Pathology 1 - Block 2 - Part 6

davidwurbel7's version from 2016-03-03 19:37

RBC Disorder III

Question Answer
Condition in which there is a mutation in spectrin, or mutation in ankyrin or both. Loss of red cell membraneHereditary Spherocytosis
Lab Investigations - Hb: decreased, Reticulocyte count: increased. Peripheral blood smear - normocytic anemia, spherocytes, red cells show absence of central pallor. Osmotic fragility test - increased osmotic fragility. Other tests - increased serum bilirubin, LDH: increasedHereditary Spherocytosis
This event is associated with acute parvovirus infection. The virus kills red cell progenitors and worsening anemia, reduced reticulocytesAplastic Crises
This event is associated with increased splenic destruction of spherocytes, enlarged tender spleen, increasing jaundice and darkening of urineHemolytic Crises
A rare, acquired disorder, chronic. Intravascular hemolysis, intermittent hemoglobinuria (occurs during the night). Acquired defect of red cell membraneParoxysmal Nocturnal Hemoglobinuria
In Paroxysmal Nocturnal Hemoglobinuria, hematopoietic stem cell acquire somatic mutation of thisPIGA (phosphatidylinositol glycan class A1)
PIGA is located on X chromosome which encodes for an enzyme that is essential component of a biosynthetic pathway that generates thisGPI (Glycosyl Phosphatidylinositol)
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Question Answer
Clinical features include Nocturnal hemoglobinuria - passage of red/brown urine in the morning (respiratory acidosis during night time augments complement attachment to cell), cyclic pattern; Chronic intravascular hemolysis. Most common feature (hemosiderinuria); Iron deficiency - iron loss in urine; Bleeding due to thrombocytopenia; Risk of thrombosis - due to release of aggregating factors from damaged platelets (hepatic vein/portal/cerebral)Paroxysmal Nocturnal Hemoglobinuria
Thrombosis occurring in the hepatic vein that may be fatalBudd Chiari Syndrome
Lab diagnosis - Hb: low at the time of diagnosis; Serum haptoglobin: decreased; Reticulocyte count: increased; Urine: hemoglobinuria, hemosiderinuria; Bone Marrow: hyperplastic, reduced iron stores. Other tests include Flow cytometry: detects granulocytes with missing anchors for inhibitors of complement. Screening test: sucrose hemolysis test. Confirmatory test: HAM testParoxysmal Nocturnal Hemoglobinuria
HbS: 40 to 45% HbA: 54 to 57% HbA2: 1 to 3%Heterozygous (Sickle Cell Trait)
HbS: 90 to 95% HbA: absent HbA2: 1 to 3% HbF: more than 5%Homozygous Sickle Cell Anemia
Lab investigations - Hb: decreased. Peripheral blood smear - normocytic, hypochromic, sickled cells (10 to 15%). Sickling test. Hb electrophoresisSickle Cell Anemia (HbS)
Observation of sickling of red cells containing HbS under cover slip when treated with 2% sodium metabisulfiteSickling Test
In the sickling test, this agent is used to remove oxygen from the area to induce sickling of the RBCs2% Sodium Metabisulfite
Sickle red cells express higher than normal levels of adhesion molecules, and are therefore sticky. Mediators release from granulocytes during inflammation up regulates expression of adhesion molecules on endothelial cells. This leads to stagnation of red cells in micro-circulationVaso-occlusive Crises
Vaso-occlusion of the vessels to the dorsal of hand and/or feet appear swollen, and painful. Micro-infarction of carpal and tarsal bones"Hand-foot" Syndrome (dactylitis)
Vaso-occlusive crises causing fever, cough, chest pain and pulmonary infiltrates, mostly seen in children. Infection with Streptococcus pneumoniae, Mycoplasma pneumonia follows lung infection, pulmonary blood flow becomes sluggish, associated with increased mortalityAcute Chest Syndrome
Vaso-occlusive crises causing seizures / strokes due to hypoxia. Catastrophic complication seen in children and young adults. Clinically: abrupt onset of hemiparesis/aphasia/seizures patients may make a complete recoveryVaso-Occlusive crises of the CNS
Vaso-occlusive crises causing loss of visual acuity or sometimes blindnessVaso-occlusive Retinopathy
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Question Answer
Massive sequestration of sickled cells in spleen. Rapid splenic enlargement, hypovolemia, and sometimes shock (dangerous). Seen in children (first 2 years of life). Must occur before spleen undergoes auto-infarction, and fibrosisSequestration Crisis
Transient bone marrow failure of erythropoiesis. infection by parvovirus B19 due to direct cytotoxicity of parvovirus to erythroid precursors (developing red cells in bone marrow). Worsening anemia and reduced reticulocyte countAplastic Crisis of HbS
This condition is characterized by sequestration crisis and aplastic crisisSickle Cell Disease
This condition is characterized by hemolytic crisis and aplastic crisisHereditary Spherocytosis
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Question Answer
Hereditary deficiency of G6PD, recessive X linked trait. Seen African Americans, Mediterranean variant (Italy/Greece). Males are at risk for symptomatic disease. Mild hemolysis mostly intravascular hemolysisG6PD Deficiency
Hb chain is oxidatized by reactive sulfhydryl group which becomes denatured, forms a membrane bound inclusionHeinz Body
Hemolysis follows oxidant stress. Drugs: anti malarials (primaquine, chloroquine, sulfonamides, nitrofurantoins). Infections: viral hepatitis, pneumonia, typhoid fever. Fava bean ingestion (favism): mostly in children between 2 to 5 yearsG6PD Deficiency
Lab diagnosis - Hb: decreased, mild to severe. Peripheral smear - normocytic anemia. Heinz bodies, bite cells. G6PD levels: low. Plasma Hb: increased (hemogobinemia). Haptoglobin: reduced. HemoglobinuriaG6PD Deficiency
Clinical features include features of acute hemolysis (2 to 3 days following oxidant stress & lasting about 7 days) and is associated with stress: drug administration (anti-malarial), infection, fava bean ingestionG6PD Deficiency