Heme Onc - 3 of 4

arold001's version from 2015-12-22 06:40

Section 1

Question Answer
what 2 drugs inhibit ADP-induced expression of gpIIb/IIIa?Ticlopidine and Clopidogrel
acanthocyte (acantho = spiny) = spur cell is associated with?liver disease and abetalipoproteinemia
what 3 diseases are associated with basophilic stippling? (TAL)thalassemia, anemia of chronic disease, lead poisoning
bite cellG6PD deficiency = decreased G6PD --> decreased NADPH --> decreased reduced glutathione --> oxidative injury --> intravascular hemolysis
macro-ovalocytemegaloblastic anemia and marrow failure
tear drop RBCbone marrow infiltration (myelofibrosis) = RBC sheds a TEAR bc its forced out of its home in bone marrow
target cell is associated with what 4 diseases? (HALT)Hemoglobin C, Asplenia, Liver disease, Thalassemia
whats the early and late presentation of anemia of chronic disease?first presents as NORMOCYTIC anemia and then presents as MICROCYTIC anemia
name 3 nonhemolytic normocytic anemias?1) anemia of chronic disease (early)
2) aplastic anemia
3) chronic kidney disease
name 5 normocytic INTRINSIC hemolytic anemia1) hereditary spherocytosis
2) G6PD defiency
3) Hb C
4) Sickle cell anemia
5) PNH
name 3 megaloblastic anemias?folate deficiency, vit B12 deficiency, OROTIC ACIDURIA
whats the triad of Plummer Vinson?iron deficiency anemia, esophageal webs, atrophic glosstis
what chromosome are the 4 alpha genes of alpha thalassemia?chromosome 16
what is Hb Barts composed of?gamma tetramere = 4 alpha deletions
what chromosome are the 2 beta genes on?chromosome 11
What 2 diseases do you see crew cut?sickle cell anemia and thalassemia
electrophoresis shows increased HbA2?beta-thalassemia MINOR (a2d2)
electrophoresis shows increased HbF?beta thalassemia MAJOR (alpha2gamma2)

Section 2

Question Answer
what 2 enzymes does lead inhibit?ferrochelatase and ALA dehydratase --> decrease HEME synthesis
whats the tx of lead poisoning in adults?Dimercaprol and EDTA
whats the tx of lead poisoning in kids?Succimer (it SUCks to be a kid who eats lead)
whats the defect in hereditary sideroblastic anemia?defect in ALA synthase or vit B6
increased iron, normal TIBC, increased ferritin, increased %sat?sideroblastic anemia
whats the tx for sideroblastic anemia?vit B6 = pyridoxine = cofactor for ALAS
how can you tell the difference btw folate deficiency vs. vit B12 lab wise?folate deficiency = NORMAL methylmalonic acid.
Vit B12 = INCREASED methylmalonic acid
child presents with megaloblastic anemia that is not responsive to folate or vit B12 supplements?orotic aciduria
whats the tx for orotic aciduria?uridine monophosphate (UMP) which bypasses the defected enzyme
what 3 drugs are associated with nonmegaloblastic MACROCYTIC anemia?5-FU, Zidovudine (AZT), hydroxyurea
what are are lab findings associated with intravacular hemolysis?decreased haptoglobin and increased LDH
what does increased LDH suggest?suggests alot of cell break down occuring
iron is trapped in macrophages = associated with what anemia?anemia of chronic disease
how does anemia of chronic disease work?inflammation --> increased liver release of hepcidin --> hepcidin binds to ferroportin on intestinal mucosa cells and macrophages --> prevents iron transfer from out of macrophages to RBCs
what is the cause of aplastic anemia?destruction of myeloid stem cells
name 4 viral causes of aplastic anemia?parvovirus B19, EBV, HIV, Hep C
how does ESRD cause anemia?decrease Epo --> decrease hematopoiesis
heinz bodies and bite cells are associated with which intrinsic hemolytic normocytic anemia?G6PD deficiency
whats the defect in Hemoglobin C?glutamic acid --> lysine mutation at residue 6 on beta chain
newborn presents with hemolytic anemia...what enzyme is defected?defect in pyruvate kinase (converts PEP --> pyruvate +ATP)

Section 3

Question Answer
whats the defect in PNH?impaired synthesis of GPI or DAF that normally protects RBCs from complement
what CD are missing from PNH?CD 55 and CD59
CD55-/CD59-paroxysmal noctural hemoglobinuria
what does a positive hams test show?RBC lysis at low acidic pH = a/w PNH
whats the tx paroxysmal nocturnal hemoglobinuria?Eculizumab = mab against C5
dactylitis, acute chest syndrome and avascular necrosis are complications of what disease?sickle cell disease
whats the tx of sickle cell anemia?hydroxyurea = increases HbF
what conditions causes sickling of sickle RBCs?low oxygen, dehydration, high osmolarity of vasa recta of renal medulla
what test is used to check newborns for hemolytic disease?DIRECT coombs test
what test is used to test mothers for anti-Rh antibody?INDIRECT coombs test
what are 2 INFECTIONS that increase RBC destruction?malaria and babesia
whats the defect in acute intermittent porphyria?Porphobilogen Deaminase
(converts porphobiliogen --> hydroxymethybilane)
what are the 5 P's associated with acute intermittent porphyria?Painful abd, Port wine colored urine, Polyneuropathy, Psychosis, Precipitated by barbituates
what enzyme is mutated in porphyria cutanea tarda?uroporphyrinogen decarboxylase
pt presents with hx of sunbathing and then skin blistering?porphyria cutanea tarda = deficiency of uroporphyrinogen decarboxylase
whats the defect in ITP?antibody against gpIIB/IIIA --> splenic macrophages consume this platelet-Ab complex
whats the tx of vWF disease?desmopressin (DDAVP) = releases vWF stored in endothelium

Section 4

Question Answer
what does a mutation in prothrombin gene lead to?hypercoaguable state = mutation in 3' untranslated region --> increased production of prothrombin --> increased thrombin --> increase CLOT production
what does Protein C and S deficiency cause?decrease ability to inactivate factor V and VIII --> hypercoagable state!!
Whats the effect of giving fresh frozen plasma?increase coagulation factor levels = tx DIC, warfarin overdose
what does cryoprecipitate contain?contains fibrinogen, fibronectin, vWF, factor 8 and 13
what is leukemia?lymphoid or myeloid tumor cells found in the peripheral blood
whats a leukomoid reaction?acute inflammatory response to infection
how can do you tell the difference btw leukemia (CML) and leukomoid reaction?leukemia = LOW leukocyte alkaline phosphatase. Leukomoid reaction = HIGH leukocye alkaline phosphatase
B-cell origin showing CD30+ and CD15+Reedsternberg cells= Hodgkins lymphoma
whats the most common type of Hodgkins Lymphoma?nodular sclerosing hodgkins lymphoma
Reed-Sternberg cells are just like dysfunctional lymphocytes and undergo what process?SOMATIC HYPERMUTATION
whats the difference btw Hodgkins Lymphoma and Non-Hodgkins Lymphoma?HL = Reed-Sternberg cells, localized single group of LNs, bimodal age distribution (young adults and >55), no spread.

NHL = no Reed-sternberg cells, wide age distribution, WIDESPREAD LNs
tumor cells in peripheral blood= think of it as liquid tumorleukemia
circulation of malignant lymphoid cells throughout bloodstreadleukemia
what are the 4 types of Non-Hodgkins Lymphoma?1) Burkitts lymphoma
2) Mantle cell lymphoma
3) Follicular Lymphoma
4) Diffuse Large B-cell Lymphoma
whats the most common adult NHL?Diffuse Large B-cell Lymphoma
whats the translocation of mantle cell lymphoma?t(11;14) = translocation of cyclin D1 (chromosome 11) and IgH
Which NHL is associated with CD5+ on flow cytometry?mantle cell lymphoma
name the 2 NHL associated with mature T-cellsAdult T-cell lymhoma (HTLV-1) and Mycosis fungoides/Sezary syndrome
pt presents with cutaneous patches/nodules of T-cellsmycosis fungoidis (NOT A FUNGUS!!)
what is sezary syndrome?NHL: cutaneous T cell lymphoma that spread to BLOODSTREAM

Section 5

Question Answer
what differentiates Waldenstroms Macroglobulinemia from Multiple Myeloma?Waldenstroms: M-spike = IgM (vs M-spike of IgG or IgA in multiple myeloma), and NO LYTIC BONE LESIONS
why does Multiple Myeloma present with lytic bone lesions?produces osteoblast activating factor by neoplastic cells
unregulated growth of leukocytes in bone marrow = definitionleukemia
what are the 2 markers of acute lymphoblastic leukemia?TdT, CALLA
whats the translocation associated with B-ALL?t(12;21)
mature B-cell tumor in the eldery, cells show spikesHairy cell leukemia
whats the tx of Hairy cell leukemia?Cladribine (adenosine analog) and pentostatin
what leukemia shows increased circulating MYELOBLASTS on peripheral smear?acute myelogenous leukemia
whats the tx of CML?Imantinib = bcr/abl tyrosine kinase inhibitor
what leukemia can undergo blast crisis back to AML or ALL?CML --> AML or ALL
t(8;21)AML = shows why Trisomy 21 is associated with AML
proliferative disorder of dendritic cells (Langerhans)Langerhans Histiocytosis
S100+ and CD1a+ Langerhan cell cytosis
pt presents with intense itch after showering?Polycythemia vera
why does JAK2 mutations play an important role in PV, ET, and myelofibrosis?constitively active JAK2 mutation is involved in hematopoietic growth factor signaling
fibrotic obliteration of bone marrowmyelofibrosis --> causes tear drop cells and pancytopenia
what 4 paraneoplastic syndromes cause increased Epo production?renal cell carcinoma, hepatocellualr carcinoma, hemangioblastoma, pheochromocytoma

Section 6

Question Answer
what drug superactivates antithrombin --> decreases thrombin --> decreases factor Xa?heparin
whats the antidote for heparin?protamine sulfate = positively charge molecule that binds to negatively charged heparin
Name 2 LMWH?Enoxaparin and Dalteparin = act more on Factor Xa (better bioavailability and half-life)
drug used as an alternative to heparin for anticoagulating pts with HIT?Lepirudin
how do you monitor wafarin?INR and PT
what do you give for warfarin ovedose?Vit K
LMWH that inhibits Factor Xa more than thrombinEnoxaparin
whats the tx of tPA overdose?aminocaproid acid = inhibitor of fibrinolysis
drug that irreversibly inhibit COX by covalent ACETYLATIONaspirin = increases BT, decreases TXA2 and prostaglandins. No effect on PT and PTT
name 2 drugs that irreversibly inhibits ADP receptors on platelets?Clopidogrel and Ticlopidine
whats a side effect of Ticlopidine thats not seen in clopidogrel?neutropenia
whats the MOA of Cilostazol?Phosphodiesterase III inhibitor --> increases cAMP --> inhibits platelet aggregation
whats the MOA of Dipyridamole?Phosphodiesterase III inhibitor --> increases cAMP --> inhibits platelet aggregation
whats the tx for intermittent claudication?Cilostazole = inhibits platelet aggregation and causes vasodilation
whats the MOA of Tirofiban?gpIIB/IIIA inhibitor
whats the MOA of Eptifibatide?gpIIB/IIIA inhibitor