Osmotic fragility of RBCs are increased in:
Correct Answer: Hereditary Spherocytosis
Description: Ans: A (Hereditary Spherocytosis) Ref: Robbins Pathologic Basis of Disease, 8th editionExplanation:"In two thirds of the patients with Hereditary Spherocytosis, the red cells are abnormally sensitive to osmotic lysis when incubated in hypotonic salt solutions. which causes the influx of water into spherocytes with little margin for expansion "Ref: Robbins.Hereditary Spherocytosis (HS)This inherited disorder is caused by intrinsic defects in the red cell membrane skeleton.Red blood cells are spheroid, less deformable, and vulnerable to splenic sequestration and destruction.Majority of cases are autosomal dominant (75%).PathogenesisThe remarkable elasticity and durability of the normal red cell are attributable to the physicochemical properties of its specialized membrane skeleton which lies closely apposed to the internal surface of the plasma membrane.Its chief protein component, spectrin, consists of two polypeptide chains, a and b. which form intertwined (helical) flexible heterodimers.The "head" regions of spectrin dimers selfassociate to form tetramers, while the "tails" associate with actin oligomers.Each actin oligomer can bind multiple spectrin tetramers. thus creating a two-dimensional speetrin-aetin skeleton that is connected to the ceil membrane by two distinct interactions.The first, involving the proteins ankyrin and band 4.2. binds spectrin to the transmembrane ion transporter, band 3.The second, involving protein 4.1. binds the "tail" of spectrin to another transmembrane protein, glycophorin A,HS is caused by diverse mutations that lead to an insufficiency of membrane skeletal components.The life span of the affected red cells is decreased on average to 10 to 20 days (Normal -120 days)The pathogenic mutations most commonly affect ankyrin. band 3. spectrin, or band 4.2.Young HS red cells are normal in shape, but the deficiency of membrane skeleton reduces the stability of the lipid hiiayer, leading to the loss of membrane fragments as red cells age in the circulation.The loss of membrane relative to cytoplasm "forces" the cells to assume the smallest possible diameter for a given volume, namely, a sphere.The invariably beneficial effects of splenectomy prove that the spleen has a cardinal role in the premature demise of spherocytes.Normal red cells must undergo extreme deformation to leave the cords of Billroth and enter the sinusoids.Because of their spheroidal shape and reduced deformability, the hapless spherocytes are trapped in the splenic cords, where they provide a happy meal for phagocytes.After splenectomy the spherocytes persist, but the anemia is correctedMorphologyThe most specific morphologic finding is spherocytosis, apparent on smears as abnormally small, dark-staining (hyperchromic) red cells lacking the central zone of pallor.Spherocytosis is distinctive but not pathognomonic, since other forms of membrane loss, such as in autoimmune hemolytic anemias, also cause the formation of spherocytes.Other features are common to all hemolytic anemias. These include:ReticulocytosisMarrow erythroid hyperplasiaHemosiderosisMild jaundice.Cholelithiasis (pigment stones - 40% to 50% cases)Moderate splenic enlargementsSplenomegaly results from congestion of the cords of Billroth and increased numbers of phagocytes needed to clear the spherocytes.Clinical FeaturesThe diagnosis is based on family history, hematologic findings, and laboratory evidence.In two thirds of the patients the red cells are abnormally sensitive to osmotic lysis when incubated in hypotonic salt solutions, which causes the influx of water into spherocytes with little margin for expansion.HS red cells also have an increased mean cell hemoglobin concentration, due to dehydration caused by the loss of K+ and H2O.The characteristic clinical features are anemia, splenomegaly, and jaundice.The generally stable clinical course is sometimes punctuated by aplastic crises, usually triggered by an acute parvovirus infection.Parvovirus infects and kills red cell progenitors, causing red cell production to cease until an effective immune response commences, generally in 1 to 2 weeks.Because of the reduced life span of HS red cells, cessation of erythropoiesis for even short time periods leads to sudden worsening of the anemia.Transfusions may be necessary to support the patient until the immune response clears the infection.Hemolytic crises are produced by intercurrent events leading to increased splenic destruction of red cells (e.g., infectious mononucleosis); these are clinically less significant than aplastic crises.Gallstones, found in many patients, can also produce symptoms.Splenectomy treats the anemia and its complications, but brings with it the risk of sepsis. (See the following Figure)
Category:
Pathology
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