B/B 01 · Acid–base balance
Three Patients, One Buffer
Read blood gas data from patients and a short experiment, and sort out which organ is doing what.
Passage
The main buffer of blood is the CO₂/bicarbonate pair. The enzyme carbonic anhydrase speeds the reversible reaction CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻. Other buffers, such as hemoglobin and plasma proteins, also contribute, but this pair is the one the body can adjust most easily. At 37 °C the effective pKa of the system is 6.1, and the dissolved CO₂ concentration (in mM) is 0.03 × PCO₂ (in mm Hg). The Henderson–Hasselbalch equation for blood is therefore:
Two organs set the two terms. Ventilation, driven by chemoreceptors that sense PCO₂ and pH, changes PCO₂ within minutes. The kidneys change plasma [HCO₃⁻] more slowly. Cells of the proximal tubule and collecting duct use carbonic anhydrase to make H⁺ and HCO₃⁻ from CO₂ and water. The H⁺ is secreted into the tubule lumen, where much of it is excreted as NH₄⁺, and the HCO₃⁻ returns to the blood. Because a gas is one of the two terms, a change in breathing shifts the pH almost at once, while a change in the kidneys’ handling of acid shows up only after hours to days. For the questions below, use log 2 ≈ 0.30 and log 10 = 1.
Part 1. A physiologist reviews the arterial blood gas results of three patients when each was first seen. Samples were drawn from the radial artery into heparinized syringes and analyzed within 15 minutes. Patient A was found unresponsive an hour after an opioid overdose and was breathing 4 times a minute. Patient B has had severe lung disease for years, with chronically reduced ventilation, and is clinically stable. Patient C has had two days of severe diarrhea (stool carries HCO₃⁻ out of the body) and is breathing deeply and quickly. Normal values are shown in the first row of Table 1.
Table 1. Arterial blood gas values at first presentation.
| pH | PCO₂ (mm Hg) | [HCO₃⁻] (mM) | |
|---|---|---|---|
| Normal | 7.40 | 40 | 24 |
| Patient A | 7.15 | 80 | 27 |
| Patient B | 7.30 | 80 | 38 |
| Patient C | 7.29 | 26 | 12 |
Part 2. The physiologist next follows the time course of compensation in two groups of ventilated patients. All had normal kidney function at enrollment and were not receiving diuretics or bicarbonate. In the hypercapnia group (n = 6), the ventilator was set to hold PCO₂ at 80 mm Hg for 5 days, a strategy sometimes used to avoid overstretching injured lungs. In the control group (n = 6), the ventilator held PCO₂ at 40 mm Hg for the same 5 days. Arterial samples were drawn daily, and urine was collected over 24 hours to measure NH₄⁺ excretion, reported as a multiple of each group’s day-0 value. In the control group, pH stayed at 7.40, [HCO₃⁻] at 24 mM, and urinary NH₄⁺ at baseline. Table 2 shows mean values for the hypercapnia group. PCO₂ stayed at 80 mm Hg throughout.
Table 2. Mean values in the hypercapnia group (n = 6).
| Day | pH | [HCO₃⁻] (mM) | Urinary NH₄⁺ (× baseline) |
|---|---|---|---|
| 0 | 7.15 | 27 | 1 |
| 1 | 7.21 | 31 | 2 |
| 3 | 7.28 | 36 | 4 |
| 5 | 7.30 | 38 | 5 |
Questions
Question 1 of 6
Which description best fits Patient A?
In a metabolic acidosis, [HCO₃⁻] falls. Patient A’s is 27 mM, slightly above normal.
An alkalosis would raise pH. Patient A’s pH is 7.15, well below normal.
Renal compensation takes days to raise [HCO₃⁻]. Patient A’s overdose began an hour ago, and pH is still far from normal. Patient B is the one who has had time to compensate.
Why the answer is what it is
The pH is low and PCO₂ is high, so the primary problem is retained CO₂ from hypoventilation (respiratory acidosis). [HCO₃⁻] is nearly normal because the kidneys have not yet had time to respond.
Review: Acid–Base Physiology · Respiratory Physiology
Question 2 of 6
Patients A and B have the same PCO₂, yet Patient B’s pH is higher. Which statement best explains this?
The PCO₂ is the same, 80 mm Hg, so ventilation is not what separates them.
The pKa of the system is a property of the chemistry (6.1 at 37 °C) and does not change between patients.
Dissolved CO₂ is on the acid side of the buffer. The dissolved CO₂ is the same in both patients anyway, since PCO₂ is the same.
Why the answer is what it is
With PCO₂ = 80, the denominator is 0.03 × 80 = 2.4 mM in both patients. Patient A’s ratio is 27 / 2.4 ≈ 11; Patient B’s is 38 / 2.4 ≈ 16. A larger ratio means a larger log term and a higher pH. The extra bicarbonate is the kidneys’ doing.
Review: Buffers · Equations: Equilibrium, Acids & Solutions · Renal Physiology
Question 3 of 6
Patient C’s PCO₂ is 26 mm Hg, well below normal. How does this help Patient C’s pH?
Ventilation does not add bicarbonate. Bicarbonate changes slightly as CO₂ is lost, but the benefit comes from the other term of the ratio.
CO₂ sits on the acid side of the buffer, since CO₂ + H₂O ⇌ H⁺ + HCO₃⁻. Removing it does not remove a base.
That would lower [HCO₃⁻] and make the acidosis worse. Also, the kidneys respond over days, not through the minute-to-minute change in PCO₂.
Why the answer is what it is
Hyperventilation is the fast compensation for a metabolic acidosis. Lowering PCO₂ shrinks the denominator of the ratio and, by Le Châtelier’s principle, pulls the reaction toward CO₂ and water, which uses up H⁺. The pH moves back toward normal but does not reach it.
Review: Acid–Base Physiology · Respiratory Physiology · Chemical Equilibrium & Le Châtelier’s Principle
Question 4 of 6
A person with normal values (PCO₂ 40 mm Hg, [HCO₃⁻] 24 mM, pH 7.40) suddenly doubles PCO₂ to 80 mm Hg, and [HCO₃⁻] does not change. What is the pH?
Higher CO₂ is an acid load. It makes the ratio smaller, so the pH falls instead of rising.
The pH stays the same only if the ratio stays the same. Doubling PCO₂ without changing [HCO₃⁻] cuts the ratio in half.
That is a fall of 0.6, which would take a fourfold rise in PCO₂. Here PCO₂ only doubled.
Why the answer is what it is
Doubling PCO₂ halves the ratio, from 24 / 1.2 = 20 to 24 / 2.4 = 10. Halving the ratio changes the log by −log 2 ≈ −0.30. Check it the other way: log 10 = 1, so pH = 6.1 + 1 = 7.10.
Review: Equations: Equilibrium, Acids & Solutions · Acid–Base Physiology
Question 5 of 6
Which conclusion do the data in Part 2 best support?
PCO₂ was held at 80 mm Hg by the ventilator throughout, so the lungs did not change it. And the pH only reached 7.30, not 7.40.
[HCO₃⁻] and pH were still rising on days 3 and 5, so compensation was not finished after day 1.
In the control group, [HCO₃⁻] stayed at 24 mM. The control group is what shows the change is tied to the high PCO₂, not to ventilation itself.
Why the answer is what it is
With PCO₂ fixed, the only thing moving the pH toward normal is the rising [HCO₃⁻], and it rises over days alongside urinary NH₄⁺, the form in which the kidney excretes H⁺. Compensation is partial: pH reaches 7.30, not 7.40. The control group, with no change in any measure, rules out ventilation alone as the cause.
Review: Acid–Base Physiology · Renal Physiology
Question 6 of 6
The researchers want to test whether the kidneys are responsible for the rise in [HCO₃⁻]. Which additional group would best test this?
This changes the acid load, but it does not tell you whether the kidneys caused the rise seen with high PCO₂. It would also change the PCO₂ condition.
A higher PCO₂ would show a dose effect, but kidney function would still be unchanged, so it cannot isolate the kidneys.
A larger sample makes the means more precise, but it repeats the same experiment and does not test the mechanism.
Why the answer is what it is
To test whether an organ is responsible, change only that organ’s function and hold everything else (here, PCO₂ at 80 mm Hg for 5 days) the same. If the kidneys cause the rise, a group with impaired renal acid excretion should show a much smaller rise in [HCO₃⁻] and a lower pH.
Review: Renal Physiology · Social Structure, Inequality, Health, & Research Methods