Heme/Onc Flashcards
(146 cards)
1
Q
Heme synthesis precursors
A
succinyl-Coa and glycine
2
Q
General cause of microcytic/hypochromic anemia
A
Hb synthesis impairment
3
Q
General cause of macrocytic/normochromic anemia
A
impaired DNA synthesis
4
Q
Cyclic flu-like sx
seizures
hemoglobinuria
sausage shaped organisms of microscopy
A
Plasmodium falciparum (malaria) worst type P vivax and P. ovale cause relapsing sx
5
Q
Tx for malaria
A
chloroquine for nonsevere
quinine/quinidine for severe
primaquine for vivax/ovale (liver hypnozoite stage)
Doxycycline for prophylaxis
All drugs use caution with G6PD deficiency or pregnancy
6
Q
Pear shaped trophoziotes
maltese cross seen
hemolytic anemia
A
Babesiosis
caused by black legged tick (ixodes scapularis), same is B. burgdorferi (Lyme’s)
7
Q
Hx of African travel
chancre
pruritis/fever
progresses into seizures/somnolence
A
Trypanosoma brucei, african sleeping sickness
tsetse fly vector
hemolytic and CNS stages
tx with suramin for hemolytic, melarsoprol for CNS
8
Q
unilateral painless periorbital edema in a child
anorexia and lesion of inflammation
chronic cardio and GI pathology
A
Trypanosomia cruzi (Chagas disease)
Romana’s sign and chagoma seen
vector is reduviid (kissing) bugs
9
Q
Dx for Trypanosomiasosis
A
Giemsa stain smear
10
Q
Ulcerating lesions that spontaneously heal
Lesions on nasal mucosa with erosion
skin blackens/systemic infection
Tx with Na+ stibogluconate
A
Leishmaniasis
L. braziliensis causes erosion on face
L. donovani causes black poison/Kalaazar (visceral necrosis)
Vector is sandflies
11
Q
Intrinsic clotting pathway
A
Factor XII, XI, IX, X (in that order)
12
Q
Extrinsic clotting pathway
A
Factor VII to X
13
Q
Common clotting pathway
A
Factor X & V, thrombin, fibrin (in that order)
14
Q
Stimulators of clotting pathways
A
intrinsic-kallikrein/kininogen
extrinsic-trauma to vasculature
15
Q
Clot formation pathway (from thrombin)
A
thrombin cleaves fibrinogen to fibrin
fibrin aggregates with platelets (via GP IIb/IIIa)
factor XIIIa cross links to hard clot (via Lysine covalent bond to N-terminus)
16
Q
Endogenous inhibits of clotting
A
thrombomodulin (activates protein C/binds thrombin)
heparan sulfate (activates ATIII)
prostacycline (inhibits platelet aggregation)
Protein C inactiveas factors Va and VIIIa
17
Q
Factor VIII deficiency
hemarthrosis
A
Hemophilia A
X linked recessive
18
Q
Factor IX deficiency
hemarthrosis
A
Hemophilia B
X linked recessive
19
Q
AD inheritance
decreased factor VIII delivery
mucous membrane bleeding
A
von Willebrand disease
normal platelet counts
20
Q
ineffective protein C/S coagulation inactivation
AD
hypercoaguability
A
Factor V Leiden mutation
factor V resistant to protein S/C inactivation
21
Q
Levels of this protein decrease with active intravascular hemolysis
A
Haptoglobin
bind free Hb
protects kidney from Hb
22
Q
AR
bronze skin color
diabetes sx
dx with hepatocellular carcinoma
A
Hemochromatosis
defect in HFE gene (chromosome 6)
excessive iron storage
23
Q
Levels of molecule are eleveated in multiple myeloma
A
gamma-globulin
24
Q
Petechial rash starts from limbs and moves to trunk
tx with doxycycline
A
Rickettsia rickettsii
dog/wood tick vector
Rocky Mountain spotted fever
liver/brain/skin sx
25
Mite vector/mice reservoir
| papule at bite site, crusts over
Rickettsia akari
| Rickettsial pox
26
body lice vector/flying squirrel
| pink macules on upper trunk, spread outward
Rickettsia prowazekii
epidemic typhus
Brill-Zinsser Disease (recurrence years later)
27
Flea vector
U.S. Gulf coast
rash on chest and abd
Rickettsia typhi
endemic typhus
low mortality
28
Chiggers/mites/rodents vector
scab at bite site
flat maculopapular rash
Orientia tsutsugamushi
scrub typhus
Asia and SW pacific
29
Infection of WBC's
tick vector
rash with thrombocytopenia
Ehrlichiosis
Monocyte-E. chaffeensis
Granulocyte-Anaplasma phagocytophilum
morulae on Giemsa stain
30
Tick vector
US NE/Wisconsin
tx with doxycycline
Borrelia burgdorferi
bulls eye rash
migratory arthralgias
31
Recent trip to Hawaii for surfing
invasion of CSF and blood
recurring sx
```
Leptospira interrogans
animal urine is cause
Weil Syndrome (liver/blood/CNS)
```
32
Poor hygiene
bone pain in back/legs
recurs every 5 days
Bartonella quintana
trench fever
tx with doxy
33
Trip to South America
anemia
Sandfly vector
blood filled nodules in skin
Bartonella bacilliformis
oroya fever/carrion disease
infects RBCs
34
Low serium Fe and ferritin
increased TIBC
GI bleed
iron deficiency anemia
| microcytic/hypochromic
35
Microcytic anemia
| esophageal webs
Plummer-Vinson syndrome
| also see atrophic glossitis
36
Hypersegmented neutrophils (5+nuclei)
vision loss
loss of sensory/motor
Pernicious anemia, megaloblastic (B12 deficiency)
| macrocytic/normochromic
37
AR
defect in DNA repair
aplastic anemia
Fanconi's syndrome
38
Assc with aplastic anemia
thymoma
39
Jaundice/anemia
increased LDH and reticulocytes
decreased Hb and haptoglobin
Hemolytic anemia
40
increased osmotic fragility
round RBCs
splenomegaly
Hereditary spherocytosis
mutated spectrin/ankyrin/band 3 or 4.2 protein
AD in whites
41
Aplastic crisis with hereditary spherocytosis assc
parvovirus B19
42
Bite and spherocyte RBCs
Heinz bodies in RBCs
AR in blacks/mediterannean
G6PD deficiency
lack of NADPH to reduce GS
causes oxidative damage to RBCs
43
```
Chronic hemolytic anemia
AR in blacks
vessel occlusions
splenomegaly
gallstones
```
Sicke Cell disease
Glutamate to Valine at pos 6 on beta globin
Heterozygote malarial resistance
44
Bug risks for Sickle Cell
encapsulated organism infection
aplastic crisis with parvovirus B19
osteomyelolitis with salmonella
45
```
Hb Bart (gamma tetramers) in blood
early death
```
Alpha-thalassemia (hydrops fetalis)
| all 4 genes deleted
46
IgG against RBC Ags
spherocytes/splenomegaly
direct Coomb's test (+)
Warm autoimmune hemolytic anemia
| hapten or drug + RBC=new Ag
47
IgM against RBC's
worse in winter
assc with MGUS
Cold autoimmune hemolytic anemia
pentamers bind in cold periphery, release when returning to body core
Causes complement/hemolysis
48
RBCs lack CD55 and CD59
chronic hemolysis
hypercoaguable
Paroxysmal noctural hemoglbinuria
CD55/CD59 usually prevents complement
lysis by endogenous complement
49
depletion of coagulation factors
concurrent clotting and fibrinolysis
has promyelocytic leukemia
Disseminated intravascular coagulation
assc with infection/malignancy
uncontrolled fibrinolytic &clotting system activation
50
Schistocytes
neuro/kidney sx
lg bruises
Thrombotic thrombocytopenic purpura
Abs or defect of ADAMTS13
pentad of sx FAT RN
51
AR
increased bleeding
platelet aggregations in blood
Bernard Soulier syndrome
defect in IbIX on platelet
cannot bind subendothelium
52
AR
increased bleeding
normal platelet morphology
Glanzmann Thrombasthenia
defect in IIb/IIIa
platelets cannot bind fibrinogen
53
Risk of thienopyridines
can cause TTP (especially ticlopidine)
inhibit ADP/platelet aggregation
ticlopidine/clopidogrel/prasugrel
54
Clopidogrel drawback
poor responders due to being a prodrug
55
Prasugrel contraindications
over 75
TIA or CVA hx
less than 60kg
56
Only nonthienopyridine ADP antagonist
ticagrelor
57
GP IIb/IIIa inhibitors
abciximab
eptifibatide
tirofiban
they prevent fibrinogen platelet aggregation
58
Phosphodiesterase inhibitors for anticoagulation
dipyridamole
cilostazol
for tx of ambulatory claudication
59
Warfarin effects
increased INR/PT
| stops factors II, VII, IX, X, C and S protein synthesis
60
Need before warfarin therapy in thrombotic pt
start heparin first
| prevents paradoxical hypercoagulability
61
Tx for warfarin overdose
Vit K and frozen plasma
62
Side effect caused by protein C and S deficiency with warfarin
skin necrosis
63
Unfractionated heparin MOA/risk
complexes with antithrombin III/thrombin
can cause heparin induced thrombocytopenia
tx with direct thrombin inhibitors
64
Tx for heparin overdose
protamine sulfate
65
Heparin induced thrombocytopenia
caused by IgG+heparin+PF4 complex
causes platelet aggregation
tx with direct thrombin inhibitor
66
Direct thrombin inhibitors
lepirudin/bivalirudin/argatroban/dabigatran
| dabigatran is only oral one
67
Factor Xa inhibitors
fondaparinux/rivaraxaban/apixaban
| no antidote
68
Fondaparinux
factor Xa inhibitor
binds antithrombin III
used for DVT/PE
69
Rivaraxaban/apixaban
```
factor Xa inhibitors
do not bind antithrombin III
used for tx of A fib to reduce stroke risk
both need renal dose adjustment
need to anticoagulate when taking off
```
70
Anticoagulation/platelet drugs needing renal adjustment dose
LMWH
dabigatran (direct thrombin inhibitor)
rivaroxaban/apixaban (Xa inhibitors)
71
Mismatch blood type rxn
type II hypersensitivity
72
MHC I and II genes
MHC I- A,B,C
| MHC II- DP, DQ, DR
73
Hyperacute graft rejection
preexisting host Abs to graft Ags
type II HS
complement activated
74
Matching needed for transplants:
heart
liver
bone marrow
heart-blood type, MHC II if possible
liver-blood type
bone marrow-HLA and ABO typing needed
75
Definitions:
autograft
isograft/syngeneic
allograft
autograft-from self
isograft-from identical twin
allograft-from same species
76
Cause of ABO blood type production
gut colonization of bacteria
A&B- IgM
O-IgG
77
Ability of A and B blood types to agglutinate
IgM larger than IgG of O type
spans zeta-potential
allows agglutination b/t RBC's
78
Rh Ag
D is most antigenic
on chromosome 1
nonagglutinating IgG
causes extravascular hemolysis
79
ABO blood typing methods
forward type- detect Ags
| Reverse type- detect Abs
80
Pt has transplant and is not infected by a bug, which is most likely?
CMV
| Hep B/C
81
Low back pain
hematuria
increased IgM/IgG
acute hemolytic rxn
| factor XII/kinin activated clotting
82
Contents of platelet granules:
alpha
dense
lysosomes
alpha-vWF/fibrinogen/factor V/PAI-1 (platelet adhesion)
dense-ADP/5HT/Ca2+ (platelet aggregation)
lysosomes-acid hydrolases
83
What prevents fibrinolysis endogenously?
PAI-1 via t-PA inhibition
| alpha2-antiplasmin via plasmin
84
What activates plasmin?
t-PA converts plasminogen to plasmin
| plasmin then degrade fibrin clots
85
Increased PT and aPTT
(+) D-dimer
bleeding/microvascular thrombi
Disseminated intravascular coagulation
| decreased platelets and fibrinogen
86
Lg multimers of vWF bound to platelets
schistocytes
normal PT and aPTT
thrombotic thrombocytopenic purpura
| ADAMTS-13 defect (normally degrades vWF multimers)
87
Mucocutaneous bleeding
AR
no clotting
Glanzmann thrombasthenia
| abn GP IIb/IIIa, no platelet aggregation
88
Giant platelet aggregates in blood
thrombocytopenia
AR
increased bleeding
Bernard-Soulier syndrome
abn GP Ib/IX-V or vWF receptor
not platelet adhesion
89
Lab seen with beta-thalassemia
compensatory increase in alpha and gamma globulins (fetal Hb)
90
Pt with vaso-occlusive events
splenomegaly
pt tx with hydroxyurea, how does it improve the condition?
for Sickle Cell, hydroxyurea increases gamma globin gene production
gamma globin does not sickle and will not cause vaso-occlusions
91
Increased LDH/AST
(+) direct Coombs test
schistocytes/spheroctyes seen
Warm autoimmune hemolytic anemia
| IgG mediated
92
Pt has anemia following a URT infection
| gets worse in the cold
Cold autoimmune hemolytic anemia
| Igm mediated
93
AR
jaundice seen in 5 day y/o child
european descent
Pyruvate kinase deficiency
| from decreased ATP production in RBC's
94
Loss of fine touch/vibration/proprioception
alcoholic
anemia
B12 deficiency anemia
megaloblastic anemia
pernicious anemia can cause
alcohol/ileum problems can cause
95
```
Normal RBCs
anemia
increased reticulocytes
AD
(-) Coombs test
```
Hereditary spherocytosis
defect in ankyrin/spectrin/band 3.1
(+) osmotic fragility test
96
Howell-Jolly bodies are seen in RBC's. What does that signify?
Pt had a splenectomy
97
Hypercoaguablility in young white male
| G1691A gene mutation
Factor V Leiden
| factor V cannot be inactivated by protein C or S
98
Prothrombin gene mutation effect
increased levels of prothrombin
hypercoaguable
due to 3' UTR gene mutation (increased transcription)
99
```
Livedo reticularis (arterial clots)
TIA's
```
Antiphospholipid syndrome
| anticoagulant and cardiolipin Abs
100
Tx for acute MI/massive PE/limb DVT/acute stroke within 90 mins of onset
thrombolytics (t-PA/streptokinase)
activate plasmin
must be followed by UFH within 24hrs
101
Location of lymphoma
tumor mass in LN
102
Leukemoid reaction
response to infection
| increasedWBC/left shit/leukocyte alkaline phosphatase
103
Hodgkin's lymphoma characteristics
```
single group of nodes (contiguous spread)
Reed-Sternberg cells
bimodal (20's and over 60)
assc with EBV
B sx (night sweat/wt loss)
```
104
Non Hodgkin's lymphoma presentation
multiple peripheral LN involved
extranodal involvement
B cells
20-40 y/o
105
Reed-Sternberg cell description
tumor giant cell
binucleate/bilobed (mirror images)
CD30 and CD15 (+)
B cell origin
106
African child
jaw lesion
Starry sky appearance
Burkitt's lymphoma
t(8:14) causing c-myc promoted by Ig heavy chain
assc with EBV
107
Mantle Cell lymphoma
t(11:14)
cyclin D1 and Ig heavy chain
CD5 (+)
108
Follicular lymphoma
t(14:18)
bcl-2 and Ig heavy chain
bcl-2 inhitis apoptosis
indolent course
109
Adult T cell lymphoma
caused by HTLV-1
in Japan/Africa/Caribbean
cutaneous lesions
110
Mycosis fungoides/Sezary syndrome
adults with cutaneous patches/nodules
CD4 (+)
indolent
111
```
Fried egg appearance
lg amounts of IgG or IgA
lytic bone lesions
renal failure
anemia
```
```
Multiple myeloma (from marrow)
M spike of protein
Bence Jones protein (light chain) damages kidney
Rouleaux formation (stacked RBC's)
clock face chromatin
```
112
Monoclonal gammopathy of undetermined significance
MGUS
increased M spike (excess Ig's made)
precursor to multiple myeloma (1%/per progress)
113
Acute lymphoblastic leukemia/lymphoma
```
children
TdT (+) and CALLA (+)
increased lymphocytes
t(12:21) better prognosis
can spread to CNS
```
114
Chronic lymphocytic leukemia (small lymphocytic lymphoma)
over 60 y/o
smudge cells on peripheral blood smear
autoimmune hemolytic anemia
SLL has less lymphocytosis in periphery
115
Hairy cell leukemia
in adults
mature B cell tumor
hair like projections on cells
stains TRAP (+)
116
Acute myelogenous leukemia
```
over 65 y/o
Auer rods
increased myeloblasts in periphery
t(15:17)
responds to retinoic acid
DIC is common presentation with M3 AML
```
117
Chronic myelogenous leukemia
```
30-60 yrs
Philadelphia chromosome t(9:22)
bcrl-abl fusion protein
blast crisis, progresses to AML/ALL
splenomegaly
responds to imatinib (tyrosine kinase inhibitor)
```
118
Auer rods
peroxidase (+) inclusions in granulocytes/myeloblasts
seen in M3 AML
can be released and cause DIC
119
CML translocation
Philadelphia chromosome
t(9:22)
bcr-abl
120
Burkitt's lymphoma translocation
t(8:14)
| c-myc activation
121
Mantle cell lymphoma translocation
t(11:14)
| cyclin D1 activation
122
Follicular lymphoma translocation
t(14:18)
| bcl-2 activation
123
M3 type of AML translocation
t(15:17)
| responds to all trans retinoic acid (Vit A)
124
Child
lytic bone lesions
skin rash
Birbeck granules (tennis rackets on EM)
Langerhans cell histiocytosis
dendritic cell disorder
cannot stimulate T lymphoctyes with Ag presenting
cells express S-100 (neural crest) and CD1a
125
Polycythemia vera
abn clone of HSCs with JAK2 receptors active
proliferate without EPO
type of myeloproliferative disorder
126
Essential thrombocytosis
uncontrolled
| proliferation of megakaryocytes
127
MOA of methotrexate
inhibits dihydrofolate reductase
| can cause mucositis
128
MOA of 5-FU
inhibits thymidylate synthase
| no dTMP, and therefor no DNA synthesis
129
MOA of 6-Merrcaptopurine/azathioprine/6-TG
purine analogs
| activated by HGPRT
130
MOA of dactinomycin
intercalates in DNA
131
MOA of doxorubicin
generates free radicals
intercalates in DNA
causes breaks
132
MOA of bleomycin
induces free radical formation
| causes DNA breaks
133
MOA of cyclophosphamide
X link DNA at guanine N-7
| activated by the liver
134
Use of nitrosoureas
for CNS tumors
135
MOA of busulfan
alkylates DNA
| for CML
136
MOA of vinblastine/vincristine
bind tubulin in M phase
| blocks polymerization
137
Side effects of vinblastine/vincristine
vincristine-neurotoxicity
| vinblastine-myelosuppression
138
MOA of cisplatin
cross links DNA
139
MOA of etoposide/teniposide
inhibits topoisomerase II
| increased DNA degradation
140
MOA of hydroxyurea
inhibits ribonucleotide reductase
decreased DNA synthesis
also for Sickle cell (increased HbF)
141
MOA of prednisone
triggers apoptosis
142
MOA of Tamoxifen
receptor antagonist in breast/agonist in bone
| blocks binding of estrogen
143
MOA of trastuzumab
Ab against HER-2 (c-erbB2), a tyrosine kinase
| for HER-2 breast cancer
144
MOA of imatinib
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
| for CML
145
MOA of rituximab
Ab against CD20 in B cell neoplasms
146
MOA of bevacizumab
Ab against VEGF
| inhibits angiogenesis of tumors
