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98 Cards in this Set
- Front
- Back
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Why are RBC's anucleate and biconcave?
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Large SA:vol ratio, great for gas exchange.
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What pump allows RBC to transport CO2 from periph to lungs for export?
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Cl/bicarb antiport (physio chloride shift)
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What kind of granules do plt have, what do they contain?
LIfespan of plt? |
Dense granules - ADP, Ca
alpha granule - vWF, fibrinogen 8-10d |
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What receptor does vWF bind? Fibrinogen?
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vWF-->Gp1b (Bernard-Soulier)
Fibrinogen-->Gp2b/3a (Glanzman) |
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What kind of granules do PMN's have, what do they contain?
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azurophilic granules (lysosomes)
lysozyme myeloperoxidase lactoferin hydrolytic enzymes |
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What are the fxn of eosinophils?
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Heminthic infxn - MBP
Phagocytose IC's Make histaminase and arylsulfatase to limit rxn after mast cell degran |
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What can cause eosinophilia?
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"NAACP"
neoplasm asthma allergic collagen vasc disease parasites (invasive) |
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What do basophilic granules contain? Fxn? Where found?
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Basophils mediate allergic rxn.
heparin histamine vasoactive amines leukotrienes (LKT4) **FOUND IN BLOOD. |
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What is in mast cell granules? Where found?
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heparin
histamine eosinophil chemotactic factors **resemble basophils structurally and functionally but not the same. FOUND IN TISSUE. |
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What prevents mast cell degran?
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Cromolyn sodium
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What do dendritic cells express on their surface? Main fxn? What are they called in the skin?
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MHCII, Fc receptor
Main inducers of primary ab response Langerhans cells |
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Extrinsic pathway coag factors?
Intrinsic pathway coag factors? |
Extrinsic - Factor 7
Intrinsic - 12, 11, 8, 9 |
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What is the fxn of kallikrein?
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-activates bradykinin - vasodilation, perm, pain
-activates fibrinoylsis via plasminogen to plasmin -activates complement via plasmin |
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What is the fxn of plasmin?
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Fibrinolytic - breaks down fibrin
Activates complement cascade |
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What is the fxn of bradykinin? What activates, inhibits?
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Vasodilation, perm, pain
Kallikrein activates, ACE inhibits. |
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What factors does antithrombin inhibit?
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thrombin, 7/9/10/11/12
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Why do neonates need a Vit K shot at birth?
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Lack enteric bacteria that MAKE vit k, so you have to give them some until they are colonized.
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What factors does Protein C inhibit?
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5a, 8a
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What converts plasminogen to plasmin?
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tPA and kallikrein
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Describe plt plug formation?
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Endothelial damage, vWF binds Gp1b, plt release ADP and Ca, ADP helps plt adhere and induces GP2b/3a, fibrinogen binds Gp2b/3a and links the plt.
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Which molecules are pro plt aggregation? Which are anti plt aggregation? What secretes these?
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Pro ag- TXA2 from plt
Anti ag - PGI2 and NO from endothelial cells |
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What is MOA of ASA as an antiplt drug?
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ASA - irrev inhibit COX1/2 via acetylation, no TXA2 (anti-plt). This occurs at low doses!
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What is the MOA of clopidrogrel and ticlodipine?
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Prevents ADP-induced expression of Gp2b/3a so fibrinogen can't bind and cross-link plt
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What is the MOA of abciximab?
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Directly inhibits Gp2b/3a (anti-Gp2b/3a antibody!)
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Where is protein S found? Alt name?
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Found on surface of endothelial cells, also called thrombomodulin.
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In what diseases can you see acanthocytes (spur cells)?
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liver disease
abetalipoproteinemia |
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In what diseases can you see basophilic stippling?
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thalassemia
ACD Fe def lead poisoning |
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In which diseases can you see macro-ovalocytes?
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megaloblastic anemia
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In which diseases can you see target cells?
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"HALT" for the target
HbC disease asplenia liver disease thalassemia |
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How do you get Heinz body?
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Oxidation of iron from ferrous to ferric leads to denatured Hgb precipitation and damage to RBC membrane.
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What are Howell-Jolly bodies?
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basophilic nuclear remnants in RBC that have not been processed well (asplenia)
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What is Hb Barts, HbH?
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Barts = gamma4 (death)
H = beta4 (deletion of 3 alpha genes) |
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What is the genetic defect in alpha-thal?
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alpha globin gene mutations decrease alpha globin syn
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What is the defect in beta-thal?
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point mutations in splicing sites and promoter sequences of beta globin gene
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How does lead poisoning cause anemia, what builds up in blood? How does it cause basophilic stippling?
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Lead inhibits ferrochelatase and ALA dehydratase, no heme syn, increase protoporphyrin. Also inhibits rRNA degradation, aggregration of ribosomes=baso stippling.
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What is the defect in hereditary sideroblastic anemia? How do you treat?
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X-linked defect in delta-aminolevulinic acid synthase (ALA synthase).
Tx=B6 |
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What are the signs/sx of lead poisoning?
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"LEAD"
lead lines on gingiva, epiphyses encephalopathy, erythrocyte stippling anemia, abd colic drops (wrist,foot), dimercaprol |
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How do you treat lead poisoning in kids? Adults?
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"It sucks to be a kid who eats lead" - treat kids with succimer.
Dimercaprol or EDTA for adults. |
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What are the causes of nonmegaloblastic macrocytic anemia?
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liver disease
EtOH - can occur without B12/folate def reticulocytosis metabolic disorder (orotic aciduria) congenital def of nucleic acid syn 5-FU, AZT, hydroxyurea |
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What is the pathophys of anemia of chronic disease?
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Inflam, increase hepcidin, Fe locked in macs.
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What happens to the BM in aplastic anemia?
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Hypocellular marrow with fatty infiltration causes pancytopenia.
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What are the causes of aplastic anemia? (drugs and other causes)
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Radiation
Drugs - benzene, chloramphenicol, alk agents, antimetabolites, PTU, methimazole Viral - parvo, EBV, HIV, HCV Fanconi's anemia (inherited) idiopathic - immune mediated |
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What happens in pyruvate kinase def? How does it present?
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No pyruvate kinase, decrease ATP, rigid RBC's. Presents as hemolytic anemia at birth.
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Where can you see "crew cut" skull on xray?
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Sickle cell
Beta-thal major **due to marrow expansion from erythropoiesis |
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What is the mutation in sickle cell disease?
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Point mutation in beta globin chain glu-->val at position 6.
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What is the mutation in HbC disease?
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Point mutation in beta globin chain glu-->lys at position 6.
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What is the defect in PND?
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impaired syn of GPI anchor, DAF, and all GPI linked proteins!
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Which are warm agglutinins? Cold?
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Warm weather is GREAT
Cold ice cream..MMMM Warm - IgG Cold - IgM |
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What is the Direct Coomb's test?
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Put ab in and binds to pt RBC
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What is the Indirect Coomb's test?
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Put RBC in and binds to pt ab
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What is transferrin the same as? What is transferrin sat?
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Transferrin=TIBC
Transferrin sat=serum Fe/TIBC |
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What is the defect in acute intermittent porphyria? Accumulated substrate?
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Defect porphobilinogen deaminase (aka uroporphyrinogen I-synthase).
Porphobilinogen, ALA, uroporphyrin |
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What are the sx of acute intermittent porphyria? Tx?
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painful abd
polyneuropathy psych distrurbance red urine **ppt by drugs (barbs, steroids, EtOH, valproate, low carb diet) Tx=glc and heme to inhibit ALA synthase |
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What is the defect in cutaneous porphyria tarda?
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Defect in uroporphyrinogen decarboxylase.
Uroporphyrin (tea-colored urine) |
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What are the sx of porphyria cutanea tarda?
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Blistering cuteneous photosen
tea-colored-urine (most common porphyria) |
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What are the starting substrates of heme? Rate lim step?
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Glycine + succinyl CoA, cofactor B6. ALA synthase.
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What are the ab's in ITP (what receptor, what isotype)?
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anti-Gp2b/3a IgG
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What is the defect in TTP?
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Deficiency of ADAMTS13 (vWF metalloprotease) decreases degradation of vWF multimers.
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How can you easily diagnose antithrombin def?
What is the mutation in prothrombin gene that causes thrombophilia? |
Give heparin, no increase in PTT (because no antithrombin to activate!)
Mutation in 3' untranslated region assoc with venous clots |
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Who is HL most commonly seen in? Exception?
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Men, bimodal distribution, 50% assoc EBV. Nodular sclerosing type more common in women, and this is most common type of HL!
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What is good prognostic sign in HL? What is seen in nodular sclerosing type HL instead of RS cells?
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High lymphocytes, low RS cells.
Lacunar cells in nodular sclerosing type. |
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What are the markers for Reed-Sternberg cells? What is their origin?
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B cell origin, CD30, CD15
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What is the translocation in Burkitt's? What gene involved, where does it go? What is the starry sky pattern?
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t(8;14)
c-myc gene moves to next heavy chain Ig Starry sky - sea of lymphocytes with some macs |
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What is the translocation in mantle cell lymphoma? Cell marker?
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t(11;14)
CD5 |
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What is the translocation in follicular lymphoma? Gene involved?
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t(14;18), increased bcl-2 expression (prevents apoptosis of tumor cells)
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What are the markers of ALL? Which translocation has a good prog?
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TdT, CALLA
t(12;21) |
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What kind of hemolytic anemia can you get with CLL?
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Warm-ab (IgG) or cold-ab (IgM)
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What kind of cells causes hairy cell leukemia? What can you stain it with?
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B cells
TRAP pos |
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How can you differentiate CML from leukemoid rxn? What is Phil Chr? What can CML transform into?
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CML has low LAP
t(9;22), bcr-abl gene Can transform into blast crisis! |
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What is the translocation in M3 AML? What can you treat it with?
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t(15;17)
all-trans retinoic acid |
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What do you see on EM in Langerhans cell histiocytosis? Which cell markers?
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tennis-racket Birbeck granules
S-100, CD1a |
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In what diseases do you see the JAK-2 mutation?
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Chronic myeloproliferative disorders (PCV, ET, myelofibrosis)
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What is the diff betwen relative, inappropriate absolute, and appropriate absolute polycythemia?
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Relative - decrease plasma vol
Appropriate - COPD, heart diseaes Inappropriate - ectopic EPO |
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What happens in HIT?
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Heparin binds to plt factor4, and body makes ab that bind/activate plt-->thrombocytopenic, hypercoag state.
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Lepirudin, bivalirudin - MOA?
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Direct thrombin inhibitors
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What do you treat tPA/streptokinase overdose with?
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Aminocaproic acid
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Aspirin - MOA? Tox?
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Irrev inhibits and acetylates COX1/2 to decrease TXA2, decrease plt aggregation
Tinnitus, bleeding, ulcers, hyperventilation |
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Which cancer drugs inhibit S phase? S and G2? G2? M?
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S - Antimetabolites
S and G2 - etoposide G2 - bleomycin M - vinca alks, taxols |
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Methotrexate - MOA, tox?
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Folic acid analog inhibits DHF reductase.
BM suppression Macrovesicular fatty change Mucositis Teratogen |
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5-FU - MOA, tox?
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Pyrimidine analog complexes folic acid, then inhibits thymidylate synthase.
BM suppression Photosen |
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6-mercaptopurine, 6-thioguanine - MOA, tox? What drug worsens its tox?
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purine analog activated by HGPRTase, inhibits purine syn.
BM, GI tox, liver 6-MG has increased tox with allopurinol (metabolized by xanthine oxidase) but not 6-TG |
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What kind of rescue do you use for MTX vs 5-FU?
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MTX - leucovorin (aka folinic acid)
5-FU - thymidine |
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Cytarabine - MOA, tox?
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Pyrimidine analog inhibits DNA pol.
BM suppression |
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Dactinomycin (actinomycin D) - MOA, tox, use?
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intercalates DNA.
Use=Childhood tumors. Tox - BM suppression |
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Doxorubicin/daunorubicin (adriamycin) - MOA, tox? How can you lessen toxicity?
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Generates free rads, noncovalently intercalates DNA to make breaks and decrease replication.
alopecia BM sup cardiotox - give dexrazoxane toxic to tissues with extravasation |
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Bleomycin - MOA, tox? What part of cell cycle?
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induces free rads, cuts in DNA in G2
pulm fibrosis skin changes minimal BM sup |
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Etoposide (VP-16), teniposide - MOA, tox?
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Inhibits Topo II, increase DNA degradation (S and G2)
BM, GI, alopecia |
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Cyclophosphamide, ifosfamide - MOA, tox?
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Covalently X-link DNA at guanine N-7, requires activation by liver.
SIADH hemorrhagic cystitis BM sup *mesna can partially prevent side effects by binding acrolein metabolite and aiding excretion |
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Nitrosureas (carmustine, lomustine, semustine, streptozocin) - MOA, tox, use?
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Alk agent, require bioactivation, can cross BBB. Brain tumors!
CNS tox -dizzy, ataxia |
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Busulfan - MOA, tox?
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Alk agent, CML or BM ablation prior to tx.
pulm fibrosis hyperpig |
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Vincristine, vinblastine - MOA, tox?
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Alkaloids that bind to tubulin in M-phase and prevent MT formation and mitosis.
vincristine - neurotox (areflexia, periph neuritis), neurogenic ileus vinblastine - BM sup |
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Paclitaxel, taxols
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Hyperstabilize polym microtubules in M so mitotic spindle can't break down (no anaphase).
BM sup, hypersen |
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Cisplatin, carboplatin - MOA, tox
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cross-link DNA
nephrotox, CN8 tox - give with amifostine |
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Hydroxyurea - MOA, tox?
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inhibits ribonucleotide reductase to prevent DNA syn in S phase
BM sup, GI upset |
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Prednisone as chemo - MOA, use?
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May trigger apoptosis, even in nondividing cells. Used in HL, CML.
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Tamoxifen, raloxifene - MOA, tox?
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SERMs, ER antag in breast and agonist in bone.
tamox - increase risk endometrial ca, hot flashers |
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Transtuzumab (herceptin) - MOA, tox?
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anti-HER2
cardiotox |
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Imatinib (gleevec) - MOA, tox?
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bcl-abl Tyr kinase inhibitor
fluid retention |
