃⁻
Chronically elevated PCO₂ (respiratory acidosis) drives pH down. Over 3–5 days, the kidneys respond by increasing distal H⁺ secretion via H⁺-ATPase and increasing ammoniagenesis, trapping more H⁺ as NH₄⁺ in the urine. Each H⁺ secreted distally generates one new HCO₃⁻ returned to blood, raising plasma [HCO₃⁻]. This renal compensation improves but does not normalize pH. Option D is superficially plausible — the equilibrium does shift — but this is a short-term chemical effect, not the sustained elevation seen days later. The lungs (option A) do not handle bicarbonate directly; they regulate CO₂. Option C would be an independent primary disorder.
Question 2 Multiple Choice
What is the primary function of H⁺ secretion in the proximal tubule in the context of acid-base balance?
ATo excrete acid from the body, reducing the body's total acid load
BTo generate new bicarbonate that is added to the blood as a buffer
CTo reclaim filtered bicarbonate before it is lost in the urine, preserving the existing buffer reservoir
DTo acidify the urine so that phosphate and ammonia can serve as urinary buffers
Proximal tubule H⁺ secretion drives the reaction HCO₃⁻ + H⁺ → CO₂ + H₂O in the tubular lumen. The CO₂ diffuses into the proximal tubule cell, is reconverted to HCO₃⁻ by carbonic anhydrase, and is returned to the blood. Net effect: filtered bicarbonate is reclaimed — this is bicarbonate recovery, not net acid excretion. The body's total H⁺ load is unchanged. Net acid excretion (and new bicarbonate generation) happens in the distal tubule and collecting duct, where secreted H⁺ is buffered by titratable acid and ammonium and permanently removed in the urine.
Question 3 True / False
When the proximal tubule reabsorbs bicarbonate by secreting H⁺ into the tubular lumen, this represents net excretion of acid from the body.
TTrue
FFalse
Answer: False
Proximal tubule bicarbonate reabsorption is not net acid excretion — it is recovery of filtered buffer. The secreted H⁺ combines with filtered HCO₃⁻ to form CO₂ and water in the lumen; this CO₂ re-enters the cell and is reconverted to HCO₃⁻, which returns to the blood. No H⁺ is permanently removed from the body by this process. Net acid excretion — actually reducing the body's acid burden — occurs only in the distal nephron, where H⁺ is trapped in the urine as titratable acid (H₂PO₄⁻) or ammonium (NH₄⁺) and cannot re-enter circulation. Each such H⁺ excreted distally corresponds to one new HCO₃⁻ generated.
Question 4 True / False
Renal compensation for a chronic respiratory acid-base disorder improves blood pH but typically does not restore it fully to the normal range of 7.35–7.45.
TTrue
FFalse
Answer: True
Renal compensation adjusts plasma [HCO₃⁻] to shift the [HCO₃⁻]/[CO₂] ratio back toward normal, improving pH toward — but not to — the normal range. This is because the renal response is calibrated to compensate, not to correct: if bicarbonate were raised enough to fully normalize pH in the presence of elevated CO₂, the set point driving continued H⁺ secretion would be removed, halting further compensation. In clinical interpretation, a fully normalized pH despite abnormal PCO₂ and HCO₃⁻ suggests a mixed disorder, not simple compensation.
Question 5 Short Answer
Explain the difference between bicarbonate reabsorption in the proximal tubule and actual acid excretion in the distal nephron, and why both processes are necessary for acid-base homeostasis.
Think about your answer, then reveal below.
Model answer: The proximal tubule reclaims the ~4,300 mEq of bicarbonate filtered daily — without this, the buffer reservoir would be lost in the urine within hours. But this is not acid excretion; no net H⁺ leaves the body. Actual acid excretion occurs in the distal tubule and collecting duct, where intercalated cells secrete H⁺ that is permanently trapped in the urine by titratable acid buffers (phosphate) and ammonium. Each H⁺ excreted this way generates a new HCO₃⁻ returned to the blood, replenishing the bicarbonate consumed by daily metabolic acid production (~70 mEq/day). Both processes are necessary: the proximal step preserves existing buffer; the distal step generates new buffer to replace what acid load has consumed.
The distinction matters clinically: a drug that blocks proximal carbonic anhydrase (like acetazolamide) causes bicarbonate wasting and metabolic acidosis not by failing to excrete acid but by failing to reabsorb buffer. Conversely, a defect in distal H⁺ secretion (as in distal renal tubular acidosis) prevents acid excretion and new bicarbonate generation, also producing metabolic acidosis — but via a completely different mechanism. The two processes address different parts of the acid-base problem and can fail independently.