Heme facts Flashcards
1
Q
Plummer Vinson Syndrome
A
Triad of iron deficiency anemia, esophageal webs and atrophic glossitis
2
Q
Abciximab - MOA
A
Block GpIIa/IIIb directly preventing fibrinogen from binding
3
Q
Clopidogrel - MOA
A
Inhibits ADP EXPRESSION of GpIIa/IIIb
4
Q
Positive selection of T cells
A
- occurs in thymic CORTEX
- test if T cells have T-cell receptor that binds to self MHC —> if don’t, then undergo apoptosis
5
Q
Negative selection of T cells
A
- occurs in thymic MEDULLA
- test if T cells with T-cell receptor binds to self antigen or MHC with OVERLY HIGH AFFINITY —> if do, then undergo apoptosis
6
Q
What is hemoglobin A2?
A
alpha2delta2 hemoglobin
7
Q
Beta-thalasemia - mutation
A
Caused by mutations that result in defective transcription, processing and translation of beta-globin mRNA
- most commonly due to aberrant precursor mRNA splicing or premature chain termination during mRNA translation
- frequent in MEDITERRANEAN populations
8
Q
PI3K/Akt/mTOR pathway
A
- tryosine kinase receptor
- mTOR induces genes involved in cell survival, anti-apoptosis and angiogensis
- is inhibited by PTEN
9
Q
Retinoblastoma protein
A
- tumor suppressor gene
- HYPOphosphorylated state: active, STOPS cells from going through G1 to S checkpoint
- HYPERphosphorylated state: inactive, PERMITS cells from going through G1 to S checkpoint
- follows two-hit model (get hyperP inactive form)
10
Q
Proteasome inhibitors - MOA in malignant plasma cells
A
- accumulation of toxic intracellular proteins
- accumulation proapoptotic proteins —> increased apoptosis
- good in multiple myeloma because make lots of monoclonal immunoglobulin
11
Q
Desmopressin (DDAVP) - therapeutic effect in clotting disorders
A
- increases circulating factor VIII
- increases endothelial secretion of vWF to stop bleeding
12
Q
Paroxysmal nocturnal hemoglobinuria
A
COMPLEMENT-mediated hemolysis of RBCs
- mutation: PIGA gene within stem cells —> decreased GPI anchor that is necessary for attachment of CD55 and CD99 cell surface proteins —> increased complement mediated hemolysis
- CD55: decay accelerating factor
- CD59: MAC inhibitory protein
- these proteins help inactive COMPLEMENT and prevent MAC complex from forming on normal cells
- also thrombotic complications, pancytopenia and aplastic anemia
13
Q
Burkitt lymphoma
A
B cell lymphomas
- t(8,14) translocation - overexpress c-MYC - increased cell proliferation
- histology: “starry sky” appearance, uniform, medium sized tumor cells with basophilic cytoplasm
- high mitotic index
14
Q
Pyruvate kinase deficiency
A
- coverts PEP to pyruvate
- if deficient, then get less ATP produced
- get defective ion movement (water and K+ loss) in RBC membrane and hemolysis —> hyperplasia of splenic red pulp that is responsible for removing damaged RBCS —> SPLENOMEGALY
15
Q
Follicular lymphoma - translocation
A
t(14;18) - overexpression BCL-2 —> decreased apoptosis
16
Q
CML - translocation
A
t(9;22) - BCR-ABL
17
Q
Hemochromatosis - clinical findings
A
- “bronze diabetes”: micronodular CIRRHOSIS, diabetes mellitus, and skin pigmentaton
- increased risk for hepatocellular carcinoma, HF and testicular atrophy
18
Q
Drainage of superior inguinal nodes
A
All skin from the umbilicus down including the anus (below dentate line) EXCLUDING the testes, glans penis and posterior calf
19
Q
Sickle cell disease effect on spleen
A
Infants: CONGESTION due to vasocclusion and splenic pooling of erythrocytes
Early adulthood: fibrosis and atrophy of spleen —> ASPLENIA due to repeated infarction
20
Q
Carbon Monoxide poisoning - physiology
A
- carboxyhemoglobin (amount of Hb bound to CO) increases
- CO decreases O2 binding to Hb —> decreases oxygen content in blood but does NOT change dissolved oxygen in blood (PaO2)
- also shifts oxygen-hemoglobin to L so less oxygen is unloaded into tissues
21
Q
Methmoglobin
A
Oxidized form of Hb that is bound to ferric Fe3+ instead of ferrous Fe2+
22
Q
Carbon monoxide poisoning - treatment
A
100% O2 and hyperbaric O2
23
Q
Kozak consensus sequence
A
Starts TRANSLATION in EUKARYOCYTES - scans sequence to find start codon AUG
24
Q
Shine-Dalgarno sequence
A
Starts TRANSLATION in PROKARYOCYTES
25
Beta-thalassemia - pathophys
- causes HYPOCHROMIC, MICROCYTIC anemia
- get reduced beta-globin synthesis —> get unpaired alpha chains —> causes RBC membrane damage —> leads to death of precursor cells in bone marrow and lysis of circulating erythrocytes
26
Polycythemia vera - mutation
Chronic myeloproliferative disorder due to JAK2 mutation, a cytoplasmic tyrosine kinase: renders hematopoetic cells more sensitive to growth factors
- get constitutive activation of its kinase domain —> CLONAL PROLIFERATION OF MYELOID CELLS
- get increased RBCs, platelets and WBC
27
Peau d'orange rash
- erythematous rash on breast that is itchy with course, firm skin (like orange peel)
- seen with breast edema in INFLAMMATORY breast cancer
- skin findings due to cancerous cells obstructing the lymphatic ducts due to spread to dermal lymphatic spaces
28
CD14, CD40
Macrophages
29
Cells in paracortex of lymph node:
T cells and dendritic cells
30
Cells in cortical follicles of lymph node:
B cells
31
Cells in medullary sinuses of lymph node:
Reticular cells and macrophages
32
Cells in medullary cords of lymph node:
B cells, plasma cells and macrophages
33
HbC
glutamic acid to lysine —> negative to positive substitution
| - HbC runs slower on gel electrophoresis than normal Hb and HbS
34
Speed of movement of hemoglobins in gel electrophoresis
HbA > HbS > HbC
35
COX2-selective inhibitors
- have potent anti-inflammatory actions because only act on COX-2
- do not have side effects of bleeding and gastrointestinal ulcerations because do not inhibit COX-1
36
Celecoxib - class
COX-2 selective NSAID
37
Most common cause of iron deficiency anemia
BLOOD LOSS (ex: with menstruation or GI loss)
38
Isoniazid as a cause of sideroblastic anemia - pathophys
- Isoniazid inhibits pyridoxine phosphokinase which converts B6 (pyridoxine) to active form
- B6 is needed as a cofactor for delta-aminolevulinic acid (ALA) synthase, an enzyme that catalyzes the RLS of heme synthesis (first step)
- inhibition of delta-ALA synthase causes a microcytic, hypo chromic anemia —> iron transported to developing erythrocytes cannot be used to form heme so they accumulate around the nucleus forming ring SIDEROBLASTS
- Need to give people B6 supplementation when taking isoniazid
39
T-cell vs. B-cell ALL
```
B-cell
- most common
- CD10+, CD19+ and CD20+
T-cell
- presents with mediastinum mass: can lead to SVC syndrome, dysphasia due to compression of esophagus, and dyspnea, stridor due to compression of trachea
- CD2, 3, 4, 5, 7, 8+
```
40
ITP - idiopathic thrombocytopenic purpura
- IgG antibodies to GpIIa/IIIb —> destroys platelets
- can be secondary to HIV OR HEPC
- treatment: corticosteroids
41
Nevirapine, efavirenz - class
NNRTIs
42
Enfuvirtide
HIV fusion inhibitor - blocks gp41
43
Auer rods
- rod shaped intracytoplasmic granules
- stain for myeloperoxidase
- seen in AML
44
Follicular lymphoma
- indolent non-Hodgkin lymphoma
- WAXING AND WANING
- middle aged
- PAINLESS lymph node involvement
- histology: mixture of cleaved and uncleaved follicle center cells in a nodular pattern
- translocation: t(14;18) —> overexpress BCL-2 —> blocks apoptosis
45
6-mercaptopurine and 6-thioguanine
- CYTOTOXIC purine analogs that inhibit de novo purine synthesis
- ACTIVATED by: HGPRT
- INACTIVATED by: xanthine oxidase and TPMT
46
Pilocytic astrocytoma
Most common brain tumor in CHILDREN
- usually in cerebellum
- have cystic (clear) component and nodular component (white on MRI)
- microscopy: pilocytic astrocytes and Rosenthal fibers
- good prognosis
47
AML
- elderly, 65 mean age
- translocation: t(15,17) —> PML/RARalpha —> unable to signal for differentiation of myeloid precursors
- Auer Rods
- Txt: ALL-TRANS RETINOIC ACID
48
Methotrexate - MOA
Inhibits dihydrofolate reductase
- dihydrofolate reductase is needed to reduce folic acid —> DHF —> THF
- when inhibited, folic acid and DHF polyglutamate accumulates
- can reverse effects of drug with folinic acid
49
Proto-oncogenes
KRAS, BRAF, HER1, HER2, ABL, c-MYC, SIS, TGFA
50
Rituximab
Targets CD20 on B cells —> used for lymphoma therapy
51
Wiskott-Aldrich Syndrome
- WATER: Wiskott-Aldrich: Thrombocytopenia, Eczema, recurrent infections
- B-cell and T-cell mixed deficiency (infections to encapsulated bacteria and opportunistic fungi, viruses)
- X-linked: mutation in WAS gene —> unable to reorganize actin cytoskeleton
52
Ristocetin aggregation test
Tests vWF-dependent platelet aggregation
- ristocetin activates GpIb receptors on platelets and makes them ready to bind vWF
- when vWF is decreased (in vWD), will get poor aggregation in presence of ristocetin
- when add plasma which has vWF, appropriate aggregation occurs
53
Hepcidin
- controls iron storage and regulation
| - made in liver
54
Aplastic crisis seen with parovirus B19
- Red cell aplasia only
| - commonly seen in patients with pre-existing hematologic disease
55
Major clinical manifestations of Factor V leiden
- DVT
- cerebral vein thrombosis
- recurrent pregnancy loss
56
Enzymes involved in non-oxidative reactions of HMP shunt
- Transketolase: transfers 2 C
- Transadolase: transfers 3 C
- some cells do not use the oxidative phase to produce NADPH but all cells can make ribose from fructose-6-phosphate and glyceraldehyde 3-phosphate
57
Trastuzumab - target
Anti-HER2 monoclonal AB
58
In which organelle is heme made?
Mitochondria: responsible for first and last three steps
| Rest occurs in cytoplasm
59
Mechanism by which human tumor cells have developed resistance to chemotherapeutic agents
ATP-dependent efflux pump
- developed human multi drug resistance gene that codes for P-glycoprotein, a transmembrane protein that functions as efflux pump
- get decreased drug into the cell and increased drug out of the cell
