Heme/Onc (U.W.) Flashcards
Leukocyte Adhesion steps?
- margination
- rolling
- crawling
- activation
- tight adhesion
- transmigration
L selectin (neutrophils) P/E selectin (endothelial cells) are involved in?
- rolling via these sialylated carbohydrate groups
CD18 (MAC1 and LFA) on neutrophils
ICAM (endothelial cells)
are involved in
tight adhesion
PECAM involved in?
transmigration
X-linked Agammaglobulinemia
- defect in Bruton Tyrosine Kinase gene
- Bcells fail to develop, so decrease in all Ig’s and lack of germinal center/ primary follicle
CD14 found on
macrophages
paracortex region of lymph node is populated by
T-cells and dendritic cells
Acute Intermittent Porphyria symptoms? Deficiency?
GI pain with neurological changes ( tingling, concentration difficulty)
- caused by deficiency of Porphobilinogen Deaminase
AIP has excess amounts of what? So what is a good treatment?
ALA and PBG
ALA synthase downregulation is a treatment. Hemin or glucose can downregulate ALA synthase.
genetics of VWF
autosomal dominant defect in VWF with variable penetrance (dont forget, factor VIII will be affected too!)
Trastuzumab
mab against tyrosine kinase receptor HER2 + breast cancer
Down’s syndrome is associated with?
- ALL
- AML
spherocytosis
increased MCHC, decreased MCV, and lack of central pallor
localized vs metastatic carcinoid
localized carcinoid (only in enterochromaffin cells of SI) vs metastatic (spread to liver) only carcinoid that has spread to the liver can cause carcinoid syndrome. localized carcinoid will have its products degraded by first pass
Dohle bodies
light blue(basophilic) peripheral granules in neutrophils. occur in toxic systemic illness like leukemoid reaction
Leukemoid reaction
leukocytosis with normal/increased LAP
usually in response to infection, malignancy, hemorrhage
its differntiated from leukemias by the increased LAP
tingling following a massive blood transfusion
due to hypocalcemia from citrate (calcium chelator) found in packed blood
how does RNAi work
inhibits posttranscriptional mRNA from being translated. usually when RISC binds the mRNA it causes degradation
Aplastic Anemia in SS patient caused by
ParvoB19, non enveloped ssDNA
most common cause of DIC in pregnancy
htt causing placental abruption releasing TF causing DIC
PNH triad
hemolytic anemia, pancytopenia, and thrombosis in strange vessels
(hemosedirin accumulation in kidneys often occurs bc of hemoglobinuria/ chronic hemolysis)
absent CD55
PNH
what is the cause of hemochromatosis
- a defect in HFE protein (which works with transferrin) causes the body to FALSELY indicate that body Fe stores are low. in response, the body starts mechanisms to increase Fe
(1) decrease Liver hepcidin- allowing an increase in ferroportin– so more Fe can be absorbed from SI and macrophages
(2) increase DMT1 levels (luminal enterocyte), to increase Fe absorption at SI
overall – increase in IRON
triad seen in Hemochromatosis
(1) micronodular cirrhosis
(2) increased skin pigmentation
(3) diabetes
hemochrotatosis predisposes to (3)
- HCC and cirrhosis
- CHF
- hypogonadism
asplenic patient, bacterial risks?
#1- strep pneumo #2- H. influenzea
osteomyelitis #1 cause is Salmonella (not S.aureus)
mutations in what gene is responsible for HIV resistance to HAART therapy
pol gene
thymic positive selection happens how?
thymic negative selection happens how?
only Tcells that have strong affinity for CORTICAL cells presenting self antigens survive
Tcells that have strong affinity for MEDULLARY cells presenting self antigens are apoptosed.
How would a proteosome inhibitor help a MM patient
MM, a malignancy of the plasma cell, causes over production of proteins such as Ig’s. Without their proteasome working, these proteins if misfolded can accumulate and bring on apoptosis
anemia/fatigue, bony pain, fatigue, and HYPERCALCEMIA is suggestive of what disease?
multiple myeloma
Myoglobin
- used as storage for O2 in skm and cardiac m… only in blood stream upon injury
- P50 is 1 mmHg (so very high O2 affinity)
- monomeric ( resembles Hgb monomer ) so “hyperbolic” curve (NOT sigmoid)
Isoniazid can predispose to what anemia?
Sideroblastic. Isoniazid inhibits the activation of B6 (pyridoxine) which is needed for ALA synthase. This causes decreased heme synthesis, as it is the rate lim step
BRCA1/BRCA2
autosomal dominant inheritance
a tumor suppressor gene
involved in repair of dsDNA breaks
pancytopenia in SLE patient
- because of autoantibodies against RBC (causing warm IgG Coombs+ AIHA), WBC, and platelets
this is a type II HS reaction (unline lupus glomerulonephritis that is a type III HS reaction)
what causes hemorrhagic cystitis in Cyclophosphamide treatment
cyclophosphamide is broken down into metabolite “acrolein” to be excreted by kidney, and this substance is toxic to urinary epithelial cells, so use MESNA that can bind and inactivate acrolein
t(14;18)
BCL2
follicular lymphoma
what kind of lung cancer can produce ectopic ACTH
small (oat) cell lung cancer
pathophys of chronic myeloproliferative disorder
a constitutively active JAK2 (which a non-receptor Tyrosine Kinase which is cytoplasmic), this results in consitutive action of the JAK-STAT pathway which promotes growth through transcription
what are the enzymes involved in the non-oxidative branch of HMP shunt? what is their purpose?
transketolase and transaldolase
they interconvert Ribose 5P between Fructose 6P depending on cell needs
if nucleotides are needed ribose5P is generated
if glycolysis/energy is needed, Fructose6P is generated
t(15;17)
APL (which is AML M3)
transfusion of RARA and PML
nucleolus role?
rRNA
only place where RNA pol 1 is found (this synthesizes all rRNA except for 5S rRNA)
what remains unchanged in anemia, methemoglobinemia, CO poisoning, polycythemia
partial pressure of O2 in blood!
because this value represents the O2 dissolved in PLASMA and is thus unchanged.
nitrite inhalation can cause
methemoglobinemia
what is methemoglobin
Iron in the 3+ state (aka the oxidized state) which inhibits its ability to bind O2
what causes hypercalcemia in MM
IL1 and IL6 being secreted by neoplastic plasma cells cause osteoclast activity. punched out bone lesions will be visible
pathophys of CO poisoning
CO poisoning causes increase in carboxyhemoglobin because CO binds RBC with 250x greater affinity that O2 can. (please not that the Fe in RBC is NOT affected)
this causes less O2 to bind to RBCs
a leftward shift in RBC O2 dissociation curve
Fanconi Syndrome
inherited form of anaplastic anemia that is notable for short stature and missing thumbs
opiod tolerance to what symptoms dont occur
constipation and miosis
which cancer am I: round, medium size uniform tumor cells with ki67> 99% (which refers to proliferation fraction)
Burkitt’s lymphoma
pancreatic insufficiency is linked to what kinds of anemia?
Megaloblastic
(1) if pancreatitis bc chronic alcoholic- folate def
(2) decreased pancreatic secretions means pancreatic enzymes are not available to cleave R-binding factor. R-binding factor binds B12 and must be cleaved so B12 can bind IF and be absorbed
G6PD mode of inheritance
XR
SSD does what to the spleen
atrophy, fibrosis and scarring due to repeated splenic infarctions, resulting in auto-splenectomy
aplastic crisis vs aplastic anemia in lab
aplastic crisis only affects RBCs. aplastic anemia should show pancytopenia
what happens in the germinal centers of follicles?
Isotype Switching (Heavy chain rearrangement which is Tcell dependent) to help make Ig’s from the initial IgM
hepcidin is made where?
hepatic parenchyma
what inactivates 6MP? what activates it?
XO inactivates
HGPRT activates
what does 2,3 BPG do? who doesnt bind well to it?
facilitates O2 release in peripheral tissues
HbF doesn’t bind well to it bc of lack of positive charge at 2,3 BPG binding pocket
why do erythrocytes sometimes not make ATP in glycolysis
once they get to the 1,3BPG step they sometimes opt to make 2,3BPG via BPG mutase instead of continuing glycolysis and getting ATP
osteolytic (lucent) vs osteoblastic (sclerotic) bone mets
if lytic then think: MM, RCC, NSCLC, non Hodgekin, melanoma
if blastic then think: PCa, SCLC, Hodgekins’
MDR1
codes of P glycoprotein which is a ATP depedent efflux pump
angiogenesis is mediated by what factors
VEGF (IL1, Infy)
FGF
a mutation in what will make anti-EGFR therapy ineffective
KRAS (b/c KRAS causes constitutional EGFR activation)
what do microsomal monooxygenases do (ex: cyp450 monooxygenase) in cancer
most carcinogens (benzene etc) are delivered to the body in an inactive pro-carcinogen phase, microsomal monoxygenases (apart from metabolizing drugs) can metabolize these pro-carcinogens into CARCINOGENS
EBV-
what cell does it infect?
what cell proliferates in response (aka seen on blood smear)
infects: CD21+ B lymphocytes
CD8+ cytotoxic lymphocytes proliferate in response to infection
Cyanide toxicity treatment?
Nitrites. Because they create methemoglobin. Cyanide is more attracted to Fe3+ so it binds the methemoglobin and stops wreaking havoc on the mitochondrial cytochrome enzymes
what kind of gene is KRAS
PROTO-oncogene
which drugs can induce aplastic anemia
chloramphenicol, carbamazepine, sulfonamides
cells that look like “wrinkled tissue paper”
Gaucher’s! these are macrophages with glucocerebroside accumulated.
AR
pancytopenia, hepatosplenomegaly
what causes the green color of a bruise
Heme Oxygenase that converts heme to BILIVERDIN
what is the monospot test
+ if patient serum causes agglutination of a horse’s RBCs
how to differentiate AML vs CML by labs
AML has >20% blasts
CML has lower numbers of blasts
LAP neg
CML
