MMSC 433 exam 1 latest version 2023

iron absorption - -ferric iron is taken in from diet -ferric iron is reduced by duodenal cytochrome B to become ferrous iron -ferrous iron is absorbed into enterocytes by DMT 1 -absorbed iron is stored as ferritin, or sent into portal hepatic circulation and carried by transferrin to developing RBCs transferrin - plasma carrier protein for ferrous iron high iron level regulation - -hepcidin is released from hepatocytes -ferroportin is inactivated, leading to decreased iron being transported into circulation low iron level regulation - -hepcidin is down regulated by hepatocytes -ferroportin becomes activated and transports iron out of the enterocytes and into circulation dietary iron sources - red meat, legumes, dark leafy vegetables, whole grains ferrous iron - the form of iron that is able to be utilized in the body for developing red cells prussian blue stain - stain that is used to identify iron in tissues and bone marrow thomas plot - a chart that is used to compare soluble transferrin receptors/ log ferritin to hemoglobin concentration of reticulocytes to identify the iron status of the patient -iron status is used to correlate to certain diseases/ anemias stage 1 iron deficiency (progressive loss of storage iron) - -asymptomatic -RBCs develop normally -*serum ferritin low* stage 2 iron deficiency (exhaustion of iron storage pool) - -subclinical symptoms -hemoglobin in retics is decreased, *hemogram appears normal still* -iron deficiency erythropoiesis is occurring -hepcidin decreased -serum iron and ferritin decreased -RDW, TIBC and sTRs increased -prussian blue stain of BM is negative for iron stage 3 iron deficiency (frank anemia) - -patient exhibits fatigue, weakness, pallor, glossitis, koilonychia and pica -*H/H decreased* -*hypochromic/ microcytic anemia* -FEP, TIBC and sTR increased -ferritin, hepcidin and serum iron decreased sideroblastic anemia - -iron deposits in the mitochondria of erythroblast cells in the bone marrow interfere with biosynthesis of heme -caused by genetic inheritance of drugs/ bone marrow toxins (*lead*, antibiotics, chemotherapeutics) -*ringed sideroblasts* are highly indicative of the disease -basophillic stippling is common in lead poisoning -normocytic normochromic cells iron deficiency anemia (IDA) - -caused by inadequate intake, increased need or malabsorption of iron, poor diet or chronic blood loss -symptoms: fatigue, weakness, pallor, spooning of the nails (koilonychia) and pica -*H/H decreased* -microcytic, hypochromic cells -marked poikilocytosis (target cells, spherocytes, tear drop cells and schistocytes) -FEP, sTR and TIBC increased -ferritin, hepcidin and serum iron decreased anemia of chronic inflammation - -anemia occurring secondary to underlying condition (chronic inflammatory disease, chronic infection or malignancy) that causes release of cell products -hepcidin, lactoferrin and inflammatory cytokines cause decreased iron status and anemia -low Hgb -*low TIBC* (hepcidin is increased due to acute phase reaction) -normocytic normochromic anemia -serum iron decreased -ferritin (acute phase reactant) and FEP increased hereditary hemochromatosis (HH) - -inheritance of mutated HFE gene inhibits production of hepcidin, leading to constant activation of ferroportin -increased levels of iron in circulation are exposed to oxygen and produce damaging superoxide ions -symptoms: begin between 30-40, iron deposits on organs (pancreas), bronzed diabetes, cell death, release of lysosomal enzymes -increased serum ferritin and transferrin saturation -genetic testing reveals mutated HFE gene hereditary hemochromatosis treatment - -therapeutic phlebotomy: 500 mL of blood is removed per week to decrease serum iron megaloblastic anemia - -impaired DNA synthesis due to deficiency of Vitamin B12 and/ or folate leads to decreased number of cell divisions -produces large macrocytes with immature nuclei -symptoms: fever, glossitis, loss of appetite, neurologic abnormalities (pins and needles, numbness, hallucinations and paranoia/ megaloblastic madness) -pancytopenia -decreased H/H -macrocytosis -increased MCV, high RDW -hypersegmented neutrophils -nuclear cytoplasmic asynchrony _M:E ratio 1:1 to 1:3 -teardrop cells, schistocytes and microspherocytes in PB -Howell jolly bodies (DNA remnants) and cabot rings (figure 8) -increased bilirubin and LDH G6PD deficiency - -decrase in G6PD enzyme causes underproduction of NADPH, leading to inability to reduce glutathione for detox of H2O2 -H2O2 oxidizes hemoglobin in the RBCs, leading to formation of *heinz bodies* -can be induced by oxidative drugs -symptoms: jaundice, anemia, hyperbilirubinemia -N/N anemia -anisocytosis, poikilocytosis -spherocytes and schistocytes in PB -*heinz bodies seen with crystal violet* -G6PD activity decreased -fluorescent spot test negative hereditary spherocytosis (HS) - -proteins in the RBC membrane disrupt *vertical* interactions and destabilize the lipid bilayer, causing loss of membrane material that leads to formation of spherocytes -mutations in genes for *ankyrin*, alpha and beta spectrin or protein 4.2 lead to increased membrane permeability to Na+ and K+, leading to cellular dehydration -splenic conditioning: abnormal RBCs are targeted by macrophages and lead to anemia -HS triad: N/N anemia, jaundice and splenomegaly -*spherocytes* and polychromasia in PB -increased MCHC and RDW -increased osmotic fragility -EMA binding test: low fluorescence -autohemolysis test: 10-50%, decreased in presence of glucose hereditary spherocytosis (HS) treatment - -splenectomy: prevents targeting of RBCs by splenic macrophages and keeps cells in circulation longer babesia - -tick transmitted disease -can be transmitted by transfusion of infected blood unit -symptoms: can be asymptomatic, fever, chills, headache, sweats, nausea, fatigue, jaundice, splenomegaly, hepatomegaly -H/H decreased