Heme Lymph Exam 2

Question 1

what are leukemias

Answer 1

white blood cell neoplasms arising in the bone marrow and spread to the blood

Question 2

what are lymphomas

Answer 2

white blood cell neoplasms that arise in lymph nodes and other tissues

Question 3

what are tests needed to diagnose leukemias and lymphomas

Answer 3

CD antigens and flow cytometry

Question 4

types of lymphoid neoplasms

Answer 4

Precursor B cell neoplasms
Peripheral B cell neoplasms
Precursor T cell neoplasms
Peripheral T cell neoplasms and NK cell neoplasms
Hodgkin Lymphoma

Question 5

what are the types of leukemia

Answer 5

-acute lymphoblastic leukemia/lymphoma, B and T cells (B-ALL, T-ALL)
-chronic leukemias (lymphocytic and myeloid)

Question 6

damage to bone marrow causes what symptoms

Answer 6

anemia (pallor, dyspnea, fatigue)
leukopenia (susceptible to infection, fever, sepsis)
thrombocytopenia (abnormal bleeding)
hypogammaglobulinemia/autoimmune complications
bone pain (expansion of marrow), splenomegaly, lymphadenopathy
hypertrophy of gingivae
meningismus and cranial nerve defects
occlusion of vessels

Question 7

acute leukemias usually have what kind of onset

Answer 7

sudden, a few months from symptoms to diagnosis

Question 8

chronic leukemias are found how

Answer 8

potentially accidental diagnosis when hospitalized for other reasons

Question 9

acute lymphoblastic leukemia/lymphoma is usually seen in who

Answer 9

children (B cell)
adolescents (T cell)
white>black

Question 10

what form of ALL is more commonly seen

Answer 10

B cell

Question 11

ALL can occur alongside what chromosome abnormality

Answer 11

trisomy 21

Question 12

ALL clinical findings

Answer 12

bone marrow neoplasia crowds out heamotpoietic cells (anemia, infections, bruising)
acute - stormy onset w CNS involvement/headaches/ CN palsy/comiting
T cell - anterior mediastinal mass
WBC increase
splenomegaly/hepatomegaly/lymph node involvement
show immature precursors (TdT positivity)

Question 13

ALL prognosis

Answer 13

dramatic improvements have occurred in children with B cell ALL
2-10 years 80% cured
worse - less than 2 or over 10, high leukocyte count, evidence of persistent disease on day 28 of tx, rearrangement of MLL and ABL-BCR (t(9;22)
better - hyperploidy, chromosomal aberrations t(12;21), low WBC

Question 14

ALL morphology

Answer 14

nuclei - coarse, clumped chromatin with 1 or 2 nucleoli
cytoplasm - scant agranular cytoplasm, cytoplasmic glycogen granules
markers - TdT, pre B cell and pre T cell

Question 15

acute myeloid lymphoma

Answer 15

neoplastic monoclonal proliferation of one+ forms of myeloid cells (RBCs, megakaryocytes, neutrophils, monocytes)

Question 16

AML presents how

Answer 16

acute - effects of crowding out normal cells (fatigue, fever, spontaneous bleeding)
myeloid - cells with more cytoplasma dnd differentiation than lymphocytic, positive expression of CD13, CD14, CD15, CD64, etc
most 50-60 years

Question 17

AML pathogenesis

Answer 17

can have promyelocytic leukemia variant t(15;17) with fusion of retinoic acid receptor alpha and PML gene
-causes block in hematopoiesis at premyelocytic stage (can be overcome with administration of all trans retinoic acid

Question 18

AML pathology

Answer 18

-myeloblasts/promyeloblasts
-auer rods (red rods in cytoplasm)
-hypercellular marrow
-positive for myeloid markers and those consistent with immature forms
-positive stain for myeloperoxidase

Question 19

AML treatment

Answer 19

stem cell transplant

Question 20

AML prognosis

Answer 20

lower survival than ALL
worse prognosis if prior myelodysplastic syndrome

Question 21

how do patients with AML present

Answer 21

within a few weeks or months of onset of symptoms
complaints related to anemia, neutropenia, thrombocytopenia
notably fatigue, fever, spontaneous mucosal/cutaneous bleeding

Question 22

involvement of tissues outside of the marrow in AML

Answer 22

less than in ALL (except monocytic)

Question 23

overall AML survival

Answer 23

15-25% but 60-70% achieve remission

Question 24

chronic lymphocytic leukemia/small cell lymphocytic lymphoma

Answer 24

CLL/SLL
neoplastic monoclonal proliferation of lymphoid cells predominantly present in blood

Question 25

neoplastic proliferation of CLL/SLL is composed mostly of what

Answer 25

mature lymphocytes smudge cells can be seen

Question 26

CLL/SLL onset

Answer 26

slow/more insidious cells more mature than acute

Question 27

difference between CLL and SLL

Answer 27

same process CLL - more circulating forms SLL - more nodal involvement

Question 28

CLL/SLL affects who

Answer 28

older males whites

Question 29

CLL/SLL symptoms

Answer 29

fatigue, weight loss, anorexia immune dysfunction - hypogammaglobinemia, autoantibodies against autoantibodies, displacement of marrow cells with corresponding symptoms, can have lymphadenopathy and skin infiltration

Question 30

CLL/SLL pathology

Answer 30

increase in WBC can have increase in cellularity with bone marrow lymphocytic cells easily disrupted (smudge cells) lymphoid proliferation causes effacement of lymph node architecture

Question 31

CLL/SLL treatment

Answer 31

drugs to inhibit BCR signaling or BCL2 functioning hematopoietic stem cell transplantation

Question 32

CLL/SLL morphology

Answer 32

effaced nodes with small lymphocytes and scattered ill defined foci of larger actively dividing cells bone marrow and liver involvement usual smudge cells bc fragile lymphocytes larger numbers of activated lymphocytes

Question 33

CLL/SLL clinical presentation

Answer 33

-constitutional B symptoms -lymphadenopathy and hepatosplenomegaly -variable WBC -hypogammaglobulinemia, hemolytic anemia and thrombocytopenia -mean 4-6 years (1 year after tranformation into prolymphocytic leukemia or diffuse large B cell lymphome)

Question 34

chronic myeloid leukemia

Answer 34

neoplastic monoclonal proliferation of granulocytes cells are granulocyte precursor responsible for 15-20% of all leukemia cases t(9;22) seen with creation of fusion protein, ABL-BCR, with tyrosine kinase activity

Question 35

CML chronic symptoms

Answer 35

constitutional symptoms, splenomegaly, sternal pain (marrow involvement) can have slow progression with sudden development with blast crisis and fast growth

Question 36

who is CML typically seen in

Answer 36

adults

Question 37

cells in CML

Answer 37

granulocytes/granulocyte precursors mainly neutrophils but also basophils and eosinophils myeloproliferative (polycythemia vera, essential thrombocytosis)

Question 38

bone marrow in CML

Answer 38

hypercellular with prominent granulopoiesis spleen can have extramedullary hematopoiesis and splenomegaly WBC can be elevated with granulocytes

Question 39

cytogenetics of CML

Answer 39

t(9;22) with BCR-ABL fusion and increased tyrosine kinase with growth factor independence can transform to AML or ALL

Question 40

CML treatment

Answer 40

progress has occurred with tyrosine kinase inhibitors

Question 41

all lymphocytes CD antigens

Answer 41

CD 45

Question 42

B cell antigens

Answer 42

CD 10, 19, 20

Question 43

T cell antigens

Answer 43

CD 3, 4 (helper), 5 (subset of B), 8 (cytotoxic)

Question 44

stem cell antigens

Answer 44

CD 34

Question 45

lymphoblast antigens

Answer 45

TdT

Question 46

myeloid antigens

Answer 46

CD 13, 14, 15, 64

Question 47

macrophage/monocytes antigens

Answer 47

CD 68

Question 48

follicular lymphoma

Answer 48

middle aged adults (male and female) 90% w t(14;18) translocation fusing BCL2 to IgH locus on chromosome 14 causing overxpression of BCL2 (anti apoptosis) generalized lymphadenopathy, waxing waning course not curable - low dose chemo and rutixamab survival 7-9 years

Question 49

morphology of follicular lymphoma

Answer 49

nodular proliferation in lymph nodes resembling B cells cells larger with angular cleaved nuclei lymphocytosis splenic and liver involvement common B cell antigens (CD 19, 10, 20) and BCL 6

Question 50

burkitt lymphoma

Answer 50

EBV infections in endemic cases (15-20% of sporadic) translocation involving MYC, t(8;14) with fusion of MYC to IgH B cell and germinal markers (CD 19, 20, 10, BCL 6) children and young adults fast growing, curable with aggressive tx

Question 51

morphology burkitt lymphoma

Answer 51

intermediate size with round to oval nuclei (2-5 muclei) moderate basophilic cytoplasm with vacuoles high proliferation and apoptosis starry sky pattern tumor lysis syndrome (hyperuricemia, hyperphosphatemia, hyperkalemia, acute renal failure risk)

Question 52

diffuse large B cell

Answer 52

most common common abnormality involving BCL6 (3q27) with rearrangements or activating point mutations in BCL6 also t(14;18) seen with overexpression BCL2 epigenetics have potential role some transformed follicular lymphomas subtypes - immunodeficiency associated large cell lymphoma, primary effusion lymphoma, mediastinal large B cell lymphoma median 60 years rapid enlarging often symptomatic mass at one or several sites treat with chemo - remission 60-80% and 40-50% remain free of disease

Question 53

immunodeficiency associated large cell lymphoma

Answer 53

EBV associated in setting of immunosuppression

Question 54

primary effusion lymphoma

Answer 54

HHV 8 associated primary effusion lymphomas

Question 55

mediastinal large B cell lymphoma

Answer 55

young women with predilection to spread to abdominal viscera and CNS

Question 56

morphology diffuse large B cell lymphoma

Answer 56

large cells variable appearance can be pleomorphic with cells resembling reed-sternberg cells B cell antigens (CD 19, 20) surface IgM and/or IgG, CD10,BCL2 variably expressed

Question 57

mantle cell lymphoma

Answer 57

resemble naive B cells in mantle zones of lymph follicles fatigue and lymphadenopathy aggressive and incurable survival 8-10 years most have t(11;14) with cyclin D1 gene fused to IgH locus express IgM and ID, pan B cell antigens (CD 19,20) and CD 5 no proliferation centers

Question 58

morphology mantle cell lymphoma

Answer 58

diffuse or vaguely nodular cells slightly larger than normal, can have larger cells bone marrow involvement in most casses w peripheral blood involvement (can arise in GI tract)

Question 59

marginal zone lymphoma

Answer 59

occurs in nodes, spleen, or mucosal tissues chronic inflammation secondary to infection or autoimmunity between lymphoid hyperplasia and lymphoma acquires genetic mutations w upregulation of BCL10 or MALTI that inactivates NF-kB that promotes growth and survival of B cells

Question 60

morphology marginal lymphoma

Answer 60

gastric lymphoma often associated with h pylori genetic alterations including t(11;18)(q21;21), t(1;14)(p22;32), and t(14;18)(q32;q21) positive CD 19, 20, 43 infiltrate lamina propria and gastric glands focally

Question 61

hairy cell leukemia

Answer 61

older males manifestation from infiltration of bone marrow and spleen can have massive splenomegaly and pancytopenia infections common indolent disease but progressive if untreated extremely sensitive to chemo (particularly purine nucleosides)

Question 62

morphology hairy cell leukemia

Answer 62

leukemic cells have fine hairlike projections nuclei round or folded with moderate pale blue cytoplasm with threadlike extensions spleen heavily infiltrated 90% with activating point mutations in serine/threonine kinase BRAF positioned downstrem of RAS in MAPK signaling positive CD 19, 20, 11c, 25, 103

Question 63

peripheral T cell lymphoma

Answer 63

aggressive and unresponsive to therapy symptomatic from tumor derived inflammatory products positive 2,3,5, t cell receptors clonal T cell receptor rearrangements

Question 64

adult t cell lymphoma

Answer 64

caused by infection with retrovirus (HTLV 1) which encodes Tax (potent activator of NF-kB which enhances lymphocyte growth and survival) results in transverse myelitis associated with skin lesions, lymphadenopathy, hepatosplenomegaly, hypercalcemia, malignant lymphocytes positive for CD 4, 25 median survival months - 1 year

Question 65

mycosis fungoides

Answer 65

tumor of CD4 t cells in skin sezary syndrome - generalized exfoliative erythroderma and leukemia with sezary cells with cerebriform nuclei possitive adhesion molecule CLA and chemokine receptors CCR4 and CCR10 which contribute to homing of CD4 cells to skin indolent with median survival of 10 years can transform to aggressive t cell lymphoma

Question 66

primary immunodeficiencies

Answer 66

genetic mutation not caused by another condition or infection part of immune system is missing or functioning abnormally

Question 67

phagocytic dysfunctions

Answer 67

leukocyte adhesion deficiency type 1 chediak higashi syndrome chronic granulomatous disease

Question 68

leukocyte adhesion deficiency type I

Answer 68

leukocytes cant leave vasculature and migrate normally into tissues defective expression of beta 2 intergin family (CD18) autosomal recessive

Question 69

normal leukocyte adhesion

Answer 69

leukocytes express integrins that let them stick integrns have alpha and beta chain

Question 70

beta 2 intergin receptors

Answer 70

consist of an alpha and beta chain beta: CD 18 alpha CD: 11a, 11b, 11c CD 18 required fro cell surface expression of alpha chains (heterodimer)

Question 71

leukocyte adhesion deficiency 1 presentation

Answer 71

delayed separation umbilical cord, recurrent skin and mucosal bacterial infections, impaired wound healing, no pus/leukocytes severity related to degree of CD 18 deficiency

Question 72

leukocyte adhesion deficiency 1 diagnosis

Answer 72

consider any infant with recurrent soft tissue infection and very high leukocyte count absent CD18 and CD11a on leukocyte by flow cytometry

Question 73

leukocyte adhesion deficiency 1 treatment

Answer 73

stem cell transplant in sever less severe - monitor for infection

Question 74

chediak higashi syndrome

Answer 74

defective vesicle fusion and lysosome transport mutation of LYST gene (lysosome trafficking regulator, vesicular transport protein) impact broad spectrum of cells

Question 75

lysosome functions

Answer 75

contain digestive enzymes, overturn cell macromolecules, degrade cell debris, help clear damaged/defective structures, critical in destruction of phagocytized pathogens

Question 76

antigen processing and presentation

Answer 76

exogenous (MHC II) endogenous (MHC I) in antigen processing, proteins are cut down into appropriate sizes to load into MHC

Question 77

chediak higashi syndrome pathology

Answer 77

altered lysosome granules found in all cell types in CHS patients and are hallmark of disease melanocytes contain enlarged pigment granules, neutrophils have giant azurophilic granules and cytotoxi t cells have enlarged mature secretory cytolytic granules (impaired microbial killing), platelet dense bodies reduced, plasma membrane repair is impaired, neuro defects

Question 78

chediak higashi syndrome characteristics

Answer 78

partial oculocutaneous albanism, recurrent pyogenic infections (make pus), abnormal platelet aggregation and bleeding time, neutropenia accelerated phase usually lethal (excessive lymphocyte) speckled hyperpigmentations and hypopigmentation of sun exposed areas, light colored eyes, hair is light with metalic sheen labs - neutropenia, hypergammaglobinemia, impaired bacterial killing, abnormal platelet aggregation and bleeding time diagnosis - giant azurophilic granules in granulocytes

Question 79

chedial higashi syndrome treatment

Answer 79

hematopoietic stem cell transplant without, death usually occurs before 7 years

Question 80

chronic granulomatous disease

Answer 80

defects in NADPH oxidase (critical for reactive oxygen species generation, poor killing of phagocytosed microbes especially catalase positive like staph aureus) lack ability to generate oxidative burst x linked lowered microbe killing, poor control of infection, increased lymphocyte recruitment to infection site, granuloma formation common

Question 81

chronic granulomatous disease characteristics

Answer 81

infection by catalase positive organisms growth failure, abnormal wound healing, infected dermatitis, fail to thrive hepatomegaly, splenomegaly, lymphadenitis pneumonia, aspergillosis, skull abcesses, pulmonary abcesses, chronic diarrhea

Question 82

CGD treatment

Answer 82

hematopoietic stem cell transplant 50% survive to 30/40

Question 83

CGD diagnosis

Answer 83

measure dihydrorhodamine reduction (flow cytometry) nitroblue tetazolium dye reduction test cytochrome c reduction assay

Question 84

B cell disorders

Answer 84

x linked agammaglobulinemia selective IgA deficiency common variable immunodeficiency

Question 85

x linked agammaglobulinemia (brutons)

Answer 85

B cell precursors fail to develop into mature B cells (absent to low B cells) almost always in males 6-18 months mutationi in bruton tyrosine kinase (essential for Ig receptor signaling)

Question 86

x linked agammaglobulinemia characteristics

Answer 86

recurretn bacterial infections of respiratory tract autoimmune diseases frequent increased risk of certain cancers labs - serum levels of all Ig classes decrease, lymph node germinal centers/peyers patches/appendix/tonsils under developed

Question 87

x linked agammaglobulinemia treatment

Answer 87

immunoglobulin replacement therapy some pts daily oral antibiotics

Question 88

selective IgA deficiency

Answer 88

multiple suspected genetic mutations 1/3 dont attract medical attention because IgM picks up slack

Question 89

selective IgA deficiency clinical manifestation

Answer 89

recurrent sinopulmonary/GI infections autoimmune disorders giardia lamblia infections and other intestinal disorders allergic disorders increased cancer risk (especially GI) anyphylactic transfusion reactions (antibodies against IgA that react in blood transfusion) labs - loww/absent IgA, normal IgM and IgG, cell counts normal

Question 90

selective IgA deficiency treatment

Answer 90

no cure treat infections

Question 91

common variable immunodeficiency

Answer 91

severe deficiency, affects both sexes and children and adults, most diagnosed btwn 20-45 broad range of clinical symptoms and autoimmunity not single disease, collection of hypogammaglobulinemia syndromes hallmark: deffective B cell differentiation into plasma cells decreased serum IgG, low IgA/IgM, poor immunization response, absence of any toher defined immunodeficiency hyperplastic B cells

Question 92

variable immunodeficiency presentation

Answer 92

recurrent sinopulmonary pyogenic infections, pneumonia, splenomegaly, bronchiectasis, autoimmunity common autoimmune diseases: RA, lymphomas, gastric cancer

Question 93

t cell disorders

Answer 93

digeorge syndrome IL 12 receptor deficiency Job syndrome chronic mucocutaneous candidiasis

Question 94

digeorge syndrome

Answer 94

thymic aplasia 22q11.2 deletion or velocardiofacial syndrome autosomal dominant incomplete development of the thymus and parathyroid glands TBX 1 commonly impacted (development of brachial arch/greater vessels so cause heart defects)

Question 95

digeorge syndrome symptoms

Answer 95

vary widely partial vs severe onset varies depending on severity severe early in life w recurrent severe infections heart defects/facial abnormalities may be first notable signs classic triad: cardia abnormalities, hypoplastic thymus, hypocalcemia (low parathyroid hormone production) facial features: small low set ears, small eye opening, hooded eyes, long face, enlarged nose tips, short flattened groove of upper lip, increased risk cleft palate diagnostics: decreased T cells with clinical findings or genetic deletions, normal/decreased serum Ig

Question 96

IL 12 receptor deficiency

Answer 96

Il 12 usually stimulates T cells to polarize into Th1, stimulates macrophages and other cells to produce IFN gamma, activates NK cells autosomal recessice

Question 97

IL 12 receptor deficiency symptoms

Answer 97

early in childhood recurrent disseminated infections (possibly post BCG vaccine) sepsis common labs - decreased IFN gamma levels high risk intracellular pathogen causes severe infections

Question 98

autosomal dominant hyper IgE syndrome (job syndrome)

Answer 98

autosomal dominant mutation in STAT3 poor Th17 differentiation poor trafficking of leukocytes to sites of infections labs - increased IgE, eosinophilia, decreased IFN gamma

Question 99

job syndrome symptoms

Answer 99

broad nasal base/bridge protruding forehead deep set eyes doughy consistency of skin retain primary teeth easy skeletal fractures dermatitis, recurrent skin/sinopulmonary infections, skin abcesses, no increased allergy rates

Question 100

B and T cell disorders

Answer 100

Severe combined immunodeficiency ataxia telangiectasia hyper IgM syndrome wiskott aldrich

Question 101

SCID

Answer 101

collection of syndromes with different genetic defects X linked and autosomal recessive

Question 102

SCID presentation

Answer 102

recurrent severe infections, chronic diarrhea, fail to thrive absend thymic shadow without HSC death usually in first year t cell receptor excision circle labs - low t cells, b cells normal or elevated, low lymphocytes, hypogammaglobulinemia treat - HSC transplant

Question 103

ataxia telangiectasia

Answer 103

autosomal recessive defective ATM gene (critical for DNA repair) poor gait/standing, jerky eye mvmt, poor mental development, discolored skin, enlarged vessels, recurrents infections, high risk o fcancer elevated alpha feroprotein, decreased IgA/G/E, poor response to vaccines tx - none

Question 104

hyper IgM syndrome

Answer 104

CD4 t cells cant deliver activating signal to b cells macrophages B cells cant class switch 70% X linked infants with recurrent sinopulmonary infections (commonly encapsulated viruses), opportunistic infections, chronic diarrhea, increased risk malignancy and autoimmune disease normal B and T cell numbers, reduced serum IgG/A/E, elevated IgM, lack antibody response, reduced memory B cells

Question 105

wiskott aldrich syndrome

Answer 105

x linked affects WASp (critical for actin remodeling in hematopoietic cells) hemorrhagic diathesis bc thrombocytopenia, recurrent bacterial/viral/fungal infections, extensive eczema decreased to normal IgG/M, increased IgA/E, decrease small platelets treat - HSC transplantation

Question 106

hodgkins disease

Answer 106

malignant lymphoma infections (EBV, HIV) often matter lymphocyte predominant is different (no reed sternberg cells) above or below diaphragm is good, both sides is bad reed sternberg cells are conductos via cytokine (CD 15, 30) localized to single axial group of nodes, orderly spread by contiguity, mesenteric nodes and waldeyer ring rarely invovlved, extranodal presentation rare

Question 107

hodgkins disease symptoms

Answer 107

painless lymphadenopathy staging important -young patients typical stage I and II with favorable subtypes and few B symptoms -advanced disease more likely to have systemic complications spreads to contiguous nodes and chains early, stereotyped spread (nodal disease followed by spleen, hepatic, finally marrow)

Question 108

hodgkins disease treatment

Answer 108

chemo and radiation anti CD30 antibodies

Question 109

hodgkins stage I

Answer 109

involvement of single node region or single extralymphatic organ or site

Question 110

hodgkins stage II

Answer 110

involvement of two or more lymph node regions on same side of diaphram alone or localized involvement of an extralymphatic organ or site

Question 111

hodgkins stage III

Answer 111

involvement or lymph node regions on both sides of the diaphragm without or with localized involvement of an extralymphatic organ or site

Question 112

hodgkins stage IV

Answer 112

diffuse involvement of one or more extralymphatic organs or sites with or without lymphatic involvement

Question 113

types of hodgkins disease

Answer 113

classic - nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depletion (reed sternberg cells have similar distinctive immunophenotype) other - lymphocyte predominance (RS cells with B cell antigens)

Question 114

nodular sclerosis

Answer 114

bands of collagen lacunar RS young, men=women excellent prognosis tend to affect lower cervical, supraclavicular, mediastinal nodes

Question 115

mixed cellularity

Answer 115

highest EBV infection rate (70%) most common >50 years mononuclear and classic RS good prognosis plentiful mononuclear and classic RS cells within heterogenous inflammatory infiltrate more likely to have disseminated and have systemic manifestations

Question 116

lymphocyte rich

Answer 116

lots of lymphocytes classic with diagnostic/c;assic and monocellular RS uncommon reactive lymphocyte are predominant cell type with diffuse effacement of nodes 40% EBV

Question 117

lymphocyte depleted

Answer 117

fewer lymphocytes HIV uncommon overall but most common in elderly paucity of lymphocytes and relative abundance of RS cells EBV in 90% of cases

Question 118

lymphocyte predominant

Answer 118

nonclassic RS cells show B antigens popcorn or lymphohistiocytic (L&H cells) CD 15 and 30 negative, positive CD20 and BCL6 younger males numerous mature looking lymphocytes cervical or axillary lymphadenopathy excellent prognosis

Question 119

IPS score

Answer 119

ranking system for advanced disease into good risk, fair risk, poor risk

Question 120

plasma cell disorders

Answer 120

b cell neoplasms composed entirely or in part of plasma cells virtually always secrete monoclonal immunoglobulin or immunoglonulin fragments multiple myeloma, monoclonal gammopathy of undetermined significance, plasmacytoma, heavy chain disease, lymphoplasmacytic lymphoma

Question 121

multiple myeloma pathogenesis

Answer 121

possible origination in stem like cells resembling small B cells cytokines important (IL 6) produces factors that lead to bone destruction (activate osteoclasts through RANKL) many with rearrangements in Ig heavy chain gene on chromosome 14q32, also t(4;14), dysregulation of D cyclins

Question 121

multiple myeloma

Answer 121

monocolonal proliferation of plasma cells, multifocal lytic bone lesions, can spread to nodes and skin, usually overproduction of immunoglobulin (M spike)

Question 122

multiple myeloma pathology

Answer 122

increased plasma cells cytoplasmic accumulation of protein RBCs stick to each other accumulation of bence jones proteins amyloidosis secondary to light chain accumulation

Question 123

multiple myeloma clinical presentation

Answer 123

bone pain due to marrow expansion lytic lesions with risk of pathologic fractures hypercalcemia due to bone resorption monoclonal immunoglobulin (m spike on electrophoresis) decreased normal immunoglobulins increased bence jone proteins (free light chains) prognosis poor if untreated

Question 124

primary of immunocytic amyloidosis

Answer 124

associated with monoclonal plasma cell proliferations associated with development of amyloidosis can be secondary to overt multiple myeloma or smaller clonal populations of plasma cells that produce pathogenic immunoglobulins

Question 125

plasmacytoma

Answer 125

single lesion composed of plasma cells osseous or extraosseous patients with osseous lesions often progress to multiple myeloma

Question 126

monoclonal gammopathy of undetermines significance

Answer 126

M protein spike without other features of multiple myelome suspicious for underlying or subsequent development of multiple myeloma

Question 127

heavy chain disease

Answer 127

overproduction of only heavy chains (IgG, IgM, IgA), IgA most common often occurs where IgA normally produced may resemble extranodal marginal lymphoma

Question 128

lymphoplasmacytic lymphoma

Answer 128

lymphoma composed of plasmacytoid cells, tumor secrete M protein seen in elderly often t(9;14) with PAX5 adjacent to Ig heavy chain gene hepatosplenomegaly and lymphadenopathy, rarely w lytic lesions/hypercalcema/retinal hemorrhages can overproduce Igm causing Waldenstrom macroglobulinemia (sludge cells in vessels, can have epistaxis/dizziness/confusion) no lytic bone lesions and rarely associated with amyloid

Question 129

myelodysplastic disorders

Answer 129

clonal stem cell disorders characterized by maturation defects that are associated with disorganized and ineffective hematopoiesis and a high risk of transformation to AML cytopenias result often splenomegaly

Question 130

myeloproliferative neoplasms

Answer 130

have constitutively active tyrosine kinase or other acquired abberations in signaling pathways that lead to growth factor independence -CML with t(9;22) fusion gene with very high WBC, mature granulocytes present, splenomegaly, hypercellular bone marrow -polycythemia vera production of myeloid cells with symptoms related to RBC production, therapeutic phlebotomy can treat, essential thrombocytosis with increase in megakaryocytes and platelets -primary myelofibrosis with fibrosis of bone marrow with decreased hematopoiesis

Question 131

histiocytic lesions

Answer 131

langerhans histiocytosis with proliferation of immature dendritic cells in epidermis and other organs cells often have mutation in serine/threonine kinase birbeck granules present

Question 132

myelodysplastic syndrome

Answer 132

marrow partially or totally replaced by clonal proliferation that retains ability to differentiate into RBCs, granulocytes, platelets differentiation ineffective and disordered cauting cytopenias considered type of cancer can transform to AML

Question 133

myelodysplastic syndrome pathology

Answer 133

megaloblastoid erythroid precursors, ringed sideroblasts, granulocytes with abnormal granules or nuclear migrations, small megakaryocytes with small nuclei and multiple nuclei response to chemo poor, worse in pts with increased marrow blasts and cytogenic abnormalities

Question 134

myeloproliferative syndrome

Answer 134

hyperproliferation of neoplastic myeloid progenitors that retain capacity for terminal differentiation causing increase in 1 or more elements in peripheral blood seed organs of secondary hematopoiesis mutations resulting in activation of tyrosine kinase (turn on paths normally activated by growth factors)

Question 135

myeloproliferative disorders types

Answer 135

CML polycythemia vera essential thrombocytosis primary myelofibrosis

Question 136

CML

Answer 136

t(9;22) philadelphia chromosome and increased unregulated tyrosine kinase activity neoplastic monoclonal proliferation of granulocytes (cels are granulocyte precursors)

Question 137

CML symptoms

Answer 137

often in adults constitutional symptoms, splenomegaly, sternal pain can have slow progression with sudden development of blast crisis hypercellular marrow with prominent granulopoiesis

Question 138

CML treatment

Answer 138

tyrosine kinase inhibitors

Question 139

polycythemia vera

Answer 139

increase in RBCs, chronic myeloproliferative disorder JAK2 V617F mutation associated wtih erythropoietin mutations and abnormalities

Question 140

polycythemia vera symptoms

Answer 140

fatigue, malaise, plethoric face, paresthesia, pruritis, increased bleeding and thrombosis, headache, peptic ulceration

Question 141

polycythemia vera morphology

Answer 141

major - elevated red cell mass, normal arterial oxygen saturation, splenomegaly WHO - increased RBC with JAK2 mutation, often low erythropoietin, marrow can be hypercellular with low storage iron

Question 142

polycythemia vera clinical course

Answer 142

chronic indolent progression, prolonged can develop spent phase/myelofibrosis or malignant transformation

Question 143

polycythemia vera treatment

Answer 143

phlebotomy ASA (thrombosis) hydroxyurea splenomegaly

Question 144

essential thrombocytosis

Answer 144

60-65 years increased platelet count marrow normocellular or mildly hypercellular with increased megakaryocytes marrow w increasd reticulin CBC with enlarged platelets can have JAK2 mutation

Question 145

essential thrombocytosis symptoms

Answer 145

splenomegaly, HA, dizziness, visual changes, burning pain in hands and feet can cause thrombosis or hemorrhage long indolent course

Question 146

primary myelofibrosis

Answer 146

development of marrow fibrosis (secondary to collagen deposition by non neoplastic fibroblasts) w decreased hematopoiesis axtramedullary hematopoiesis common premature release of nucleated erythrocytic and early granulocytic precursors tear drop shaped cells

Question 147

primary myelofibrosis symptoms

Answer 147

secondary to splenomegaly and progressive anemia cosntitutional symptoms hyperuricemia and gout CBC w normochromic normocytic anemia w leukoerythroblastosis course variable bone marrow transplant

Question 148

histiocytosis

Answer 148

proliferations of histiocytic cells ranging from malignant to lymphomas to benign proliferations

Question 149

langerhans histiocytosis

Answer 149

proliferation of immature dendritic cells in epidermis and other organs cells often have mutations in serine/threonine kinase langerhans cells secrete class II MHC antigens, CD 1a, langerin birebeck granules appear similar to tennis rackets cells appear more like macrophages

Question 150

multisystem histiocytosis

Answer 150

litterer siwe disease in children under 2 with cutaneous lesions, hepatosplenomegaly, lymphadenopathy, pulmonary lesions, osteolytic bone lesions, pancytopenia

Question 151

unisystem histiocytosis

Answer 151

medullary cavity of bones, skin, lungs, stomach admixed with other inflammatory cells most often bones with pain, tenderness, pathalogic fractures can be mutlifocal hand schuller christian triad - calvarias bone defects, diabetes insipidus, exophthalmos

Question 152

pulmonary histiocytosis

Answer 152

seen in adult smokers regress with smoking cessation

Question 153

PIDs commonly associated with autoimmune diseases

Answer 153

common variable immunodeficiency selective IgA deficiency chronic mucocutaneous candidiasis complement pathway deficiencies

Question 154

normal infection rates

Answer 154

children get multiple viral infections in first years of life children under 2 more likely to get ear infections babies get thrush healthy children, teens, adults generally only get sick a few times a year and dont often need antibiotics

Question 155

types of PIDs

Answer 155

innate immunodeficiencies adaptive immunodeficiencies

Question 156

innate immunodeficiencies

Answer 156

phagocytic deficiencies (pyrogenic infections) complement deficiencies (encapsulated organisms)

Question 157

adaptive immunodeficiencies

Answer 157

B cell/Ab deficiencies (sinopulmonary infects and diarrhea) t cell deficiencies (viruses, fungi, pneumocytosis) combined b and t cell deficiencies

Question 158

chemo treatment goal

Answer 158

complete inhibition of growth of cancer cell

Question 159

selective targeting of chemo

Answer 159

want to target cancer cell only inhibit paths or targets that are critical for cancer cell survival and replication at concentrations lower than those required to affect critical host paths

Question 160

selectivity accomplished by attacking

Answer 160

targets unique to cancer cells that are not present in host targets in cancer cell that are similar but not identical to those in host target in cancer cells that are shared with host but vary in importance between cancer cells and host and thus impart selectivity

Question 161

unique drug targets

Answer 161

metabolic pathways enzymes other gene products that are present in cancer cells but absent in hsot

Question 162

common drug targets

Answer 162

able to target bc cancer cells arise from transformed normal cells (nearly identical cellular machinery) try to exploit differences to narrow therapeutic index

Question 163

cell cycle non specific drugs

Answer 163

alkylating agents nitrosoureas cisplatin dactinomycin doxorubicin plicamycin mitomycin

Question 164

G1 phase drugs

Answer 164

asparginase

Question 165

S phase drugs

Answer 165

antimetabolites hydroxyurea topoisomerase inhibitors

Question 166

G2 phase drugs

Answer 166

bleomycin topoisomerase inhibitors

Question 167

M phase drugs

Answer 167

vinca alkaloids taxanes

Question 168

carcinogenesis

Answer 168

progression from normal cell to malignant tumor is multistep process that requires multiple mutations 3 steps - transformation, proliferation, metastasis

Question 169

transformation

Answer 169

change in phenotype from cell with normal growth to cell with dysregulated growth progeny with higher survival capacity selected with increased cell proliferation and tumor progresses to greater heterogeneity

Question 170

proliferation

Answer 170

daughter cell becomes quiescent daughter cell enters cell cycle and proliferates daughter cell dies growth fraction important

Question 171

metastasis

Answer 171

cancer cells acquire capacity to invade tissues and metastasize throughout body must acquire mutations that allow invasion, spread, and growth tumor cells can evolve differential receptor expression patterns and drug sensitivities most dedifferentiated metastatic cells respond poorly to same agents

Question 172

chemo early diagnosis

Answer 172

survival time inversely related to initial number of tumor cells aging cancer cells less susceptible to chemo (decreased dividing cells, overcrowding of cells) most antineoplastics target dividing cells and G0 cells may not be killed small rapidly growing tumors respond better to chemo

Question 173

log kill method

Answer 173

tendency of anticancer therapy to kill constant fraction of tumor cell population not a fixed number -1st order kinetics -each dose kills constant fraction of cells all chemo drugs cause apoptosis most antineoplastics used intermittently to reduce toxic side effects

Question 174

administer intermittent therapy until

Answer 174

all cancer cells killed tumor develops resistance drug resistant cells continue to grow resulting in death

Question 175

how to improve outcomes with log cell kill

Answer 175

higher doses of chemo initiate therapu when tumor has fewer cells earlier detection adjuvant therapy surgery and radiation reduce number of cells before chemo is initiated recruit more cells into cell cycle and increase cells susceptibility to drug

Question 176

antineoplastic drug resistance

Answer 176

primary/inherent - absence of response on first exposure (genomic instability) acquired - absence of response which develops in an originally drug sensitive tumor type

Question 177

single drug resistance mechanism

Answer 177

decreased sensitivity of target enzyme decrease cellular uptake of the drug increase drug activation decrease prodrug activation

Question 178

multidrug resistance mechanism

Answer 178

resistance to variety of structures which develops after exposure to single agent increased efflux of drug from cell inceased DNA repair

Question 179

primary therapy

Answer 179

when used by itself accepted as best treatment advanced metastatic disease -relieve tumor related symptoms, improve quality of life, prolong time to tumor progression can involve salvage therapy (tx after cancer has not responded to treatment)

Question 180

neo-adjuvant therapy

Answer 180

decrease size of tumor before primary treatment for pts presenting with localized disease in whom local forms of therapy are inadequate by themselves -improve operability, preserve anatomic structure, assess responsiveness of tumor chemo

Question 181

chemo as adjuvant therapy

Answer 181

chemo given after treatment to lower risk of recurrence -reduce incidence of local and systemic recurrence, improve overall survival of patients

Question 182

combo chemo

Answer 182

combo therapy with two or more anticancer drugs is the rule for most malignancies provides broader coverage against resistant cell lines -each drug should be active when used alone -drug must have different mechanism of action and act at different phase of cell cycle -drugs with different toxicity pattern should be selected when possible -cross resistance between drugs should be minimal

Question 183

therapeutic safety index

Answer 183

ratio of dose that causes therapeutic effect to toxic effect low index has lower selectivity and greater toxicity higher index has greater selectivity and lower toxicity

Question 184

narrow therapeutic index

Answer 184

small dose changes cause large effects in toxicity potential lethal toxicities wide range of drug dosing for some drugs

Question 185

complex regimens

Answer 185

multidrug, multiday many research protocols

Question 186

efficacy

Answer 186

prefer drugs that produce complete remission

Question 187

toxicity

Answer 187

prefer agents with different toxic effects

Question 188

optimum scheduling

Answer 188

treatment free interval should be shortest time necessary for recovery of most sensitive normal target tissue

Question 189

mechanism of interaction

Answer 189

want combination therapy to allow for maximal effect

Question 190

avoidance of arbitrary dose changes

Answer 190

may fall below threshold of effectiveness and eliminate ability of combo to cure disease

Question 191

hodgkins disease combo therapy

Answer 191

ABVD - adriamycin, bleomycin, vinblastine, dacarbazine MOPP - mechlorethamine, oncovin, procarbazine, prednisone

Question 192

non hodgkins lymphoma combo therapy

Answer 192

R-CHOP - rituximab, cyclophophamide, H doxorubicin, oncovin, prednisone

Question 193

testicular cancer combo therapy

Answer 193

BEP - bleomycin, etoposide, platinol

Question 194

breast cancer combo therapy

Answer 194

CMF - cyclophosphamide, methotrexate, fluorouracil

Question 195

cholorectal cancer combo therapy

Answer 195

FOLFOXIRI - folinic acid, fluorouracil, oxaliplatin, irinotecan

Question 196

pulse therapy

Answer 196

intermittent treatment can allow high doses of anticancer drugs acute leukemias, testicular cancer, wilms tumor

Question 197

recruitment therapy

Answer 197

recruitment involves the initial use of CCNS to achieve significant kill resulting in recruitment into cell division of previously resting cells with subsequent administration of CCS drug maximal cell kill can be achieved

Question 198

rescue therapy

Answer 198

administration of drugs to counteract effect of anticancer drugs -leucovorin after methotrexate -MESNA with cyclophosphamide -filgrastim or sargramostim to prevent chemo induced neutropenia

Question 199

to minimize toxicity

Answer 199

reduce dose improve elimination of metabolites hydration/diuresis alter schedule of therapy limit extent of delivery improve recovery from toxicity

Question 200

adjunct agents

Answer 200

leucovorin, filgrastim, epoetin alfa, oprelvekin, allopurinol, 5-HT3 antagonists, corticosteroids, aprepitant, BDZ

Question 201

chemo less sensitive in

Answer 201

colorectal, carcinoma stomach, carcinoma esophagus, hepatoma, malignant melanoma, sarcoma

Question 202

chemo can only be palliative in

Answer 202

breast, ovarian, endometrial, prostatic, chronic myeloid leukemia, head and neck, lung small cell cancer

Question 203

philadelphia chromosome

Answer 203

associated with CML first malignancy identified with chromosome rearragement : t(9;22)(q34.1;q11.2) fuses promoter and coding sequence of BCR on 22 with most of ABL protooncogene from 9 (splice exon 2 of ABL to part of BCR) tyrosine kinase promotes cell proliferation

Question 204

CML

Answer 204

90% philadelphia chromosme BCRABL fusion provides proliferative advantage other mutations accumulate leads to blast crisis with large numbers or precursors most common in adults

Question 205

micro bio of CML

Answer 205

ABL is tyrosine kinase receptor normally must dimerize after ligand binds BCR region will dimerize normally fusion protein will dimerize (tyrosine kinase activity constitutive)

Question 206

burkitt lymphoma

Answer 206

multiple forms manifestations generally extranodal all forms c-MYC on 8 and immunoglobulin promoter (8;14 for IgH, 2;8 for kappa, 8;22 for delta)

Question 207

burkitt lymphoma endemic

Answer 207

tumors have latent EBV commonly in mandible and abdominal viscera

Question 208

burkitt lymphoma sporadic

Answer 208

found in ileocecum and peritoneum

Question 209

burkitt lymphoma HIV associated

Answer 209

aggressive 25% have HIV

Question 210

follicular lymphoma

Answer 210

common translocation t(14;18) antiapoptotic gene BCL2 under control of IgH promoter increase cell survival

Question 211

mantle cell lymphoma

Answer 211

look like mantle cell zone B cells that surround germinal centers t(11;14) - cyclin D1 controlled by IgH promoter

Question 212

philadelphia chromosome

Answer 212

t(9;22)(q34.1;q11.2) fuse promoter w inital coding sequence of BCR on 22 with most of ABL proto-oncogene from 9 (splice exon 2 of ABL to part of BCR) tyrosine kinase promotes cell proliferation

Question 213

CML

Answer 213

90% philadelphia chromosome cells proliferate without differentiation causing blast crisis w large number of precursors ABL is tyrosine kinase receptor (must dimerize after ligand binds to phosphorylate targets), BCR will dimerize with no ligand so fused proteins dimerize

Question 214

burkitt lymphoma

Answer 214

c MYC on 8 and an immunoglobulin promoter involved in all mutations high expression of c MYC may have point mutations (favored by p53)

Question 215

follicular lymphoma

Answer 215

translocation t(14;18) puts antiapoptotic BCL2 under control IgH promoter

Question 216

mantle cell lymphoma

Answer 216

t(11;14) translocation so cyclin D1 controlled by IgH promoter promotes G1 to S phase transition

Question 217

ALL

Answer 217

abnormal transcription factor regulation NOTCH1 gain of function in pre t, loss of PAX5/E2A/EBF in pre b

Question 218

AML

Answer 218

4 categories with multiple subtypes different genetic causes of subtypes -loss of transcription factors for myeloid differentiation (cbf1 alpha/ cbf1 beta) -tyrosine kinase PML fused with RAR alpha, inhibits granulocyte maturation

Question 219

gene amplification done how

Answer 219

homogenous staining regions double minutes

Question 220

homogenous staining regions

Answer 220

many tandem copies of the amplified gene present in location other than normal one produce lots of protein

Question 221

double minutes

Answer 221

extra small chromosomes carry extra copies of the genes

Question 222

MYC

Answer 222

targeted as transcription factor, active early in cell division amplified in some breast, colon, lung tumors

Question 223

cyclin dependent kinase 4

Answer 223

melanomas, sarcomas, glioblastomas

Question 224

ERBB2 in what

Answer 224

20% breast cancers

Question 225

DHFR

Answer 225

seen in cells after treatment with methotrexate

Question 226

miRNA

Answer 226

helps regulate expression

Question 227

decreased miRNA

Answer 227

increased expression in targets

Question 228

increased miRNA

Answer 228

decreased expression in targets

Question 229

radiation

Answer 229

energy that travels in terms of waves or high speed particles ionizing radiation has sufficient energy to remove tightly bound electrons

Question 230

x rays and gamma rays

Answer 230

electromagnetic nonparticulate waves that cause ejection of orbital electrons when absorbed causing ionization longer deeper course with less damage per unit of tissue

Question 231

particulate waves with high energy neutrons

Answer 231

alpha particles (2 protons and 2 neutrons) and beta particles (electrons) -alpha induce heavy damage in restricted area -electron beams have low penetrance

Question 232

absorbed dose

Answer 232

measured in grays (Gy)

Question 233

seivert

Answer 233

factors in potency and type of radiation amount of radiation necessary to produce same effect on living tissue

Question 234

teletherapy/external beam therapy

Answer 234

radiation produced outside body and delivered to internal targets

Question 235

brachytherapy

Answer 235

radiation placed within or near tumors

Question 236

systemic therapy

Answer 236

radioisotopes injected into blood and travel to tumor for treatment

Question 237

photodynamic therapy

Answer 237

chemicals taken up by cancer cells when laser light shone on cells free radicals generated to fight cancer

Question 238

effects of radiation

Answer 238

double stranded breaks in DNA mechanism of cell death of tumor breaks secondary to free radical generation survival related to 4 R's - repair, redistribution, repopulation, reoxygenation

Question 239

radiation complications

Answer 239

acute radiation syndrome acute effects on hematopoietic and lymphoid systems fibrosis DNA damage and carcinogenesis

Question 240

chronic radiation damage

Answer 240

head and neck - thyroid damage, cataracts and retinal damage, decreased salivation chest - MI, constrictive pericarditis, pulmonary fibrosis, viscus strictures, spinal cord transection, radiation enteritis

Question 241

lymphocyte focused response against tumor

Answer 241

TCR (t cells) and antibodies (B cells) for tumor related antigens

Question 242

cancer isnt cured by immune system bc

Answer 242

mutations cause it to be immunosuppressive and immunevasive

Question 243

tumors produce what to suppress the immune system

Answer 243

immunosuppresive cytokines (IL10, TGF beta) and regulatory cells (TREGS)

Question 244

how does the immune system recognize cancer cells

Answer 244

mutations in cancer genes themselves -distinct proteins

Question 245

some cancers are associated with viruses

Answer 245

cervical cancer and HPV cancer cells targeted by host immune system bc viral antigens

Question 246

immune defense against cancer

Answer 246

main defense is t cells -PAMPs are signals provided by infects -activation of APCs (done by DAMPs)

Question 247

cancers suppression of immune system

Answer 247

cancer divides rapidly (outpace killing rate) loss of MHC I (target cells for destruction by NK cells) express inhibitory receptors that block t cell activation (PD 1 and CTLA 4) express CD47 (inhibitory signal for phagocytes) secrete inhibitory cytokines (IL10 and TGF beta) TREGS (suppress lymphocytes) secrete CCL22 (attract TREGS to cell) FasL (induce death of lymphocytes)

Question 248

treatment modalities against cancer

Answer 248

passive immunotherapy with monoclonal antibodies adoptive transfer of antitumor t cells stimulation of host immune response

Question 249

passive immunotherapy

Answer 249

monoclonal antibodies injected into patient -bind surface of cancer cells, target for elimination by host immune response -anti CD 20 (utilized in B cell lymphoma, target b cells for destruction) -anti Her2/neu (growth factor receptor blocked in breast cancer) -anti VEGF (block angiogenesis)

Question 250

adoptive transfer of anti tumor t cells

Answer 250

enhance t cell response t cells harvested from patient, stimulated, placed back in patient -chimeric antigen receptor expressing t cells : transfect t cells with viral vector that expresses receptor that recognize surface antigens on cancer cells -can cause cytokine release syndrome

Question 251

stimulation of hosts immune response

Answer 251

-block inhibitory receptors on t cells or their ligands (anti PD1 and anti CTLA4) -vaccinate with persons own tumor cells or antigens from these cells

Question 252

syngeneic transplant

Answer 252

between animals identical

Question 253

allogenic transplant

Answer 253

between same species

Question 254

xenogenic transplant

Answer 254

between different species

Question 255

allografts

Answer 255

tissue from same speciesx

Question 256

xenografts

Answer 256

tissue from different species

Question 257

autografts

Answer 257

tissue from self

Question 258

immune response against transplants

Answer 258

graft antigens expressed on donor dendritic cells captured by recipient dendritic cells transported to peripheral lymphoid organs where t cells activated t cells migrate to graft and destroy graft antibodies produced against graft antigens

Question 259

direct allorecognition

Answer 259

recipient t cells recognize donor MHC molecules and t cells activated alloreactive t cells recognize and attack cells of graft

Question 260

indirect allorecognition

Answer 260

graft cells ingested by recipient dendritic cells donor alloantigens processed and presented by self MHC molecules on recipient APCs

Question 261

hyperacute rejection

Answer 261

within minutes thrombosis of graft vessel causing ischemic necrosis of graft mediated by circulating antibodies specific for antigens on graft endothelial cells

Question 262

acute rejection

Answer 262

days or weeks mediated by t cells and antibodies specific for alloantigens in gaft

Question 263

chronic rejection

Answer 263

months to years progressive loss of graft function may be fibrosis of graft or gradual narrowing of graft vessels -caused by t cells reacting to graft alloantigens and secreting cytokines

Question 264

hematopoietic transplant

Answer 264

recipient bone marrow eliminated and replaced by donors bone marrow period of severely immunocompromised complication - graft verses host disease

Question 265

acute GvHD

Answer 265

symptoms occur within 100 days rash, burning, redness that can spread all over body and followed by nausea, vomiting, diarrhea, jaundice, weight loss

Question 266

chronic GvHD

Answer 266

symptoms occur after 100 days similar to acute but more slowly dermatologic symptoms usually first signs

Question 267

immunosuppressive drugs target what kind of transplant rejection

Answer 267

acute

Question 268

cytotoxic drugs

Answer 268

azathioprine cyclophosphamide methotrexate

Question 269

lymphotoxic drugs

Answer 269

corticosteroids muromonoab CD3

Question 270

drugs acting on subpopulations of immunocompetent cells

Answer 270

cyclosporine tacrolimus sirolimus mycophenolate mofetil

Question 271

drugs acting on cytokines or on cytokine receptors

Answer 271

infliximab etanercept thalidomide

Question 272

other immunosuppresants

Answer 272

rho(D) immune globulin anythymocyte globulin (ATG)

Question 273

vaccines - immunostimulant

Answer 273

bacille calmette guerin (BCG)

Question 274

recombinant interleukins - immunostimulant

Answer 274

aldesleukin

Question 275

recombinant interferons - immunostimulant

Answer 275

interferon-alpha-2a interferon-beta-1b interferon-gamma-1b

Question 276

major classes of immunosuppressant drugs

Answer 276

glucocorticoids calcineurin inhibitors (antibiotics) antiproliferative/antimetabolic drugs (cytotoxic agents) biologicals (antibodies)

Question 277

glucocorticoids

Answer 277

slightly affect humoral immunity strongly inhibit cellular immunity -inhibit macrophage mediated production of IL1/6, inhibit t cel mediated production of IL2, lympholytic effect on subset of t cells (including cytotoxic) -inhibit cytokines, inhibit antigen release from grafted tissue, stimulate catabolism of IgG -antiinflammatory effect

Question 278

immunosuppressant antibiotics

Answer 278

interfere w t cells function by binding immunophilins metabolized by liver

Question 279

cyclosporine

Answer 279

bind cyclophilin to form complex and bind/inhbit calcineurin AE - nephrotoxicity, neurotoxicity, hypertension, hypertipidemia, hirsutism, gingival hyperplasia

Question 280

tacrolimus

Answer 280

bind FK binding protein and inhibit calcineurin AE: nephrotoxicity, neurotoxicity, hypertension, hyperglycemia

Question 281

sirolimus

Answer 281

sirolimus FKBP complex blocks mTOR (mammalian target of rapamycin) and inhibits b and t cell proliferation AE: hyperlipidemia, hypertension, anemia, leukopenia, thrombocytopenia

Question 282

cytotoxic agents

Answer 282

inhibit clonal expansion of t and b lymphocytes

Question 283

cyclophosphamide

Answer 283

alkylating agent

Question 284

methotrexate

Answer 284

for RA and sarcoidosis

Question 285

azathioprine

Answer 285

prodrug, transformed into mercaptopurin and then into false nucleotide, inhibits proliferation b and t lymphocytes AE: bone marrow suppression with leukopenia, thrombocytopenia and anemia, hepatotoxicity

Question 286

anti thymocyte globulin

Answer 286

ATG bind t cells and causes them to be destroyed by complement, selectively inhibit cellular immunity AE: hypersensitivity

Question 287

rho (D) immunoglobulin

Answer 287

antibodies against rho(D) antigens bind and destruct fetal Rh D positive RBCs AE: hypersensitivity reactions

Question 288

enzyme inhibitors

Answer 288

antiproliferative bc inhibit enzymes involved in purine or pyrimidine synthesis

Question 289

mycophenolate mofetil

Answer 289

prodrug, transformed into mycophenolic acid inhibitor of IMP dehydrogenase for purine synthesis both b and t lymphocyte proliferation inhibited AE: bone marrow suppression, GI effects

Question 290

leflunomide

Answer 290

inhibit dihydroorotate dehydrogenase in pyrimidine synthesis both b and t lymphocyte proliferation inhibited AE: diarrhea, nausea, vomiting, alopecia, skin rash

Question 291

monoclonal antibodies

Answer 291

IgG immunoglobulins that recognize antigenic determinant and block its function AE: infusion related reactions

Question 292

muromonab CD3

Answer 292

binds and neutralizes CD3 protein receptor complex, causing death of t cells by antibody mediated activation of complement AE: infusion related reactions, pulmonary edema, secondary malignancy

Question 293

infliximab

Answer 293

binds TNF alpha, inhibiting the proinflammatory actions monocytes and macrophages AE: infusion related reactions, GI symptoms, infections

Question 294

etanercept

Answer 294

recombinant TNF receptor that binds and neutralizes TNF alpha, inhibiting proinflammatory actions AE: reaction at injection site, infection, pancytopenia

Question 295

thalidomide

Answer 295

selectively reduce circulating TNF alpha by suppressing production, also inhibits angiogenesis by blocking fibroblast growth factor AE: drowsiness, constipation, peripheral neuropathy, teratogenesis

Question 296

BCG vaccine

Answer 296

activate cells involved in immune response including macrophages, t , b lymphocyte and NK cells AE: flu like symptoms, systemic infection

Question 297

aldesleukin

Answer 297

recombinant IL2, induce proliferation of b and t cells and activate NK cells and lymphokine activated killer cells AE: hypotension, sinus tachycardia, pulmonary congestion and edema, acute renal failure, mental changes, N//V/D, anemia, thrombocytopenia

Question 298

interferons

Answer 298

all IFNs have antiviral, antiproliferative, immunomodulating actions AE: acute flu like symptoms, myelopsuppression

Question 299

types of chemo

Answer 299

alkylating agents antimetabolites antimicrotubular -anthracyclines (doxorubicin) -topoisomerase inhibitors (irinotecan, topotecan) -taxanes (paclitaxel, docetaxel, cabazitaxel) -vinca alkaloids (vinblastine, vincristine, vinorelbine) antitumor antibiotics (bleomycin, daunomycin) monoclonal antibodies small molecule targets miscellaneous (hydroxyurea)

Question 300

antitumor antibiotics

Answer 300

cell cycle nonspecific (except bleomycin is G2/M specific) bleomycin dactinomycin anthracyclines (doxorubicin, daunorubicin)

Question 301

bleomycin

Answer 301

induces free radical formation causing breaks in DNA strands -pulmonary fibrosis, skin hyperpigmentation

Question 302

dactinomycin

Answer 302

intercalates DNA and prevent RNA synthesis -myelosuppression

Question 303

anthracyclines (doxorubicin, daunorubicin)

Answer 303

generate free radicals, intercalate in DNA causing breaks in DNA and decrease replication also inhibit topoisomerase II -myelosuppression, dilated cardiomyopathy (prevent w dexrazoxane)

Question 304

antimetabolites

Answer 304

S phase specific thiopurines (azathioprine/6MP) cladribine/pentostatin cytarabine 5-fluoruracil hydroxyurea methotrexate

Question 305

thiopurines (azathioprins/6 MP)

Answer 305

purine analogs cause decrease in purine synthesis -myelosuppression, GI, liver toxicity

Question 306

cladribine/pentostatin

Answer 306

purine analogs are unable to be processed by ADA and interfere with DNA synthesis -myelosuppression

Question 307

cytarabine

Answer 307

pyrimidine analog causes DNA termination and inhibits DNA polymerase -myelosuppression

Question 308

5-fluorouracil

Answer 308

pyrimidine analog bio activated to 5-FdUMP which is a thymidylate synthestase inhibitor which decreases dTMP and decreases DNA synthesis -myelosuppression, palmar plantar erythrodysethesia

Question 309

hydroxyurea

Answer 309

inhibit ribonucleotide reductace causing decrease in DNA synthesis -severe myelosuppression, megaloblastic anemia

Question 310

methotrexate

Answer 310

folic acid analog that competitively inhibits dihydrofolate reductase causing decrease dTMP and decrease in DNA synthesis -myelosupression (reverse with leucovorin), hepatotoxicity, mucositis, pulmonary fibrosis, folate deficiency, teratogenic, nephrotoxicity

Question 311

alkylating agents

Answer 311

cell cycle nonspecific busulfan nitrogen mustards (cyclophosphamide, ifosphamide) nitrosureas (carmustine, lomustine) procarbazine

Question 312

busulfan

Answer 312

cross links DNA -severe myelosuppression, pulmonary fibrosis, hyperpigmentation

Question 313

nitrogen mustards (cyclophosphamide, ifosfamide)

Answer 313

cross link DNA and require bioactivation by liver -myelosuppression, SIADH, fanconi syndrome, hemorrhagic cystitis and bladder cancer (prevent w mesna)

Question 314

nitrosoureas (carmustine, lomustine)

Answer 314

cross link DNA require bioactivation by liver, can cross BBB and enter CNS -CNS toxicity (convulsions, dizziness, ataxia)

Question 315

procarbazine

Answer 315

unknown mech, weak MAO inhibition -myelosuppression, pulmonary toxicity, leukemia, disulfaram like reactions

Question 316

platinum compounds

Answer 316

cell cycle nonspecific cisplatin/carboplatin/oxaliplatin cross link DNA -nephrotoxicity (fanconi syndrome prevent w amifostine), peripheral neuropathy, ototoxicity

Question 317

microtubule inhibitors

Answer 317

M phase specific taxanes (docetaxel, paclitaxel) vinca alkaloids (vincristine, vinblastine)

Question 318

taxanes (docetaxel, paclitaxel)

Answer 318

hyperstabilize polymerized microtubules and prevent mitotic spindle breakdown -myelosuppression, neuropathy, hypersensitivity

Question 319

vinca alkaloids (vincristine, vinblastine)

Answer 319

bind B tubulin and inhibit its polymerization into microtubules and prevent mitotic spindle formation -neurotoxicity, constipation, myelosuppression

Question 320

topoisomerase inhibitors

Answer 320

increase DNA degradation causing arrest in S and G2 phases irinotecan/toptecan etoposide/teniposide

Question 321

irinotecan/topotecan

Answer 321

inhibit topoisomerase 1 -severe myelosuppression, diarrhea

Question 322

etoposide/teniposide

Answer 322

inhibit topoisomerase 2 -myelosuppression, alopecia

Question 323

monoclonal antibodies

Answer 323

rituximab trastuzumab

Question 324

rituximab

Answer 324

CD20 inhibitor -infusion reactions

Question 325

trastuzumab

Answer 325

HER2 inhibitor -dilated cardiomyopathy

Question 326

anticancer small molecule inhibitors

Answer 326

imatinib

Question 327

imatinib

Answer 327

BCRABL tyrosine kinase inhibitor -myelosuppression, increase LFTs, edema, myalgia

Question 328

arbovirus

Answer 328

arhtopod borne virus transmitted through bites of insects tend to be multisystem infections cause encephalitis or hemmorhagic fever

Question 329

flaviviruses

Answer 329

positive stranded RNA enveloped icosahedral capsid diagnose with serology, ELISA, hemagglutination inhibition, latex particle inhibition

Question 330

st louis encephalitis

Answer 330

flavivirus most widespread culex mosquito (night feeders) people dead end no vaccine most asymptomatic, but present 4-14 days with fever/headache/dizziness/weakness most recover others develop CNS infection (stiff neck, confusion, dissoriented, dizzy, tremors) 5-20% die

Question 331

west nile virus

Answer 331

flavivirus culex mosquito (night feeder) humans dead end spread vertically from mom to baby, also in blood and organ transplants most asymptomatic, febrile illness in some, some get serious illness (encephalitis/meningitis) and 10% die older/med conditions more at risk immunity is lifelong

Question 332

powassan virus

Answer 332

flavivirus ixodes tick humans dead end donating blood is risk most asymptomatic, incubation 1 week - 1 month, general illness initially, severe illness (encephalitits/meningitis) and 10% die prevent by protecting from tick

Question 333

zika virus

Answer 333

flavivirus aedes mosquito (day and night biter) serious threat to immunocompromised can pass person to person with sexual contact most have minor symptoms congenital causes microcephaly and skull partially collapses perinatal within 2 weeks of delivery, baby develops rash/fever/conjunctivitis/arthralgia in pregnant IgM bad, IgG good

Question 334

togaviridae

Answer 334

positive ss RNA icosahedral capsid envelope transitted by mosquito (summertime disease) eastern equine encephalitis (EEE) western equine encephalitis (WEE) venezuelan equine encephalitis (VEE) important in travelers fever, headache, chills, vomiting - severe with dowsiness and neck rigidity (increased lymphocytes in CSF) infectious arthritis following 2-3 day incubation IgM to diagnose

Question 335

chikungunya virus

Answer 335

widespread in africa, india, asia wide scale epidemics

Question 336

malaria

Answer 336

caused by plasmodium 4 types P. vivax P. falciparum P. malariae P. ovale paraxysm - cyclic febrile disease (chills and fever at regular intervals) spread by anopheline mosquito (day and night feeder)

Question 337

some populations resistant to malaria

Answer 337

duffy negative resistant to vivax sickle cell trait develop less severe falciparum

Question 338

most vulnerable to malaria

Answer 338

immunocompromised young children pregnant women travelers Africa south of sahara

Question 339

malaria life cycle

Answer 339

sexual reproduction in mosquito asexual reproduction in human -exoerythrocytic: sporozites injected into human, invade liver cells, form shizonts with merozoites (vivax and ovale form dormant state in liver called hypnozoites), shizont ruptures and releases merozoited into circulation -erythrocytic: merozoites invade RBCs, form trophozoite that enlarges and becomes more active (appearance of ring structures), multinucleated schizont forms, at 48-72 hours infected erythrocytes rupture

Question 340

pathogenesis

Answer 340

fever - after release of merozoites by RBC and occur in paroxysms anemia - due to loss of RBCs, massive hemolysis in falciparum (blackwater fever bc dark urine) circulatory changes - vasodilation, adhesion of RBCs to endothelium, falciparum cause local tissue anoxia immune events - increase in immunoglobulins, immune complexes deposited in kidneys

Question 341

clinical

Answer 341

incubation for 8-30 days prodrome - last a week or more (nonspecific flu like symptoms) acute phase - shaking chills, fever, lasts 2-10 hours paroxysms - end when fever breaks, patient is weak, duration and intensity vary with each species

Question 342

vivax

Answer 342

benign tertiary malaria 48 hour cycle paroxysms occuring on 1st and 3rd day, paroxysms last 8 hours schuffner dots single ring structure

Question 343

falciparum

Answer 343

malignant tertiary malaria 20% fatality 48 hour cycle paroxysms occur on 1st and 3rd days paroxysms last 20-36 hours sever headaches common double ring structure

Question 344

malariae

Answer 344

quartan malaria 72 hour cycle attacks begin similar to vivax band forms and rosette pattern

Question 345

ovale

Answer 345

ovale malaria similar to vivax

Question 346

treatment of malaria

Answer 346

bark of cinchona tree chloroquine if susceptible if not susceptible use atovaquone proguanil or artemether lumefantrine (for all falciparum)

Question 347

babesia

Answer 347

nantucket island fever ixodes tick giemsa stain of thin smear has maltese cross shaking chill, fever, no regular cyclic febrile paroxysms tx - mild with atovaquone and azithromycin, severe with clindamycin and quinine

Question 348

HIV

Answer 348

retroviridae, genera lentivirus dimer of 2 single stranded positive RNA encode 3 genes - gag (capsid proteins), pol (polymerase, protease, integrase), env (envelope glycoproteins) capsid has outer protein shell and nucleocapsid spherical virion (d type) with cone shaped core

Question 349

env encodes what

Answer 349

SU - larger protein forming surface spike (attachment) TM - smaller protein forming transmembrane region (fusion) made as precursor protein that is cleaved by protease

Question 350

pol encodes what

Answer 350

reverse transcriptase - digests RNA bound to DNA, transcribes RNA genome into dsDNA intermediate (provirus), target of RT inhibitors integrase - splices provirus into host cell chromosomal DNA allowing viral gene expression

Question 351

gag encodes what

Answer 351

protease - cleaves gag and pol polyproteins precursors into individual mature proteins (target of protease inhibitors

Question 352

accessory proteins

Answer 352

tat rev nef vif vpr vpu

Question 353

tat

Answer 353

transactivator protein antiterminator of transcription binds transacting response (TAR) on mRNA increases viral transcription essential for HIV replication

Question 354

REV

Answer 354

regulator of expression of virion proteins critical in HIV1 replication promotes transport of viral mRNAs from nucleus to cytoplasm

Question 355

VIF

Answer 355

virion infectivity factor appears to increase frequency of virus entry and/or maturation

Question 356

NEF

Answer 356

negative factor promotes progression to AIDS essential for replication of HIV in macrophages and monocytes downregulates CD4 and IL2

Question 357

VPR

Answer 357

viral protein R stimulate virus replication in non dividing macrophages and monocytes

Question 358

VPU

Answer 358

viral protein U enhance release of virus from plasma membrane bind and degrade CD4 in ER

Question 359

HIV transmission

Answer 359

relatively non communicable - requires large volume and repeated exposure sexual contact in utero or perinatal (blood in birth and breast milk) blood (IV drug users and at first transfusions)

Question 360

HIV pathogenesis

Answer 360

infection initiated when virus attaches a cell that expresses CD4 co receptor (CXCR4/CCR5) acute - seroconversion, flu like symptoms within 2 weeks, resolves and pt develops antibodies latency - found in lymphocytes and lymphoid tissue, can be transmitted, parallels CD4 levels symptomatic - AIDS, CD4 below 450, ARC develops

Question 361

what cells are first infected

Answer 361

dendritic cells

Question 362

when is HIV DNA detectable

Answer 362

within 2 days of infection

Question 363

where is virus delivered to CD4 t cells

Answer 363

in lymph node (para cortical region)

Question 364

what happens to virus production initially

Answer 364

there is a large burst

Question 365

what happens in the latent phase

Answer 365

virus levels in blood decrease but replication will increase

Question 366

what responses do the body have to HIV

Answer 366

HIV specific Ab response HIV specific CTL cytokines (early high levels of IFN gamma, TNF alpha, IL 10 that are lost eventually)

Question 367

when does full blown AIDs occur

Answer 367

when CD4 t cells are <200

Question 368

what presents with ARC

Answer 368

lymphadenopathy and fever can persist or progress may have diarrhea, night sweats, fatigue

Question 369

lab markers of HIV

Answer 369

CD4 t cell count serum levels of beta 2 microglobulin TNF alpha

Question 370

markers of viral load

Answer 370

P24 capsid protein HIV mRNA in serum plasma RNA levels

Question 371

HTLV

Answer 371

human t cell leukemia virus C type particles encodes gag pol env also encodes tax and rex most asymptomatic carriers

Question 372

tax

Answer 372

transactivator of viral and host genes increase IL2 and IL2R upregulate protooncogenes (fos, PDFG)

Question 373

rex

Answer 373

regulates splicing of mRNA promotes production viral progeny inhibit production of itself and tax (latency)

Question 374

HTLV is spread how

Answer 374

mother to infant (perinatal or breast feeding) sex contact with blood

Question 375

HTLV pathogenesis

Answer 375

infects CD4 t cells initial replication then goes latent later replication begins and causes disease

Question 376

HTLV disease manifestations

Answer 376

adult t cell leukemia chronic progressive myelopathy

Question 377

adult t cell leukemia

Answer 377

aggressive malignancy of mature t cells tax stimulates IL2/IL2R so has uncontrolled excretion causing uncontrolled proliferation and activation of oncogenes lymphocytosis, lymphadenopathy, hepatosplenomegaly, skin and CNS involvement, immunosuppressed

Question 378

kaposis sarcoma

Answer 378

human herpesvirus 8 especially homosexual men seropositivity correlates with number of sexual partners infects oral epithelium (also found in B cell fraction of peripheral blood mononucleocytes)

Question 379

tumors the KSHV is found are where

Answer 379

spindle cell (endothelial origin) also genes that turn on VEGF in mouth/torso/face/organs and look like spots on the skin

Question 380

HIV acute retroviral syndrome

Answer 380

monolike illness 3-6 weeks after infection spontaneously resolves after 2-4 weeks

Question 381

HIV chronic infection/latency

Answer 381

lymph nodes and spleen are sites of replication few clinical manifestations viral titers decline CD4 declines with time 7-10 years HIV RNA number correlates with long term disease progression

Question 382

HIV symptomatic disease

Answer 382

increase in viral load and severe disease

Question 383

lymphomas in HIV

Answer 383

diffuse large B cell burkitts primary CNS lymphoma

Question 384

AIDs crisis

Answer 384

fever, weight loss, lymphadenopathy, opportunistic infections

Question 385

infants with HIV

Answer 385

failure to thrive oral candidiasis hepatosplenomegaly lymphadenopathy diarrhea bacterial infections neuro findings

Question 386

HIV hematologic disorders

Answer 386

anemia, neutropenia, granulocytopenia, thrombocytopenia, venous thrombosis

Question 387

HIV tumors

Answer 387

kaposi sarcoma B cell lymphoma/hodgkin lymphoma carvical carcinoma anal carcinoma

Question 388

HIV CNS disease

Answer 388

HIV encephalopathy

Question 389

HIV MSK

Answer 389

peripheral neuropathy myopathy wasting disease

Question 390

HIV meds backbone

Answer 390

2 NRTI + INSTI tenofovir + emtricitabine + bictegravir/dolutagravir

Question 391

how long does ART take to make viral load reach an undetectable level

Answer 391

usually 3-6 months

Question 392

NRTI

Answer 392

nucleoside reverse transcriptase inhibitor abacavir lamivudine tenofovir zidovudine emtricitabine didanosine stavudine (SLEAZED + tenofovir)

Question 393

NRTI MOA

Answer 393

competitively inhibit HIV reverse transcriptase, incoorporated into growing viral chain, result in DNA chain termination

Question 394

NRTI side effects

Answer 394

lactic acidosis hepatic steatosis peripheral neuropathy bone marrow suppression exacerbate hep B when d/c abacavir - hypersensitivity (screen for HLA B 5701 emtricitabine - hyperpigmentation tenofovir - exacerbate hep b when d/c, renal insufficiency, fanconi syndrome, osteomalacia, decreased bone density

Question 395

ziduvadine

Answer 395

prevent maternal fetal HIV transmission -bone marrow suppression/hematologic toxicities, myopathy

Question 396

lamivudine

Answer 396

lactic acidosis hep b exacerbation

Question 397

abacavir

Answer 397

hypersensitivity screen for HLA B 5701 allele lactic acidosis and severe hepatomegaly

Question 398

emtricitabine

Answer 398

used for HBV hyperpigmentation

Question 399

tenofovir

Answer 399

nucleotide inhibitor HIV and hep B hepatomegaly w steatosis and post treatment exacerbation hep b

Question 400

NNRTI

Answer 400

non nucleoside revere transcriptase inhibitors efavirenz vecirapine relpivirine navirapine

Question 401

NNRTI MOA

Answer 401

bind directly to HIV RT, block RNA and DNA dependent pol, dont compete w nucleoside triphosphates or require phosphorylation

Question 402

NNRTI side effects

Answer 402

rash increased LFTs CYP inducer efavirenz - CNS/psych symptoms nevirapine - severe hepatotoxic reaction, life threatening skin reactions

Question 403

protease inhibitors

Answer 403

end in "navir" all given with ritonavir

Question 404

PI side effects

Answer 404

hyperglycemia lipodystrophy GI intolerance dyslipidemia hepatitis immune reconstitution syndrome CYP inhibitors atazanavir - PR interval prolongation, hyperbilirubinemia, rash, nephrolithiasis

Question 405

PI MOA

Answer 405

prevent cleavage of precursor molecules associated with structural proteins of mature virion core (bind aspartate protease) produce immature noninfectious viral particles

Question 406

INSTI

Answer 406

integrase strand transfer inhibitor end in "gravir"

Question 407

INSTI side effects

Answer 407

N/V/D insomnia muscle weakness/rhabdomyolysis rash

Question 408

INSTi MOA

Answer 408

bind integrase preventing integration of viral genome in host cell DNA

Question 409

cabotegravir

Answer 409

long acting injectable -insomnia, psych/mental disorders, weight gain

Question 410

fusion inhibitor

Answer 410

enfuvirtide block entry of virus into cells by binding gp41 subunit of viral envelope glycoprotein only experienced patients injection site reactions, hypersensitivity, eosinophilia

Question 411

CCR5 antagonist

Answer 411

maraviroc binds CCR5 co receptor necessary for HIV entrance experienced adult patients hepatotoxicity, cough, RTI, muscle pain, diarrhea, rash

Question 412

filoviridae

Answer 412

ebola and marburg long pleomorphic filamentous shapes genome composed of single negative ssRNA helical capsid enveloped

Question 413

ebola/marburg epidemiology

Answer 413

believed to start by handling infected meat spreads person to person and by nosocomial contact

Question 414

ebola/marburg pathogenesis

Answer 414

virus concentrates everywhere cause alteration of endothelial metabolism replication causes necrosis or parenchymal cels proinflammatory cytokines released platelets disfunctional

Question 415

antibody dependent enhancement

Answer 415

people with antibodies have enhanced infectivity and virulence

Question 416

clinical presentation

Answer 416

incubation 2-21 days abrupt onset of illness (fever, headache, lethargy, myalgia) second/third day sore throat develops fifth day profuse bleeding begins and become hypovolemic

Question 417

flaviviruses

Answer 417

positive ssRNA enveloped icosahedral capsid arbo viruses

Question 418

dengue virus

Answer 418

flavivirus aedes mosquito host break bone fever 2-8 day incubation abrupt onset of fever with retroorbital pain and macular rash myalgia and bone pain 2-6 days after fever (N/V/lymphadenopathy) primary infection self limiting second infection - hemorrhagic after several days have rapid deterioration hematuria and GI bleeding

Question 419

yellow fever

Answer 419

flavivirus - aedes mosquito mainly hepatotropic incubation 3-6 days present with fever, headache, malaise damage to kidney and petichial hemorrhages may progress to severe jaundice and kidney disease, GI bleeding cause black vomit

Question 420

bioterrorism

Answer 420

intentional release of viruses, bacteria or germs that can sicken or kill people, livestock, or crop

Question 421

category A

Answer 421

easily disseminated or transmitted, high mortality and potential major public health impact, might cause panic and social disruption, require special action for public health preparedness

Question 422

category B

Answer 422

moderately easy to disseminate, moderate morbidity and low mortality rates, specific enhancement of CDC diagnostic capacity and surveillance

Question 423

category C

Answer 423

could be engineered for mass dissemination due to availability, ease of production and dissemination, potential for high morbidity and mortality rates and major health impact

Question 424

guanosine analogs

Answer 424

acyclovir valacyclovir famcyclovir penciclovir gancyclovir valgancyclovir

Question 425

thymidine analogs

Answer 425

trifluridine - HSV topical

Question 426

other antivirals

Answer 426

docosanol cidofovir foscarnet interferon alpha

Question 427

CMV treatment

Answer 427

gancyclovir, valgancyclovir, foscarnet, cidofovir

Question 428

HSV and VZV

Answer 428

acyclovir, valacyclovir, famcyclovir -use foscarnet only for resistant HSV

Question 429

"clovir" mechanism of action

Answer 429

guanosine derivative activated by virus dependent thymidine kinase and converted to monophosphate host enzymes convert to diphosphate then triphosphate inhibit viral DNA pol DNA chain termination (inhibits DNA synth)

Question 430

acyclovir side effects

Answer 430

nausea, diarrhea, headache

Question 431

valacyclovir side effects

Answer 431

nausea, headache, vomiting, rash

Question 432

famciclovir side effects

Answer 432

headache, nausea, diarrhea

Question 433

ganciclovir side effects

Answer 433

bone marrow toxicity CNS toxicity possible teratogen

Question 434

trifluridine

Answer 434

HSV ketatitis topical activated intracellularly to triphosphate, inhibit DNA pol, drug incoorporated into viral DNA, cause faulty DNA and inability to infect/reproduce side effects - irritation, pruritis, inflammation

Question 435

docosanol

Answer 435

recurrent orolabila herpes (OTC) saturated 22 carbon aliphatic alcohol, inhibit fusion between plasma membrane and HSV envelope, prevent viral entry into cells thus inhibit viral replication

Question 436

cidofovir

Answer 436

CMV retinitis in AIDs pts cytosine nucleotide analog, phosphorylation independent, inhibitor of viral DNA pol, inhibits DNA synth renal side effects and neutropenia

Question 437

foscarnet

Answer 437

acyclovir resistant HSV inorganic pyrophosphate compound, competes with pyrophosphate binding site, inhibit viral DNA/RNA pol and HIV RT side effects - renal impairment, seizures, headache, nausea, fever, fatigue, increase LFTs

Question 438

interferon alpha

Answer 438

Hep b/c recombinant cytokine with antiviral props, inhibit viral replication in RNA/DNA viruses, augements antiviral immune response, activate ribonucleases that degrade viral mRNA, block protein synth by inhibiting translation initiation complex side effects - CNS, dermatologic, weight loss, GI, heme

Question 439

all CD4 counts

Answer 439

tuberculosis

Question 440

CD4 less than 250

Answer 440

coccidioidomycoses (arizona and california)

Question 441

CD4 less than 200

Answer 441

pneumpcystitis

Question 442

CD4 less than 150

Answer 442

histoplasmosis (south america, french guiana, mississippi and ohio river valley)

Question 443

CD4 less than 100

Answer 443

toxoplasma cryptococcus

Question 444

CD4 less than 50

Answer 444

mycobacterium avium complex

Question 445

candidiasis

Answer 445

oral fluconazole

Question 446

coccidioidomycosis

Answer 446

if positive use fluconazole or itra and d/c after 6 mo of CD4 greater than 250 (amphotericin B if bad and d/c after 1 year of CD4 greater than 250) must continue lifelong therapy for fungal coccidioidomycosis

Question 447

cryptococcus

Answer 447

fluconazole for at least a year then can d/c after 3 months of CD4 greater than 100

Question 448

CMV retinitis

Answer 448

gancyclovir and valgancyclovir until CD4 greater than 100 for 3-6 months

Question 449

HSV

Answer 449

acyclovir, valacyclovir, famcyclovir

Question 450

Kaposis sarcoma

Answer 450

gancyclovir, valgancyclovir, chemo

Question 451

histoplasmosis

Answer 451

prophylaxis in ohio/mississippi with itra until >150 for 6 mo tx - itra or amphotericin B second prophylaxis - itra for 1 year, negative fungal blood cultures, CD4 > 150 for 6 mo

Question 452

TB

Answer 452

latent tb tested with isoniazid start ART therapy 2 weeks after starting TB therapy

Question 453

MAC

Answer 453

prophylaxis - azithromycin/clarithromycin and d/c when >100 for 3 mo tx - azithromycin/clarithromycin +ethambutol for at least 12 months (begin ART therapy 2 weeks after starting MAC therapy) secondary - treat for 1 year and CD4 > 100 for 6 mo

Question 454

PCP

Answer 454

prophylaxis - TMP/SMX d/c when > 200 for > 3 mo tx - TMP/SMX for 21 days second - TMP.SMX until > 200 for 3 mo

Question 455

toxoplasmosis

Answer 455

seropositive suppression - TMP/SMX d/c when > 200 for 3 mo tx - primethamine + sulfadiazine + leucovorin second - primethamine + sulfadiazine + leucovorin until CD4 > 200 for 6 mo

Question 456

chloroquine sensitive areas

Answer 456

central america west south america

Question 457

use doxycycline to treat malaria when

Answer 457

when high multidrug resistance occurs

Question 458

drugs for liver forms of malaria

Answer 458

primaquine tafenoquine

Question 459

how to treat P. falciparum

Answer 459

IV quinine

Question 460

most used malaria treatments

Answer 460

atovoquone - proguanil artemether - lumefantrine mefloquine

Question 461

chloroquine

Answer 461

inhibit RNA/DNA pol, increase pH, inhibit prostoglandin effects causes pruritis

Question 462

quinine

Answer 462

depress oxygen uptake and carb metabolism side effects - cinchonism, hypersensitivity, blackwater fever, hematologic abnormalities, hypoglycemia/hypotension

Question 463

mefloquine

Answer 463

destroy asexual blood forms side effects - vivid dreams, N/V, dizziness, headache, rash

Question 464

primaquine

Answer 464

oxidation reduction mediator causing ROS and interfere with electron transport chain side effects - nausea, epigastric pain, headaches, hemolysis MUST TEST G6PD

Question 465

atovaquone

Answer 465

selective on mitochondrial cytochrome bc1 to inhibit electron transport side effects - fever, rash, nausea, vomiting, diarrhea, headache, insomnia

Question 465

tafenoquine

Answer 465

antiliver form

Question 466

inhibit folate synthesis

Answer 466

sulfadoxine primethamine proguanil

Question 467

artemisinins

Answer 467

artermether and artesunate cause oxidative stress, inhibit protein and nuc acid synth, structural changes, decrease growth and survival

Question 468

yersinia pestis

Answer 468

gram negative coccobacilli causing plague lactose negative on MacConkeys grow slowly prefer lower temps bipolar/safety pin staining

Question 469

plague virulence factors

Answer 469

low calcium response - genes activated when calcium is low and temp is up

Question 470

salvatic plague

Answer 470

zootic cycle fleas spread between rodent pop US west and southwest

Question 471

urban plague

Answer 471

inclusion of humans into infectious cycle oriental rat flea transmits to humans

Question 472

demic plague

Answer 472

human to human spread via respiratory droplets

Question 473

life cycle

Answer 473

rapidly phagocytosed by macrophages express virulence factors in macrophages macrophages killed and yersiniae enter circulation multiply rapidly and cause tissue damage disseminated intravscular coagulation can spread to lungs

Question 474

3 major presentations

Answer 474

bubonic - 2-6 days after bite get constitutional symps and form bubos that are very tender and ulcerate septicemic - extension of bubonic, causes DIC and vascular collapse pneumonic - hemorrhagic pneumonia with respiratory distress 2-3 days after infection (extensive lower lobe consolidation)

Question 475

treatment

Answer 475

quarantine, report to authorities, exterminate fleas and rats antibiotics within first 12-15 hours can cause jarisch Herxheimer rxn bc release of endotoxin

Question 476

franscisella

Answer 476

causes tularemia small gram negative rod w bipolar staining require cystine or cysteine to grow highly virulent can survive in unstimulated macrophages (killed by oxidative burst)

Question 477

franscisella/tularemia transmission

Answer 477

arthropod vector bites contact with infected animal or animal products enter in skin/mucous membranes bacteria trapped by macrophages

Question 478

pathogenesis

Answer 478

countered initially by localized neutrophilic response can spread to distant site (lymph tissue/spleen causing splenomegaly and bubos w/o ulceration)

Question 479

3 main kinds

Answer 479

ulceroglandular - papule at site of infection that becomes ulcerated and may develop rash/bubos (fever, headache, rigors, myalgia, splenomegaly) typhoidal - ingesting undercooked meat pulmonic - from inhaling infected droplets (highly fatal fulminating pneumonia)

Question 480

tularemia treatment

Answer 480

aminoglycosides tetracyclines

Question 481

bacillus anthracis

Answer 481

anthrax large gram positive rod that grows in chains forms spores that are infectious capsule is antiphagocytic

Question 482

anthrax toxin

Answer 482

protective antigen - binds high affinity receptors edema factor - adenylate cyclase that causes hypersecretion and edema lethal factor - cause apoptosis

Question 483

anthrax epidemiology

Answer 483

mainly disease of pasture animals spores in poop, wool, hides

Question 484

anthrax clinical presentation

Answer 484

cutaneous - spores inoculated into cut, 2-5 days lesion develops, itching papule becomes ulcer then black eshar cutaneous anthrax - ulcer becomes black eshar than heals into scar, can spread pulmonary - presents as onspecific illness, quickly develops to respiratory distress and cyanosis, inhaled spores are phagocytosed, mediastinal edema prominent

Question 485

brucellosis

Answer 485

gram negative coccobacilli (aerobes) intracellular parasites, produce calatase and superoxide dismutase very slow growth cause abortion in animals

Question 486

humans acquire brucella how

Answer 486

ingesting undercooked meat/unpasteurized dairy contact with tissues, blood, or bodily fluid of infected animals inhale organisms while working on them in labratory

Question 487

infection cycle

Answer 487

cross mucosae and enter blood stream taken up by PMNs and macrophages intermittent periods of bacteremia specific cell mediated imunity required for complete clearance

Question 488

clinical presentation

Answer 488

subclinical - vague symptoms (fatigue/headaches) bacteremia - undulant fever/night sweats (hepatosplenomegaly) serologic - mild symptoms from drinking raw milk localized - gradual onset with sranulomas in lymphoid tissues chronic - symptoms recur for months to years

Question 489

tx

Answer 489

must use long term combo therapy live attenuated vaccine for cattle