-In stomach, partieal cells produce HCL and IF -gastric acid converts pepsinogen to pepsin -pepsin frees B12 from ingested proteins, intrinsic factor (synthesized by parietal cells) binds to B12 -IF-B12 complex is reabsorbed in the terminal ileum
Vitamine B12 deficiency causes?
-folate is converted into monoglutamates by intestinal conjugate (which can be inhibited by phenytoin) -monoglutamates are reabsorbed in the jejunum (reabsorption can be inhibited by alcohol and oral contraceptives)
-pancytopenia = decreased RBC's, WBC's, AND platelets
Aplastic anemia -C?
-fever (d/t infection from neutropenia) -bleeding (d/t thrombocytopenia (low platelets)) -hypocellular bone marrow
Aplastic anemia -P?
Antigenic alteration of myeloid stem cells -> T cell activation & release of cytokins that SUPPRESSES myeloid stem cells
Bone marrow is damaged = makes NO cells
Chronic renal failure -blood effects?
-causes decreased EPO production --> normocytic anemia -burr cells -platelet dysfunction = prolonged bleeding time
Aplastic anemia -E?
-can be d/t drugs, chemical agents, infection, radiation, malignancy
Intrinsic vs. Extrinsic hemolytic anemia:
-defect in RBC causes anemia lead to hemolysis -factors outside RBC lead to hemolysis
RBC's hemolyzed in the spleen & liver --> increase in unconjugated bilirubin (an end product of MACROphage degradation of Hb) --> jaundice
hemolysis WITHIN blood vessels -causes decreased serum haptoglobin , and hemoglobinuria
an acute phase reactant that combines with Hb to form a complex that is degraded by macrophages
-lots of hemolysis = more haptoglobin bound to it, then phagocytosed = decreased haptoglobin level in blood during intravascular hemolysis
-jaundice not produced because NOT much unconjugated bili is produced
Hereditary spherocytosis -E?
autosomal dominant -intrinsic defect with extravascular hemolysis -mutation in ankyrin cell membrane = dysfunctional Na+/K+atpase pump = cells more permeable to Na = sphereocytes
Hereditary spherocytosis -Rx?
Hereditary elliptocytosis -P?
autosomal dominant -defective spectrin and band 4.1
Hereditary elliptocytosis -T?
Paroxysymal ncoturnal hemoglobinuria -P?
Acquired defect in myeloid stem cells -mutation casues loss of anchor for decay accelerating factor = unstable C3 and C5 convertase, that adhere;s to RBC's platelets and neutrophils -At NIGHT, respiratory acidosis --> complement mediated lysis of RBC's neutrophils, and platelets -intrinsic defects, intravascular hemolysis
Paroxysymal ncoturnal hemoglobinuria -C?
Sickle Cell anemia -E?
autosomal recessive -d/t missense point mutation, valine substituted for glutamic acid at sixth position of the Beta globin chain
Why no sickling for the first 6 months of life?
HbF prevents sickling
Sickle Cell anemia -hand and foot syndrome=
painful swelling of feet and hands d/t bone infarcts, usually occurs in infants
Sickle Cell anemia -acute chest=
Chest pain, wheezing, and dyspnea -d/t pneumonia, infarction, or fat embolism
Howell Jolly bodies=
nuclear remnants in RBC's -occurs in sickled cell d/t loss of function of macrophages in spleen (autosplenectomy)
-protective against plasmodium falciparum malaria -decreased synthesis of NADPH and GSH --> oxidation of Hb --> Heinz bodies
Heniz bodies get removed -> bite cells
G6DP deficiency -C/L?
-Episodic hemolytic anemia, often after exposure to oxidant stress (Fava beans, drugs (primaquine, dapsone, sulfonamides, nitrofuranotoin) -presents as sudden onset back pain with hemoglobinuria 2-3 days after oxidant stress
Pyruvate kinase deficiency -E?
Pyruvate kinase deficiency -P?
causes intrinsic defect with extravascular hemolysis
Pyruvate kinase deficiency -C/L?
Jaundice beginning at birth -increased in 2,3 BPG causing Right shift -RBC's with thorny projections (echinocytes)