Hematology Flashcards
(170 cards)
1
Q
t(14,18) vs t (9,22)
A
Follicular lymphoma (B-cell lymphoma) over expression of Bcl-2 (protoncogene with anti-apoptotic effects)
chronic myleogenous leukemia (CML)- Philadelphia chromosome (22), bcr-abl hybrid
2
Q
myc-oncogene is located where? associated with what cancer?
A
?chromosome 8, translocations coding for immunoglobin heavy chain (14), kappa light chain (2) and lambda light chain (22) can result in Burkitt’s lymphoma
3
Q
ErbB2 aka?
A
HER2- over expressed in some breast cancers
4
Q
LiFraumeni syndrome
A
autosomal dominant cancer syndrome caused by mutation in P53
5
Q
GpIIb/IIIa receptor
blocked by which drug?
deficient in which dz? classical presentation? test result?
A
blocked by abciximab
defiecient or defective in pts with Glanzamann thrombasthenia. (child with mucocutaneous bleeding and no platelet clumping on blood smear)
6
Q
clopidogrel ticlopidine
abciximab
ristocetin
A
- irreversible inhibitor of ADP receptor (signals expression of GpIIb/IIIa)
- blocks GpIIb/IIIa
- activates vWF to bind GpIb
7
Q
majority of atypical cells seen in EBV is
A
although EBV infects CD21+ (receptor for C3d complement) cells (B-cells) the majority of atypical cells are CD8+ t-lymphocytes which destroy the infected B-cells.
8
Q
appearance of CD8+ atypical cells
A
large cells with abundant cytoplasm and eccentrically placed nucleus and a cell membrane that adheres to borders to neighboring cells
9
Q
appearance of activated plasma cells
A
ovoid cells, abundant cytoplasm and eccentric nucleus with wagon-wheel appearance and zone of perinuclear clearing (golgi body)
10
Q
CD14
A
cell surface marker expressed on monocytes and macs. binds LPS (lipopolysaccharide) resulting in activation of mac
11
Q
what is cause of negative transepithelial potental difference seen in CF pts? which cells are not effected? does normal sweat test=no CF?
A
reduced chloride secretion due to mutated CFTR leads to increased Na+ and water absorption-widened negative transepithelial potential difference. electrolyte changes occur in most exocrine glands (other than sweat glands)- in other words some pts with mild mutations in CFTR can have a normal sweat test. also sweat glands have no change in potential b/c they use the same mutated receptor (CFTR) to absorb Na+ as well.
12
Q
Age that e.coli can cause HUS? transmission (3) presentation (3)?
A
children under 10 to eat undercooked ground beef, unpasturized milk, and person-to-person
microangiopathic hemolytic anemia “fragmented erythrocytes, lethargy, somnolence”, thrombocytopenia “bloody diarrhea”, and renal insuffciency “oligouria, elevated BUN and Cr”
13
Q
raw oyster consumption can cause what type of diarrhea?
A
watery from vibro cholera
14
Q
name 5 steps of inflammatory leukocyte entry into inflammatory tissue
A
margination, rolling, activation, tight adhesion and crawling, and transmigration
15
Q
def margination in inflammatory leukocyte accummulation
A
increased vascular leakage in microvasculature leads to hemoconcentration and decreased wall stress improving neutrophil contact with endothelial lining
16
Q
which receptors are required for rolling in inflammatory leukocyte accummulation
A
neutrophil: endothelial cell
- Sialyl Lewis X:E-selectin
- Sialyl Lewis X: P-selectin
- L-selectin:GlyCAM-I,CD 34
17
Q
which receptors are required for tight-binding in inflammatory leukocyte accummulation
A
neutrophil: endo
- CD11/18 integrins (Mac-1, LFA-1):ICAM-1 aka (CD54)
- VLA-4 integrin:VACM-1 aka (CD106)
18
Q
which receptors are required for transmigration (aka?) in inflammatory leukocyte accummulation
A
diapedesis
neutrophil:endo
platelet endothelial cell adhesion molecule 1 (PECAM-1) aka CD 31: PECAM-1 (CD 31)
19
Q
recurrent skin infections W/O PUS FORMATION & DELAYED DETACHMENT OF UMBILICAL CORD, poor wound healing
A
leukocyte adhesion deficiencies (LAD) type 1-absence of CD 18, affects tight adhesion, crawling, and migration of neutrophils, autosomal recessive
20
Q
describe pedigree of X-linked recessive diseases
vs autosomal recessive
A
affected males will always produce unaffected males and carrier daughters
carrier females have 50% of producing an affected son or carrier daughter
-both parents must be carriers (either have disease of come from same family- consanguineous partners)
21
Q
describe pedigree of mitochondrial inheritance
A
only affected mothers transmit disease
22
Q
pt has expressly asked not to be informed and is competent to make decision (evaluate for depression). you could also encourage pt to deem someone a surrogate decision maker who doesn’t necessarily have to know is diagnosis
A
health care information should be fully disclosed unless, what should pts be evaluated for, what other options are there?
23
Q
nondisjunction after conception-give examples
non disjunction before conception-give examples
A
-mosacism
Downs, McCune Albright’s
-trisomy
Downs, Patau’s, Edwards
24
Q
G6PD-process affected, similar clinical pic to which enzyme deficiency?
A
HMP shunt
glutathione reductase def- leads to decreased NADPH, and increased suceptibility to RBCs oxidative damage
25
karyotype analysis seen in
Downs
CML
Fragile X syndrome
- trisomy 21
- elongation of chromosome 9 and shortened chromosome 22 t,(9,22)
- discontinuity of staining on long arm of X chromosome
26
iron deficiency anemia presents as, compared to anemia due to erythopoietin deficiency, vit B12/folate, pyridoxine.
- difficulty swallowing (dysphagia), and disfigured fingernails (spoon nails or koilonychia)
- chronic renal failure
- megaloblastic anemia
- leads to decreased heme production. sideroblastic anemia or microcytic, hypochromic pyridoxine-responsive anemia
27
which cofactor is essential for carboxylation of glutamyl residues in liver. esp essential in which 4 pt populations
- vitamin K/ need for clotting factor production.
- neonates b/c of limited hepatic reserve, lack of intestinal flora, and limited amts of vit K in breast milk
- those with malabsorption syndromes
- those taking broad spectrum antibiotics that destroy intestinal flora
- those with generalized liver disease
28
relative polycythemia vs absolute polycythemia is determined using
measurement of RBC mass. normal mass=relative (polycythemia due to plasma volume contraction-dehydration or excessive diuresis)
abnormal mall=absolute
29
primary vs secondary erythrocytosis is determined using
serum erythropoietin levels
primary=low erythropoietin (myeloproliferative disorder i.e. polycythemia vera)
secondary=high erythropoietin (chronic hypoxia, smoking, COPD, or neoplasm)
30
hypoxic vs other causes of secondary erythrocytosis is measured using
oxygen sat and PaO2
| hypoxic=sat<65mmHG
31
hemolytic disease of newborn-aka, mech, presentation, hypersensitivity type?
- erythroblastosis,
- mother IgG antibodies attack fetal blood causing hemolysis,
- anemia, hepatosplenomegaly, jaundice
- type II (antibody mediated)
32
Dubin-Johnson Syndrome-inheritance, mech, presentation (important negatives-4)
autosomal recessive
- mild conjugated hyperbilirubinemia
- mildly icteric; mostly do not feel ill, no pruritus, normal liver enzymes and no hepatosplenomegaly
33
mutation found in HbS, HbC, HbM
- valine in place of glutamic acid on 6th a.a position of beta subunit
- lysine in place of glutaminc acid on 6th a.a. potions on beta subunit
- histidine in place of tyrosine in heme pocket, results in formation of ferric (Fe3+) iron from ferrous iron (Fe2+)
34
why is does sickle cell cause hydrophobic interactions among hemoglobin molecules and not impairment of proper folding of alpha helix in beta-globin chain
because sickle cell is a mutation of valine in place of glutatmic acid. valine is a nonpolar a.a. that creates a hydrophobic bulge in beta-globin chain that fits into alpha globin causing polymerization of RBCs
-impairment of folding would be caused by a mutation to proline (proper folding is sterically hindered)
35
antibody found in colostrum
IgA is present in mother breast milk and provides protection from ingested pathogens by baby
36
with maternal blood type A and B erythroblastosis fetalis and hemolytic disease of newborn do not occur however with type O mothers it can. why?
- In A or b type blood, anti-A and -B are IgM and do not cross the placenta
- in O type blood, anti A and anti B are IgG and can cross the placenta
37
lymph node (function, and disease if missing):
- follicle
- medulla (func only)
- paracortex
- subscapular sinuses/trabeculae (func only)
- site of B-cell localization and proliferation- primary (dense and dormant); secondary (pale central germinal centers and are active). missing results in Bruton's agammaglobinemia, X-link recessive
- contain medullary cords (closely packed lymphocytes and plasma cells) and medullar sinuses.
- contains T cells, and high endothelial venules through which t and b cells enter from blood. not well developed in pts with DiGeorge syndrome (thymic, parathyroid, and cardiac defects triad).
- sinuses communicate with efferent lymphatics and contain reticular cells and macrophages
38
Fab vs Fc region (location, what binds here?, isotype vs idiotype, carboxy end, where carbohydrate side chains are found)
- FAB; heavy and light chain, antigen binding fragment, determines idiotype (unique antigen binding pocket)
- Fc; c=constant, just bottom part of heavy chain, complement binds near hinge and phagocytic cells (macs) bind near end, determines isotype (IgG, IgD etc...), also carboxy terminal and carbohydrate side chains
39
which antibody isotype is better at activating C1 complement cascade? why? where does it bind?
classical cascade can begin with binding of C1 to either 2 IgGs or 2 IgMs. IgM is better because it circulates in pentameric form vs IgG which circulates alone.
-C1 binds to heavy chain near hinge point
40
t (15:17)-disease, gene created, function of gene
acute promyelocytic leukemia type M3, translocaitn of gene for retinoic acid receptor alpha from 17 to 15 to create fusion gene PML/RARalpha
abnormal gene inhibits differentiation of myelopblasts s and triggers development of AML
41
positive vs negative selection (def, location, cells involved)
- positive: thymic cortex, T cells TCRs capable to binding surface self MHC molecules presented by thymic cortical epithelial cells survive.
- negative: medulla. T cells expressing TCRs with very high affinity for self antigens presented by thymic medullary epithelial and dendritic cells undergo apoptosis.
42
name vitamin that take 4 years to deplete in body due to dietary intake. name another vitamin that rarely depletes due to decreased dietary intake.
- vitamin B12. b/c of large hepatic stores
| - vit K, b/c of production by colonic bacteria
43
Nef and Tat genes
HIV
- Nef= viral replication
- Tat=decreased expression of MHC class I in infected cells
44
mechanism of young pt with recurrent DVTs that's resistant to activated protein C is most likely? not immune because
- something inherited b/c of age
- factor V leiden (factor Va resistance) b/c of resistance to protein C
- thrombosis due to autoimmune conditions like Lupus (lupus anticoagulants) would not be resistant to protein C but would should show aPTT prolongation
45
failure of prolonged PT to correct with vitamin K indicates? not intrinsic plt dysfunction b/c
liver disease i.e coagulation factor VII deficiency.
| -pt dysfunction would like to increased bleeding time
46
changes of PTT, PT, TT and bleeding time seen in Hemophila A or B?
-PTT is abnormal everything else is normal
47
drug of choice for prevention of venous thrombosis in non-ambulatory pts or pts undergoing elective surgery (hip, knee). mech of this drug?
- heparin
| - increases effect of naturally occuring antithrombin III
48
name viral family in which members are non-enveloped and contain single-strained DNA. what does disease are associated with this virus (3)
- parvoviridae
- Parvovirus B19 cause erythema infectiosum (5th disease)
- aplastic crisese in sickle cell anemia
- hydrops fetalis
49
role of HMP shunt in pts with G6PD deficiency
HMP is responsible for generating NADPH to protect against oxidative damage
- glucose-6-phosphate dehydrogenase catalyzes the first step is oxidation of glucose-6- phosphate to 6-phophogluconolactone
- this produces 1 molecule of NADPH
50
example of selective COX-2 inhibitors. benefits over NSAIDS. risk associated with COX-2 inhbitors
- celecoxib
- have no effect on platelet aggregation and cause little GI irritation. (plts predominantly express COX-1)
- COX-2 is expressed on vascular endothelial cell and play a role in local production of PGI2 that promotes anti-coagulation and vascular dilation. blocking this pathway can leads to increased risk of cardiovascular events
51
def and name disease where are auer rods are found? name cytogenic abnormality?
- rod shaped intracytoplasmic inclusion seen in AML
| - M3 variant of AML is associated with t(15,17)
52
AML M2 subtype vs AML M3 subtype
both have auer rods present
- M2= t, 8,21
- M3= t 15, 17. DIC is common,
53
which class of drugs can be used to increase PT, PTT but not TT? which drugs prolong TT
- factor Xa inhibitors (fondaparinux). at junction of intrinsic (aPTT) and extrinsic (PT) pathways
- heparin (directly inhibits thrombin formation)
54
define PI3K/Akt/mTOR pathway. mutations in which factors can lead to what complication?
intracellular signaling pathway important for anti-apoptosis, cellular proliferation and angiogenesis
-mutations in grow factor receptors, Akt, mTOR or PTEN (all enhance activity of this pathway) can lead to cancer.
55
role of mTOR
- inhbitor (endogenous and drugs)
- actvivator
- final signaling molecule in PI3/Akt/mTOR pathway
- protein kinase B aka Akt activates mTOR
- PTEN inihbits mTOR
- rapamycin inhibits mTOR
56
where does isotype switching occur? what does it require?
germinal centers of lymph nodes
- requires interaction of CD40 receptor on B-cells with CD 40 ligand aka CD 154 expressed by activated T-cells
- usually switch from IgM to IgG
57
why does fetal hemoglobin bind better to oxygen?
b/c normally 2,3-DPG forms ionic bonds with two beta subunits of HbA in tissues after hemoglobin has been deoxygenated
-feta hemoglobin binds oxy with higher affinity due to inability to interact with2,3 DPG.
58
presentation of APL (aka). bone marrow shows? genetic abnormality?
- M3, AML
- persistent infection and coagulopathy causing hemorrhagic signs (bruising and oozing) and symptoms
- bone marrow reveals promyelocytes with intracytoplasmic Auer rods
- t,15,17. causes fusion of alpha retinoic acid receptor gene and PML gene
59
t 14,18
| inv (16)
- non-Hogkins follicular small cleaved cell lymphoma
| - M4Eo (eosinophilic) subtype of AML
60
which organelle is needed for heme synthesis? which steps?
mitochondria
| -necessary for first and final 3 steps
61
increased affinity of Hb for oxy leads to what changes in ? (curve, P50 value, and compensation) not hypoxia induce hemolysis because?
- left shift, P50 (partial pressure of oxy at which heme is 50% sat) is decreased, and erythropoietin synthesis because of renal hypoia
- this results from sickle cell anemia b/c of cell damage from sickling. this causes a shift of the curve to right not left
62
haptoglobin-def decreases when?
serum protein that binds to free hemoglobin and promotes it uptake by reticuloendothelial system
-decreases when significant levels of hemoglobin are released into blood
63
intravascular anemia
- when does it occur?
- blood smear findings?
- levels of haptoglobin, hemoglobin, LDH, and bilirubin
- secondary to mechanical trauma from microangiopathic hemolytic anemias or prosthetic valves
- schistocytes (aka helmet cells) fragmented erythrocytes
- decreased haptoglobin
- increased hemoglobin, LDH, and bilirubin
64
action of CO on hemoglobin vs Fe
- CO binds to hemoglobin with affinity 220 times that of oxy and competes with it. both are reversible
- oxidation of iron from ferrouus to ferric state leads to formation of methemoglobin which is unable to bind oxy
65
presentation of age-related macular degeneration. two types. how should they be treated
- degeneration of central retina. pts have difficulty driving, reading, watching TV.
- dry form has subrentinal drusen deposits or pigment changes
- wet form has abnormal blood vessel with subretinal fluid/hemorrhage, gray subrential membrane, or neovascularization
- anti-VEGF (to prevent neo-vascularization) for severe wet or antioxidant vitamins and zinc for dry and less advanced wet
66
name viron/viron protein associated with host cell receptor:
- CD4 on Tcells
- CD21 on B cells
- P antigen on mature and immature erythtocytes
HIV gp120
EBV gp350
parvovirus B19
67
mutation in beta globin gene leads to what disease:
- A (gluatmate) to T (valine) at position 6
- mutatation in Kozak gene
- sickle cell
| - thalassemia intermedia
68
Kozak sequence
sequence on mRNA that surrounds AUG start codon
- plays a role in initiation of translation. (mRNA binding to ribosomes)
- mutation can lead to thalassemia intermedia
69
thalassemia intermedia presents how
hypochromic, microcytic anemia
70
ways to revere warfarin. which takes more time?
vitamin K and fresh frozen plasma
| -vitamin K takes more time b/c it requires clotting factor re-synthesis to be effective
71
aminocaproic acid- mech of action and used when?
antifibriolytic agent that inhibits plasminogen activators and antiplasmin activity
-used when fibrinolydsis is cause of bleeding
72
reason for bluish color in large RBCs after Wright-Giemsa stain?
-reticulocytes have bluish cytoplasm and reticular precipitates of ribosomal RNA that appear blue on wright-giemsa stain
73
Samter's triad. caused by
- asthma, aspirin hypersensisity (nasa symptoms, bronchospams, facial flushing), nasal polyps
- due to overproduction of leukotrines from blocked cycloxygenase pathway
74
salicylism- triad, caused by, metabolic disturbance(s)
- veritgo, tinnitus, and hearing loss
- very high does of asprin stimulate respiratory drive causing hyperpnea leading to respiratory alkaolsis and salicylate accumulation leading to metabolic acidosis
75
presentation of TIA, how to treat, complication risk
- sudden onset of focal numbness and tingling that fully resolved within minutes
- low dose aspirin
- chronic use can lead to GI bleeding from ulcer formation
76
Henoch-Schonlein Purpura-def, mech, presentation, epi
- leukocytoclastic vasculitis
- deposition of IgA- containing immune complexes
- palpable lower extremity purpura, abdominal pain, arthralgias, and renal involvement
- mc cause of systemic vascular disease in children, seen in young males 3-10 yrs old
77
G6PD can cause hemolytic episodes induced by
| -blood smear
infections,
medications (TMP-SMX*, dapsone, antimalarials)
-DKA
-favism (ingestion of fresh fava beans)
-blood smear shows bite cells and Heinz bodies
78
hemoglobin Gower
| vs hemoglobin Bart
- zeta2, epsilion2 is earliest hemoglobin found in fetus. synthesized by yolk sac
- four gamma protein subunits. found in homozygous alpha thalassemia and is incompatible with life b/c oxygen does cannot be released causing tissue hypoxia
79
```
hemoglobinopathy electrophoresis patterns
normal
sickle cell trait
sickle cell disease
hemoglobin trait
hemoglobin disease
hemoglobin SC disease
```
- in electrophoresis molecule move from cathode (-) to anode (+)
- hemoglobin A moves the farthest b/c it's neutral. HbS is next in line b/c it's negative gluamate is replaced with a neutral valine. last and closes to cathode is HbC b/c it's mutation replaces A with positively charges amino acid lysine
- 1 band for HbA
- 1 HbA and 1 HbS
- 1 band for HbS
- 1 for HbA and 1 for HbC
- 1 band for HbC
- 1 for HbS and 1 for HbC
80
greenish color seen in bruises is due to. not uroporphyrinogen decarboxylase b/c?
heme oxygenase conversion of heme to biliverdin
| -involved in production of heme not it's destruction. it's defective in porphyria cutanea tarda (PCT) mc porphyria
81
classic histology description for Burkitt's lymphoma
-diffuse medium-sized lymphocytes and an high proliferation index represented by high Ki-67 fraction approaching 100%
82
lack of vitamin K at birth can lead to what life threatening complication
-hemorrhagic disease of newborn-cutaneous, GI, and intracranial bleeding.
note* it takes 6 months for vit D def symptoms to appear so it doesn't have to be given right away
83
name some biologic response modifiers. which one is used against CD 20 antigen?
- rituximab is antibody directed towards CD20 lymphomas
- others include infliximab (chimeric-RA), IL-2 (cytokine-renal cell carcinoma and melanoma), Imatinib (used for CML), abciximab (chimeric-acute coronary syndrome)
84
mechanism behind paresthesias seen in pts with multiple blood transfusions
-stored blood contains citrate a calcium and magnesium chelator. reduces levels of these ions can lead to paraesthesias
85
presentation of 5th disease, aka, virus involved, invades which cell type? found where?
- erythema infectiosum
- febrile upper respiratory illness in child followed by sudden appearance of red-flushed cheeks 2-5 days and then a reticular lacelike patterned rash on trunks and extremeties
- parvovirus B19
- found in erythroid precursor cells and replicates in bone marrow
86
beta thalassemia-pt pop,mutation leads to? heterozygous presentation? lab test (Hb levels, smear, anemia type)
- Mediterranean. note SE Asians tend to get alpha-thalassemia
- results in defective transcription, processing, and translation of beta-goblin mRMA
- asymptomatic
- mild hypochromic microcytic* anemia
- increased HbF*, hemoglobin A2
- target cells*
87
bone marrow presentation in
- aplastic anemia
- myelofibrosis
- hairy cell leukemia
- myelodysplastic syndrome
- acute lymphocytic anemia
- folic acid deficiency
- myelophthisic anemia
- dry, marrow is replaced with fat cells and fibrous tissue
- dry at first but then replaced by collagen
- neoplasic cells with fried egg appearance
- disordered (dsyplastic) differentiation all all non-lymphoid lineages (ringed sideroblasts and megaloblastiod maturation)
- hypercellular with high % of lymphoblasts
- hypercellular with erythroid and granulocytic hyperplasia
- infiltration by metastiac carcinoma with assocaited fibrosis leads to space-occupying lesions (fibrosis, granulomas)
88
which antibiotic drug can cause aplastic anemia. not metronidazole b/c?
- chloramphenicol can lead to dose-dependent (reversible) and dose-independent (irreversible) pancytopenia
- metronidazole can cause GI and neruologic disturbances or a disulfiram like rxn when taken with alcohol
89
Tzanck smear vs Monospot test
- detects HSV or VZV infection. take sample and use Wright-Giemsa stain to examine for multinucleated giant cells and intranuclear inclusions
- detects EBV by measuring heterophil antibodies they cause B cells to produce. horse RBCs are agglutinated in vitro by heterophil antibodies
90
Laboratory characterisitics of various coagulopathies (PT, aPTT, Plt count, Bleeding time)
- Hemophila A and B
- Von Willebrand factor def
- Disseminated Intravascular coagulation
- Uremic Plt dsyfunction
- Heparin administration
- coumadin use
- everything is normal expect aPTT (factor VIII def)
- aPTT (factor VIII) and BT (qualitative plt dsyfunc) are increased (sometimes aPTT is normal). PT and plt count are normal.
- everything increases except plt count which decreases (comsumptive coagulopathy)
- everything normal except BT which increases (uremia causes a qualitative plt disorder; seen in pts needing dialysis)
- everything is normal except aPTT which is increased. note* HIT causes the same results except that plt count decreases)
- PT increases and aPTT has a delayed increase. everything else is normal
91
histology of follicular lymphoma, mutation leads to what protein overexpression
- aggregates of packed follicles that obscure the normal lymph node architecture
- t 14,18 leads to overexpression of BCL-2 protein
92
name some drugs that increase or decrease efficacy of warfarin explain mechanism
- warfarin is degraded by P-450 system
- enhancers of system (rifampin, phenobarbital, and phenytoin) cause decreased efficacy
- supressors (cimetidine, amiodarone, and TMP-SMX) lead to increased efficacy
93
ristocetin test
| ADP test
- used to measure VWF-dependent plt aggregation
- ristocetin activates GP Ib-IX receptors on plts and makes them available for vWF binding
- used to measure plt to plt adhesion via GPIIb-IIIa receptors
- mutation in receptor leads to Glansmann thrombasthenia
94
disease associated with
- C-myc overexpression: t8,14
- N-myc overexpression
- BCR-ABL rearrangement: t 14,18
- BCL2 overexpression
- burkitt's lymphoma
- neuroblastoma
- CML and some forms of ALL, causes increased tyrosine kinase activation
- follicular lymphoma
95
mechanism of nitrate treatment for cyanide poisoning
- nitrates convert hemoglobin to methmoglobin (ferrous to ferric)
- CN binds to ferric more than mitochondrial cytochrome enzymes
- prevents CN's toxic effect
96
pyruvate kinase deficiency leads to hepatosplenomegaly due to work hypertrophy not intracellular substrate accumulation because
- lack of pyruvate kinase causes hemolytic anemia due to failure of glycolysis and resusltant failure to generate enough ATP to maintain RBC structure. this leads to increased work by spleen to remove the RBCs causing hypertrophy of the organ.
- hypertrophy due to increased intracellular accumulation is due to sphingomyelin (Niemann-Pick dz) and glucocerebrosides (Gaucher)
97
causes of splenomegaly
- passive congestion
- inflammatory infiltration
- neoplastic lesion
- portal HTN, splenic vein thrombosis, or CHF
- proliferation of lymphoid tissue to fight infection
- leukemia, and lymphoma
98
hereditary sphereocytosis (MCHC, signs of hemolysis confirm with which test?
increased mean corpuscular hemoglobin concentration be/c of mild dehydration of cell
- indicators of hemolysis: elevated LDH, reticuloytosis, and decreased haptoglobin
- fragile osmotic testing
99
a retained fetus in uterus can cause DIC how?
chronic release of tissue factor (thromboplastin) which activates intravascular coagulation cascade
100
findings of DIC? how is it monitored? not wit antithrombin because?
- prolonged PT and PTT, thrombocytopenia and macroangiopathic anemia, low fibrinogen, elevated fibrin split products (D-dimers) low factor V and VIII levels
- fibrinogen and plt count
- both protein C and antithrombin are anticoagulants and have no involvement in pathology of DIC
101
complication of chemotherapy for tumors with rapid cell turnover? presentation? (ion levels) treatment with (3)? not probenecid because?
- tumor lysis syndrome
- hyperphosphatemia, hypocalemia, hyperkalemia (causes arrhythmias), and hyperuricemia (obstructive uropathy and acute renal failure)
- hydration and hypouricemic agents (allopurinal or rasburicase)
102
autoimmune plt destruction-def, and when to suspect?
- common cause of thrombocytopenia aka immune thrombocytopenic pupura (ITP)
- suspect in pts with eccymoses, petichiae, mucosal bleeding without signs of TTP/HUS, pancytopenia, marrow failure or splenomegaly.
103
causes of vit B12 deficiency and megaloblastic anemia
- dietary deficiencye, pernicious anemia, or malabsorption
- Schilling test: give radiolabel oral vit B12 and intramuscular injection.
- normal urinary excretion suggests normal absorption, think decreased dietary intake
- if low urinary excretion differentiate between pernicious anemia and malabsorption by giving radiolabeled B12 with intrinsic factor. if normal excretion then think pernicious anemia if low excretion think malabsorption syndrome
104
pol gene mutations allow HIV to resist what? env gene mutations?
- resistance to antiretrovirals (reverse transcriptase and protease inhibitors)
- resistance to host neutralizing antibodies
105
presentation of lead poisioning- blood smear, pt pop
- lead lines at junction of teeth and gingivae
- RBC basophilic stippling and microcytice hypochromic anemia
- children and industrial workers
106
name serious drug effects of
- ZDV, ganciclovir therapy
- ganciclovir alone
- neutropenia, both affect DNA synthesis in hematopoietic stem cells
- impaired renal function
107
triad of PNH, PNH commonly causes, deficiency in what cell markers and mech
- hemolytic anemia, hypercoagulable state, pancytopenia
- thrombosis and pancytopenia (b/c it's also a stem cell disorder)
- CD 55 and CD 59 proteins work to inactivate complement and without them hemolysis results
108
presentation of pt with iron deficiency anemia (serum ferritin, circulating transferrin, MCV, hyper-segmented neutrophils, serum folate)
low ferritin, high transferrin, low MCV, normal folate, no hypersegmented neutrophils
109
things that cause a right shift on oxygen hemoglobin curve
BAT-ACE
- increased 2,3-BPG
- Altitude
- Temperature
- Acid (H+) not pH (b/c pH is low)
- CO2
- Excercise
110
Reed Sternburg cells-description, associated disease. histological appearance of B-cell lymphoma
- ample cytoplasm, bilobel or double nuclei (owl eyes), inclusion-like eosinophilic nucleoi
- Hodgkin's disease
- diffuse sheets or large lymphocytes with nuclei at leads 5x size of small lymphocytes
111
candida vs cryptococcus neoformans appearance
- budding yeast with pseudohypae aka germ tubes (blood cultures incubated at 37C for 3 hrs)
- oval budding yeast with thick capsule (india ink stain)
112
diagnostic features/mutations seen in chronic myeloprolifeartive disorders:
- chronic myelogenous leukemia
- essential thrombocytosis
- polycythemia vera
- constitutional symptoms (b symptoms), leukocytosis with marked left shift*. mutation is philadephila chromosome, t (9:22) BCR-ABL fusion protein
- thrombocytosis* hemorrhagic and thrombotic symptoms (easy bruising microangiopathic occlusion) megakaryocytic hyperplasia
- erythrocytosis* and thrombocytosis, pruritus, splenomegaly, thrombotic complications
- bone marrow fibrosis*, severe fatigue, splenomegaly, hepatomegaly
note the last three conditions have mutation (V617F) in tyrosine kinase, JAK2. this results in constitutive tyrosine kinase activity and activation of STAT transcription factors
113
most common malignancy in childhood, name two types and % of all cases. presentation of both types
- ALL (acute lymphoblastic leukemia), "blast in peripheral blood"
- B cell 7-9% and T vell 15-17%
- B cell presents with fever, malaise, bleeding, bone pain, and hepatosplenomegaly
- T cell presents similar to B cell but often presents as a mediastinal mass that can cause respiratory symptoms, dsyphagia, or superior vena cava syndrome
114
chemical in rodenticides that causes coagulopathy, how to treat. not cryoprecipitate because? not syrup of ipecac because?
- brodifacoum,a long acting 4-hydroxycoumarin derivative
- treat with fresh frozen plasma to replenish vit K dependent clotting factors. can also give vit K (but doesn't work as fast)
- cryoprecipitate contains factors VIII, XIII and vWF and fibrinogen so it wouldn't help here
- emetic treatment is helpful only after immediate ingestion, if pt is bleeding already then it's too late to use this
115
CML vs leukemoid reaction vs AML
- both cause WBC count to increase with left shift (bands, metamyelocytes, and myelocytes) with few blasts
- CML has decreased alkaline phosphatase
- leukemoid has increased or normal alkaline phosphatase
- large number of blasts (myeloblasts)
116
associated cancers
- stains melyoperoxidase positive
- terminal deoxynucleotudyl transferase
- TRAP
- platelet-dervied growth factor receptor mutations
- auer rods in AML
- TdT responsible for adding nucleotides to antibody gene for diversity. marker of immature lymphocytes both B and T cells (ALL)
- mutations in these factors are seen in chronic myelomonocytic leukemia
117
DIC vs TTP-HUS (bleeding, activation, PT and PTT, fibrinogen levels)
- DIC pts bleed, coagulation cascade is activated, PT and PTT are prolonged, low fibrinogen adn increase firbin degradation products (FDP)
- TTP-HUS usually do not bleed, not platelets are activated, normal PT and PTT, normal fibrinogen
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- teardrop cells
- acanthocytes/Spur cells
- target cells
- bite cells/Heinz bodies
- spherocytes
- schistocytes
- myelofibrosis (RBCs have to squeeze through fibrosis in bone marrow)
- cells with irregularly-spaced surface projections. spur cells are extreme form of this and are seen in abetalipoproteinemia
- obstructive live disease, thalassemia, iron defieciency anemia, and asplenism
- G6PD def. causes heinz bodies. spleen removes heinz bodies from RBCs
- autoimmune hemolytic anemia, burns, un-fresh blood smaples
- caused by microemboli, can be seen in DIC
119
atrophic gastritis is associated with malabsorption of
- autoimmune destruction of parietal cells leads to decreased secretion of intrinsic factor
- vit B12, pernicious anemia
120
need to add what to pts blood to help with clotting in hemophilia A or B? why not fibrinogen?
- mutation in factor VIII and factor IX
- add thrombin- converts fibrinogen to fibrin
- fibrinogen is synthesized by liver. don't need to add anymore need thrombin
121
splenic changes in pts with sickle cells anemia
fibrosis, atrophy, brownish discoloration, and eventual autosplenectomy
122
splenic sequestration-mech, age
yong children with sickle cell due to vasoclusion and splenic pooling for RBCs. medical emergency that results in decrease in hemoglobin concentration, rapidly enlarging spleen, and possible hypovolemic shock
-not seen in adults b/c by then autosplenectomy (fibrosis and atrophy) has occur. instead look for infections with encapsulated bac organisms (SHiN+ S. typhi)
123
pts with chronic hemolytic anemia causes macrocytic anemia due to what? not extramedullary erthropoiesis?
- folic acid deficiency. increased erythropoiesis turnover leads to low folic acid. not enough DNA, RNA is not affected. cytoplasmic components accumulate within slowly dividing RBCs leading to macrocytic changes
- b/c this would only cause increased RBC number and not MCV volume
124
presentation of B12 def vs folate def
both cause megaloblastic anemia
- vit B12 leads to neurologic dysfunction while folate does not.
- treatment of vit B12 def with folate alone can worsen neurologic condition due to depleting the concentration for unmethylated cobalamin available for methylmalonyl-CoA processing
125
two treatments for DVT. which is safe in pregnacy?
- warfarin (long term) and heparin (short term)
| - heparin is safe, warfarin is teratogenic
126
amiocaproic acid and tranexamic acid
both in inhibit fibrinolysis by inhibiting plasminogen activation
127
why do RBCS make 2,3 BPG? how is it made? replaces which ATP producing step in glycolysis?
increased 2,3 BPG allows RBCs to release oxygen in peripheral tissues b/c it decreases hb affinity for oxygen.
- 2,3 BPG is produced from 1,3BPG by bisphosphoglycerate mutase
- this consumes energy that would have otherwise been used to make ATP (1,3 BPG to 3-phosphogycerate by phosphoglycerate kinase)
128
AML diagnosis requires? vs ALL and CML?
- more than 20% myleoblasts.
- in ALL there are leukoblasts but no rods
- in CML that are more mature cells and fewer blasts (less than 20% of total leukocytes)
129
which is used long term warfarin or heparin?
warfarin
130
name two direct thrombin inhibitors
lepirudin and agatroban
131
type II and type III hypersensitivity rxns seen in SLE
type II is caused by formation of autoantibodies towards blood cells. this leads to pancytopenia
type III is caused by formation of immune complexes and their deposition within the glomerulus.
132
which portion of the HMP shunt can all cells participate in? which two enzymes mediate this part? name the rxns and necessary cofactors
- non oxidative reversible part
- transketolase and transaldolase
- purpose is to synthesize ribose from fructose-6-phosphate
- tranaldolase converts fructose-6-phophate to glyceraldehyde-3-phosphate
- transketolase converts glyceraldehyde -3 phosphate to ribose-5-phosphate
133
complication of hereditary sphereocytosis is? not autosplenectomy because?
- pigmented gallstones (seen in any form of hemolytic anemia). due to increased bilirubin precipitating as calcium bilirubinate forming pigmented stones in gallbladder
- this is a complication seen in sickle cell anemia
133
complication of hereditary sphereocytosis is? not autosplenectomy because?
- pigmented gallstones (seen in any form of hemolytic anemia). due to increased bilirubin precipitating as calcium bilirubinate forming pigmented stones in gallbladder
- this is a complication seen in sickle cell anemia
134
female pt with iron deficiency anemia and intermittent mucosal bleeding has? not immune thrombocytopenic purpura b/c?
- von willebrand factor deficency, most pts with this disease have a history of gingical bleeding, epistaxis, mucosal bleeding, and or menorrhagia
- causes isolate thrombocytopenia with episodic bleeding which is typically mucocutanteous (petchiae and purpura). also bleeding is not chronic and is unlikely to cause iron def anemia
134
female pt with iron deficiency anemia and intermittent mucosal bleeding has? not immune thrombocytopenic purpura b/c?
- von willebrand factor deficency, most pts with this disease have a history of gingical bleeding, epistaxis, mucosal bleeding, and or menorrhagia
- causes isolate thrombocytopenia with episodic bleeding which is typically mucocutanteous (petchiae and purpura). also bleeding is not chronic and is unlikely to cause iron def anemia
135
fondaparinux vs enoxaparin
- synthetic pentasaccharide factor Xa inhibitor. does not inhibit thrombin
- low molecular weight heparin that inhibits factor X but doesn't inhibit thrombin
135
HUS affects which lab value complement or bleeding time? why?
bleeding time
not complement b/c even though there's renal damage in HUS (oligouria) it's not due to immune-complex depositions like in post-streptococcal glomerulonephritis
136
which form of heparin can bind antithrombin to inhibit both factor Xa and thrombin? which can only inhibit factor X
- unfractionated heparin (largest one)
| - low molecular weight (i.e enoxaparin)
137
fondaparinux vs enoxaparin
- synthetic pentasaccharide factor Xa inhibitor. does not inhibit thrombin
- low molecular weight heparin that inhibits factor X but doesn't inhibit thrombin
138
name some diseases that can cause autoimmune hemolytic anemia
-mycoplasma and EBV
139
HUS-TTP vs DIC
- normal PT and PTT
| - abnormal PT and PTT
140
HUS vs TTP
both have pentad: fever, CNS manifestations, renal involvement, thrombocytopenia, microangiopathic hemolytic anemia
- children predominant renal involvement
- adults predominant CNS involvment
141
% values for sickle cell trait. addition of which factor can cause sickling.
- >50% HbA and 35-40% HbS
| - sodium metabisulfite
142
mech of drugs used to treat sickle cell anemia
- increased fetal hemoglobin
- hinder eflflux of potassium and water from cel
- hydroxyurea
| - Gardos channel blockers (prevent dehydration)
143
which deficiency is more common in alcoholics b12 (cobalamin) or folate? blood smear findings?
- folate is more common
| - macrocytosis, ovalocytosis and neutrophils with hypersegemented nuclei
144
role of desmospressin acetate (DDAVP) in renal ds and hematological ds
- ADH analog used in treatment of diabetes insipidus
- acts on endothelial* cells to increase release of vWF and factor VIII in mild to moderate hemophilia A but has no effect on hemophila B
145
mech of drugs used to treat sickle cell anemia
- increased fetal hemoglobin
- hinder eflflux of potassium and water from cel
- hydroxyurea
| - Gardos channel blockers (prevent dehydration)
146
which deficiency is more common in alcoholics b12 (cobalamin) or folate? blood smear findings?
- folate is more common
| - macrocytosis, ovalocytosis and neutrophils with hypersegemented nuclei
150
role of desmospressin acetate (DDAVP) in renal ds and hematological ds
- ADH analog used in treatment of diabetes insipidus
| - acts on endothelial* cells to increase release of vWF and factor VIII
151
presence of erythoid precursors in organs such as liver and spleen indicates? not EPO deficiency because?
- extramedullary hematopoiesis from chronic hemolytic anemias like beta thalassemia-chimpmunk facies
- not EPO b/c that would cause anemia from chronic renal disease not extramedullary hematopoiesis
152
PV is associated with what mutation? not an over expression of endothelial growth factor because?
- mutation in JAK2, a non-receptor tyrosine kinase* associated with EPO receptor a type 1 cytokine receptor
- VEGF is required for tumor angiogenesis and is seen in tumors
153
non-receptor tyrosine kinase signaling vs receptor tyrosine kinase signalling
- receptor is not an enzyme. so binding of antigen cause recruitment of Janus kinase (or any cytoplasmic tyrosine kinase) to phosphorylate the cytosolic portion of the receptor. phosphorylation leads to recruitment and activation of STAT which dimerizes and translocates to nucleus
- receptor is an enzyme, so binding of antigen leads to auto-phosphorylation leading to recruitment of SH2 adapter protein which then activates RAS GTPase and further downstream signaling.
154
if you see a pt with hypochromic, microcytic anemia. what should be ruled out first?
most likely caused by iron deficiency, rule out blood loss (esp in GI tract) first
155
mech of warfarin skin necrosis. not allergic drug rxn b/c.
- it's not due to a drug rxn
- instead warfarin can induce a transient procoagulant state due to decreased protein C/S at initiation of treatment (short 1/2 life). in a pt with protein C or S deficiency this can cause a relative hypercoaguable state with thrombotic occlusion of microvasculature and skin necrosis
156
process of bilirubin uptake and secretion. which can be excreted in urine
- liver takes up indirect (unconjugated bilirubin) through a passive process
- liver secretes direct (conjugated) bilirubin through an active process
- conjugated bilirubin is water soluble, non toxic, and only loosely bound to albumin
157
def pure red cell aplasia. what is it associated with?
rare form of marrow failure with severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis
-thymoma/ lymphcytic leukemias (IgG autoantibodies and cytotoxic T lymphocytes) and parvovirus B19 (preferentially attacks and destroys proerythroblasts)
158
uterine fibroids can cause what two blood disorders?
- microcytic hypochromic anemia (bleeding decreases iron)
| - polycythemia if it produces EPO
159
serious complication of
- ticlopidine
- abciximab
- heparin
- neutropenia is seen in about 1% ofpt. WBC show be monitored bi weekly for 1st 3 months
- thrombocytopenia (usually within 24hrs)
- thrombocytopenia
160
vit B12 deficiency result in homocystienemia due to decreased levels of? not methymalonyl CoA because?
- methylmalonyl CoA is converted to succinyl CoA via methylmalony-CoA mutase which requires B12 as a cofactor. without B12 mm-CoA is increased
- homocysteine+ N-5 methyl THF is converted to methionine+THF via methionine synthase which requires B12. This leads to increased homocystien levels and decreased methionine levels
161
subluxation of eyes
- down and in
- up and out
- homocystinuria
| - Marfan's
162
multiple mylenoma is associated with what complicaitons
- normocytic and nonmorchromic anemia (bone marrow infiltration and normal cell replacement)
- neoplastic cells secrete IL-1 (osteoclast activating factor) and IL-6 leading to bone resorption (punched out lytic lesions on x-ray)
- hypercalcemia (increased bone resorption); manifests as fatigue, confusion, and constipation
- increased susceptibility to infection
- M protein and serum monoclonal light chains (Bence-Jones protein)
- Al amyloid (accumulation of monoclonal immunoglobin light chains)
- renal failure (crom amyloid, Bence-Jones cast, calcification from hypercalcemia, and inflammation from macs and giant cells)
THINK CRABS (Hyper Ca2+, Renal insufficiency, Anemia, Bone lytic lesions/Back pain)
163
levels of what increase with B12 replacement therapy
reticulocyte levels increase dramatically and hemoglobin more gradually.
-both homocysteine and methylmalonic levels are increased in B12 def and return to normal once B12 is added to therapy
164
bone marrow blast identification:
- TdT+ and PAS material?
- CD 19 and CD 10 vs CD 1, CD2, or CD 5
- peroxidase positive granules (aka?)
-lymphoblast (i.e ALL)
underneath lymphoblast it can be precursor B cell type (CD19/CD10) or precursor T cell type (CD1/CD2/CD5)
-peroxidase positive granules are also known as Auer rods
165
if a sickle cell pt is septic think
| if they have osteomyelitis think
- encapsulated organisms (Streptococcus pneumoss and H. influenza)
- salmonella* Staph aureus and E. coli
166
anemia caused by vit b6
hypochromic, microcytic, pyridoxine-responsive sideroblastic anemia
167
when is HbA2 elevated
| when is HbA1c elevated
- beta-thalassemia minor and beta-thalassemin intermedia
| - DM
168
dusky discoloration of the skin?
methmeoglobinemia
169
inheritance of G6PD and herediatary sphereocytosis
- X-linked recessive
| - autosomal dominant
170
treating vit B12 def it what can worsen neurological symptoms?
folate. both present similarly
