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37 Cards in this Set
- Front
- Back
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Common features of hemolytic anemias |
-RBC life span less than 120 day normal -Elevated erythropoietin levels/compensatory rise increase in erythropoiesis -Accumulation of Hb degradation products created as a part of hemolysis |
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Where does hemolysis occur? |
Macrophages within the spleen, liver, and bone marrow |
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What triggers hemolysis? |
Age-dependent changes in red cell surface proteins. In hemolytic anemias, premature degradation occurs frequently in phagocytes |
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Extravascular hemolysis |
RBC premature destruction in phagocytes. If persistent hyperplasia of phagocytes leads to splenomegaly (splenic cords) |
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What causes extravascular hemolysis? |
Generally, alterations in the red cell that make them less deformable - |
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Clinical features of extravascular hemolysis |
-Anemia -Splenomegaly -Jaundice -Variable decreases in plasma haptoglobin leading to increased urine Hb -Tx is splenectomy |
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Intravascular hemolysis and why it occurs |
-Less commonly the dominant hemolytic pathway -Mechanical injury (trauma d/t cardiac valves, thrombotic narrowing of microvasculature, repetitive physical trauma) -Complement fixation (Ab recognition of RBC) -intracellular parasites (Falciparum malaria) -Exogenous toxic factors (clostroidal sepsis which releases enzymes that digest RBC membrane |
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Manifestations of intravascular hemolysis |
-Anemia -Hemoglobinemia -Hemoglobinuria -Hemosiderinuria -Jaundice |
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Haptoglobin and intravascular hemolysis |
Serum haptoglobin is depleted after heavy lysis levels, and free Hb is oxidized to methemoglobin. While proximal tubule can absorb and fix some of this, still will see dark brown urine. Iron accumulation in renal PT cells = renal hemosiderosis, and excess bilirubin from haptoglobin complexes= jaundice. NO SPLENOMEGALY |
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Serum bilirubin and ALL anemias |
Excess is always unconjugated (indirect) -Level of hyperbilirubinemia is dependent on rate of hemolysis and functional capacity of liver -If liver is fine, unlikely to see severe jaundice, but increased fecal urobilin and gallstones occur |
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Hereditary spherocytosis |
-RBCs are spheroid and less deformable, tagging them for splenic hemolysis -Autosomal dominant that leads to diverse mutations leading to insufficiency of RBC membrane components (ankyrin, spectrin, band 3 or 4.2) -Life span more like 100-110 days -Destabilized lipid bilayer prefers spherical shape once shedded components |
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Tx for HS |
Splenectomy. Spherocytosis still occurs, but anemia does not Increased risk of sepsis since spleen is blood borne bacteria killer |
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Clinical features of HS |
-Dx based on family history, hematologic findings, and laboratory evidence. -Osmotic lysis w/ hypotonic salt solutions -RBCs have increased average cell Hb concentration d/t loss of K+ and water -ANEMIA, SPLENOMEGALY, JAUNDICE -Aplastic crisis- Parvovirus causes death of RBC progenitors and anemia worsens Hemolytic crisis- Mono makes it worse |
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G6PDH deficiency |
-Lead to problems in HMP shunt and Glutathione metabolism decrease RBC ability to protect self from oxidative injury -Recessive X linked Trait -G6PD- and G6PDM for plasmodium facliparum protection. Older cells more marked for degradation |
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Why does episodic hemolysis happen w/ G6PD deficiency |
-Exposures that generate oxidative stress -Infections (viral hepatitis, pneumonia, typhoid) -Drugs (antimalarials (primaquine, chlorquine), sulfonamides, nitrofurantoins) -Food (Fava beans in G6PDM) |
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G6PD deficiency and Heinz Bodies |
-After oxidant exposure, Sulfhydryl groups on globin chains crosslink |
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2-3 Days after oxidant exposure in G6PD deficient individuals |
Acute intravascular hemolysis marked by anemia, hemoglobinemia, and hemoglobinuria. Hemolysis is greater in G6PDM. Self limiting when only young cells remain. |
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Sickle Cell Disease |
Hemoglobinopathy caused by point mutation in B globin that promotes polymerization of deoxygenated hemoglobin -Leads to red cell distortion, hemolytic anemia, microvascular occlusion, and ischemic tissue damage |
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What is the Hb variant in SCD |
HbS which is point mutation in sixth codon resulting in replacement of glutamate residue with valine residue |
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Heterozygous for HbS |
Sickle cell trait. 2 heterozygotes have 1/4 chance of homozygosity in offspring. |
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Sickle cell disease |
Homozygotes for HbS (a2bs2). Protection against endemic malaria. Parasite densities lower in AS than AA and AA more likely to contract and die from malaria infection. |
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Parasitic effect SCD |
Intracellular parasites consume O2 and decrease intracellular pH- promoting sickling. Sickling impairs PfEMP-1 protein from parasite |
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Clinical features SCD |
-Moderately severe hemolytic anemia (hematocrit 18%-30%) -Associated w/ reticulocytosis, hyperbilirubinemia, and irreversibly sickled cells -Pain crises- episodes of hypoxic injury and infarction of tissues (bones brain liver spleen lungs penis) |
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Thalassemia |
-Microcytic hypochromic anemias caused by mutations in either Hb chain -Autosomal codominant -B Thal- unpaired a globin chains form aggregates that damage red cell precursors |
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B thalassemia problems |
-Insoluble aglobin aggregates -Ineffective erythropoiesis d/t erythroblasts dying in bone marrow -Hypochromic red cell -EXTRAVASCULAR HEMOLYSIS -Systemic Iron Overload (secondary hemochromotosis) -Skeletal deformities d/t marrow expanison |
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A thalassemia problem |
Hydrops fetalis - deletion all 4 a globin genes -Lifelong dependence blood transfusion |
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Immunohemolytic anemias |
-Antibodies against either normal red cell constituents or antigens modified by haptins -Ab binding results in either red cell opsonization and extravascular hemolysis most commonly -Less commonly, complement fixation and intravascular hemolysis |
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Megaloblastic Anemia |
Impairment of DNA synthesis that leads to ineffective hematopoiesis and abnormally large erythroid precursors and red cells |
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Causes of Megaloblastic anemia |
-VB12 deficiency -Folic Acid Deficiency -Unresponsive to VB12 or Folic Acid therapy -Both are coenzymes required for the synthesis of thymidine |
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Common morphology among all megaloblastic anemias |
-MACRO-OVALOCYTES -Nuclear hypersegmentation -Giant metamyelocytes and band forms |
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Pernicious Anemia |
Megaloblastic anemia caused by autoimmune gastritis that impairs production of intrinsic factor required for VB12 uptake from gut |
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VB12 Deficiency causes/effects |
-Decreased intake- inadequate diet or vegetarianism -Impaired absorption- IF deficiency causing pernicious anemia and gastrectomy d/t compensation attempt. Malsborption states, diffuse intestinal disease (lymphoma/systemic sclerosis), ileal resection, ileitis, Parasitic uptake, fish tapeworm, bacterial overgrowth in blind loops and diverticula |
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Folic Acid deficiency causes/effects |
-Decreased intake- inadequate diet, alcoholism, infancy, Antoconvulsants, oral contraceptives, hemodialysis -Increased requirement- Pregnancy, infancy, disseminated cancer, increased hematopoiesis -Folic acid antagonists |
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Pernicious anemia morphology and signs |
Fundic gland atrophy, intestinalization, atrophic glossitis, CNS lesions of dorsal/lateral spinal trcats |
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Shared blood levels? |
Serum homocyteine levels up, methylmalonate normal, Folate def- no neuro changes |
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IDA |
Iron deficiency most common nutritional deficiency in the world. Iron absorption regulated by hepcidin from liver in response to increases in intrahepatic iron Can result from 1. dietary lack 2. impaired absorption 3. increased requirement 4. chronic blood loss |
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Clinical features IDA |
Disappearance of stainable iron from macrophages of bone marrow Microcytic, hypochromic Narrow rim peripheral hemoglobin and pencil cells |
