Heme/Onc Flashcards
Heme synthesis precursors
succinyl-Coa and glycine
General cause of microcytic/hypochromic anemia
Hb synthesis impairment
General cause of macrocytic/normochromic anemia
impaired DNA synthesis
Cyclic flu-like sx
seizures
hemoglobinuria
sausage shaped organisms of microscopy
Plasmodium falciparum (malaria) worst type P vivax and P. ovale cause relapsing sx
Tx for malaria
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
Pear shaped trophoziotes
maltese cross seen
hemolytic anemia
Babesiosis
caused by black legged tick (ixodes scapularis), same is B. burgdorferi (Lyme’s)
Hx of African travel
chancre
pruritis/fever
progresses into seizures/somnolence
Trypanosoma brucei, african sleeping sickness
tsetse fly vector
hemolytic and CNS stages
tx with suramin for hemolytic, melarsoprol for CNS
unilateral painless periorbital edema in a child
anorexia and lesion of inflammation
chronic cardio and GI pathology
Trypanosomia cruzi (Chagas disease)
Romana’s sign and chagoma seen
vector is reduviid (kissing) bugs
Dx for Trypanosomiasosis
Giemsa stain smear
Ulcerating lesions that spontaneously heal
Lesions on nasal mucosa with erosion
skin blackens/systemic infection
Tx with Na+ stibogluconate
Leishmaniasis
L. braziliensis causes erosion on face
L. donovani causes black poison/Kalaazar (visceral necrosis)
Vector is sandflies
Intrinsic clotting pathway
Factor XII, XI, IX, X (in that order)
Extrinsic clotting pathway
Factor VII to X
Common clotting pathway
Factor X & V, thrombin, fibrin (in that order)
Stimulators of clotting pathways
intrinsic-kallikrein/kininogen
extrinsic-trauma to vasculature
Clot formation pathway (from thrombin)
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)
Endogenous inhibits of clotting
thrombomodulin (activates protein C/binds thrombin)
heparan sulfate (activates ATIII)
prostacycline (inhibits platelet aggregation)
Protein C inactiveas factors Va and VIIIa
Factor VIII deficiency
hemarthrosis
Hemophilia A
X linked recessive
Factor IX deficiency
hemarthrosis
Hemophilia B
X linked recessive
AD inheritance
decreased factor VIII delivery
mucous membrane bleeding
von Willebrand disease
normal platelet counts
ineffective protein C/S coagulation inactivation
AD
hypercoaguability
Factor V Leiden mutation
factor V resistant to protein S/C inactivation
Levels of this protein decrease with active intravascular hemolysis
Haptoglobin
bind free Hb
protects kidney from Hb
AR
bronze skin color
diabetes sx
dx with hepatocellular carcinoma
Hemochromatosis
defect in HFE gene (chromosome 6)
excessive iron storage
Levels of molecule are eleveated in multiple myeloma
gamma-globulin
Petechial rash starts from limbs and moves to trunk
tx with doxycycline
Rickettsia rickettsii
dog/wood tick vector
Rocky Mountain spotted fever
liver/brain/skin sx
Mite vector/mice reservoir
papule at bite site, crusts over
Rickettsia akari
Rickettsial pox
body lice vector/flying squirrel
pink macules on upper trunk, spread outward
Rickettsia prowazekii
epidemic typhus
Brill-Zinsser Disease (recurrence years later)
Flea vector
U.S. Gulf coast
rash on chest and abd
Rickettsia typhi
endemic typhus
low mortality
Chiggers/mites/rodents vector
scab at bite site
flat maculopapular rash
Orientia tsutsugamushi
scrub typhus
Asia and SW pacific
Infection of WBC’s
tick vector
rash with thrombocytopenia
Ehrlichiosis
Monocyte-E. chaffeensis
Granulocyte-Anaplasma phagocytophilum
morulae on Giemsa stain
Tick vector
US NE/Wisconsin
tx with doxycycline
Borrelia burgdorferi
bulls eye rash
migratory arthralgias
Recent trip to Hawaii for surfing
invasion of CSF and blood
recurring sx
Leptospira interrogans animal urine is cause Weil Syndrome (liver/blood/CNS)
Poor hygiene
bone pain in back/legs
recurs every 5 days
Bartonella quintana
trench fever
tx with doxy
Trip to South America
anemia
Sandfly vector
blood filled nodules in skin
Bartonella bacilliformis
oroya fever/carrion disease
infects RBCs
Low serium Fe and ferritin
increased TIBC
GI bleed
iron deficiency anemia
microcytic/hypochromic
Microcytic anemia
esophageal webs
Plummer-Vinson syndrome
also see atrophic glossitis
Hypersegmented neutrophils (5+nuclei)
vision loss
loss of sensory/motor
Pernicious anemia, megaloblastic (B12 deficiency)
macrocytic/normochromic
AR
defect in DNA repair
aplastic anemia
Fanconi’s syndrome
Assc with aplastic anemia
thymoma
Jaundice/anemia
increased LDH and reticulocytes
decreased Hb and haptoglobin
Hemolytic anemia
increased osmotic fragility
round RBCs
splenomegaly
Hereditary spherocytosis
mutated spectrin/ankyrin/band 3 or 4.2 protein
AD in whites
Aplastic crisis with hereditary spherocytosis assc
parvovirus B19
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
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
Bug risks for Sickle Cell
encapsulated organism infection
aplastic crisis with parvovirus B19
osteomyelolitis with salmonella
Hb Bart (gamma tetramers) in blood early death
Alpha-thalassemia (hydrops fetalis)
all 4 genes deleted
IgG against RBC Ags
spherocytes/splenomegaly
direct Coomb’s test (+)
Warm autoimmune hemolytic anemia
hapten or drug + RBC=new Ag
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
RBCs lack CD55 and CD59
chronic hemolysis
hypercoaguable
Paroxysmal noctural hemoglbinuria
CD55/CD59 usually prevents complement
lysis by endogenous complement
depletion of coagulation factors
concurrent clotting and fibrinolysis
has promyelocytic leukemia
Disseminated intravascular coagulation
assc with infection/malignancy
uncontrolled fibrinolytic &clotting system activation
Schistocytes
neuro/kidney sx
lg bruises
Thrombotic thrombocytopenic purpura
Abs or defect of ADAMTS13
pentad of sx FAT RN
AR
increased bleeding
platelet aggregations in blood
Bernard Soulier syndrome
defect in IbIX on platelet
cannot bind subendothelium
AR
increased bleeding
normal platelet morphology
Glanzmann Thrombasthenia
defect in IIb/IIIa
platelets cannot bind fibrinogen
Risk of thienopyridines
can cause TTP (especially ticlopidine)
inhibit ADP/platelet aggregation
ticlopidine/clopidogrel/prasugrel
Clopidogrel drawback
poor responders due to being a prodrug
Prasugrel contraindications
over 75
TIA or CVA hx
less than 60kg
Only nonthienopyridine ADP antagonist
ticagrelor
GP IIb/IIIa inhibitors
abciximab
eptifibatide
tirofiban
they prevent fibrinogen platelet aggregation
Phosphodiesterase inhibitors for anticoagulation
dipyridamole
cilostazol
for tx of ambulatory claudication
Warfarin effects
increased INR/PT
stops factors II, VII, IX, X, C and S protein synthesis
Need before warfarin therapy in thrombotic pt
start heparin first
prevents paradoxical hypercoagulability
Tx for warfarin overdose
Vit K and frozen plasma
Side effect caused by protein C and S deficiency with warfarin
skin necrosis
Unfractionated heparin MOA/risk
complexes with antithrombin III/thrombin
can cause heparin induced thrombocytopenia
tx with direct thrombin inhibitors
Tx for heparin overdose
protamine sulfate
Heparin induced thrombocytopenia
caused by IgG+heparin+PF4 complex
causes platelet aggregation
tx with direct thrombin inhibitor
Direct thrombin inhibitors
lepirudin/bivalirudin/argatroban/dabigatran
dabigatran is only oral one
Factor Xa inhibitors
fondaparinux/rivaraxaban/apixaban
no antidote
Fondaparinux
factor Xa inhibitor
binds antithrombin III
used for DVT/PE
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
Anticoagulation/platelet drugs needing renal adjustment dose
LMWH
dabigatran (direct thrombin inhibitor)
rivaroxaban/apixaban (Xa inhibitors)
Mismatch blood type rxn
type II hypersensitivity
MHC I and II genes
MHC I- A,B,C
MHC II- DP, DQ, DR
Hyperacute graft rejection
preexisting host Abs to graft Ags
type II HS
complement activated
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
Definitions:
autograft
isograft/syngeneic
allograft
autograft-from self
isograft-from identical twin
allograft-from same species
Cause of ABO blood type production
gut colonization of bacteria
A&B- IgM
O-IgG
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
Rh Ag
D is most antigenic
on chromosome 1
nonagglutinating IgG
causes extravascular hemolysis
ABO blood typing methods
forward type- detect Ags
Reverse type- detect Abs
Pt has transplant and is not infected by a bug, which is most likely?
CMV
Hep B/C
Low back pain
hematuria
increased IgM/IgG
acute hemolytic rxn
factor XII/kinin activated clotting
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
What prevents fibrinolysis endogenously?
PAI-1 via t-PA inhibition
alpha2-antiplasmin via plasmin
What activates plasmin?
t-PA converts plasminogen to plasmin
plasmin then degrade fibrin clots
Increased PT and aPTT
(+) D-dimer
bleeding/microvascular thrombi
Disseminated intravascular coagulation
decreased platelets and fibrinogen
Lg multimers of vWF bound to platelets
schistocytes
normal PT and aPTT
thrombotic thrombocytopenic purpura
ADAMTS-13 defect (normally degrades vWF multimers)
Mucocutaneous bleeding
AR
no clotting
Glanzmann thrombasthenia
abn GP IIb/IIIa, no platelet aggregation
Giant platelet aggregates in blood
thrombocytopenia
AR
increased bleeding
Bernard-Soulier syndrome
abn GP Ib/IX-V or vWF receptor
not platelet adhesion
Lab seen with beta-thalassemia
compensatory increase in alpha and gamma globulins (fetal Hb)
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
Increased LDH/AST
(+) direct Coombs test
schistocytes/spheroctyes seen
Warm autoimmune hemolytic anemia
IgG mediated
Pt has anemia following a URT infection
gets worse in the cold
Cold autoimmune hemolytic anemia
Igm mediated
AR
jaundice seen in 5 day y/o child
european descent
Pyruvate kinase deficiency
from decreased ATP production in RBC’s
Loss of fine touch/vibration/proprioception
alcoholic
anemia
B12 deficiency anemia
megaloblastic anemia
pernicious anemia can cause
alcohol/ileum problems can cause
Normal RBCs anemia increased reticulocytes AD (-) Coombs test
Hereditary spherocytosis
defect in ankyrin/spectrin/band 3.1
(+) osmotic fragility test
Howell-Jolly bodies are seen in RBC’s. What does that signify?
Pt had a splenectomy
Hypercoaguablility in young white male
G1691A gene mutation
Factor V Leiden
factor V cannot be inactivated by protein C or S
Prothrombin gene mutation effect
increased levels of prothrombin
hypercoaguable
due to 3’ UTR gene mutation (increased transcription)
Livedo reticularis (arterial clots) TIA's
Antiphospholipid syndrome
anticoagulant and cardiolipin Abs
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
Location of lymphoma
tumor mass in LN
Leukemoid reaction
response to infection
increasedWBC/left shit/leukocyte alkaline phosphatase
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)
Non Hodgkin’s lymphoma presentation
multiple peripheral LN involved
extranodal involvement
B cells
20-40 y/o
Reed-Sternberg cell description
tumor giant cell
binucleate/bilobed (mirror images)
CD30 and CD15 (+)
B cell origin
African child
jaw lesion
Starry sky appearance
Burkitt’s lymphoma
t(8:14) causing c-myc promoted by Ig heavy chain
assc with EBV
Mantle Cell lymphoma
t(11:14)
cyclin D1 and Ig heavy chain
CD5 (+)
Follicular lymphoma
t(14:18)
bcl-2 and Ig heavy chain
bcl-2 inhitis apoptosis
indolent course
Adult T cell lymphoma
caused by HTLV-1
in Japan/Africa/Caribbean
cutaneous lesions
Mycosis fungoides/Sezary syndrome
adults with cutaneous patches/nodules
CD4 (+)
indolent
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
Monoclonal gammopathy of undetermined significance
MGUS
increased M spike (excess Ig’s made)
precursor to multiple myeloma (1%/per progress)
Acute lymphoblastic leukemia/lymphoma
children TdT (+) and CALLA (+) increased lymphocytes t(12:21) better prognosis can spread to CNS
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
Hairy cell leukemia
in adults
mature B cell tumor
hair like projections on cells
stains TRAP (+)
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
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)
Auer rods
peroxidase (+) inclusions in granulocytes/myeloblasts
seen in M3 AML
can be released and cause DIC
CML translocation
Philadelphia chromosome
t(9:22)
bcr-abl
Burkitt’s lymphoma translocation
t(8:14)
c-myc activation
Mantle cell lymphoma translocation
t(11:14)
cyclin D1 activation
Follicular lymphoma translocation
t(14:18)
bcl-2 activation
M3 type of AML translocation
t(15:17)
responds to all trans retinoic acid (Vit A)
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
Polycythemia vera
abn clone of HSCs with JAK2 receptors active
proliferate without EPO
type of myeloproliferative disorder
Essential thrombocytosis
uncontrolled
proliferation of megakaryocytes
MOA of methotrexate
inhibits dihydrofolate reductase
can cause mucositis
MOA of 5-FU
inhibits thymidylate synthase
no dTMP, and therefor no DNA synthesis
MOA of 6-Merrcaptopurine/azathioprine/6-TG
purine analogs
activated by HGPRT
MOA of dactinomycin
intercalates in DNA
MOA of doxorubicin
generates free radicals
intercalates in DNA
causes breaks
MOA of bleomycin
induces free radical formation
causes DNA breaks
MOA of cyclophosphamide
X link DNA at guanine N-7
activated by the liver
Use of nitrosoureas
for CNS tumors
MOA of busulfan
alkylates DNA
for CML
MOA of vinblastine/vincristine
bind tubulin in M phase
blocks polymerization
Side effects of vinblastine/vincristine
vincristine-neurotoxicity
vinblastine-myelosuppression
MOA of cisplatin
cross links DNA
MOA of etoposide/teniposide
inhibits topoisomerase II
increased DNA degradation
MOA of hydroxyurea
inhibits ribonucleotide reductase
decreased DNA synthesis
also for Sickle cell (increased HbF)
MOA of prednisone
triggers apoptosis
MOA of Tamoxifen
receptor antagonist in breast/agonist in bone
blocks binding of estrogen
MOA of trastuzumab
Ab against HER-2 (c-erbB2), a tyrosine kinase
for HER-2 breast cancer
MOA of imatinib
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
for CML
MOA of rituximab
Ab against CD20 in B cell neoplasms
MOA of bevacizumab
Ab against VEGF
inhibits angiogenesis of tumors
