A 13-year-old girl is undergoing hematologic evaluation. She is found to have a hemoglobin mutation that changes the partial pressure of oxygen at which hemoglobin is 50% saturated to 20 mm Hg. In comparison, normal hemoglobin becomes 50% saturated with oxygen at 26 mm Hg. Which of the following sequelae is this patient most likely to develop as a result of her mutation?

Question

A 13-year-old girl is undergoing hematologic evaluation.  She is found to have a hemoglobin mutation that changes the partial pressure of oxygen at which hemoglobin is 50% saturated to 20 mm Hg.  In comparison, normal hemoglobin becomes 50% saturated with oxygen at 26 mm Hg.  Which of the following sequelae is this patient most likely to develop as a result of her mutation?

Quizplus · Accepted Answer

11ec160b_36e5_6f61_9249_8db1a6f44a6c_MD0001_00 The oxygen-hemoglobin dissociation curve describes the relationship between the partial pressure of oxygen in the blood and the oxygen saturation of hemoglobin. The partial pressure of oxygen at which hemoglobin is 50% saturated (P₅₀) is a value used as a conventional measure of hemoglobin's affinity for oxygen. The P₅₀ is about 26 mm Hg in normal individuals. A P₅₀ shift from 26 to 20 mm Hg indicates that the affinity of hemoglobin for oxygen is increased (left shift of the oxygen dissociation curve). Mutations that cause production of hemoglobin with high oxygen affinity (eg, hemoglobins Chesapeake and Kempsey) reduce the ability of hemoglobin to release oxygen within the peripheral tissues. Low oxygen levels stimulate the kidneys to increase erythropoietin synthesis, which results in a compensatory erythrocytosis that helps maintain normal oxygen delivery. Therefore, patients with high oxygen affinity hemoglobins are typically asymptomatic. (Choice B) Sickle cell disease can result in hypoxia-induced hemolysis due to the ability of deoxygenated hemoglobin S to polymerize and cause excessive erythrocyte sickling and irreversible cell membrane damage. The oxygen dissociation curve for hemoglobin S is shifted to the right (↓ oxygen affinity) due to the stabilizing effects of polymerization on the deoxygenated form. (Choice C) Hereditary spherocytosis results from a variety of molecular defects involving erythrocyte structural proteins responsible for linking the plasma membrane to the cytoskeleton (eg, spectrin, ankyrin). The resulting membrane instability leads to the formation of spherocytes - small, rounded erythrocytes with increased susceptibility to lyse in hypotonic solutions. (Choice D) Megaloblastic erythrocyte changes (↑ MCV) are characteristically seen in vitamin B₁₂ and folic acid deficiency due to impaired DNA synthesis. (Choice E) Individuals with glucose-6-phosphate dehydrogenase deficiency develop rapid hemolysis during periods of increased oxidant stress, such as when taking antimalarials or sulfonamides or after ingestion of fava beans. Educational objective: P₅₀ refers to the partial pressure of oxygen at which hemoglobin is 50% saturated. Hemoglobins with high oxygen affinity have a decreased P₅₀ that is represented by a leftward shift of the oxygen dissociation curve. The reduced ability to release oxygen within the peripheral tissues leads to renal hypoxia, increased erythropoietin synthesis, and compensatory erythrocytosis. __________ References: Hemoglobins with high oxygen affinity leading to erythrocytosis. New variants and new concepts. (http://www.ncbi.nlm.nih.gov/pubmed/15921161)

A 13-Year-Old Girl Is Undergoing Hematologic Evaluation