A 55-year-old man undergoing evaluation for fatigue and exertional dyspnea is diagnosed with macrocytic anemia. Upper gastrointestinal endoscopy is consistent with atrophic gastritis. He is started on intramuscular cyanocobalamin, with the resulting changes shown in the graph below. The blue curve most likely corresponds to which of the following parameters?

Question

A 55-year-old man undergoing evaluation for fatigue and exertional dyspnea is diagnosed with macrocytic anemia.  Upper gastrointestinal endoscopy is consistent with atrophic gastritis.  He is started on intramuscular cyanocobalamin, with the resulting changes shown in the graph below.  The blue curve most likely corresponds to which of the following parameters?

Quizplus · Accepted Answer

The graph shows the treatment response to vitamin B₁₂ (cyanocobalamin) in a patient with vitamin B₁₂ deficiency secondary to atrophic gastritis. Vitamin B₁₂ deficiency impairs nucleic acid metabolism, causing delayed nuclear maturation and reduced cell division of erythrocyte precursors in the bone marrow (megaloblastic anemia). Once vitamin B₁₂replacement therapy is begun, erythrocyte precursors begin to change from megaloblastic to normoblastic. As the rate of effective erythropoiesis increases, immature erythrocytes (reticulocytes) are released from the bone marrow into the bloodstream. The peripheral count of these reticulocytes begins rising within 3 to 4 days and peaks at around 1 week, as indicated by the blue curve. The reticulocyte response peaks early during vitamin replacement as the reticulocytes that are initially released are left-shifted and take longer to mature in the circulation than later reticulocytes. However, hemoglobin levels (~1 g/week) are slower to rise, and the anemia typically takes as long as 8 weeks to correct. (Choice A) The erythrocyte count curve would be expected to follow the contour of the hemoglobin curve as the total red blood cell pool returns to normal levels. (Choice B) In chronic atrophic gastritis, parietal cell loss results in profound hypochlorhydria, increased serum gastrin levels, and inadequate intrinsic factor production. This patient most likely has elevated gastrin levels that would be unaffected by vitamin B₁₂ replacement. (Choice C) Vitamin B₁₂ deficiency causes increased red cell breakdown due to ineffective erythropoiesis, and the resulting release of free hemoglobin leads to a decrease in serum haptoglobin levels. Haptoglobin levels would normalize (increase) with therapy. (Choice D) Homocysteine and methylmalonic acid levels are elevated in vitamin B₁₂ deficiency due to decreased metabolism. In contrast, only homocysteine is elevated in folate deficiency. Vitamin B₁₂ replacement would cause a reduction in homocysteine and methylmalonic acid levels. However, the blue curve shows a high initial peak before declining, which is more consistent with the reticulocyte response. Educational objective: Atrophic gastritis can result in profound hypochlorhydria, inadequate intrinsic factor production, vitamin B₁₂ deficiency, and elevated methylmalonic acid levels. The reticulocyte count increases dramatically once vitamin B₁₂ replacement therapy is initiated in an individual with pernicious anemia. Hemoglobin and erythrocyte count levels rise more gradually and take up to 8 weeks to normalize.

A 55-Year-Old Man Undergoing Evaluation for Fatigue and Exertional Dyspnea