A 45-year-old man comes to the emergency department due to epigastric abdominal pain and fatigue. He has had similar episodes of pain in the past. Temperature is 37.1 C (98.8 F), blood pressure is 128/69 mm Hg, pulse is 92/min, and respirations are 16/min. Physical examination shows mild epigastric tenderness and hepatomegaly. There is no jaundice or lymphadenopathy. Laboratory results are as follows: CT scan of the abdomen shows pancreatic calcifications. Right upper quadrant ultrasound reveals no evidence of gallstones. Which of the following processes is most likely responsible for this patient's anemia?

Question

A 45-year-old man comes to the emergency department due to epigastric abdominal pain and fatigue.  He has had similar episodes of pain in the past.  Temperature is 37.1 C (98.8 F), blood pressure is 128/69 mm Hg, pulse is 92/min, and respirations are 16/min.  Physical examination shows mild epigastric tenderness and hepatomegaly.  There is no jaundice or lymphadenopathy.  Laboratory results are as follows:  CT scan of the abdomen shows pancreatic calcifications.  Right upper quadrant ultrasound reveals no evidence of gallstones.  Which of the following processes is most likely responsible for this patient's anemia?

Quizplus · Accepted Answer

This patient's recurrent abdominal pain and pancreatic calcifications suggest chronic pancreatitis, the most common cause of which is ethanol abuse. His hepatomegaly is likely due to alcohol-associated hepatic steatosis. The patient also has macrocytic anemia (low hemoglobin and elevated mean corpuscular volume [MCV] >100 µm³), which often develops in patients with chronic alcohol use due to folic acid deficiency (within months) or vitamin B₁₂ deficiency (within years). Both deficiencies lead to megaloblastosis, the underlying biochemical feature of which is a defect in DNA synthesis. Folic acid is a single carbon donor required for synthesis of purine and pyrimidine (eg, thymidine) bases incorporated in DNA. RNA and protein synthesis may continue relatively unaltered, leading to a state of unbalanced cytoplasmic growth with impaired cell division. Pancreatic insufficiency is also associated with vitamin B₁₂ deficiency as pancreatic enzymes normally cleave R factor from B₁₂, allowing B₁₂ to bind to intrinsic factor and be absorbed. (Choice B) The thalassemias are disorders presenting with reduced or absent globin chain production. Almost all thalassemia cases result in hypochromia and microcytosis (low MCV). (Choice C) Oxidative decarboxylation of pyruvate by pyruvate dehydrogenase requires thiamine pyrophosphate (TPP), a derivative of thiamine (vitamin B₁). Patients with alcohol use disorder may be prone to thiamine deficiency and could therefore suffer from impaired pyruvate decarboxylation, but this does not cause macrocytic anemia. (Choice D) Vitamin B₆ (pyridoxine) catalyzes the transaminase reactions by acting as a carrier of the amino group. B₆ deficiency can cause an anemia that is hypochromic, microcytic (low MCV), and sideroblastic. (Choice E) Iron deficiency anemia is typically hypochromic and microcytic (low MCV <80 µm³). Educational objective: The underlying biochemical feature of megaloblastosis is a defect in DNA synthesis. In patients with chronic alcohol use, megaloblastic macrocytic anemia can result from a nutritional deficiency of vitamin B₁₂ or of folate, which impairs synthesis of purine and pyrimidine bases.

A 45-Year-Old Man Comes to the Emergency Department Due to Epigastric