Mkgrady8 Gpmdc Anemias 2

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definition of anemia

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a reduction in the oxygen transporting capacity of blood which usually stems from a reduction of the total circulating red cell mass to below normal amount

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causes of anemia

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blood loss (hemorrhage); increased red cell destruction (hemolysis); decreased red cell production

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what is the anemia resulting from acute blood loss called? how do you recover?

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hypovolemia (shock) rather than anemia; normocytic/normochromic anemia; recovery is enhanced by a rise in the erythropoietin within several days; the onset of the marrow response is marked by reticulocytosis

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what about is the blood loss is chronic

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iron stores are gradually depleted which is essential for hemoglobin synthesis and effective erythropoiesis and its deficiency leads to a chronic anemia of underproduction

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the hemolytic anemias: what is the cause?

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remember normal red cells have a life span of 120 days; anemias that are associated with accelerated destruction of red cells are termed hemolytic anemias; destruction can be caused by either intracorpuscular red cell defects, which are usually inherited, or extracorpuscular factors, which are usually aquired

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general features of hemolytic anemias

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an increased rate of red cell destruction; marked erythroid hyperplasia within the marrow and an increased reticulocyte count in peripheral blood; the retention of the products of red cell destruction (including iron) by the body; in severe hemolytic anemias, extramedullary hematopoiesis often develops in the spleen, liver, and lymph nodes

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hereditary spherocytosis: what is it, presentation

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AD; cell skeleton defect; pts with anemia, jaundice, splenomegaly (they are abnormal so the spleen tries to get rid of them) and gall bladder stones; increased MCHC (mean corpuscular hemoglobin concentration); increased osmotic fragility (burst faster when placed in a hypotonic solution (they're spheres so they don't have as much capacity to expand)); how can you tell on smear? there is no central pallor (they're spheres and not donuts)

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hereditary elliptocytosis: what do the cells look like

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red blood cells appear hot dog shaped

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sickle cell anemia: what causes it

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the most prevalent hemoglobinopathy; mutation in the B globin chain gene that creates sickle hemoglobin (HbS); substitution of valine for glutamic acid at the 6th position of the B chain produces HbS; in homozygous all HbA is replaced by HbS whereas in heterozygous only about half is replaced

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sickle cell anemia: incidence

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about 8% of american blacks are heterozygous for HbS; in parts of africa where malaria is endemic the gene frequency approaches 30% as a result significant protective effect of HbS against plasmodium falciparum malaria; in US sickle cell anemia affects about one in every 600 blacks; worldwide sickle cell anemia is the most common form of familial hemolytic anemia

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sickle cell anemia: mean life span of RBCs, sickled cell characteristics, what can happen in those affected

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severe chronic extravascular hemolytic anemia; the mean life span of RBCs averages only 20 days (1/6 of normal); most Hgb is HgbS; deoxygenation results in sickling which is initially reversible but membrane damage occurs with each episode and eventually the cells accumulate Ca, lose K and H2O, and become irreversibly sickled; irreversibly sickled cells sequestered and destroyed in spleen (extravascular hemolysis); aplasic crisis (overworked BM shuts down)/parvovirus B19; sequestration crisis (children with splenomegaly

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sickle cell anemia: other clinical features

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bone marrow hypercellular (it's trying); marrow expansion; vascular congestion, thrombosis, and infarction can affect any organ, including bones, liver, kidney, retina, brain, lung and skin; susceptible to blood borne infections (splenic dysfunction in children and adults); prone to infections by S pneumoniae and H influenzae (encapsulated organisms; why? because the spleen is the best killers of these and here the spleen is overworked so can't help as much); septicemia and meningitis common causes of death; salmonella osteomyelitis also a problem; vascular crisis= very painful, acute chest syndrome, triggered by pulmonary infections or fat emboli from necrotic marrow, stroke, seizures, heat and kidney involvement, leg ulcers

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the effect of the various Hb types on this sickling

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HbA slows the rate of polymerization as it interacts weakly with the deoxygenated HbS; HbF interacts more weakly with HbS (newborns); HbC, another B globin, has a greater tendency to aggregate with HbS and those with HbS and HbC (called HbSC disease) are symptomatic

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other variables influencing sickling

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red cell dehydration increases Hb concentration and facilitates sickling and trigger occlusion of small BVs; conversely the coexistence of alpha thalassemia reduces the Hb concentration and the severity of sickling; low O2 tension (hypoxia) and sluggish blood flow as in microvascular beds increase sickling; inflamed tissues have slow blood flow making sickling more likely

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sickle cell trait: rate in pop

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the heterozygous condition; 8% of black americans; protects against malarial infection; 30% heterozygosity in endemic areas; normally asymptomatic

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sickle cell: treatment

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hydroxyurea, a gentle inhibitor of DNA synthesis, has been shown to reduce pain crises and decreases the anemia; it increases the red cell levels of HbF; acts as an anti inflammatory agent by inhibiting the production of white cells; increase the MCV; oxidized by heme groups to produce NO which is a potent vasodilator and inhibitor of platelet aggregation

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thalassemias: what are they, what are the names of the 2

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a heterogeneous groups of inherited disorders caused by mutation that decrease the rate of synthesis of either alpha or beta globin chains; as a consequence there is a deficiency of hemoglobin, with additional secondary red cell abnormalities caused by the relative excess of the other unaffected globin chain; alpha thalassemias and beta thalassemias

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alpha thalassemias: the 4 forms of the disease, newborns versus adults

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silent carrier state (1 gene deletion) (asymptomatic, normal red cells), alpha thal trait (2 gene deletion) (similar to beta thalassemia trait), Hgb H disease (3 gene deletion) (moderately severe anemia), hydrops fetalis (4 gene deletion) (fatal in utero); newborns excess unpaired gamma chains form tetramers (Hgb Barts); adults excess unpaired beta chains form tetramers (Hgb H); both HbH and Hb Bart have an abnormally high affinity for O2 which renders them ineffective at delivering O2 to the tissue; severity correlates to number of gene deletions

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beta thalassemias: where is it found, what forms

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highest frequency in mediterranean, african, and southeast asia; heterozygosity protects agaisnt malaria; large number of variants but the important ones: beta thal minor (causes microcytosis and minimal or no anemia and no abnormal physical signs), thalassemia intermedia (severe but no transfusion requires), thalassemia major (Cooley's anemia) (severe requires blood transfusion regularly); like alpha thals, often misdiagnosed as iron deficiency anemia

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beta thalassemias: physical findings

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peripheral smear shows= microcytic/hypochromic, marked anisocytosis (RBCs are not al the same size), target cells (look like a bull's eye), nucleated RBCs, basophilic stippling, Hb electrophoresis shows decrease or absence of HbA (because not making beta chain) and increased HbF; skeletal deformities- it wants to make RBCs for you soo badly and increases in size but it just can't make them correctly); splenomegaly (again tries to eat bad cells), hepatomegaly, and lymphadenopathy; cachexia; serum iron and ferritin increased, severe hemosiderosis; can have secondary hemochromatosis (too much iron on the RBCs due to abnormal chain)

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G6PD: what is it, what do you see on smear

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a hemolytic anemia; X linked disorder; pts have hemolysis after exposure to oxidant stress; abnormality of the hexose monophosphate shunt; pts are resistant to malaria infection; smear shows heinz bodies (RBCs look like they have dots of ketchup in them) and bite cells (RBCs that look like someone took a nibble)

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2 other hemolytic anemias that are due to acquired RBC membrane defects

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paroxysmal nocturnal hemoglobinuria (PNH) and paroxysmal cold hemoglobinuria (PCH)

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paroxysmal nocturnal hemoglobinuria (PNH)

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rare, acquired stem cell disorder; RBCs, grans and plt prone to complement mediated lysis (membrane protein deficiency); hemolysis episodic and worse at night (resp rate is slower and so increased CO2 which causes the complement to activate and destroy the RBCs); sucrose hemolysis test and Ham's test; median survival 10 yrs

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antibody mediated hemolysis

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isohemagglutinins and autoimmune hemolytic anemias

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isohemagglutinins

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preformed antibodies to non self antigens; transfusion reactions and HDN (hemolytic disease of newborn)

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autoimmune hemolytic anemias

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warm type= 60% idiopathic, drugs, lymphomas, SLE etc, IgG bind at 37 degrees C; cold agglutin type= mycoplasma infection and EBV (ebstein barr virus), IgM bind in cold, Reynaud's

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paroxysmal cold hemoglobinuria (PCH)

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acute intermittent massive hemolysis in cold; IgG against P blood group antigen; binds complement at low temp; resulting complement activation and intravascular hemolysis at body temp (when you try to warm yourself up it DESTROYS you); biphasic antibody called Donath-Landsteiner antibody; associated with measels, mumps, viral, flu like, self limiting

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other causes of hemolytic anemia

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mechanical trauma to RBCs; microangiopathic hemolytic anemias (MAHA)= DIC (disseminated intravascular coagulopathy), HUS (hemolytic uremic syndrome), TTP (thrombotic thrombocytopenic purpura); macroangiopathic hemolytic anemias (mechanical heart valves); infections= malaria, babesiosis; chemical injury (lead poisoning)

Front 29

how do we look at the types of hemoglobin in the blood?

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SHE SAID WAKE UP BECAUSE WE NEED TO UNDERSTAND THIS; hemoglobin electrophoresis or the most prevalent sickle hemoglobinopathies; A (for alkaline)= cellulose acetate at alkaline pH where the hemoglobins move from the cathode to the anode, order is A, F, S, C (a fat santa klaus), in this one a lot of things (all the baddies) migrate under S so if you get a band you need to do B where only S migrates to S) (so A is ONLY a screening test and need B to confirm) (if you only get a big A band and a C band then the person is fine, you worry when they have any banding at S); B (for... acid)= citrate agar at acid pH where the hemoglobins move from anode to cathode; separating different hemoglobins based on charge; SHE SAID SHES NOT GOING TO MOVE UNTIL YOU GET IT