A 68-year-old man comes to the emergency department due to abdominal pain and nausea for the past 2 days. He has a history of atherosclerotic cardiovascular disease and underwent coronary artery bypass surgery 2 years ago. Blood pressure is 105/65 mm Hg and heart rate is 120/min and irregular. Abdominal examination reveals mild diffuse tenderness and decreased bowel sounds. Laboratory studies are as follows:
| Serum chemistry | |
| Sodium | 142 mEq/L |
| Chloride | 104 mEq/L |
| Bicarbonate | 12 mEq/L |
| Creatinine | 0.8 mg/dL |
| Arterial blood gases | |
| pH | 7.25 |
| PaCO2 | 29 mm Hg |
| Lactic acid, venous blood | 5.6 mmol/L (normal: 0.5 - 2.0 mmol/L) |
ECG shows absent P waves and an irregular rate and rhythm. CT scan of the abdomen reveals colonic wall thickening and no enhancement with intravenous contrast. Urinalysis shows acidic urine. Renal metabolism of which of the following amino acids is most important for maximizing acid excretion in this patient?
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This patient has acute ischemic colitis, which is most likely due to embolic disease related to his atrial fibrillation. The ischemic bowel undergoes anaerobic metabolism, causing lactate accumulation in the blood that leads to an anion gap metabolic acidosis. Acidosis stimulates renal ammoniagenesis, a process by which renal epithelial cells metabolize glutamine, generating ammonium and bicarbonate. Ammonium ions are transported into the tubular fluid and excreted in the urine while peritubular capillaries absorb bicarbonate, which functions to buffer acids in the blood.
Under normal physiologic conditions, about half of the total amount of acid secreted in the urine is in the form of ammonium, and the remainder is excreted primarily as titratable acids, particularly inorganic phosphate. However, increased ammonium production is almost entirely responsible for the increase in renal acid excretion seen with chronic acidosis.
(Choices A and C) Alanine and aspartate are glucogenic amino acids. Alanine is metabolized in the liver to produce pyruvate and aspartate can be readily interconverted with oxaloacetate.
(Choice B) Arginine is a urea cycle intermediate that helps to remove nitrogenous waste products (eg, ammonium) from the blood. Hepatic metabolism of arginine results in the production of urea and ornithine.
(Choice E) Histidine, an essential amino acid, is converted to histamine by histidine decarboxylase. Histamine is involved in the acute inflammatory response and gastric acid secretion; it also functions as a neurotransmitter.
Educational objective:
Acidosis stimulates renal ammoniagenesis, a process by which renal tubular epithelial cells metabolize glutamine to glutamate, generating ammonium that is excreted in the urine and bicarbonate that is absorbed into the blood. This process is responsible for the vast majority of renal acid excretion in chronic acidotic states.