A patient is going skiing high in the Rockies and is given acetazolamide to protect against altitude sickness. Unfortunately, the patient is also a type 1 diabetic. He is admitted to the hospital in a worsening ketoacidosis. In which of the following cells has acetazolamide inhibited a reaction that has led to the severity of the metabolic acidosis?
Acetazolamide is a carbonic anhydrase inhibitor, which is found primarily in red blood cells. The red blood cells contain carbonic anhydrase that catalyzes the reaction that forms carbonic acid from CO2 andH2 O. Under high- altitude conditions, the inhibition of carbonic anhydrase will lead to a decrease in blood pH, which stabilizes the deoxygenated form of Hb. This is due to an increased loss of bicarbonate in the urine by the inhibition of carbonic anhydrase within the kidney. The change in pH increases oxygen delivery to the tissues and can overcome, in part, the symptoms of altitude sickness.However, in the case of the person with type I diabetes who begins to produce ketone bodies, the body's main compensatory mechanism to overcome the acidosis is blocked. As ketone bodies are formed and protons generated, the H+ will react with bicarbonate to form carbonic acid. Carbonic anhydrase, which catalyzes a reversible reaction, will then convert the carbonic acid to CO2 andH2 O, with the CO2 being exhaled. These reactions soak up excess protons and help to buffer against the acidosis. If, however, carbonic anhydrase has been inhibited by acetazolamide, then the bicarbonate cannot buffer the blood pH, and the acidosis could become more severe. White blood cells, muscle cells, liver cells, and the lens of the eye do not contribute to the buffering of the blood, and inhibition of carbonic anhydrase in those cells would not affect the ability to overcome an acidosis.
White blood cells
Red blood cells
Lens of the eye
Hepatocyte
Carbohydrates