| The following vignette applies to the next 2 items. The items in the set must be answered in sequential order. Once you click Proceed to Next Item, you will not be able to add or change an answer. |
An 87-year-old nursing home resident is brought to the emergency department with a 2-day history of fever, vomiting, and progressive lethargy. The patient's past medical history is significant for advanced dementia and stroke. Temperature is 38.3 C (101 F), blood pressure is 88/62 mm Hg, and pulse is 120/min and regular. On examination, he is lethargic but arousable. Coarse rhonchi are heard over the right midlung. Laboratory results are as follows:
| Leukocytes | 23,000/mm3 |
| Platelets | 210,000/mm3 |
| Sodium | 140 mEq/L |
| Potassium | 4.2 mEq/L |
| Chloride | 101 mEq/L |
| Bicarbonate | 18 mEq/L |
| Creatinine | 0.9 mg/dL |
| Glucose | 121 mg/dL |
| Lactic acid | 4.0 mmol/L (normal: <2 mmol/L) |
Item 1 of 2
Which of the following is the most likely cause of this patient's increased anion gap?
Causes of lactic acidosis | |
Underlying mechanism | Etiology |
Enhanced metabolic rate |
|
Reduced oxygen delivery |
|
Diminished lactate catabolism |
|
Decreased oxygen utilization |
|
Enzymatic defects |
|
This patient's clinical presentation (eg, fever, leukocytosis, hypotension, tachycardia) is indicative of septic shock; laboratory studies also show a corresponding anion gap metabolic acidosis secondary to an elevated lactic acid level.
Lactic acidosis may result from overproduction and/or impaired clearance of lactic acid. End-organ hypoperfusion in septic shock impairs tissue oxygenation and decreases oxidative phosphorylation, leading to a buildup of NADH during glycolysis and shunting of pyruvate to lactate. Hepatic hypoperfusion during sepsis also contributes to the accumulation of lactic acid as the liver is the primary site of lactate clearance (via gluconeogenesis).
(Choice B) Lactic acidosis due to primary impairment of hepatic gluconeogenesis can occur with certain inborn errors of metabolism (eg, pyruvate carboxylase or glucose-6-phosphatase deficiency). However, these diseases usually present in infancy (not elderly adults) and affected patients have fasting hypoglycemia.
(Choice C) Impaired renal tubular bicarbonate reabsorption is seen in type 2 (proximal) renal tubular acidosis. Poor bicarbonate reabsorption can occur in a variety of inherited or acquired conditions, including multiple myeloma and drug toxicity (eg, acetazolamide). Affected patients have a non-anion gap metabolic acidosis.
(Choice D) Increased lipolysis and ketogenesis occur in patients with diabetic ketoacidosis (DKA), which also presents with anion gap metabolic acidosis. However, serum glucose is much higher in DKA (on average >350 mg/dL), and ketones can be detected in blood and urine.
(Choice E) Increased protein breakdown can occur in the setting of chronic metabolic acidosis. However, it is not a direct cause of acidosis.
Educational objective:
Lactic acidosis in septic shock results from tissue hypoxia, which impairs oxidative phosphorylation and causes shunting of pyruvate to lactate following glycolysis. Hepatic hypoperfusion also contributes to the buildup of lactic acid as the liver is the primary site of lactate clearance.