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UWorld Facts > Heme facts > Flashcards

Heme facts Flashcards

1
Q

Plummer Vinson Syndrome

A

Triad of iron deficiency anemia, esophageal webs and atrophic glossitis

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2
Q

Abciximab - MOA

A

Block GpIIa/IIIb directly preventing fibrinogen from binding

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3
Q

Clopidogrel - MOA

A

Inhibits ADP EXPRESSION of GpIIa/IIIb

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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

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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
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6
Q

What is hemoglobin A2?

A

alpha2delta2 hemoglobin

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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
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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
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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)
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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
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11
Q

Desmopressin (DDAVP) - therapeutic effect in clotting disorders

A
  • increases circulating factor VIII

- increases endothelial secretion of vWF to stop bleeding

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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
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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
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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
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15
Q

Follicular lymphoma - translocation

A

t(14;18) - overexpression BCL-2 —> decreased apoptosis

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16
Q

CML - translocation

A

t(9;22) - BCR-ABL

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17
Q

Hemochromatosis - clinical findings

A
  • “bronze diabetes”: micronodular CIRRHOSIS, diabetes mellitus, and skin pigmentaton
  • increased risk for hepatocellular carcinoma, HF and testicular atrophy
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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

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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

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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
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21
Q

Methmoglobin

A

Oxidized form of Hb that is bound to ferric Fe3+ instead of ferrous Fe2+

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22
Q

Carbon monoxide poisoning - treatment

A

100% O2 and hyperbaric O2

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23
Q

Kozak consensus sequence

A

Starts TRANSLATION in EUKARYOCYTES - scans sequence to find start codon AUG

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24
Q

Shine-Dalgarno sequence

A

Starts TRANSLATION in PROKARYOCYTES

25
Q

Beta-thalassemia - pathophys

A
  • 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
Q

Polycythemia vera - mutation

A

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
Q

Peau d’orange rash

A
  • 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
Q

CD14, CD40

A

Macrophages

29
Q

Cells in paracortex of lymph node:

A

T cells and dendritic cells

30
Q

Cells in cortical follicles of lymph node:

A

B cells

31
Q

Cells in medullary sinuses of lymph node:

A

Reticular cells and macrophages

32
Q

Cells in medullary cords of lymph node:

A

B cells, plasma cells and macrophages

33
Q

HbC

A

glutamic acid to lysine —> negative to positive substitution

- HbC runs slower on gel electrophoresis than normal Hb and HbS

34
Q

Speed of movement of hemoglobins in gel electrophoresis

A

HbA > HbS > HbC

35
Q

COX2-selective inhibitors

A
  • 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
Q

Celecoxib - class

A

COX-2 selective NSAID

37
Q

Most common cause of iron deficiency anemia

A

BLOOD LOSS (ex: with menstruation or GI loss)

38
Q

Isoniazid as a cause of sideroblastic anemia - pathophys

A
  • 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
Q

T-cell vs. B-cell ALL

A 
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
Q

ITP - idiopathic thrombocytopenic purpura

A
  • IgG antibodies to GpIIa/IIIb —> destroys platelets
  • can be secondary to HIV OR HEPC
  • treatment: corticosteroids
41
Q

Nevirapine, efavirenz - class

A

NNRTIs

42
Q

Enfuvirtide

A

HIV fusion inhibitor - blocks gp41

43
Q

Auer rods

A
  • rod shaped intracytoplasmic granules
  • stain for myeloperoxidase
  • seen in AML
44
Q

Follicular lymphoma

A
  • 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
Q

6-mercaptopurine and 6-thioguanine

A
  • CYTOTOXIC purine analogs that inhibit de novo purine synthesis
  • ACTIVATED by: HGPRT
  • INACTIVATED by: xanthine oxidase and TPMT
46
Q

Pilocytic astrocytoma

A

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
Q

AML

A
  • 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
Q

Methotrexate - MOA

A

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
Q

Proto-oncogenes

A

KRAS, BRAF, HER1, HER2, ABL, c-MYC, SIS, TGFA

50
Q

Rituximab

A

Targets CD20 on B cells —> used for lymphoma therapy

51
Q

Wiskott-Aldrich Syndrome

A
  • 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
Q

Ristocetin aggregation test

A

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
Q

Hepcidin

A
  • controls iron storage and regulation

- made in liver

54
Q

Aplastic crisis seen with parovirus B19

A
  • Red cell aplasia only

- commonly seen in patients with pre-existing hematologic disease

55
Q

Major clinical manifestations of Factor V leiden

A
  • DVT
  • cerebral vein thrombosis
  • recurrent pregnancy loss
56
Q

Enzymes involved in non-oxidative reactions of HMP shunt

A
  • 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
Q

Trastuzumab - target

A

Anti-HER2 monoclonal AB

58
Q

In which organelle is heme made?

A

Mitochondria: responsible for first and last three steps

Rest occurs in cytoplasm

59
Q

Mechanism by which human tumor cells have developed resistance to chemotherapeutic agents

A

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

UWorld Facts (12 decks)

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