A 45-year-old man comes to the office due to several months of easy fatigability and exertional dyspnea. The patient had a subtotal gastrectomy for a nonhealing gastric ulcer 5 years ago. He takes daily iron supplementation. Blood pressure is 120/70 mm Hg, pulse is 80/min, and respirations are 16/min. Physical examination shows a shiny tongue and pale palmar creases. No lymphadenopathy, hepatomegaly, or splenomegaly is present. Laboratory results are as follows: Stool tests for occult blood are repeatedly negative. This patient's condition involves which of the following pathophysiologic mechanisms?

Question

A 45-year-old man comes to the office due to several months of easy fatigability and exertional dyspnea.  The patient had a subtotal gastrectomy for a nonhealing gastric ulcer 5 years ago.  He takes daily iron supplementation.  Blood pressure is 120/70 mm Hg, pulse is 80/min, and respirations are 16/min.  Physical examination shows a shiny tongue and pale palmar creases.  No lymphadenopathy, hepatomegaly, or splenomegaly is present.  Laboratory results are as follows:  Stool tests for occult blood are repeatedly negative.  This patient's condition involves which of the following pathophysiologic mechanisms?

Quizplus · Accepted Answer

Explanation: This patient, with chronic anemia following subtotal gastrectomy, has characteristic features of vitamin B₁₂ deficiency. Loss of intrinsic factor, whether due to gastric resection or autoimmune gastritis, is a common cause of B₁₂ deficiency. Vitamin B₁₂ is a required cofactor for the formation of thymidylate and purine molecules for DNA synthesis. B₁₂ deficiency therefore causes ineffective erythropoiesis due to delayed nuclear maturation, resulting in decreased transition to mature red blood cell (RBC) forms and high numbers of immature megaloblasts in the bone marrow. Increased intramedullary hemolysis of these megaloblasts releases heme, causing indirect hyperbilirubinemia, which may manifest as jaundice. Hemolysis also releases the intracellular enzyme lactate dehydrogenase (LDH), raising serum levels. Total RBC count and reticulocyte count will be low. Patients may also develop thrombocytopenia and leukopenia with hypersegmented polymorphonuclear cells. ₁₂ ₁₂ ₁₂ (Choices A, D, E, and F) Hyperbilirubinemia and high LDH may be seen in any cause of hemolysis, such as the following: Autoimmune hemolytic anemia Glucose-6-phosphate dehydrogenase deficiency due to impaired glutathione synthesis Mechanical injury to RBCs (artificial heart valves/foreign material within vasculature) Hereditary spherocytosis (increased membrane fragility) However, history of gastrectomy and presence of glossitis are more suggestive of B₁₂ deficiency in this patient. Glossitis may also be seen in deficiency of other micronutrients such as riboflavin, niacin, folic acid, or iron. ₁₂ (Choice C) Defective globin chain synthesis is seen in diseases such as sickle cell anemia and α- and β-thalassemia. Educational objective: Vitamin B₁₂ deficiency is common after a total or partial gastrectomy. Vitamin B₁₂ is a necessary cofactor in purine synthesis, and its deficiency causes defective DNA synthesis. This results in ineffective erythropoiesis, presenting as megaloblastic anemia. ₁₂ ₁₂ References: Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. (http://www.ncbi.nlm.nih.gov/pubmed/22093367) New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. (http://www.ncbi.nlm.nih.gov/pubmed/15189115)

A 45-Year-Old Man Comes to the Office Due to Several