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61 Cards in this Set
- Front
- Back
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Erythrocytes
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Membrane contains chloride-bicarbonate antiport
- important in physiologic chloride shift, allowing RBCs to transport CO2 from the periphery to the lungs for elimination Chloride shift: many bicarb ions diffuse OUT of RBCs intok plasma; to maintain electrical neutrality, Cl- ions diffuse into RBCs to take their place. 1* cause of high RBC Cl- content in venous blood |
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Leukocytes
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Granulocytes = basophils, eosinophils, neutrophils
Mononuclear cells = lymphocytes, monocytes |
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Basophils
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Contain heparin, histamine, LTD-4
Found in BLOOD |
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Mast cell
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Degranulation --> histamine, heparin, eosinophil chemotactic factors
FOUND IN TISSUE |
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Caues of eosinophilia
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NAACP:
Neoplastic Asthma Allergic processes Collagen vascular dz Parasites |
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Neutrophils
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40-75% WBCs
Acute inflammatory response cell - PHAGOCYTIC w/ hydrolytic enzymes, lysozymes, lysozymes, myeloperoxidase, lactoferrin Hypersegmented in B12 defic Toxic granulations + Dohle Bodies (dilated ER) - reactive changes of neutrophils indicative of overwhelming infec's like bacterial sepsis |
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Platelet
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Dense granules = ADP, Ca2+
Alpha granules = vWF, fibrinogen |
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Dendritic cells
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Main inducers of 1* antibody response
If on skin = Langerhans cells Express on surface: MHC II FcR |
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Vascular endothelial cells
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Inside endothelial cells:
- vWF - thromboplastin = tissue factor (VII --> VIIa in extrinsic pathway) - tPA - PGI2 & NO --> decrease platelet aggregation On surface of endothelial cells: - thrombomodulin activates ProtC Activated ProtC cleaves & inactivates Va, VIIIa |
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Platelet adhesion to collagen
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Subendothelial collagen exposed
vWF binds to collagen Gp1b (on platelet surface) binds to vWF |
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Platelet-platelet adhesion
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Binding of ADP on platelet receptors --> insertion of GpIIb/IIIa on platelet membrane --> platelet cohesion
Increased aggregation w/ TXA2 released by platelets |
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Antithrombin III
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inactivates factors II, VII, IX, X, XI
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Pure Red Cell Aplasia
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Rare form of marrow failure
- marked hypoplasia of marrow erythroid cells w/ normal granulopoiesis and thrombopoiesis assoc w/ thymoma or parvoB19 infection |
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Fibrinolytic system
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Plasminogen --> Plasmin
* facilitated by kallikrein Fibrin --> Fibrin split products * facilitated by Plasmin |
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Microcytic, Hypochromic Anemia
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MCV<80
Fe2+ defic Thalassemias - target cells Lead poisoning |
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Macrocytic Anemia
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MCV>100
VitB12/folate defic Drugs that block DNA synth Marked reticulocytosis |
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Normocytic, Normochromic Anemia
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Acute hemorrhage
Enzyme defects - G6PD (XR), PK defic (AR) RBC membrane defects BM disorders Hemoglobinopathies Autoimmune hemolytic anemia Anemia of chronic disease |
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Hepcidin
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Low Fe --> inc hepcidin synth
Adeq Fe --> dec hepcidin synth |
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Haptoglobin
& LDH |
Dec Haptoglobin (binds free Hb)
& Inc sr LDH = RBC hemolysis |
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ACD
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Inc ferritin
Dec TIBC Inc cytokines (IL-1, IFN-y, TNF) --> Fe sequestered in macrophages, poor utilization for erythropoiesis |
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Ferritin
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Measure of storage Fe
Derived from total body pool in liver, spleen, marrow Dec in Fe-defic |
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Transferrin
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Transports iron through plasma
Inc synth in Fe-defic |
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Myelophthisic Anemia
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Inc. alk phosphatase
Hypercalcemia Leukoerythroblastic pattern All consequences of tumor = space occupying lesion ex. prostatic adenoCA (mets to bone or infection) |
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Hemoconcentration
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Dehydration --> Relative polycythemia
Usually you also see hypernatremia |
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Lead Poisoning
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Affected enzymes:
1. Ferrochelatase 2. ALA dehydratase Accumulated substrate in urine: 1. Coproporphyrin 2. ALA |
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Acute intermittent porphyria
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Affected enzymes:
1. Uroporphyrinogen I synthase Accumulated substrate in urine: 1. Porphobilinogen 2. d-ALA Sx's: Painful abd, pink urine, polyneuropathy, psychological disturbances, precipitated by drugs |
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Porphyria cutanea tarda
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Affected enzyme:
1. Uroporphyrinogen decarboxylase Accumulated substrate in urine: 1. Uroporphyrin (tea-colored) |
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Hb Synthesis
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Starting substrates:
Succinyl Co-A + Glycine |
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Hb synth
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Mitochondria:
1. ALA Synthase + B6 Succinyl coA + Glycine --> dAminolevulinic acid Cytosol: 2. ALA dehydratase dAminolevulinic acid --> Porphobilinogen 3. Porphobilinogen deaminase Porphobilinogen --> Pre-uroporphyrinogen |
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Hb synth
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4. Pre-uroporphyrinogen --> Uroporphyrinogen III
5. Uroporphyrinogen decarboxylase Uroporphyrinogen III --> Coproporphyrinogen MITOCHONDRIA: 6. Coproporphyrinogen --> Protoporphyrin |
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Hb synth
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Iron (ferritin) --> Trasferrin --> Fe2+
7. Ferrochelatase Protoporphyrin + Fe2 --> Heme 8. Heme + Globin --> Hb |
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Aplastic Anemia
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Pancytopenia
Causes: Radiation, Benzene, Chloramphenicol, Alkylating agents, Antimetabolites, Viral agents (B19, EBV, HIV), Fanconi's anemia |
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HbC
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Beta-chain mutation
Milder type of sickling than HbSS |
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Alpha thalassemia
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Underproduced alpha-globin chain
HbH = beta-4 tetramers; lack 3 alpha-globin genes HbBarts = gamma-4 tetramers; lack 4 alpha-globin genes |
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Beta-thalassemia
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Due to mutations in splicing sites and promoter sequences
Inc HbF and HbA2 Requires blood transfusions --> 2* hemochromatosis --> cardiac failure Marrow expansion --> skeletal deformities ("crew cut" skull) |
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Autoimmune anemia
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IgG = warm, CHRONIC
- SLE, CLL, drugs - extravascular hemolysis IgM = cold, ACUTE - triggered by cold, M. pneumoniae, mono - erythroblastosis fetalis |
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Paroxysmal nocturnal hemoglobinuria
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Intravascular hemolysis from lytic activity of complement
Impaired GPI anchor/decay-accelerating factor in RBC membrane PIGA gene mut |
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Hereditory spherocytosis
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Extravascular hemolysis
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Microangiopathic anemia
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Intravascular hemolysis
DIC TTP/HUS SLE malign HTN Schistocytes |
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TTP
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Platelet abnormality
sx's of classic pentad: 1. Neuro problems 2. Fever 3. Thrombocytopenia 4. MAHA 5. Acute renal failure Inher/acq defic of vWF metalloprotein ADAMST13) --> multimers of vWF --> aggreg & organ dysfxn |
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Defect in Platelet plug formation
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Inc. BT
1. Glanzmann's thrombasthenia = dec GpIIb/IIIa --> platelet-platelet aggregation defic 2. Bernard Soulier dz = dec Gp1b --> defect in platelet-collagen adhesion 3. vW dz = dec vWF --> defect in platelet-collagen adhesion |
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Desmopressin
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Inc vwF release from endothelial cells in 30-60 min
Good in surgery /mild defic to control bleeding ; not good to use in severe def |
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Hodgkin's Lymphoma
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RS cells
LOCALIZED SINGLE group of nodes - rare extranodal - CONTIGUOUS spread (stage = strongest px) constitutional sx's mediastinal lymphadenopathy 50% assoc w/ EBV bimodal distrib. |
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NHL
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HIV/immunosuppression related
MULTIPLE PERIPHREAL nodoes extranodal invovlemet is common NONCONTIGUOUS spread Majority involve B-cells Fewer constitutional signs/sx's |
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Sinus histiocytosis
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Immunologic response to cancer Ag
thus not all enlarged lymph nodes are metastatic |
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Leukemoid Reaction
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Marked leukocytosis and immature myeloid cells in peripheral blood --> exag response to infection
DIFFERENTIATE from CLL: alkaline phosphatase Inc = leukemoid Dec = CML (phil chr) Both have inc WBC |
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MALT lymphoma
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middle aged adults
at site of autoimmune/infectious stimulus (ex. H pylori or rugal folds) common sites - thyroid (hashimoto's), salivary glands (Sjogrens), stomach (H. pylori) Monoclonal in origin (=malignant) regress w/ antibiotic tx * Can transform to diffuse large B-cell lymphoma |
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Waldenstrom's macroglobulinemia
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M spike = IgM
hyperviscosity sx's no lytic bone lesions |
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MGUS
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monoclonal gammopathy of undetermined significance
- asymptomatic - M protein spike in absence of any assoc dz of B-cells - no BJ proteinuria - progress to MM in 20% pts |
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MM
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IgG or IgA overproduction
Characteristic sx's: 1. Normocytic/chromic anemia 2. IL-6 --> osteoclast activation --> bone resorption (pathologic fractures, soap bubble lytic lesions) - RANKL cytokine --> activates osteoclasts 3. Hypercalcemia 4. Monoclonal Ig 5. AL amyloid - apple green birefring 6. Renal failure |
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t(9;22)
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Philadelphia chr
bcr-abl hybrid uncontrolled tyrosine kinase of fusion gene |
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t(8;14)
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Burkitt's lymphoma
c-myc activation starry sky appearance EBV assoc |
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t(14:18)
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Follicular lymphoma
bcl-2 activation |
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t(15;17)
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M3 type of AML
Auer rods - peroxidase(+) cytoplasmic inclusions in granulocytes and myeloblasts greatly inc. circulating myeloblasts on peripheral smear responsive to all-trans retinoic acid |
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t(11;22)
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Ewing's sarcoma
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t(11;14)
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mantle cell lymphoma
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CLL/SLL
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older adults (>60y)
lymphadenopathy, hepatosplenomegaly indolent course inc smudge cells in peripheral blood smear warm Ab autoimmune hemolytic anemia NO BLAST PHASE |
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CML
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bcr-abl phil chr
inc neutrophils, metamyelocytes, basophils, splenomegaly may acclerate to AML or ALL via BLAST CRISIS L-shift with all stages of myeloid maturation on peripheral smear VERY LOW leukocyte alkaline phosphatase (v. leukemoid rxn) Responsive to imatinib (anti bcr-abl) |
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Hairy cell leukemia
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TRAP stain (+)
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Langerhans cell histiocytoses
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Prolif disorder of dendritic cells from monocyte lineage
Defective cells express S100 & CD1a Birbeck granules gen sx's: seborrheic skin eruptions, fever, recurrent otitis media infec's, lymphadenopathy, hepatomegaly, splenomegaly Letterer-Siew dz = lytic skull lesions Hand-Schuller-Christian dz = exophthalmos, diab insipidus Eosinophilic granulomas |
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Myelodysplasia
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Cellular marrow w/ maturation defects in MULTIPLE lesions
- jak2 mut's implicated in myeloprof disorders other than CML (polycy vera, essential thrombocytosis, myelofibrosis) Failure of hematop. cells to mature normally --> not released into peripheral blood --> pancytopenia --> susceptible to infections clonal cell disorders can be due to: 1. de novo 2. post tx w/ alkylating agents = 5q deletion |
