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144 Cards in this Set
- Front
- Back
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what odoe sthe myeloid lineage include?
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eyerhitn except lymphoblasts and NK cells
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what is the order of differentiaton from a myeloblast?
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promyelocyte, myelocyte, metamyelocyte, stab (band) cell
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what % of glucose is used to make energy, what percent for HMP shunt?
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90 for ATP
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what odoe sthe myeloid lineage include?
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eyerhitn except lymphoblasts and NK cells
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what is poikilocytosis?
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varying shapes
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why are reticulocytes blue? do they have a nucleus?
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no nucleus
blue cytoplasm are precipitates of ribosomal RNA |
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what is the order of differentiaton from a myeloblast?
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promyelocyte, myelocyte, metamyelocyte, stab (band) cell
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what % of glucose is used to make energy, what percent for HMP shunt?
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90 for ATP
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what is poikilocytosis?
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varying shapes
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why are reticulocytes blue? do they have a nucleus?
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no nucleus
blue cytoplasm are precipitates of ribosomal RNA |
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what are in dense granules? alpha granules? what is the life span of a platelet?
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dense granules = calcium, ADP
alpha = vWF, fibrinogen, PF4 lifespan 8-10 days |
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what do basophil granules contain?
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heparin, histamine, other vasoactive amines, LTD4
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mast cell granules stain how on Giemsa? what do they contain? how do they recruit eosinophils? what is a specific marker
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stain METACHROMASIA.
contain histamine, heparin, esoniphil chemotactic factors. typtase is a good marker of mast cell activation |
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how do eosinophils limit mast cells? what processes develop eosinophilia?
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produce histainase, arylsulfatase
Neoplasia asthma allerigc processes collagen vascular disorders parasites (invasive) NAACP |
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what are in neutrophil azurophilic granules?
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lysosomes - which contain hydrolytic enzymes, lysozyme, MPO, and lactoferrin
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what is the cytoplasm look like in a monocyte? what is the nucleus like
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frosted glass
kidney shaped nucleus |
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how do you distinguish different types of erythrocytosis?
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RBC mass (total RBCs in body)
can also look at EPO |
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what does the plasma cell nucleus look like?
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off center nuclues
clock face chromatin distribution in nucleus. lots of RER and golgi |
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what percentage of lyphocytes are t cells?
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80%
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why is ABO incompatability in newborn not as bad as Rh? where does kernicterus deposit?
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AB antibodies are IgM and do not cross placenta.
kernicterus in basal ganglia, some hippocampus |
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what is platelet activating factor? what pathway does it use? what does it cause?
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uses Gq pathways
causes platelet aggregation and constricts bronchi and vessels |
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what 5 factors does antithrombin inhibit?
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2, 9-12 (activated forms)
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what things activate factor 12? what does factor 12 activate?
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activatecd by collagen, BM, platelets, and HMWK.
It activates factor 11, prokallikrein to kallikrein |
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what reactions require calcium and phospholipds? (name 4)
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7-->7A
9-->9a (via 11a) 10-->10a (via 7A and 8,9A) 2-->2A (via 10A and 5A) note this are all the vitamin K dependent factors |
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what factors does thrombin activate?
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13, 5, 8
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what 2 pathways does kallikrein activate?
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HMWK--> bradykinin (for vasodilation, permeability, and pain)
plasminogen-> plasmin (which itself activates C3 and degrades fibrin plug) |
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where is factor 8 made? where is it stored?
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made in liver, stored in endothelium
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what is the chloride shift?
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CO2 in veins creates bicarb, which diffuses into cytoplasm of RBC in exchange for chloride, thus venous blood has lots of chloride
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name 4 things inside endothelium?
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vWF, thromboplastin (tissue factor = factor 3), tPA, PGI2
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what does thrombomodulin do?
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takes thrombin and makes it a procoagulant by activating protein C
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steps in primary hemostasis (no coagulation cascade to cross link fibrinogen)
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adhesion, aggregation 9TxSA2), swelling (binding of ADP-->inserts GPIIb/IIIa allowing platelet cohesion, with calcium strengthening the plug)
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what does warfarin inhibit?
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epoxide reductase to make activated vitamin K
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how is protein C activated? on what surface?
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activated by protein S and thrombomodulin on enodthelial cells, which cleaves 5 and 8
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what diseases do you see acanthocytes in? what are they also called? what cells do they resemble?h
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liver disease, abetalipoproteinemia
(spur cells) resemble ecchinocytes (burr cells) |
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when do you see macro-ovalocytes?
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megaloblastic anemia, marrow failure
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what are the causes of schistocytes? what is another name?
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TTP/HUS (increased bleeding time with thrombocytopenia), DIC, traumatic hemolysis (valve)
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2 diseases with spherocytes?
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hereditary spherocytosis, autoimmune hemolysis
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target cells?
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HbC disease, asplenia, liver disease, thalassemia
target cells have extra membrane in the center |
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what are burr cells? when do you see them?
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short, evenly spaced projections
ecchinocytes artifact or mechanical damage, uremia, PK deficiency, MAHA |
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what are heinz bodies composed of? what 2 diseases have them?
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denatured hemoglobin that was a result of oxidaito nof iron from ferrous to ferric form. leads to bite cells
seen in G6PD deficiency and alpha thalassemia |
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Hb barts ahs a tetramer of what? what about HbH disease?
what is clinical manifestation of 2 gene deletion? |
Hb Barts = gamm4, drops fetalis
HbH = beta4 tetramer 2 gene deletion = mild anemia |
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how do you confirm a diagnosis of b-thal minor (heterozygote)
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HbA2>3.5%
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how does lead poisoning create basophilic stipling?
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inhibits degradation of ribosomal RNA
inhibits 5' nucleotidase |
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how is sideroblastic anemia inherited/ what is the gene defect
what are the iron stores, TIBC, ferritin? |
x-linked defect in delta-ALA synthase gene, treated with B6
reversible etiologies = alcohol, lead increased iron, normal TIBC, increased ferritin sideroblasts = iron laden mitochondria |
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what are nonmegaloblastic macrocytic anemia causes? (think 100-110, cause if greater than 110, = folate/B12 deficiency)
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liver disease, alcohlism (bone marrow suppression can occur in absence of folate/B12 deficiency), reticulocytosis, metabolic disorders (orotic aciduria), 5-FU, AZT, hydroxyurea.
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name 3 causes of intravscaulr hemolytic anemias?
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PNH, cold agglutinin autoimmune anemia, mechanical destructions.
will see decreased haptoglobin, hemolgobinuria |
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what are causes of extravascular hemolysis?
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hereditary spherocytosis, G6PD deficiency, PK deficiency, sickle cell anemia, HbC defect, warm agglutinin anemia, MAHA
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whhat is the key mediator in anemia of chronic disease? is it normocytic or microcytic?
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hepcidin is the mediator (an acute phase reactant increased in diseases of inflammation)
it is normocytic, but can be microcytic/hypochromic in long standing dsiease |
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what are causes of aplastic anemia?
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radiationa d drugs (benzene, chlorampheicol, alkylating agents, antimetabolites), viral agents (parvovirus, EBV, HIV), fanconi's anemia (inherited defect in DNA repair), idiopathic (primary stem cell defect, which may follow acute hepatitis)
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what is the most common spherocytosis defect? why?
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spectrin, because it's the root cause of spherocytosis. ankyrin and band 3.1 contribute to a relative defect in spectrin
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sickle cell prevalence? what bone diseases does it cause? why does valine polymerize and in what conditions?
resistant to what orgnaism? what is special channel associated? |
prevlaence = .2% (8% carrier rate)
bone disease = avascular necoris (like SLE, steroids, alcohol) or osteomeylitis from salmonella paratyphi valine = hydrophobic, depolarizes in deoxygatend, low pH, high 2,3DPG, dehydration protects against falciparum. Gardos K_+ channel blockers are good therapy to prevent dehydration (calcium-dependent (Gardos) potassium channel. = sickling, cytosolic calcium transiently increases and activates the potassium channel with consequent loss of potassium and water from the cell Also other channel: K-Cl cotransporter in sickle erythrocytes can induce significant potassium, chloride, and water loss even at a low PO2, as occurs, for example, in the renal medulla |
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in PNH, what is the gene defect
what do labs shows |
defec tin GPI anchor (PIG-A gene) for decay accelerating factor
labs - urine hemosiderin, hemolytic anemia, hypercoaguable state, pancytopneia |
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2 causes of cold agglutini? what about association so fwarm agglutinin/
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cold = mycoplasma, infectious mono
wamr - SLE, CLL, alpha methyldopa |
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what do you take form patient in direct coombs? what aobu tindirect?
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direct - use patients' RBCs
indirect - use their serum |
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in TTP, what do kids have more? what about adults?
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kids = renal fialure
adults = neurologic |
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what are the lab values of prenancy and OCP use?
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no change in serum iron
increased TIBC no change in ferritin decreases % saturation = serum iron/TIBC (serum iron = iron bound to transferrin) |
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what enzmes does lead inhibit, and what metal does it have?
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inhibit ferrochelatase (incorporates iron into protoporphyrin) and ala dehydtase (takes ALA to porphobilinogen) - a zinc containing enzyme
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what symptoms doe slead poisoning cause in kids? in adults?
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children - mental deterioration
adults - headahce, memory loss, demyelination, abodominal colic, constipation |
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what enzyme is deficient in AIP? what are 2 other names for it? Why is it worse with alcohol and CYP induces? what are the 5P's?
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porphobilinogen deaminase aka hydroxymethyulbilane synthase aka uroporphyrinogen I synthase (cause HMB = uroporyphorinogen)
worse with inducers cause CYP has heme in it Painful abodmen pink urine, dark upon standing polyneuropathy psychological disturbances precipitated by drugs |
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porphyria cutanea tarda enzyme? accumulated substrate?
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defect in urophoryinogen decarboxylase, what make coproporphyrinogen III
accumulates uroporphyrin III (tea colored urine). causes blistering photosensitivity, edema, puruitus. most common porphyria. |
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name the pathway if heme synthesis
which steps are in the mitochondria? |
glycine+succinyl coA (B6)-->delta ALA
delta ALA--> porphobilinogen porphobilinogen--> hydroxymethylbilane HMB-->uroporphyrinogen III UPIII--> coproporphyrinogen III CPIII--> protoporphyrin protoporphyrin-->heme in mitochondria = ALA syntehsis (1st step) and protoporphyrin and heme syntehsis (last 2 steps) |
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what is the rate limitng step in heme syntehsis and what 2 things can inhibit that enzem?
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ALA synthase is rate limitng step
heme and glucose inhibit it |
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what drug for lead poisoning for encephalopathy? 1st line treatment? kids?
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encephalopathhy = dimercaprol 9crosses BBB)
EDTA is first line treatment succimer for kids also causes anorexia, abdominal colic, lead lines on gingivae and epiphyses of long bones |
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abnormal ristocetin assay? ADP assay?
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ristocetin assay = bernard soulier diseae or vWF
ADP = glanzmann's thromboasthenia |
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does Bernard-S disease have thrombocytopenia? what about Glanzmann?
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only bernard soulier
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what is the characteristic blood smear finding of Glanzmann's thrombasthenia?
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no platelet clumping
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ITP in kids occurs when? awhat is treatment? is there splenomegaly?
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in kids occurs after viral infection
no splenomegaly give steroids |
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what 2 factors does PTT not check?
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7 and 13
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if mild hemophilia, what do you give? what about major?
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mild = DDAVP to release vWF and 8 from endothelium
if major - give recombinant factor 8 (no risk of HIV) |
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what does uremia cause in term of paltelets?
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platelet defect which increases bleeding time
no deficiency in platelets |
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if failure of vitamin K to correct PT?
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liver disease
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what is the PC, BT, PT, PTT in DIC? What is the inciting event?
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decreased platelets
increased BT, PT, PTTT inciting event - tissue factor = factor 3 (TTP starts with platelet activation) |
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causes of DIC?
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Sepsis
Trauma Obstetric complciations (dead fetus in uterus, abruptio) Pancreatitis Malignancy Nephrotic syndrome Transfusion STOP Making New Thrombi |
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DIC
what are the labs like? what factors are specifically decreased? |
decreased factor 5 and 8 (consumed in clot), dereased fibriongen, low platelets
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prothrombin gene mutation is located where?
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in 3' untranslated region
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What is characteristic finding in ATIII deficiency?
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no increase in PTT after heparin administration
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hodgkins' - extranodal sites? contiguous spread or no? symptoms? how many cases are associated with EBV (is it integrated into genome)
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no extranodal sites
contigous spread pruritus and B symptoms 50% of cases have EBV in episomal form |
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NHL - associated with what 2 states?
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immunocompromised
HIV |
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what hodkin's has greatest prognosis? which is highest EBV associated? which is associated with male s<35 years old? which is associated with older males and disseminated disease?
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best = lympohcyte predominant
mixed celluarity is most associated with EBV young males = lymphocyte predominat older males = lymphocyte depleted |
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Burkitts -
which form is associated with EBV? in starry sky apperance, what the stars? what is cMyc gene? all translocation involve what chrom? |
African form is EBV associated?
stars = macrophages Myc = transcription regulatory in nucleus all involve chrom 8 (8,14) (8,22) |
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DLBCL - what percentage are kids? What are the neoplastic cells?
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20% in kids
may be mature T cell in origin in 20% |
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mantle cell lymphoma has what CD marker? good or bad prognosis?
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bad prognosis
CD5+ |
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follciular lymphoma - what are the cells like? cure rate?
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cells are small cleaved cells (centrocytes) and some blasts (centroblasts)
inodlent waxing and waning course difficult to cure |
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MM - why lytic lesions?
why constipation? Russel bodies? what is most common monoclonal spike? |
IL-6 activaets osteoclsats
constipation -= hypercalcemia usually IgG in 55% with kappa chain (VkCk = variable and constant region kappa)q Russel bodies - IgG |
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waldenstrom M spike? how does it cause blindness?
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IgM
hypervisocsity syndrome |
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plasmacytoma located? characteristics?
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localize myeloma in lungs, nasopharynx, and inuses
M spike with IgG and plasma cells, but not mets |
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pure red cell aplasia associations?
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bone marrow failure associated with parvovirus and thymoma
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in CLL/SLL - what is CD marker? what agent do you use? blood smear?
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CD5
chlorambucil (alkylating agent) spherocytes (warm antibody autoimmune) and smudge cells |
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what is M6?
M5? associated with M7? |
M5 = monocytic (stain with nonspecific esterase)
M6 - eryhtroid (50% blasts) M7 = down syndrome associated (megakaryocytic) |
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What does CD34 indicate?
if cytoplasmic mu-, what does that mean? what is TdT used for? |
CD34 = stem cell
mu- = VDJ recombination has not finished yet TdT - for VDJ arrangement adding nucleotides at end |
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does CLL produces hypergammaglobulinemia?
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no, hypogammablobulinemia
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langerhans cell histiocytosis - express what 2 markers?
what do birbeck granules look like? |
CD1 and S-100
monocytic lineage tennis rackets on EM Appearance |
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in PV - what is the leukiocyte alk phos? what is WBC count an dplatelt count?
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increase leuk alk phos
increased WBCs and platelets |
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myelofibrosis can be a result of what?
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PV after bone marrow is spent
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what re advatnages of newer LMWH?
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act more on 10a
better bioavailability, 2-4 times longer half life administered subQ without lab monitoring, but not easily reversible |
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what is HIT?
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heparin bnds to platelet factor 4, causing autoantibody production, need to treat with direc tthrombin inhibitor
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what are the DTIs
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lepirudin, bivalirudin, argatraban
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what is first clotting factor to decline? when does protein C decline?
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first in factor 7
Protein C is second to fall, so paradoxial thrombosis must occur within first few days |
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what is structure of heparin v warfarin
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heparin - anioninc acidic polymer
warfarin - small lipid soluble molecule |
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which 2 things reverse thrombolytics?
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aminocaproic acid
tranexamic acid |
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name the thrombolytics
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streptokinase
urokinase tPA (alteplase) APSAC (anistreplase) tenectoplase reteplase, alteplase are recombinant |
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what is the composition of anistreplase
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it's streptokinase with a proactivator
it's antigenic like streptokinase APSAC = anisoylated plasminogen streptokinase activator complex |
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what is GP 1a?
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It binds platelet to collagen without intervening vWF
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in aspirin toxicity, what is first side effect? what are other sigsn?
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first is tinnitus. can cause hyperventilation initially, bleeding, swaeating, CV collapse
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what is side effect of ticlopidine?
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bone marrow toxic (fever, mouth ulcers)
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etoposide acts in which 2 phases?
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S, G2
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how is MTX trapped in cells as? toxicities?
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macrovesicular fatty change in liver
mucositis |
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5FU uses? toxicity? how do you rescue?
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use for colon cancers, topical with basal cell carcinoma
rescue with thymidine |
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6-MP and 6-TG are activated by what enzyme? which can you give with allopurinol?
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HGPRT
can give 6-TG with allopurinol |
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what drugs are good for hairy cell?
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purine analogues
cladribien (2-chloro-2deoxyadenosine) is adenosine deaminase resistant |
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what is mechanicms of dactinomycin? doxorubicin? what drug can reduce toxicity of doxorubin?
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dactinomycin - intercalates in DNA
doxorubicin - generates free radicals, so give dexrazoxane (toxic to tissues with extravasation) cardiotoxicity - sarcoplasmic reticulum swelling and myuofibrillar dropout |
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how is MTX trapped in cells as? toxicities?
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macrovesicular fatty change in liver
mucositis polyglutamate form |
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5FU uses? toxicity? how do you rescue?
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use for colon cancers, topical with basal cell carcinoma
rescue with thymidine photosensitivity |
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6-MP and 6-TG are activated by what enzyme? which can you give with allopurinol?
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HGPRT
can give 6-TG with allopurinol |
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what drugs are good for hairy cell?
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purine analogues
cladribien (2-chloro-2deoxyadenosine) is adenosine deaminase resistant |
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what is mechanicms of dactinomycin? doxorubicin? what drug can reduce toxicity of doxorubin?
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dactinomycin - intercalates in DNA
doxorubicin - generates free radicals, so give dexrazoxane (toxic to tissues with extravasation) cardiotoxicity - sarcoplasmic reticulum swelling and myuofibrillar dropout |
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how is MTX trapped in cells as? toxicities?
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macrovesicular fatty change in liver
mucositis |
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5FU uses? toxicity? how do you rescue?
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use for colon cancers, topical with basal cell carcinoma
rescue with thymidine SE - phototoxic |
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6-MP and 6-TG are activated by what enzyme? which can you give with allopurinol?
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HGPRT
can give 6-TG with allopurinol |
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what drugs are good for hairy cell?
|
purine analogues
cladribien (2-chloro-2deoxyadenosine) is adenosine deaminase resistant |
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what is mechanicms of dactinomycin? doxorubicin? what drug can reduce toxicity of doxorubin?
|
dactinomycin - intercalates in DNA
doxorubicin - generates free radicals, so give dexrazoxane (toxic to tissues with extravasation) cardiotoxicity - sarcoplasmic reticulum swelling and myuofibrillar dropout |
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how is MTX trapped in cells as? toxicities?
|
macrovesicular fatty change in liver
mucositis |
|
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5FU uses? toxicity? how do you rescue?
|
use for colon cancers, topical with basal cell carcinoma
rescue with thymidine |
|
|
6-MP and 6-TG are activated by what enzyme? which can you give with allopurinol?
|
HGPRT
can give 6-TG with allopurinol |
|
|
what drugs are good for hairy cell?
|
purine analogues
cladribien (2-chloro-2deoxyadenosine) is adenosine deaminase resistant |
|
|
what is mechanicms of dactinomycin? doxorubicin? what drug can reduce toxicity of doxorubin?
|
dactinomycin - intercalates in DNA
doxorubicin - generates free radicals, so give dexrazoxane (toxic to tissues with extravasation) cardiotoxicity - sarcoplasmic reticulum swelling and myuofibrillar dropout |
|
|
how is MTX trapped in cells as? toxicities?
|
macrovesicular fatty change in liver
mucositis |
|
|
5FU uses? toxicity? how do you rescue?
|
use for colon cancers, topical with basal cell carcinoma
rescue with thymidine |
|
|
6-MP and 6-TG are activated by what enzyme? which can you give with allopurinol?
|
HGPRT
can give 6-TG with allopurinol |
|
|
what drugs are good for hairy cell?
|
purine analogues
cladribien (2-chloro-2deoxyadenosine) is adenosine deaminase resistant |
|
|
what is mechanicms of dactinomycin? doxorubicin? what drug can reduce toxicity of doxorubin?
|
dactinomycin - intercalates in DNA
doxorubicin - generates free radicals, so give dexrazoxane (toxic to tissues with extravasation) cardiotoxicity - sarcoplasmic reticulum swelling and myuofibrillar dropout |
|
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bleomycin
phase spcific? MOA? toxicity? |
G2
produces free radicals which cause breaks in DNA strands pulmonary fibrosis, skin chagnes (flagellate skin discoloration), minimal myelosuppression |
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etoposide - Top I or II?
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II
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cyclophosphade - how is it activated? what does it crosslink?
|
bioactivated in liver
crosslinks at guanine N7 |
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nitrosoureas?
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carmustine, lomustine, semustine, streptozocin
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busulfan toxicity?
|
hyperpigmentation, pulmonary fibrosis
|
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what do you give to prevent cisplatin toxicitity?
|
amifostine
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inhibition of ribonucleotide reductase lowers what?
|
DNA syntehsis (S phase specific)
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why is raloxifen better than tamoxifen?
|
tamoxifen is an estrogen agonist on endometrial tissue (carcinoma)
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toxicity of trastuzumab? what is HER-2?
|
cardiotoxic
HER-2 is EGFR |
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toxicity of imatininb?
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fluid retention, ascites, pulmonary effusion hepatotoxic
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what is megestrol used for?
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progestational drug (a progestin) used for increasing appetite
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aprepitant?
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neurokinin-1/substance P antagonist used to prevent chemo vomting
|
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sorafenib?
|
TK inhibitor used in RCC and HCC
anti-angiogenic Multikinase inhibitor; inhibits tumor growth and angiogenesis by inhibiting intracellular Raf kinases (CRAF, BRAF, and mutant BRAF), and cell surface kinase receptors (VEGFR-2, VEGFR-3, PDGFR-beta, cKIT, and FLT-3) |
