Heme/Onc Flashcards
Pyruvate Kinase deficiency has what effect on RBC’s?
last step in glycolysis , no PK–> you can’t generate the ATP from glycolysis in your RBC’s, they become senescent and the spleen removes them Spleen will hypertrophy from this overwork
mTOR signaling pathway (the more this is turned on, more cancer)
growth factor binds to Tyrosine Kinase –> autophosphorylation of tyrosine –> activation of PI3K –> activation of PK-B (akt) –> akt activates mTOR –> mTOR goes to nucleus to induce genes involved in cell survival / anti apoptosis
Soon after a woman is started on Warfarin, she develops areas of skin and fat necrosis… why?
Warfarin inhibits all the vit. K dep factors (Factors 2,7,9,10 & protein C & S)—> but proteins C & S have shorter half lives & are therefore depleted first this leaves you with a period of time with no protein C (which normally INactivates factor V & VII) and plenty of the other clotting factors this sets you up for clots & “ Warfarin Skin Necrosis” —> so you must always give Heparin too for the 1st few days of warfarin therapy
Protein C function
inactivates factors V & VII by proteolysis
In HbS – what causes the Hb to be able to polymerize under low oxygen conditions and therefore “sickle”?
HbS contains a valine in place of the glutamic acid at position 6 in the beta subunit, this promotes HYDROPHOBIC INTERACTION among the Hb molecules and polymerization
HbC and Sickle cell disease are result of ________ mutations
Missense mutations (one aa sub’d for another aa) HbC = lysine for glu at position 6 HbS = valine for glu at position 6
blasts in peripheral smear w/ TdT + and PAS + material
Lymphoblasts (ex: Acute Lymphoblastic Leukemia) -CD 19 & 10 = B cell blasts -CD 1, 2, 5 = T cell blasts
blasts in peripheral smear w/ peroxidase + granules
Auer Rods – this means Myeloblasts (AML) (found abundantly in AML M3)
treatment of Tumor Lysis Syndrome (hyperkalemia, hyperphosphatemia, hyperuricemia)
Rasburicase or Allopurinol
anemia with decreased Ferritin, increased Transferrin, increased TIBC, MCV < 80
Iron deficiency anemia (microcytic, hypochromic anemia)
reasons for Burr cells on peripheral smear
Uremia, Pyruvate Kinase deficiency, Microangiopathic hemolytic anemias (TTP & HUS), or mechanical trauma to the RBC
2,3 BPG effect on O2 binding Hb
2.3 BPG allosterically decreases the affinity of Hb for O2 –> makes it easier to dump oxygen in the tissues
a pt with ESRD who has not had dialysis for over a week develops excessive bleeding when changing his catheter
Uremic platelet dysfunction - only the bleeding time will be prolonged
most commonly used drug for long term anticoagulation after a PE
Warfarin -inhibits Vit K dependent carboxylation of glutamic acid residues on the Vit K dep clotting factors & inhibits Epoxide Reductase
drug of choice for ACUTE management of DVT
Heparin (activates antithrombin III)
type of leukemia that is more likely to present with a large mass in the mediastinum or neck, and cause symptoms like dysphagia
T-cell ALL (as apposed to B-cell ALL which presents w/ fever, malaise, bleeding, bone pain, hep/splenomegaly)
in a normal distribution, _____% lie within 1 SD, _____% within 2 SD and _______% within 3 SD’d
68% – 1 SD 95% – 2 SD 99.7% – 3 SD
most common inherited bleeding disorder, causes a prolonged bleeding time and PTT
von Willebrand disease
what has the main control over Iron absorption and excretion in the body?
the liver – specifically Hepcidin -Hepcidin is increased when you don’t need to absorb any more Iron, it binds to and causes downregulation and degradation of Ferroportin
What enzyme converts Heme —> Biliverdin and is thereby responsible for the greenish color of bruises
Heme Oxygenase
woman with heavy periods, her platelet count is normal & they aggregate normally in response to ADP but not to Ristocetin
vWF deficiency
drug treatment for vWF deficiency
Desmopressin — b/c ADH stimulates the release of vWF from endothelial cells
A man with non-tender cervical lymph nodes has a biopsy shown here, cytogenetic analysis would likely show overexpression of _______________
Bcl-2
- Follicular lymphoma
- t(14,18)
patient with mild jaundice, RBC peripheral smear is shown, the dx was made by osmotic fragility testing & an increased MCHC
Hereditary Spherocytosis
-no central pallor, spherocytes seen on smear
megaloblastic anemia with foot numbness, difficulty walking , took years to develop b/c of large stores of _______ in the liver
B12 (cobalamin) deficiency
t(15,17) – would likely be associated with a malfunctioning _______ receptor
- M3 AML (Acute Promyelocytic Leukemia)
- assoc w/ defect in RETINOIC ACID RECEPTOR
- hence you treat w/ ATRA
a mutation 3 bases upstream from the AUG start codon on a mRNA would impair ________
-mutation in the “Kozak sequence” causes impaired mRNA binding to ribosomes and INITIATING translation
What cancer drug’s toxicity is increased if given with Allopurinol?
6-Mercaptopurine
- b/c it’s metabolized by Xanthine Oxidase
mechanism of Celecoxib
- Selective COX 2 inhibitor
- does not cause GI problems or decr platelet aggregation
Common precipitating factors of G6PD deficiency anemia:
1- Infection
2- Drugs (Dapsone, Malaria drugs, TMP-SMX)
3- DKA
4- Fava beans
a bone marrow sample w/ > 30% plasma cells in diagnostic for ____________
Multiple Myeloma
- IL-1, IL-6 –> bone resorption , “punched out” lytic lesions on Xray
- Rouleaux formation
- Bence -Jones proteins (monoclonal light chains) in the urine
- Amyloid deposits
all characteristic of **Multiple Myeloma **
What kind of cancer is associated with this cell?
Hodgkin’s Lymphoma
((Reed Sternberg cell))
Use & Mechanism of HYDROXYUREA
- treatment of Sickle Cell Anemia
- increases the amount of HbF (which protects against sickling)
tumor with a high Ki-67 fraction (nearing 100%)
Burkitt’s Lymphoma (as a high mitotic index)
things that can induce Sickling
- low oxygen states
- acidity or high 2,3 DPG
Upper respiratory tract infection + pancytopenia
Parvovirus (can cause aplastic anemia)
hypocellular marrow filled with fat and fibrosis
Aplastic anemia
mainstay of DVT treatment in a pregnant woman
Heparin
(Warfarin is a teratogen & Aspirin & Clopidogrel are insufficient to treat a DVT)
increased indirect bilirubin
should associate w/ _hemolysis / hemolytic anemias _
the bluish color of reticulocytes is due to ______
increased r RNA
child w/ Down Syndrome – at risk for ___________ leukemia before age 5 and _________ leukemias after age 5
before age 5 = megakaryoblastic leukemia
after age 5 = ALL
Diseases associated with target cells
“HALT said the hunter to his Target”
- HbC disease
- Asplenia
- Liver disease
- Thalassemia
conditions associated w/ Basophilic stippling of the rbc
“Baste the ox *TAIL*“
- Thalassemias
- Anemia of chronic dz
- Iron deficiency
- Lead poisoning
Megaloblastic anemia with INCREASED methylmalonic acid
B12 deficiency
(folate deficiency has normal mm acid)
Pt w/ pallor, early satiety, splenomegaly, fatigue – found to have a Jak 2 mutation that causes constitutive tyrosine kinase activity and STAT activation…
**Myelofibrosis **
- excess megakaryocytes –> produce PDGF –> causes marrow fibrosis
- the splenomegaly can cause early satiaty & abd discomfort
((The 2 other chronic myeloproliferative disorders –> Polycythemia Vera & Essential Thrombocythemia also have a Jak2 mutation))
Leukemia that classically has increased BASOPHILS
CML
- t(9,22) , Bcr-ABL
- Basophilia, translocation, and a negative Leukocyte Alk Phos (diff from leukemoid rxn)
Beta- Thalassemias are caused by __________
mutations that cause defective mRNA processing & therby low levels of globin chain synthesis
lab abnormalities found in HUS
- prolonged Bleeding Time (due to decrs platelets)
- incrs BUN, Cr & LDH
bleeding after unfractionated Heparin treatment should be treated w/ ________
Protamine sulfate
increased levels of HbA2 indicate ______
- Beta thalassemia minor (trait)
- or B-Thalassemia intermedia
the _____ will be normal in pt’s with CO poisoning, Anemia, Polycythemia, and Methemoglobinemia…
the partial pressure of Oxygen in the blood (the amount dissolved in plasma - doesn’t change even if the Hb isn’t binding O2)
Pancytopenia in a patient with SLE is due to _______
formation of autoantibodies against blood cells ( a type II hypersensitivity rxn)
a patient with recurrent DVT’s and PE’s , the PT & PTT are normal, and the PTT does not change with addition of activated protein C…
-Factor V Leiden mutation
(normally activated protein C would inactivate factor V and prolong the PTT)
Why are patients w/ sickle cell dz (or another chronic hemolytic dz) predisposed to becoming Folic acid deficient and developing macrocytic changes
- b/c they are constantly turning over erythrocytes and making new ones (using up folic acid)
phosphorylation of the Rb gene causes it to be ____________
-inactive (ie: let down it’s guard of the genome and ALLOW progression from G1 –> S phase)
Her-2/Neu is also known as _________
ERB-B2
the N-myc proto-oncogene is overexpressed in __________
Neuroblastoma
the chemo drug Etoposide, works by ________
inhiibiting the activity of Topoisomerase II (causing double strand breaks to accumulate in the cancer cells)
Small cell carcinoma of the lung is thought to have a ___________ origin
Neuroendocrine (will stain for markers such as chromogranin, synaptophysin…)
How do you calculate Atrributable Risk %
ARP = (RR -1) / RR
or (Risk in the exposed - risk in unexposed) / Risk in the exposed
most common indolent (lymph node gets bigger, then smaller in cycles) form of non-Hodgkin’s lymphoma in adults
Follicular lymphoma
T-cell lymphoma, affects skin causing “Pautrier microabscesses”
Mycosis Fungoides
(CD4+ cells invade skin)
splenomegaly, pancytopenia in an older man, leukemic cells are + for TRAP (tartrate resistant acid phosphatase)
Hairy Cell Leukemia
formula for “Number needed to harm”
NNH = 1/ Attributable risk
What drug can be used to prevent the nephrotoxicity from Cisplatin (a DNA crosslinker) treatment?
Amifostine (and hydration)
mechanism of Cladribine
- a purine analog that gets to high concentrations within the cell b/c it is resistan to degradation by ADA
- tx of choice for Hairy Cell Leukemia
