RBC Disorders

reduction in red cell mass with consequent decrease in oxygen transport capacity of the blood

• 1. red cell count
• 2. hemoglobin concentration
• 3. hematocrit

increase in red cell mass

• 1. RBC (blood) loss
• 2. decreased RBC survival
• 3. decreased RBC production

characterized by shortened red cell survival and retention of products of red cell destruction (iron).

• rbcs are destroyed in circulation. Hb released from RBC bind to haptoglobin and cleared from circulation by the liver. decrease in serum haptoglobin is a key feature of intravascular hemolysis.
• when Hb levels exceed haptoglobin, free Hb is excreted in the urine (hemoglobinuria).

• destruction of RBCs in the reticuloendothelial system (spleen, liver). examples include hereditary spherocytosis, sickle cell, and erythroblastosis fetalis.
• Hb breakdown products are increased (hyperbilirubinemia) and jaundice may result. spleen and liver become enlarged. chronic elevated levels of bilirubin can cause gallstones.

intrinsic defects are usually inherited while extrinsic defects are usually acquired.

• 1. membrane defects
• 2. abnormal Hb
• 3. lack of globin chains
• 4. metabolic defect

• an autosomal dominant inherited defect in the red cell membrane that results in less deformability of RBC causing them to be sequestered and destroyed in the spleen (extravascular hemolysis). the specific defect is usually a qualitative or quantitative deficiency of spectrin (cytoskeletal protein).
• Example: hereditary spherocytosis

an autosomal codominant single amino acid substitution inherited disorder in the structure of globin chain that causes Hb to gel upon deoxygenation. under low oxygen conditions, the abnormal Hb polymerizes causing the RBC to form into a sickle shape. the sickled cells are rigid and prone to splenic sequestration (decreased survival) and can also block microcirculation causing ischemia and/or infarction.

• inherited autosomal codominant (deletion mutation or mRNA instability) disorder causing diminished or absent synthesis of either the alpha or beta globin chains of Hb.
• Example: thalassemia (extravascular hemolysis) - reduced globin chain amounts causes decreased Hb. anemia is principal clinical manifestation.

x-linked inherited defect causing G6PD deficiency in which red cells are susceptible to oxidant injury by drugs or toxins. denaturation of oxidized Hb causes it to precipitate within the cell and attach to the RBC membrane. RBC membrane flexibility is reduced and causes extravascular hemolysis. this is asymptomatic in absence of oxidant.

• example: erythroblastosis fetalis.
• blood group incompatibility between mother and fetus. fetal RBC express antigens inherited from the father that are not present in the mother. the mother's immune system creates antibodies (IgG) that cross the placenta and attach to fetal RBCs resulting in extravascular hemolysis in the fetus.
• Rh- mothers are giving anti-D within 72 hours of delivering an Rh+ fetus. anti-D binds to the Rh+ fetal RBCs and removes them from maternal circulation before the mother can generate an antibody response and become sensitized.

• 1. erythroblastosis fetalis
• 2. hemolytic transfusion reaction - transfusion of incompatible RBCs into a sensitized patient resulting in binding of Ab to RBC Ag causing immediate intravascular hemolysis
• 3. autoimmune hemolysis

RBCs are disrupted by physical trauma as they pass through areas of turbulence and abnormal pressure related to abnormal valve function (can be due to a cardiac valve prosthesis). an example is DIC where RBCs are lysed as they pass through fibrin clots/strands in the microcirculation

malaria: parasites infect RBC and cause lysis of RBC during maturation

• 1. iron deficiency
• 2. B12 deficiency
• 3. folate deficiency

red cells are smaller and contain less Hb than usual. most common cause of anemia worldwide.

caused by a B12/folate deficiency. both are involved directly or as cofactors for thymidine production. impaired dna synthesis causes a delay in mitotic division causing increased nuclear size but normal RNA synthesis and cytoplasmic maturation. the end result is an abnormally large red cell precursor (megaloblast), decreased production of mature RBCs and abnormally large red cells. the megaloblasts accumulate in the bone marrow, releasing too few RBCs into peripheral blood and causing anemia.

• stem cell abnormality resulting in decreased red cell production and all cellular elements of the blood (pancytopenia). usually idopathic but viruses (hepatitis), drugs (chloramphenicol) and toxins (benzene, radiation have been implicated
• two theories of pathogenesis: acquired defect in stem cell production or suppression of stem cells by T-lymphocytes

normal elements of marrow are crowded out by a tumor of fibrosis leading to decreased production of red cells.