A 62-year-old man comes to the office due to worsening fatigue. The patient has long-standing type 2 diabetes mellitus complicated by nephropathy. Laboratory results are as follows: After appropriate treatment is initiated for his anemia, which of the following changes is most likely to occur in this patient's erythroid cells?

Question

A 62-year-old man comes to the office due to worsening fatigue.  The patient has long-standing type 2 diabetes mellitus complicated by nephropathy.  Laboratory results are as follows:  After appropriate treatment is initiated for his anemia, which of the following changes is most likely to occur in this patient's erythroid cells?

Quizplus · Accepted Answer

Patients with chronic kidney disease (CKD) often develop normocytic anemia as the glomerular filtration rate worsens due to inadequate production of erythropoietin (EPO), a glycoprotein hormone produced by peritubular fibroblast cells in the renal cortex. EPO is released into the bloodstream in response to renal tissue hypoxia and subsequently acts on erythrocyte progenitor cells (erythroid colony-forming unit cells) in the bone marrow to reduce apoptosis and increase differentiation into mature red blood cells. Although healthy individuals respond to anemia by increasing EPO levels up to 10,000-fold, patients with CKD have chronic inflammatory damage to renal EPO-producing cells and are often unable to generate sufficient levels of EPO to maintain adequate erythrocytosis. These individuals are often treated with synthetic forms of EPO (eg, epoetin, darbepoetin) to supplement intrinsic EPO production and stimulate erythropoiesis. Because synthetic forms of EPO can rapidly deplete iron stores (due to increased red blood cell production), patients should be tested for iron deficiency prior to treatment with these agents. (Choice A) Protoporphyrins (heme precursors) are elevated in patients with iron deficiency anemia. Treatment of iron deficiency anemia (eg, iron supplementation) leads to the conversion of protoporphyrins to heme, thereby reducing free protoporphyrin levels. Patients with iron deficiency anemia usually have low serum ferritin levels and transferrin saturation. (Choice B) Warm autoimmune hemolytic anemia is characterized by antibodies against antigens on the red cell membrane that result in phagocytosis in the reticuloendothelial system (eg, spleen). Autoimmune hemolytic anemia is usually treated with immune-suppressing agents (eg, prednisone), which blunt antibody production and reduce red cell destruction. This patient with a normal bilirubin level is unlikely to have hemolytic anemia. (Choice D) Sickle cell anemia is caused by mutations in the beta globin chain, which results in the polymerization of deoxygenated hemoglobin molecules ("sickling"). Treatment with hydroxyurea induces expression of fetal hemoglobin (which is unaffected by the sickle mutation) over adult hemoglobin, thereby preventing polymerization of hemoglobin molecules. (Choice E) Deficiency of vitamin B₁₂/folate (megaloblastic anemia) impairs nucleic acid metabolism, which results in slowed production of erythrocyte precursors in the bone marrow. Replacement of vitamin B₁₂/folate corrects the anemia by improving nuclear maturation. Megaloblastic anemia is typically associated with macrocytic (elevated mean corpuscular volume) anemia. Educational objective: Erythropoietin (EPO) is produced by peritubular fibroblast cells in the renal cortex in response to decreased renal oxygen delivery. EPO acts on erythrocyte precursors in the bone marrow to increase red blood cell production. Patients with chronic kidney disease often have damage to renal EPO-producing cells, which results in normocytic anemia. __________ References: Renal erythropoietin-producing cells in health and disease. (http://www.ncbi.nlm.nih.gov/pubmed/26089800)

A 62-Year-Old Man Comes to the Office Due to Worsening