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49 Cards in this Set
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Neutrophil Function
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Circulation-> margination-> diapedesis-> chemotaxis-> adherence-> phaygocytosis-> (phagosome)-> lysis or apoptosis
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selectins
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receptors that recognize carbohydrate moieties
one on blood vessel wall and one on PMN for reciprocal recog. |
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L-selectin and E-selectin
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L: leukocyte selctin
E: endothelial selectin (also P) |
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chemotactic factors for PMNs
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1. Proteins: complement (C3a, C5a), thrombin, kallikrein
2. Leukotrienes: LTA4, LTE4 3. peptides: N-formyl-methionyl-oligopeptide |
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opsonization
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neutrophils bind bavcteria through
antibody bridge (Fc-receptor-Ab) and complement bridge (CR1-C3b) |
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PMN: phagocytosis
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engulfing-> phagosome-> attracts lysosome-> merge-> phagolysosome
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PMN: Killing of bacteria
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Proteases: primary granules: myeloperoxidase, elastase AND secondary granules: lactoferrin, etc.
oxidative burst |
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oxidative burst
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Hexose shunt-> NADPH oxidase-> superoxide and H2O2-> oxygen radicals-> kill bacteria in lysozome
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myeloperoxidase deficiency
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no problem
unless w/ diabetes: poor circulation-> ^infection-> can have problems |
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inhibitors of oxygen radicals and proteases
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to minimize collateral damage
oxygen radicals: superoxide-> H2O2-> (catalase)-> water & Oxygen and H2O2-> (glutathione)-> water proteases: |
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proteases in oxy radical inhibition
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neutralized by
alpha1-antitrypsin, alpha2-macroglobulin, elafin, secretory leukoprotease inhibitor |
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Alpha1-antitrypsin
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there to protect body from digesting own tissues
made in liver, 2 alleles: MM: normal MZ: mild deficiency ZZ: uncontrolled protease activity |
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alpha1-antitrypsin deficiency
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MZ: cigarette smoke inactivates alpha1-antitr.-> collateral damage-> fibrous tissue in lungs-> can't expand-> barrel chest
emphysema and liver disease |
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alpha1-antitryp. deficiency diagnosis and treatment
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liver disease in ZZ children-> hepatic coma (can't clear toxins)
isoelectrc focusing finish alter |
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monocytes
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short-lived
small % inefficient in phagocytosis |
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macrophages
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Kuppfer cells:liver sinuses
Osteoclasts: bone Microglia: brain (HIV haven, MS) Alveolar macrophage: lung (Silica dust-> mesotheliomas) Dendritic cell: in L-Node for antigen processing |
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Vit B12
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=cobalamin
-> ^Homocysteine -> ^MM CoA -> v Folate |
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Folate deficiency
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megaloblastic anemia
big RBCs, oval shaped anemia, no neurological probs |
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Iron: char and defic
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xferrin(blood)-> ferritin in cytoplasm for "storage iron"
deficiency-> microcytic hypochromic anemia |
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red cell indices
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MCV: avg. vol of RBC (90 fL)
MCH: Hb in each RBC (30pg) MCHC: %RBC mass that's Hb (35%) PCV: 50% |
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Classical aplastic anemia
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-loss of CD34 cells
-50% idiopathic -dry bone tap -marrow xplant needed -maybe autoimmune? |
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Megaloblastic anemia: fxn prob, marrow char, RBC morpho, causes
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v DNA synthesis
hyperplastic, megaloblastic macrocytic RBCs Causes: v Cobalamin, v folate |
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Hypochromic anemia: fxn prob, marrow char, RBC morpho, causes
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v HB synthesis
hyperplastic, deficient Hbzation microcytic, hypochromic causes: Fe deficiency, chronic disease, THALASSEMIAS |
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cobalamin deficiency
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neurological probs
megaloblastic anemia |
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polycythemias
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2Ί or physiologic: hypoxia-> EPO-> RBCs released early
Vera: hypersensitivity to EPO (bleed them) |
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CML
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stem cell prolif->
^white blood cells, block of lymphoid cell creation philadelphia chromosome: abl-bcr (9-22) marrow xplant |
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AML
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acute myelogenous leukemia
^committed stem cells no chronic phase, need chemo-> marrow xplant |
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Howell Jolly Bodies
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when orthochromatic e-blasts don't get rid of all nucleus
-> trapped in spleen, destroyed no spleen-> see lots |
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reticulocytes
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1 day in circ before -> mature RBC
cytoplasmic RNA stains w/supravital dye .5 to 2% ^ w/ bleeding or hemolysis v w/ aplastic anemias & other v production issues |
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Rouleaux
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how RBCs are forced into central, fast stream in large BV
in small BV-> umbrella shape |
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RBC cytoskeleton components
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spectrin: most abundant, α & β chains
interlinked by actin, ankyrin & band 4.1, and band 3 |
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RBC destruction
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b/c they can't un-bend
extra (spleen) and intravascularly (blood stream) |
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extravascular hemolysis
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engulfed by Mphages in liver and spleen
globin chains and Fe stripped-> bilirubin-> liver-> excreted |
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intravascular destruction of RBC
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10% of RBCs
Haptoglobin binds Hb-> hepatic parenchyma Hemopexin binds heme-> catabolized by liver cells |
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Hereditary Spherocytosis
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spectrin defect-> obese, rigid RBCs
use osmotic fragility test treatment: splenectomy (b/c gettin caught in narrow spleen passages) |
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G-6-(P) DH deficiency
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no NADPH to protect RBCs from H2O2
x-linked look for Heinz bodies (denatured Hb precipitates) |
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Different Hbs
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adult: HbA: alpha2beta2
embryonic: Gower-1: E2zeta2 fetal: alpha2gamma2 HbA2: alpha2delta2 (3% adult) Hb Barts: gamma4: v alpha, ^O2 affinity HbH: beta4: = Barts, but unstable |
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α Thalassemia minor
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deletion of α genes
hypochromic, microcytic anemia |
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Hemoglobin H disease
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deletion of 3 α genes
embryonic Hb ok, but-> fetal Hb-> Hb Barts (γ4: useless)-> adult-> HbH (RBC w/ precipitates) microcytic hypochromic anemia, hemolysis |
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hydrops fetalis
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no alpha globin-> fatal in utero
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beta Thalassemias
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minor: pretty OK
major: homozygote, server anemia, w/ loss of HbF-> ^erythropoesis-> chipmunk face, etc. |
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sickle cell anemia
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Hb S, polymerizes
-> hemolysis, blockage Hb AS-> trait (carrier) |
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porphyrias
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early block: neuro and mental symptoms
AIP late: dermatological sensitivity PCT |
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eosinophils
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bilobed nucleus
participate in opsonization parasites: hydrolytic enzymes |
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basophils, mast cells
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in skin and mucosa
histamine, serotonin, L-trienes, etc. IgE (aillergEEEE!) receptors |
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neutrophil: margination
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epinephrine & corticosteroids cause demargination
IL-1 & TNF-α attract PMNs from BM to circ.-> L-selectin (leukocyte) on PMN binds BV and E-selectin (endothel.) binds PMN surface |
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neutrophil: diapedesis and chemotaxis
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ICAM-1 w/ E-selectin-> spreading-> makes openings betw. cells-> diapedesis
chemotactic factors (C3a, C5a, clotting factors, etc.) |
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Neutrphil: phagocytosis
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tethers Igs (@ Fab) to PMN (@Fc receptor)= opsonization
bactericidal agents released into phagolysosome |
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Neutrophil probs
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Chronic Granulamatous Disease (CGD): can't generate oxygen species to kill b/c no NADPH oxidase
Use NBT test to see if cells make H2O2, etc. |