Hematology Exam

Front 1

Complete deficiencies of which molecules are not compatible with life?

Back 1

Hb alpha (Hydrops fetalis, --/--)
Protein C
Protein S
Antithrombin
Prothrombin
Tissue factor

Front 2

1. How does TF activate coagulation in vitro and in vivo?
2. What protein is responsible for this discrepancy?

Back 2

1. In vitro: TF converts VII-->VIIa, VIIa converts X-->Xa
In vivo: TF converts IX-->IXa, IXa+VIIIa converts X-->Xa

2. TFPI (tissue factor pathway inhibotr) binds/inhibits Xa and then binds/inhibits VIIa:TF

Front 3

1. Which molecules are Vitamin K dependent?
2. Which has the shortest half-life?

Back 3

1. II
VII
IX
X
Protein C
Protein S

2. VII

Front 4

Why would an antibody to TFPI cure an animal model with hemophilia A or B?

Back 4

Hemophilia A (VIII deficiency)
Hemophilia B (IX deficiency)
Intrinsic pathway cannot activate
Antibody to TFPI allows VII-->VIIa:TF and X-->Xa in vivo (like PT in vitro)

Front 5

1. Which three molecules does antithrombin inactivate?
2. What is the difference in the mechanisms of action of low and high MW versions of heparin and heparin-like proteoglycans?

Back 5

1. Thrombin, Xa, IXa

2. Low MW heparins + Antithrombin --> Xa inactivation
High MW heparins + Antithrombin --> Thrombin, Xa, IXa inactivation

Front 6

What are the different actions/states of Plasmin, alpha-2-PI, and PAI-1 when in the plasma versus in a fibrin clot?

Back 6

Plasmin binds to lysine residues of fibrin and degrades fibrin. Free circulating plasmin degrades Va and VIIIa, decreasing fibrin formation.

Alpha-2-PI is covalently linked to fibrin by XIIIa and inhibits plasmin. Free Alpha-2-PI is rapidly degraded, increasing fibrinolytic activity.

PAI-1 is bound to subendothelial vitronectin or secreted where tPA is actively secreted, and it inhibits tPA, inhibiting overall fibrinolysis. Free PAI-1 is rapidly degraded, increasing fibrinolytic activity.

Front 7

1. How is TAFI activated?
2. What is TAFI's function?
3. What is TAFI's effect?

Back 7

1. Thrombin+Thrombomodulin activates TAFI.
2. TAFI removes terminal lysine and arginine residues, which are required for tPA and plasminogen to bind.
3. TAFI inhibits the generation and activity of plasmin, thus decreasing fibrinolysis.

Front 8

What does the protamine paracoagulation test test for?

Back 8

Soluble fibrin monomer

Front 9

What are the 6 major causes of disseminated DIC?

Back 9

Infection
Obstetrical complications
Neoplastic disease
-PML
-Disseminated neoplasm
Massive tissue necrosis
Prolonged shock
Miscellaneous

Front 10

What are the 5 major causes of localized DIC?

Back 10

Kasabach-Merritt Syndrome
Phlegmasia Cerulean Doleans
Aortic aneurysm
Hyperacute renal transplant rejection
Miscellaneous

Front 11

DIC is characterized by which form of fibrinolysis?

Back 11

Secondary fibrinolysis

Front 12

What are the 4 consequences of DIC?

Back 12

Bleeding
Ischemic tissue damage
Stroke/acute MI
Fragmentation hemolytic anemia

Front 13

What does cryoprecipitate contain?

Back 13

VIII
Fibrinogen
vWF
XIII

Front 14

1. Aside from curing the underlying cause, what is the standard treatment for bleeding and consumption of coagulation factors caused by DIC?
2. When is heparin indicated for DIC management?
3. When is heparin contraindicated for DIC management?

Back 14

If bleeding and significant depletion of clotting factors and/or platelets are clinical problems, FFP or cryoprecipitate should be given.

Heparin indications:
-Long term DIC causing poor response to replacement therapy
-Thrombosis or ischemia

Heparin contraindications:
-Easily removed or short-lived DIC
-No bleeding or thrombotic complications
-Bleeding easily controlled by factor replacement

Front 15

What are the characteristics of arterial thrombi?

Back 15

High shear conditions
Platelet and vWF dependent
Associated with atherosclerosis
Often occurring at branch points

Front 16

What are the characteristics of venous thrombi?

Back 16

Low shear conditions
Thrombin and fibrinogen dependent
Minimally associated with atherosclerosis

Front 17

What substrates does platelet GpIIb/IIIa bind to, and under what conditions does the binding occur?

Back 17

High shear (arteries)
vWF:GpIIb/IIIa

Low shear (veins)
Fibrinogen:GpIIb/IIIa

Front 18

Which hemostatic molecules play a role in normal and pathologic angiogenesis? How?

Back 18

TF:VIIa signals via PAR2, inducing VEGF production.
Thrombin signals via PAR4, inducing VEGF, IL-8, and IL-6 production.

Front 19

What is the primary method of inhibiting venous thrombus formation?

Back 19

Inhibition of thrombin formation

Front 20

What is the mechanism of action of Hirudin and Bivalirudin?

Back 20

Thrombin inhibition

Front 21

Which drugs are used to inhibit thrombin formation as prophylaxis or treatment of thrombi?

Back 21

Hirudin
Bivalirudin

Front 22

What is the mechanism of action of thienopyridines (Ticlopidine, Clopidogrel)?

Back 22

ADP-Receptor/P2Y₁₂ antagonism

Front 23

Which drugs are used to antagonize ADP-Receptors/P2Y₁₂?

Back 23

Thienopyridines
-Ticlopidine
-Clopidogrel

Front 24

What is the mechanism of action of Abciximab, Eptifibatide, and Tirofiban?

Back 24

GpIIb/IIIa aggregation inhibition

Front 25

Which drugs are used to inhibit GpIIb/IIIa aggregation?

Back 25

Abciximab
Eptifibatide
Tirofiban

Front 26

What dose of aspirin is required for antithrombotic effect?

Back 26

<u>></u>75mg

Front 27

Which drugs will mimic Glanzman's Thrombasthenia?

Back 27

GpIIb/IIIa receptor antagonists:
Abciximab (irreversible)
Eptifibatide, Tirofibam (reversible)

Front 28

Where do the stages of T cell maturation occur?
What are the stages of T cell maturation?

Back 28

Thymic cortex: Positive selection
-ensures T cells can recognize MHCII/I:Peptide complexes with their TCR and CD4/8
Thymic medulla: negative selection
-Medullary epithelial cells transcribe the aire locus and express self-antigens to destroy self-reactive T cells

Front 29

How do T_reg cells arise?

Back 29

Some self-reactive T cells in the thymic medulla bypass negative selection and become T_reg cells (CD4⁺CD25⁺)

Front 30

Where do the stages of B cell maturation occur?
What are the stages of B cell maturation?

Back 30

Bone marrow: positive selection
-heavy then light chain rearrangements in the bone marrow are tested for efficacy
Bone marrow: Negative selection
-B cells which bind strongly to expressed self-antigen rearrange their light chains or are clonally deleted

Front 31

How is T cell anergy and peripheral tolerance developed?

Back 31

T cells in the periphery recognize self-antigens on APCs in peripheral tissues, but the T cells in the periperhy do not receive costimulatory signals from the APC or receive inhibitory signals from the APC B7 binding to the T cell CTLA-4

Front 32

Explain activation-induced death of T lymphocytes

Back 32

Repeated stimulation of activated T cells by self-antigen without the APC co-stimulatory signal leadss to a brief period of cell division, expression of Fas and FasL, and apoptosis

Front 33

Explain T_reg inhibition of T lymphocytes

Back 33

T_reg cells expressing CD4 and CD25 recognize self-antigen and indirectly or directly inhibit other T cells by releasing inhibitory cytokines or through inhibitory physical mechanisms

Front 34

How is B cell anergy and peripheral tolerance developed?

Back 34

B cells in the periphery which bind strongly to soluble self antigen decrease their expression of IgM (but retain normal IgD expression) and become inactive until they die

Front 35

Hereditary deficiencies or dysfunctions in phagocytic cells leads to what pathologies?

Back 35

Recurrent skin, lymph node, or deep tissue infections with
<i>S. aureus</i>
gm(-) (<i>Serratia spp.</i>)
fungi (<i>Candida albicans</i>, <i>Aspergillus spp.</i>)
Hepatosplenomegaly, lymphadenopathy

Front 36

What causes CGD?
What are the associated pathologies?

Back 36

X-linked recessive deficiency of Phagocyte NADPH Oxidase (<i>Phox</i> gene) leads to ineffective destruction of phagocytosed microbes and recurrent infections with <i>S. aureus</i>, gm(-) bacteria, and fungi.
Dx: NBT test for Phox activity

Front 37

What is the mechanism of increased recurrent infections of those with phagocytic cell deficiencies?

Back 37

Ubiquitous organisms (<i>S. aureus</i>, gm(-)'s, and fungi) do not require opsonizing antibodies for clearance, but the innate response is essential and, in this case, impaired.

Front 38

Hyposplenism leads to what pathologies?

Back 38

Recurrent bacterial sepsis due to encapsulated organisms (<i>S. pneumoniae</i>, <i>H. influenzae</i> type B)

Front 39

What is the mechanism of recurrent bacterial sepsis due to encapsulated organisms in hyposplenic patients?

Back 39

The spleen normally produces very rapid, natural, opsonizing antibodies which are necessary for clearance of <i>S. pneumoniae</i> and <i>H. influenzae</i>

Front 40

What causes DiGeorge Syndrome?
What is the mechanism of immune dysfunction?

Back 40

Chromosome 22 deletion causes varying T cell deficiencies (T cell maturation and signalling, deficient T cell-mediated responses, and deficient B cell help) ranging from asymptomatic, mild T-lymphocytopenia to thymic agenesis with a complete absence of T cells

Front 41

What is the clinical phenotype of DiGeorge syndrome?

Back 41

Viral, fungal, mycobacterial infections by opportunistic pathogens
GI symptoms
Oral candiasis
Hepatosplenomegaly/lymphadenopathy
Severe seborrhea-like dermatitis
Variable craniofacial dysmorphisms, cardiovascular conotruncal malformations, parathyroid hypocalcemia, and T lymphocytopenia

Front 42

What is the clinical phenotype of B cell deficiency?

Back 42

Upper/lower respiratory tract infections with the usual pathogens
Gi symptoms
Granulocytopenia or JRA-like arthritis

Front 43

What is the mechanism of the clinical phenotype of B cell deficiency?

Back 43

Mutations in B cell maturation and signalling lead to local or systemic deficient ag-specific antibodies required for efficient opsonization of encapsulated

Front 44

What is the cause of X-linked agammaglobulinemia?
What are the characteristics of the syndrome?

Back 44

Defective Btk on the X-chromosome results in a maturation block after the pre-B cell stage.
X-linked agammaglobulinemia is characterized by a complete lack of mature B cells, absent IgM and IgA antibodies, and normal T cell count and function.

Front 45

What is the most common primary immune deficiency?

Back 45

Selective IgA deficiency

Front 46

What is the likely cause of Selective IgA deficiency?
What are the characteristics of the syndrome?

Back 46

Variable genetic patterns cause a signalling defect resulting in failure of IgA isotype class-switching.
Selective IgA deficiency is characterized by <5mg/dL of serum IgA and undetectable levels of secretory IgA

Front 47

What is the clinical phenotype of Selective IgA Deficiency?
What is the mechanism of this phenotype?

Back 47

A lack of IgA can be asymptomatic or cause an increase in compensatory mechanisms, leading to atopic disease, recurrent infections, and auto-immune disorders

Front 48

What is the cause of CVID?
What are the characteristics of CVID?

Back 48

Variable genetic mutations can cause CVID.
CVID is characterized by variable hypoglobulinemia, age of onset, and degree of T cell abnormalities.

Front 49

What is the clinical phenotype of CVID?
What is the mechanism of this phenotype?

Back 49

CVID presents with recurrent bacterial infections due to hypogammaglobulinemia and impaired Ag-specific antibody responses, but a normal number of B cells.

Front 50

Deficiencies in C5-C9 lead to susceptibility to which organism?

Back 50

<i>Neisseria spp.</i>

Front 51

Deficiencies in IFN-g lead to susceptibility to which organism?

Back 51

Atypical mycobacteria

Front 52

Deficiencies in TLR3 lead to susceptibility to which organism?

Back 52

Herpes simplex encephalitis

Front 53

What is the mechanism and phenotype of Grave's Disease?

Back 53

Anti-TSH Receptor antibodies (agonism) cause hyperthyroidism

Front 54

What is the mechanism and phenotype of Myasthenia Gravis?

Back 54

Anti-ACh Receptor antibodies (antagonism) cause muscle weakness

Front 55

What is the mechanism and phenotype of Insulin-Resistant Diabetes?

Back 55

Anti-Insulin Receptor antibodies (antagonism) cause hyperglycemia and ketoacidosis

Front 56

What is the mechanism and phenotype of Autoimmune Hypoglycemia?

Back 56

Anti-Insulin Receptor antibodies (agonism) cause hypoglycemia

Front 57

What is the mechanism and phenotype of Insulin-Dependent Diabetes Mellitus?

Back 57

Effector T Cells target beta-antigen on beta cells of the pancreas, causing destruction of beta cells and the ability to produce insulin

Front 58

What is the mechanism and phenotype of Rheumatoid Arthritis?

Back 58

Effector T Cells target an unknown synovial joint antigen, causing destruction and inflammation of joints

Front 59

What is the mechanism and phenotype of Multiple Sclerosis?

Back 59

Effector T Cells target myelin basic protein, causing destruction of myelin, brain damage, and paralysis

Front 60

Mutations in Fas and FasL lead to which autoimmune disorder?
What is the mechanism of pathology?

Back 60

Fas, FasL
ALPS (Autoimmune Lymphoproliferative Disorder)
Defective elimination of self-reactive T and B cells by AICD (Activation Induced Cell Death)

Front 61

Mutations in AIRE lead to which autoimmune disorder?
What is the mechanism of pathology?

Back 61

AIRE
Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dysplasia
Defective elimination of self-reactive T cells in the thymus due to an inability for negative selection

Front 62

Mutations in FoxP3 lead to which autoimmune disorder?
What is the mechanism of pathology?

Back 62

Foxp3
Immune dysfunction polyendocrinopathy enteropathy/X-linked
Defective T_reg Cells do not downregulate Effector T Cells

Front 63

Mutations in C2 and C4 lead to which autoimmune disorder?
What is the mechanism of pathology?

Back 63

C2, C4
Lupus-Like Disease
Defective clearance of immune complexes

Front 64

The HLA-B27 allele leads to an increase risk of what autoimmune disorder?
What is the mechanism of pathology?

Back 64

HLA-B27
Ankylosing Spondylitis
Inflammation of the spine results in fusion and rigidity

Front 65

Infection with EBV is associated with what autoimmune disorder?

Back 65

Multiple Sclerosis

Front 66

Infection with Group A Strep (<i>Streptococcus pneumoniae</i>) is associated with what autoimmune disorder?

Back 66

Acute rheumatic fever
Acute glomerulonephritis

Front 67

What is the most effective treatment for Multiple Sclerosis?

Back 67

Natalizumab
MAB to alpha-4-integrin

Front 68

What situations can lead to non-clonal thrombocytosis?

Back 68

Iron deficiency
Chronic inflammation

Front 69

1. What is polycythemia vera?
2. What are its CBC findings?

Back 69

1. Accelerated normoblast maturation and differentiation into RBCs.
2. Drastically increased Hgb or Hct levels.

Front 70

1. What is essential thrombocythaemia?
2. What are its diagnostic criteria?

Back 70

1. Megakaryocyte proliferation and differentiation.
2. Platelet count <u>></u>450x10⁹

Front 71

What is primary myelofibrosis?

Back 71

Megakaryocyte proliferation and atypia accompanied by reticulin and/or collagen fibrosis.

Front 72

1. What is the most common myeloproliferative disease?

Back 72

Chronic Myeloid Leukemia (CML)

Front 73

1. What chromosome abberation is associated with CML?
2. What is the protein product of the chromosome abnormality and its function?

Back 73

1. Philadelphia Chromosome t(9;22)
2. bcr-abl fusion protein has constitutive tyrosine kinase activity causing increased cell division and DNA repair inhibition

Front 74

What is the clinical presentation of chronic phase CML?
What is the clinical presentation of blast phase CML?

Back 74

Chronic phase: Splenomegaly with elevated WBC count, with neutrophils from all maturation stages
Blast phase: Transformation to acute leukemia (70% myeloid, 30% lymphoid), anemia, thrombocytopenia, lymphoblasts or myeloblasts

Front 75

How do we know that the HSC is involved in CML?

Back 75

Chronic phase CML can progress to blast phase AML (70%) or ALL (30%), indicating that the progenitor to both cell lines is affected.

Front 76

How do patients die from CML?

Back 76

Increased proliferation and accumulation of mutation leads to an acute blastic crisis.

Front 77

What is the cure for CML?

Back 77

Allogeneic stem cell transplant

Front 78

1. What is the non-specific treatment for CML?
2. What is the targeted treatment for CML?

Back 78

1. Hydroxyurea, cytarabine
2. Imatinib

Front 79

What is the mechanism of action of Imatinib?

Back 79

Imatinib binds to the ATP binding pocket of the Bcr-Abl fusion protein.

Front 80

What is the common gene mutation for PV, ET, and PM?

Back 80

JAK2

Front 81

1. What happens to leukocyte and platelet counts in PV?
2. What happens to Epo in PV?

Back 81

1. mild or no leukocytosis and/or thrombocytosis
2. Epo suppression

Front 82

What are 4 non-clonal causes of elevated RBC mass?

Back 82

1. Epo secretion from liver or kidney tumors or cysts or from leiomyomatas.
2. High altitude
3. Testosterone therapy
4. High affinity hemoglobinopathies

Front 83

1. What is the function of mutant JAK2?
2. What is the normal substrate of JAK2?

Back 83

Mutant JAK2 is constitutively active and does not require its normal substrate, Epo, for activation.

Front 84

How does essential thrombocythemia lead to its clinical presentation?

Back 84

Platelets derived from the abnormal megakaryocytes do not function properly, leading to bleeding and thrombosis.

Front 85

Myelofibrosis can be caused by what other myeloproliferative neoplasms?

Back 85

Polycythemia vera and essential thrombocythemia

Front 86

What is the cure for myelofibrosis?

Back 86

Allogeneic stem cell transplant

Front 87

Tear drop cells are associated with what condition?

Back 87

Myelofibrosis

Front 88

80y female:
-abdominal pain
-portal venous thrombosis
-mild splenomegaly
-CBC: WBC 8, Hgb 14.9, Platelets 578,000
-Creatinine 1.4
1. What diagnostic tests would you order?
2. What is the most likely diagnosis?

Back 88

1. Epo levels (if low=PV), JAK2 mutation, ESR/CRP (markers of inflammation)
2. PV

Front 89

30y male
-acute appendicitis
-CBC: WBC 19,000 (mostly PMNs, bands), Hgb 12.3, Platelets 812,000
1. What is the most likely cause of the thrombocytosis?

Back 89

1. Reactive inflammatory response to acute appendicitis

Front 90

32y male
-CBC: WBC 7, Hgb 14.9, Platelet 970,000
1. What diagnostic tests would you order?
2. What is the most likely cause of the thrombocytosis?

Back 90

1. ESR/CRP (markers of inflammation, JAK2 mutation
2. Essential thrombocythaemia

Front 91

Are children more prone to getting ALL or AML?

Back 91

ALL

Front 92

What is the affect of acute leukemia on the bone marrow, organs, and system? How does this lead to the clinical presentation of acute leukemia?

Back 92

BM failure causing:
-anemia, weakness, fatigue
-thrombocytopenia, bleeding
-neutropenia/leukopenia, infection
Organ/tissue infiltration causing:
-hepatosplenomegaly, lymphadenopathy
-gum hypertrophy
-bone pain
-CNS, skin, testis, any organ
Systemic symptoms
-Fever, sweats, weight loss

Front 93

What is the diagnostic criteria for acute leukemia?

Back 93

>20 (30%) blasts in the bone marrow

Front 94

Which are myeloid markers in AML?

Back 94

CD13
CD33

Front 95

Which are pre B cell markers in ALL?

Back 95

CD10 CALLA
CD19
CD20

Front 96

Which myeloproliferative neoplasm has auer rods?

Back 96

AML

Front 97

1. What are FLT3 and NPM1 mutations associated with?
2. What is the prognostic effect of FLT3 and/or NPM1?

Back 97

1. AML
2. FLT3 = poor prognosis
NPM1 = good prognosis
FLT3 + NPM1 = poor prognosis

Front 98

1. What chromosome abberation is associated with APL?
2. What is the protein product of the chromosome abnormality and its function?

Back 98

1. t(15;17)
2. PML-RARa fusion gene causes maturation arrest

Front 99

Which form of AML is most easily cured?

Back 99

APL

Front 100

What are the two treatments for APL?

Back 100

ATRA to promote differentiation
As₂O₃ to kill of stem cell (hopefully)

Front 101

What is the prognostic effect of the Ph chromosome on ALL?

Back 101

bad

Front 102

Which are monocytic markers in AML?

Back 102

CD14
CD15

Front 103

Which are megakaryocytic markers in AML?

Back 103

CD41
CD62

Front 104

Which are pre T cell markers in ALL?

Back 104

CD2
CD3
CD5
CD7

Front 105

1. What is the function of NPM1?
2. What is the effect of NPM1 mutations?

Back 105

1. Nuclear/cytoplasmic shuttle
2. Mutant NPM1 cannot transport ribosomes out of the nucleus into the cytoplasm, decreasing protein synthesis

Front 106

1. What is the prognostic indicator of MLL rearrangements in AML?
2. What phenotype of AML are MLL rearrangement associated with?

Back 106

1. Intermediate risk
2. M4/M5 phenotypes

Front 107

1. What is the function of FLT3?
2. What is the effect of FLT3 mutations?

Back 107

1. Trans-membrane tyrosine kinase receptor.
2. Mutant FLT3 does not auto-inhibit and becomes a constitutive tyrosine kinase.

Front 108

What is the standard remission induction therapy of newly diagnosed AML?

Back 108

7+3 schedule
7 days Cytarabine infusion
Anthracycline on days 1-3

Front 109

What is the first remission post-remission treatment of AML if <60y?

Back 109

2-3 courses of high dose cytarabine
HSC transplantation in intermediate and high risk patients

Front 110

1. What is a major clinical concern of APL?
2. What is the treatment?

Back 110

1. Coagulopathy leads to bleeding
2. Platelet transfusion until DIC stops and cryoprecipitate to maintain fibrinogen

Front 111

DIC is a hallmark of what leukemia?

Back 111

APL

Front 112

What are the molecular markers for plasma cells?

Back 112

CD38
CD138

Front 113

What is the most common indolent NHL?

Back 113

Follicular lymphoma

Front 114

What is the most common aggressive NHL?

Back 114

Diffuse Large B-Cell Lymphoma

Front 115

1. What is the most common B cell lymphoma in children?
2. What is the most common T cell lymphoma in children?

Back 115

1. B Burkitt (Burkitt-like)
2. T Lymphoblastic

Front 116

What are the two most common B cell lymphoma in adults?

Back 116

1. Follicular BCL
2. DLBCL

Front 117

What clinical presentation of lymphadenopathy is more likely to be benign?

Back 117

Lymphadenopathy lasting <2w or >1y without a change in size has a low likelihood of being neoplastic.

Front 118

What is the leukemia equivalent of B Cell lymphocytic lymphoma?

Back 118

B CLL

Front 119

What is the lymphoma equivalent of B CLL?

Back 119

B Cell lymphocytic lymphoma

Front 120

1. Which lymphoma is t(14;18) associated with?
2. What is the gene product?
3. What is the protein's effect?

Back 120

1. Follicular Center Cell Lymphoma
2. Bcl-2
3. Antiapoptosis

Front 121

1. Which chromosomal aberration is associated with Follicular Center Cell Lymphoma?
2. What is the gene product?
3. What is the protein's effect?

Back 121

1. t(14;18)
2. Bcl-2
3. Antiapoptosis

Front 122

1. Which lymphoma is t(8;14) associated with?
2. What is the gene product?
3. What is the protein's effect?

Back 122

1. Burkitt Lymphoma
2. C-myc
3. Hyperproliferation

Front 123

1. Which chromosomal aberration is associated with Burkitt Lymphoma?
2. What is the gene product?
3. What is the protein's effect?

Back 123

1. t(8;14)
2. C-myc
3. Hyperproliferation

Front 124

1. Which lymphoma is associated with t(11;14)?
2. What is the gene product?
3. What is the protein's effect?

Back 124

1. Mantle Cell Lymphoma
2. Bcl-1/Cyclin-D1
3. Hyperproliferation

Front 125

1. Which chromosomal aberration is associated with mantle cell lymphoma?
2. What is the gene product?
3. What is the protein's effect?

Back 125

1. t(11;14)
2. Bcl-1/Cyclin-D1
3. Hyperproliferation

Front 126

Which is more likely in young adults, HL or NHL?

Back 126

HL has bimodal age distribution (20-29) and >65

Front 127

Which is more likely in the elderly, HL or NHL?

Back 127

NHL

Front 128

Are males or females more prone to T lymphoblastic lymphoma?

Back 128

Males

Front 129

Are young or old people more prone to T lymphoblastic lymphoma?

Back 129

Young people

Front 130

Which virus is associated with Adult T Cell Leukemia/Lymphoma?

Back 130

HTLV-1

Front 131

Which lymphoma/leukemia is associated with HTLV-1?

Back 131

Adult T Cell Leukemia/Lymphoma

Front 132

Which form of HL is typically associated with young women?

Back 132

Nodular sclerosing HL

Front 133

Are women or men more prone to NSHL?

Back 133

Women

Front 134

1. Which cell line does GCSF increase?
2. What are GCSF's short-term and long-term mechanisms of action?

Back 134

1. neutrophils
2. Release from BM (3-4h)
Increased production (3-5d)
Decreased apoptosis

Front 135

What is Kostmann's syndrome?

Back 135

Severe Congenital Neutropenia
Autosomal recessive disorder leading to lack of maturation of promyelocytes into neutrophils

Front 136

Where are the majority of neutrophils?

Back 136

In the bone marrow reserves

Front 137

What happens to patients without any neutrophils?

Back 137

Fulminant sepsis from regular ubiquitous organisms such as E. coli and Klebsiella spp. leading to death within 12h

Front 138

Do patients with neutrophils in their bone marrow but not their circulation get infections?

Back 138

No

Front 139

How does CXCR4 mediate neutrophil maturation, life, and death?

Back 139

CXCR4 is expressed as neutrophils mature in the bone marrow, internalized so they can enter the circulation, and externalized 1-3d later to re-enter the bone marrow for destruction.

Front 140

What level of neutropenia poses a significant risk for infection?

Back 140

ANC <300

Front 141

What is a normal ANC for caucasians? For africans?

Back 141

1500 for caucasians
1200 for africans

Front 142

What should be considered in the case of neutropenia and anemia?

Back 142

Possible malignancy

Front 143

What compounds do neutrophil primary azurophilic granules contain?

Back 143

Defensins
Myeloperoxidase

Front 144

What compounds do neutrophil secondary specific granules contain?

Back 144

NADPH-dependent neutrophil peroxidase

Front 145

1. What is the defect in CGD?
2. What is its inheritance pattern?
3. How is it diagnosed?

Back 145

1. Defective Phox gene creates inactive NADPH-dependent Neutrophil peroxidase
2. X-linked (2/3), recessive (1/3)
3. NBT test will not turn blue if CGD is present

Front 146

In a population of more than 250,000,000 in the US, what is the approximate annual number of cancer deaths?

Back 146

500,000

Front 147

In a population of more than 250,000,000 in the US, what is the approximate annual incidence of cancer?

Back 147

1,000,000

Front 148

In a population of more than 250,000,000 in the US, what is the approximate annual number of lymphoma/leukemia deaths?

Back 148

50,000

Front 149

What is the marker phenotype of lymphocyte predominant HL?

Back 149

CD20+
CD15-
CD30-

Front 150

What is the marker phenotype of all classical HL?

Back 150

CD20-
CD15+
CD30+

Front 151

Which surface marker is found on follicular b cells?

Back 151

CD20

Front 152

1. What are B symptoms?
2. What causes B symptoms?
3. What is their effect on prognosis?

Back 152

1. Fever, night sweats, weight loss >10%
2. IL-6, IL-1
3. Worse prognosis

Front 153

1. What chromosomal aberration is associated with MALT?
2. What is the gene product?
3. What is the protein's effect?

Back 153

1. t(11;18)
2. API2:MALT1 fusion protein
3. Antiapoptosis

Front 154

1. What lymphoma is t(11;18) associated with?
2. What is the gene defect?
3. What is the protein's effect?

Back 154

1. MALT
2. API2:MALT1 fusion protein
3. Antiapoptosis

Front 155

What causes hemolysis in lymphoma?

Back 155

Immune dysregulation

Front 156

1. How is MALT associated with H. pylori infection cured?
2. What is the appropriate chemical therapy?

Back 156

1. Treatment of the H. pylori
2. Proton pump inhibitor + clarithromycin + amoxicillin or metronidazole

Front 157

Do plasma cells express CD20?

Back 157

No, only follicular B cells express CD20

Front 158

How are IL-6 and MM connected?

Back 158

IL-6 is secreted by bone marrow stromal cells and supports the proliferation of plasma cells.

Front 159

How are MIP-1 and MM connected?

Back 159

Plasma cells secrete MIP-1, leading to increased osteoclast activity.

Front 160

How are VEGF and MM connected?

Back 160

Plasma cells secrete VEGF, leading to increased vascularization of their bone marrow microenvironment.

Front 161

How does MM lead to humoral immune suppression and susceptibility to infection?

Back 161

Multiple myeloma cells suppress the growth of normal plasma cells.

Front 162

How are M-proteins or paraproteins characterized?

Back 162

SPEP (serum protein electrotrophoresis) or UPEP (urine protein electrophoresis) reveals an M-spike.
S/UIEP (Serum/urine immunofixation electrophoresis) characterizes the type of immunoglobulin.

Front 163

What are the S/S of MM and their 4 causes?

Back 163

Anemia, thrombocytopenia, +/- neutropenia from BM replacement.
Bone pain and fractures from lytic lesions of bone.
Heart and kidney failure from monoclonal light chain deposition.
Hypogammaglobulinemia and increased risk of infection due to suppression of normal plasma cell growth.

Front 164

What are 4 major plasma cell disorders characterized by a monoclonal spike?

Back 164

Multiple Myeloma
Waldenstroms macroglobulinemia
Solitary Osseus Plasmacytoma
Amyloidosis

Front 165

What are the CRAB diagnostic criteria for MM?

Back 165

Hyper<b>c</b>alcemia
<b>R</b>enal Insufficiency
<b>A</b>nemia
Lytic <b>B</b>one lesions or osteoporosis

Front 166

A patient with hypercalcemia and renal insufficiency may have what?

Back 166

Multiple myeloma

Front 167

What is the criteria for MGUS?

Back 167

&lt;3g M spike<br>&lt;10% Plasma cells in BM

Front 168

What is the criteria for smoldering MM?

Back 168

<u>></u>3g M spike
<b>OR</b>
<u>></u>10% Plasma cells in BM

Front 169

What is the criteria for active MM?

Back 169

<u>></u>Positive M spike
<u>></u>10% Plasma cells in BM
<b>and</b>
Anemia, bone lesions, high calcium, or abnormal kidney function

Front 170

Which two proteins are measured to determine the staging of MM?

Back 170

Serum B₂M
Serum albumin

Front 171

What are the staging criteria for stage I MM?

Back 171

Normal albumin (>3.5)
Low B₂M (<3.5)

Front 172

What are the staging criteria for stage II MM?

Back 172

Albumin less than 3.5 + B₂M less than 3.5
OR
Normal albumin with B₂M 3.5-5.5

Front 173

What are the staging criteria for stage III MM?

Back 173

B₂M greater than 5.5

Front 174

1. What are Bence-Jones proteins?
2. Where are they found?
3. Why?

Back 174

Bence-Jones proteins are light chain molecules from globulins usually found in the urine due to kidney damage leading to proteinuria.

Front 175

Which molecules regulate osteoclast and osteoblast function?

Back 175

RANKL activates osteoclasts
OPG (osteoprotegrin) is a decoy receptor for RANKL
DKK-1 inhibits osteoblasts

Front 176

1. How are RANKL, OPG, and DKK-1 modified in MM?
2. What is the overall effect?

Back 176

1. RANKL production is increased
OPG production is decreased
DKK-1 production is increased
2. The overall effect is a decrease in osteoblast differentiation and function and an increase in osteoclast differentiation and function.

Front 177

Why are bisphosphonates given to those with MM?

Back 177

Bisphosphonates inhibit DKK-1, the osteoblast inhibitor

Front 178

What drugs inhibit DKK-1?

Back 178

Bisphosphonates

Front 179

What is the rate of conversion from MGUS to MM?

Back 179

1-2% per year

Front 180

What are the current chemotherapy treatments for MM?

Back 180

Revlimid+dexamethasone
Velcade+dexamethasone

Front 181

What is Revlimid and Dexamethasone used to treat?

Back 181

MM

Front 182

What is Velcade and Dexamethasone used to treat?

Back 182

MM

Front 183

How is MM progression or response measured?

Back 183

The M-protein spike

Front 184

What are the two most important factors in the viscosity of whole blood?

Back 184

[RBCs]
[fibrinogen]

Front 185

What are the most important factors in the viscosity of serum?

Back 185

[proteins]
asymmetry of proteins
M.W. proteins

Front 186

1. What is the cell of origin of Waldenstrom's Macroglobulinemia?
2. What is the general term for the tumor?

Back 186

1. Lymphoplasmacyte
2. Lymphoplasmacytic lymphoma

Front 187

What is the treatment for APL?

Back 187

All-trans retinoic acid

Front 188

What is the most common cause of APL?

Back 188

Chromosomal translocation:
-Retinoic acid receptor alpha gene (RARa) on ch17
-Promyelocitic leukemia gene (PML) on ch15

Front 189

What is the normal HCT range for men? For women?

Back 189

HCT
Men: 39-51
Women: 37-47

Front 190

What is the normal Hgb range for men? For women?

Back 190

Hgb
Men: 13-17
Women: 12-16

Front 191

What is the normal RBC range for men? For women?

Back 191

RBC
Men: 4.5-6
Women: 4-5.3

Front 192

How is MCV calculated? What is the normal range?

Back 192

MCV = Hct/RBC*10
(80 - 100)

Front 193

How is MCH calculated? What is the normal range?

Back 193

MCH = Hgb/RBC*10
(28 - 33)

Front 194

How is MCHC calculated? What is the normal range?

Back 194

MCHC = Hgb/Hct*100
(31 - 35)

Front 195

What is the normal reticulocyte range in percent and absolute count? How is the reticulocyte index calculated if shift cells are present?

Back 195

.5-1.5%
30,000-70,000
If shift cells are present, reticulocyte index = reticulocyte count/2

Front 196

What is the normal WBC count range?

Back 196

WBC
5,000-10,000

Front 197

What is the normal platelet count range?

Back 197

Platelet
150,000-350,000

Front 198

What is the normal plasma iron range?

Back 198

Plasma Iron
70-150

Front 199

What does TIBC measure? What is the normal range?

Back 199

TIBC = Transferrin
250-350

Front 200

What is the normal % iron saturation range?

Back 200

15-45%

Front 201

What is the normal ferritin range for men? For women?

Back 201

Ferritin
Men: >100 ng/mL
Women: >20 ng/mL

Front 202

Allergic reactions are mediated by which WBC?

Back 202

Eosinophils

Front 203

Hypersensitivity reactions are mediated by which WBC?

Back 203

Basophils

Front 204

What is the prognosis of untreated acute leukemia? How differentiated are the cells in acute leukemia?

Back 204

Acute leukemia
Death in &lt;6mo if not treated
Blast cells with little or no differentiation

Front 205

What is the prognosis of untreated chronic leukemia? How differentiated are the cells in chronic leukemia?

Back 205

Chronic leukemia
Death in >1y if not treated
Mature cells more differentiated than blast cells

Front 206

A leukemia composed of precursors of one or more of the following cell lines is referred to as which type of leukemia:
Erythroid
Neutrophil
Monocyte
Eosinophil
Basophil
Megakaryocyte

Back 206

Myeloid leukemia

Front 207

A leukemia composed of precursors of one or more of the following cell lines is referred to as which type of leukemia:
T Cell
B Cell

Back 207

Lymphoid leukemia

Front 208

Describe the leukemic phase of lymphoma

Back 208

When the lymphocytic cells of a lymphoma disseminate and involve the bone marrow and peripheral blood, resembling an acute or a chronic leukemia, depending on the stage of differentiation of the lymphocyte

Front 209

Describe a plasma cell myeloma

Back 209

A clonal proliferative disorder of plasma cells which usually involves the bone marrow and presents with lytic bone lesions, but can sometimes present as plasma cell leukemia or progress into a leukemic phase

Front 210

What does this image of bone marrow show?

Back 210

Aplastic anemia

Front 211

What is the ddx of aplastic anemia including hereditary causes and acquired causes (direct toxicity, indirect toxicity, and unknown)?

Back 211

<b>Hereditary</b>
-Fanconi's anemia
<b>Acquired</b>
<u>Direct Toxicity</u>
-Radiation
-Chemotherapeutic drugs
-Toxins (benzene)
<u>Indirect toxicity</u>
-Idiopathic
-Drugs (chloramphenicol)
-Infections (TB, HIV, EBV, CMV, HBV)
-Pregnancy
<u>Unknown</u>
-Paroxysmal Nocturnal Hemoglobinuria

Front 212

What mechanism is probably required for indirect toxicity causing aplastic anemia?

Back 212

Immune mediation

Front 213

What are the two treatments for Aplastic anemia?

Back 213

Best: Bone marrow transplantation with matched sibling HLA-type
If no matched sibling is available, then:
Antithymocyte globulin + high dose steroids x2 weeks with taper
Cyclosporin A x1-2 years
This destroys T cells, then WBC comes back, then RBC comes back
If unsuccessful with pharmacologic intervention, use matched unrelated donor

Front 214

Describe feedback regulation of heme synthesis in nonerythroid tissue. Which isoform is present here?

Back 214

Heme inhibits ALA-synthase 1 (ALA-S1) activity and gene expression, required for the first step in heme synthesis, and mitochondrial translocation

Front 215

What is the first step of heme synthesis? What enzyme catalyzes the reaction? What co-factor is required? How is this step regulated? Where does this reaction occur?

Back 215

glycine + succinyl CoA --> d-aminolevulinicacid + CoASH
+ CO2
ALA synthase
Vitamin B6 (Pyridoxal phosphate)
Inhibited by heme
Mitochondria

Front 216

What other enzymes require heme?

Back 216

Cyt P450
Catalase
Mitochondrial cytochromes

Front 217

What is the metabolic capacity of RBCs?

Back 217

Glycolysis
Pentose Phosphate Pathway

Front 218

How many moles of glycine and succinyl CoA are required for one molecule of heme?

Back 218

8

Front 219

What is the final enzymatic step of heme synthesis? What enzyme catalyzes this reaction? Where does this reaction occur?

Back 219

Protoporphyrin IX + Fe²⁺ --> Heme + 2H⁺
Ferrochetalase
Mitochondria

Front 220

Describe feedback regulation of heme synthesis in erythroid tissue. Which isoform is involved here?

Back 220

The 5' UTR of the ALA-S2 mRNA contains IREs, which are tightly bound to IRP in the absence of iron, blocking translation.
When iron is present, the IRP binds to iron and cannot bind to the 5' UTR of ALA-S2, therefore translation occurs

Front 221

How is expression of the transferrin receptor regulated?

Back 221

In the absence of iron, IRP bind to IRE in the 3' UTR of transferring mRNA, increasing the stability of the mRNA.
In the presence of iron, Fe binds to the IRP, exposing the IRE in the 3' UTR leading to unstable mRNA which is degraded.

Front 222

What is the cause of Congetinal Erythropoietic Porphyria?
What compound builds up?
What is the treatment?

Back 222

Congenital Erythropoietic Porphyria
Cause: Deficiency of Uroporphyrinogen III cosynthase activity
Accumulation: Uroporphyrinogen I/Coporphyrinogen I
Tx: sun avoidance, skin protection, marrow suppression, marrow transplantation, possible gene therapy, possible I.V. hematin

Front 223

What is the cause of Acute Intermittent Porphyria?
What compound accumulates?
What is the treatment?
Which drugs does this condition contraindicate?

Back 223

Acute Intermittent Porphyria
Cause: Deficiency of porphobiliogen deaminase
Accumulation: d-ALA, porphobilinogen
Tx: hematin
Contraindicates: stimulators of ALA synthase and ALA dehydratase

Front 224

Which form of Hb is taught?

Back 224

deoxy

Front 225

Which form of Hb is relaxed?

Back 225

oxy

Front 226

Which has a greater P₅₀, Hemoglobin or myoglobin?

Back 226

Hemoglobin

Front 227

1. What is the hill coefficient of myoglobin?
2. What is the hill coefficient of oxygen?
3. What does this mean?

Back 227

1. Myoglobin = 1.0
2. Hemoglobin = 2.8
3. Hemoglobin is cooperative

Front 228

What is P₅₀?

Back 228

The concentration at which 50% of the units are occupied

Front 229

What is the normal adult isoform of hemoglobin? what is its relative abundance?

Back 229

HgbA₁: alpha₂beta₂
~92%

Front 230

What are the subunits of HbA₂? What is its relative abundance?

Back 230

HgbA₂: alpha₂delta₂
~2.5%

Front 231

What is the isoform of hemoglobin caused by non-enzymatic glycosylation? What is its normal relative abundance?

Back 231

HgbA_1c: alpha₂beta₂^a-N-glucose
~5%

Front 232

What is the fetal isoform of hemoglobin? What is its normal relative abundance?

Back 232

HgbF: alpha₂gamma₂
&lt;1%

Front 233

What sort of region in the globin chain does heme reside? Why?

Back 233

Hydrophobic pocket
Protects Fe2+ from oxidizing to Fe3+ due to water

Front 234

How does O₂ binding to hemo affect the tertiary structure of hemoglobin?

Back 234

When O₂ is not bound, the iron is out of the heme plane. Once O₂ binds, the iron moves into the heme plane and pulls the proximal His ligand along with it, causing a minimal change (.29A) which increases overall O₂ binding cooperatively.

Front 235

What two chemical reactions are important for the Bohr Effect? Which way does it shift the Oxygen dissociation curve? What are the two outcomes?

Back 235

Hb(O₂)₄ + xH⁺ --> Hb₄ + 4O₂ [x=1.8-2.8]
CO₂ + H₂O <--> H₂CO₃ <--> HCO₃^- + H⁺
Right Shift
1. Easier release of O₂ in tissues where CO₂ creates an acidic environment
2. Easier venting of CO₂ in the lungs where O₂ tension pushes the H⁺ to form CO₂ and H₂O

Front 236

What is the biochemical mechanism of the Bohr effect?

Back 236

Protonation at low pH stabilizes the deoxy taught form of hemoglobin

Front 237

What is the effect of DPG (BPG, 2,3-diphosphoglycerate) on the oxygen dissociation curve of hemoglobin? Where does DPG bind to the hemoglobin molecule?

Back 237

DPG binds between the two b-chains on + charged amino acids

Front 238

What chemical reaction is important for the effect of CO₂ binding to hemoglobin? Where does CO₂ bind to hemoglobin? What is the result of that binding?

Back 238

CO₂ + H₂N-Hemoglobin <--> ^-O(C=O)NH-Hemoglobin
1. CO₂ binds to deoxy Hb more than oxy Hb
2. CO₂ binds to a-amino groups of b-chains more than a-chains
3. Carbamino group forms a salt bridge with + charged groups in deoxy form to stabilize deoxy form

Front 239

How does temperature affect the oxygen dissociation curve?

Back 239

Higher temp shifts the curve to the right, lower temp shifts the curve to the left

Front 240

What are the genetic mechanisms of hemoglobinopathies?

Back 240

Single point mutation (sick cell HbS)
Double Amino Acid Substitution (HbC Harlem)
Variants with deletions (Hb Gun Hill)
Chain Termination mutants (Hb Constant Spring)
Frame Shift Mutations (Hb Wayne)
Fusion Chain (Hb Lepore)
Insertion (Hb Grady)

Front 241

What is the mutation for sickle cell anemia? How does the HbS contribute to sickling?

Back 241

AA#6 glu --> val (hydrophilic to hydrophobic change)
Hbs has lower O2 affinity, releases O2 easier to account for anemia
deoxyHbS aggregates, blocking capillaries and causing stasis
Stasis --> acidosis --> oxygen curve shifts right --> O₂ release --> more sickling

Front 242

Which two hemoglobinopathies lead to denatured hemoglobin inclusions? What are these called?

Back 242

Hb Hammersmith (severe)
Hb Koln (mild)
Heinz Bodies

Front 243

What are the possible causes of methemoglobinemia?

Back 243

Acquired/Toxic: Drug-induced oxidation of HbA
Hereditary HbM: distal or proximal His --> Tyr mutation
Hereditary NADH Cytochrome B5 Reductase deficiency

Front 244

How much ATP is generated per mole of glucose? What is ATP's purpose in the RBC?

Back 244

1 mole glucose --> 2 mole ATP
ATP powers the Na⁺/K⁺ATPase and the Ca²⁺ATPase to keep intracellular sodium low, potassium high and calcium low

Front 245

How do SS RBCs become dehydrated and rigid?

Back 245

SS RBCs have reduced Ca²⁺ATPase activity which causes increased rigidity and increases the influx of calcium which causes the Gardos effect and opening of K⁺ channels leading to dehydration.

Front 246

Heterozygous patients with a partial NADH Cytochrome B5 Reductase deficiency should not be given what drugs? Why?

Back 246

Oxidant drugs (primaquine, chloroquine)
They will develop acute methemoglobinemia due to hemoglobin oxidation and reduced reduction.

Front 247

How does a pyruvate kinase deficiency lead to hemolytic anemia?

Back 247

Pyruvate kinase deficient patients have ~5-25% of normal PK activity, thus their rate of glycolysis is decreased and less ATP is produced.

Front 248

What are the first and second most common causes of hemolytic anemia?

Back 248

1. G-6-P Dehydrogenase deficiency
2. Pyruvate Kinase deficiency

Front 249

Where are phosphatidyl choline, sphingomyelin, phosphatidyl ethanolamine, and phosphatidyl serine found in the RBC membrane? What happens if PS is in the wrong leaflet?

Back 249

PC and SM are in the outer leaflet
PE and PS are in the inner leaflet
If PS is in the outer leaflet, as can occur in sick cell disease, increased coagulation can occur.

Front 250

What is the cause of hereditary spherocytosis? What is the clinical result?

Back 250

Autosomal dominant spectrin deficiency leads to mild anemia.

Front 251

What is the cause of hereditary elliptocytosis? What is the clinical result?

Back 251

Autosomal dominant failure of spectrin molecules to form tetramers leads to mild anemia

Front 252

What is the cause of acanthocytosis? What patients are at risk??

Back 252

Autosomal recessive increase in cholesterol and sphingomyelin increases RBC rigidity and leads to hemolytic anemia, more often in patients with liver disease especially due to chronic alcoholism.

Front 253

What conditions increase the propensity of HbS to polymerize and cause sickling?

Back 253

Increased Temp (fever)
Low pH (acidosis)
Dehydration
Hypoxia (stasis, high elevation)

Front 254

What are the treatment options for Sickle Cell Disease (SCD)?

Back 254

Lower fever
Correct acidosis
Increase fluid intake
Hydroxyurea increases fetal HbF (alpha2gamma2), known teratogen
Prevent adhesion of SS RBC to endothelium

Front 255

Chronic hemolytic anemia, vaso-occlusive crises, frequent infections, leukocytosis, pulmonary hypertension, and asthma are clinical manifestations of what disease?

Back 255

Sickle Cell Disease

Front 256

What are the 4 major mechanisms of anemia due to chronic disease and/or inflammation?

Back 256

1. Activation of macrophages and spleen
2. Faulty iron re-utilization
3. Blunted EPO response
4. Cytokine inhibition of erythropoiesis

Front 257

How do proinflammatory cytokines lead to RBC lifespan being decreased by 10-20d?

Back 257

Proinflammatory cytokines (TNF-a) upregulate macrophage and splenic function and cause RBC membrane changes, leading to erythrophagocytosis

Front 258

How does chronic disease and/or inflammation lead to faulty iron-reutilization?

Back 258

Lactoferrin is released from PMNs which selectively transports iron to macrophages.
The liver synthesizes hepcidin which reduces intestinal absorption and transferring production while increasing macrophage retention of iron as ferritin, decreasing serum iron levels.

Front 259

How does chronic disease and/or inflammation lead to a blunted EPO response?

Back 259

IL-1 and TNF-a directly inhibit EPO mRNA via ROS that damage EPO producing cells

Front 260

Pancytopenia with decreased reticulocyte count, increased MCV RDW LDH and indirect Bilirubin is what form of anemia? What type of anemia is this?

Back 260

Megaloblastic anemia
Ineffective hematopoiesis

Front 261

How is B12 deficiency a self-impairing cycle?

Back 261

Vitamin B12 is especially required in cells with a high turnover, such as gut epithelial cells. Atrophy of gut cells due to a lack of B12 leads to decreased absorption of B12

Front 262

What is the cause of pernicious anemia?

Back 262

Autoimmune antibody to gastric H+/K+ ATPase --> gastric atrophy

Front 263

Ab to intrinsic factor are specific to what disease? How specific?

Back 263

Pernicious anemia
~100% specific

Front 264

How many base pairs are in the human genome?

Back 264

3 billion

Front 265

How many genes are in the human genome?

Back 265

25,000-35,000

Front 266

By how much do individuals differ from one another genetically?

Back 266

1 base per 1000

Front 267

What is the difference between an early myeloblast and a PMN in terms of phenotypic markers?

Back 267

Early myeloblast: CD33+, CD34+
PMN: CD33+, CD34-

Front 268

What is the most sensitive method of genetic detection?

Back 268

PCR (1/1,000,000)

Front 269

1. How is the immune system dysregulated in Hodgkin Disease?
2. What sort of infections are individuals prone to?

Back 269

1. T cell function appears to be abnormal
2. Patients have increased susceptibility to TB, L. monocytogenes, Candida, Herpes simplex and to opportunistic infections by P. carinii, vaccinia, and herpes zoster

Front 270

1. How does HD spread typically?
2. How does HD spread in HIV+ patients?

Back 270

1. HD typically spreads in a linear nodal fashion (mediastinal mass-->axillary/cervical nodes)
2. Skipped nodes are more common (retroperitoneal-->supraclavicular)

Front 271

Describe liver and splenic involvement in HD

Back 271

HD can involve the spleen, and often will also involve the liver
HD rarely involves the liver only

Front 272

What is the differential diagnosis of a mediastinal mass?

Back 272

4Ts
Thyroid (substernal goiter)
Teratoma
Thymoma
Terrible lymphomas
-T Cell lymphoma/leukemia
-B cell lymphoma
-Hodgkin lymphoma

Front 273

1. What is the role of APOBEC3?
2. How does HIV block APOBEC3?

Back 273

1. APOBEC3 deaminates C to U in retroviral cDNA, leading to fatal mutations
2. HIV Vif inhibits APOBEC3

Front 274

1. What is the role of HIV Vif?

Back 274

Vif inhibits APOBEC3 from deaminating C to U in retroviral cDNA

Front 275

1. What is the role of TRIM5a?

Back 275

TRIM5a restricts HIV infection in other primates and prevents capsid shedding and release of viral RNA

Front 276

1. What is the role of Tetherin/CD317?
2. How does HIV block Tetherin?

Back 276

1. Tetherin prevents HIV virion release from the cell membrane
2. HIV Vpu inhibits tetherin

Front 277

What is the role of HIV Vpu?

Back 277

Vpu inhibits tetherin/CD317 from preventing the release of HIV virion particles

Front 278

What is the role of HIV Vpr?

Back 278

HIV Vpr blocks IL-12 production by macrophages

Front 279

What is the role of Nef?

Back 279

Nef blocks CD4 expression and inhibits apoptosis in infected cells

Front 280

What are the two ways in which HIV depletes CD4+ T cells?

Back 280

1. Direct cytotoxicity from virion production
2. Syncytia formation from gp120 binding to other T cell CD4 and causing membrane fusion

Front 281

During the acute HIV infection, which test is the most likely to confirm a diagnosis of HIV?

Back 281

HIV viral load will detect the rapid rise in viral load which follows from HIV innoculation and acute HIV syndrome, before the immune system reduces the viral load.

Front 282

A patient with fevers, chills, and a maculopapular rash x3w saying "this is the worst cold I've ever had" has what condition?

Back 282

Acute retroviral syndrome from HIV infection

Front 283

When will HIV viral RNA become detectable in a patient?

Back 283

2-4w (5-14days)

Front 284

When will viral load HIV RNA become positive in a patient?

Back 284

2-4w (5-14d)

Front 285

When will anti-HIV ab become positive in a patient using EIA?

Back 285

+/- @ 4-6w
+ @ 2mo

Front 286

When will anti-HIV ab become positive in a patient using western blotting?

Back 286

+/- @ 2mo
+(3) @ 3mo
+(8) @ 6mo

Front 287

What are the clinical signs of chronic, symptomatic HIV in men? In women?

Back 287

Men: Wasting (loss of >15% bw), Thrush, Fever>2w, Diarrhea >1mo, ITP, Oral hairy leukoplakia, Hepes Zoster
Women: Same as men plus Recurrent Vulvovaginal Candidiasis, Cervical dysplasia, CA in situ of cervix, PID

Front 288

Why is HIV associated with cervical dysplasia and CA in situ of the cervix?

Back 288

There is a high rate of HPV + HIV coinfection

Front 289

At what CD4 levels can herpes zoster occur in HIV?

Back 289

Any

Front 290

Which virus is oral hairy leukoplakia associated with?

Back 290

EBV

Front 291

Which test is most likely to confirm a diganosis during a chronic HIV infection?

Back 291

Western blot for anti-HIV ab

Front 292

What is the lethal disease and causative organism in AIDS?

Back 292

PCP (pneumocystis pnuemonia) caused by pneumocystis jiroveci

Front 293

What is the clinical defintion of AIDS?

Back 293

Any of the following
CD4 <200
CD4 <15%
Opportunistic infection or disease

Front 294

Is invasive cervical cancer a sign of chronic HIV or AIDS?

Back 294

AIDS

Front 295

When is a patient at risk for PCP?

Back 295

CD4<200

Front 296

What is the treatment of PCP?

Back 296

TMP/SMX x21d + Prednisone

Front 297

When is a patient at risk for CMV retinitis?

Back 297

CD4 <50

Front 298

1. When is an HIV patient at risk for Kaposi Sarcoma?
2. What is the causative agent of kaposi sarcoma?

Back 298

1. Any CD4 level
2. HSV 8

Front 299

When is a patient at risk for Cryptococcus meningitis?

Back 299

CD4<100

Front 300

How is cryptococcus meningitis diagnosed?

Back 300

India Ink stain of LP, confirmatory CSF and serum crypto antigen titers

Front 301

When is a patient at risk for CNS toxoplasmosis?

Back 301

CD4<100

Front 302

How is CNS toxoplasmosis diagnosed?

Back 302

multiple ring enhancing lesions

Front 303

How is cryptococcus meningitis treated?

Back 303

Amphotericin and 5-flucytosine followed by diflucan

Front 304

How is toxoplasmosis treated?

Back 304

sulfadiazine, pyremethamine, leukovorin

Front 305

Lymphoma of the brain causing a CNS mass lesion is associated with what virus?

Back 305

EBV

Front 306

Who should be tested for HIV under CDC testing recommendations?

Back 306

All peoples aged 13-64
Anyone:
-tested or treated for an STD
-initiating TB tx
-pregnant women
-women with undocumented HIV status at L&D

Front 307

Is written informed consent for HIV testing required?

Back 307

no

Front 308

Who should be started on ART?

Back 308

Strong recommendation: AIDS or CD4 <300, pregnant, chronic HepB, or HIV nephropathy
Moderate-strong recommendation: CD4 350-500
50% optional, 50% in favor: CD4 >500

Front 309

1. What is the mechanism of action of Emtricitabine?
2. What are its side effects?

Back 309

1. Nucleoside reverse transcriptase inhibitor for the treatment of HIV
2. None

Front 310

1. What is the mechanism of action of Tenofovir?
2. What are its side effects?

Back 310

1. Nucleoside reverse transcriptase inhibitor for the treatment of HIV
2. Decreased mineral bone density, rare fanconi syndrome

Front 311

1. Which two nucleoside reverse transcriptase inhibitors are common prescribed during HAART?
2. What are their side effects?

Back 311

Emtricitabine - None
Tenofovir - decreased mineral bone density, rare fanconi syndrome

Front 312

1. What is the mechanism of action of Atazanavir?
2. What are its side effects?

Back 312

1. Protease inhibitor for the treatment of HIV
2. increased indirect bilirubin, prolonged PR, CYP3A4 inhibition

Front 313

1. What is the mechanism of action of Darunavir?
2. What are its side effects?

Back 313

1. Protease inhibitor for the treatment of HIV
2. Rash, CYP3A4 inhibition

Front 314

1. Which two protease inhibitors are commonly prescribed during HAART?
2. What are their side effects?

Back 314

Atazanavir - increased indirect bilirubin, prolonged PR, CYP3A4 inhibition
Darunavir - rash, CYP3A4 inhibition

Front 315

1. What is the mechanism of action of Efavirenz?
2. What are the commonly associated side effects of Efavirenz?

Back 315

1. Non-nucleoside reverse transcriptase inhibitor for the treatment of HIV
2. CNS side effects, rash, CYP3A4 induction

Front 316

1. What is the common side effect of nucleoside reverse transcriptase inhibitors?
2. What are two commonly prescribed NRTIs?

Back 316

CYP3A4 inhibition
Atazanavir
Darunavir

Front 317

Which drugs inhibit CYP3A4?

Back 317

Atazanavir
Darunavir
Nucleoside reverse transcriptase inhibitors

Front 318

Which drug induces CYP3A4?

Back 318

Efavirenz
non-nucleoside reverse transcriptase inhibitor

Front 319

1. What is the mechanism of action of Raltegravir?
2. What are its side effects?

Back 319

1. Integrase inhibitor for the treatment of HIV
2. none common or severe, headache, nausea, and diarrhea can occur

Front 320

What are the antiretroviral guidelines?

Back 320

2 nucleoside RT inhibitors (emtricitabine + tenofovir)
Plus one of the following:
-protease inhibitor(s) atazanavir or darunavir
-non-nucleoside RT inhibitor efavirenz
-integrase inhibitor raltegravir

Front 321

1. Which drug inhibits integrase?
2. What are its side effects?

Back 321

Raltegravir - none common or severe, headache, nausea, diarrhea may occur

Front 322

What is the current recommended regimen for HIV+ pregnant women?

Back 322

Lopinavir/ritonavir + AZT/3TC(lamivudine)

Front 323

1. What is the mechanism of action of Chloroquine, quinine, quinidine, and mefloquine?
2. Are they blood schizonticides or hepatic hypnozoiticides?

Back 323

1. Drug is concentrated in infected erythrocytes and raises the pH in the food vacuole of the parasite, preventing heme polymerization to hemozoin; heme accumulates and kills the parasite.
2. Blood schizonticides

Front 324

What is the mechanism of action of primaquine?
2. Is it a blood schizonticide or a hepatic hypnozoiticide?

Back 324

1. Redox cycle generates oxidants, interferes with electron transport chain in mitochondria.
2. Hepatic hypnozoiticide

Front 325

Which antimalarial drug is safe for pregnant women?

Back 325

Chloroquine

Front 326

Which antimalarials should not be combined?

Back 326

Mefloquine with any other quinoline (quinine, quinidine, chloroquine)

Front 327

Which antimalarial drug contributes to oxidative damage of RBCs?

Back 327

Primaquine

Front 328

1. What is the mechanism of action of Pyrimethamine?
2. What is the mechanism of action of sulfadoxine?
3. What are they used to treat?

Back 328

1. Pyrimethamine inhibits DHFR
2. Sulfadoxine inhibits dihydropteroate synthase
3. They are used to treat Chloroquine-resistant P. falciparum

Front 329

1. What is the mechanism of action of Proguanil?
2. What is the mechanism of action of Atovaquone?
3. What are they used to treat?

Back 329

1. Proguanil inhibits DHFR
2. Atovaquone binds to Cyt bc1 and inhibits electron transport, collapsing the mitochondrial membrane potential.
3. Proguanil/Atovaquone (malarone) are used to treat chloroquine and MDR P. falciparum

Front 330

Describe the synergy of Proguanil and Atovaquone

Back 330

Proguanil inhibits DHFR, but also enhances atovaquone. Atovaquone binds to Cyt bc1 and collapses the mitochondrial membrane potential.

Front 331

What is the WHO recommendation for the treatment of falciparum malaria?

Back 331

Artemisin-based combination therapy for 3 days (Artemether+lumefantrine or Artesunate+something else)

Front 332

What is the WHO recommendation for the treatment of severe malaria?

Back 332

Artesunate (quinine or quinidine in the US)

Front 333

What is the diagnostic test for malaria?

Back 333

Thick and thin smears of blood

Front 334

Which forms of malaria form hypnozoites?

Back 334

P. vivax
P. ovale

Front 335

1. What is the treatment recommendation for P. vivax or P. ovale?
2. What are the contraindications for this treatment?

Back 335

1. Chloroquine x3d + Primaquine x14d
2. Primaquine is contraindicated in those with G6PD deficiency

Front 336

Coma, metabolic acidosis, severe anemia, hypoglycemia, acute renal failure, and pulmonary edema due to a parasitic infections are signs of infection by what organism and what disesae?

Back 336

Severe malaria due to P. falciparum

Front 337

Which forms of malaria cause a tertian fever?

Back 337

P. vivax
P. ovale
P. falciparum

Front 338

Which forms of malaria cause a quartan fever?

Back 338

P. malariae

Front 339

What causes the fevers in malaria?

Back 339

TNF-a release due to macrophages being stimulated by gycosyl phosphatidylinositol moieties as the schizonts rupture in the blood

Front 340

What are 3 causes of thrombocytosis?

Back 340

1. Fe deficiency
2. Chronic disease
3. Essential thrombocytopenia
4. Cancer

Front 341

In what conditions is the RDW not increased?

Back 341

Thalassemia minor
Anemia of chronic disease
Aplastic anemia

Front 342

Which conditions cause a microcytic anemia?

Back 342

Fe deficiency
Thalassemia
Anemia of chronic disease (20%)
Sideroblastic anemia

Front 343

Which conditions cause a macrocytic anemia?

Back 343

Sideroblastic anemia
Pernicious anemia
Folate deficiency
Liver disease

Front 344

Which conditions cause a normocytic anemia?

Back 344

Aplastic anemia
Blood loss
Anemia of chronic disease (80%)

Front 345

For which patients is HAART strongly recommended?

Back 345

AIDS
CD4 <350
Pregnancy
Chronic Hepatitis B needing tx
HIV nephropathy

Front 346

For which patients is there a 55% strong and 45% moderate recommendation for HAART?

Back 346

CD4 350-500

Front 347

For which patients is there a 50% favorable and 50% optional view of HAART?

Back 347

CD4 >500

Front 348

What is the mechanism of action of enfuvirtide?

Back 348

HIV fusion inhibitor

Front 349

What is the mechanism of action of T-20?

Back 349

HIV fusion inhibitor

Front 350

What is the mechanism of action of maraviroc?

Back 350

CCR5 receptor antagonist

Front 351

What are the 3 possible regimens and their side effects for HAART?

Back 351

2xNRTIs: Emtricitabine (none) + Tenofovir (decreased mineral bone density)
and 1 of the following:
NNRTIs: Efavirenz (CNS, rash, hypersensitivity)
OR
Integrase Inh: Raltegravir (none common or severe, HA, N, D)
OR
Protease inhibitors: Darunavir/r (Rash) or Atazanavir/r (PR elongation, increased indirect bilirubin)

Front 352

What is the HAART for pregnant women?

Back 352

LPV/r + AZT/3TC

Front 353

Describe the important steps in heme synthesis

Back 353

<b>Mitochondria</b>
Sucincyl Coa + Glycine -[d-ALA synthase]-> d-ALA
<b>Cytoplasm</b>
2x d-ALA -[PBG synthase]-> PBG
4x PBG -[PBG deaminase]-> HMB
HMB -[Uroporphyrinogen III Cosynthase]-> Uroporphyrinogen III
Uroporphyrinogen III --> Coproporphyrinogen III
<b>Mitochondria</b>
Coporporphyrinogen III --> Protoporhyrin IX
Protoporphyrin IX -[Ferrochetalase]-> Heme

Front 354

1. What is the deficient enzyme of AIP?
2. What step of heme synthesis is affected?
3. What molecules build up?
4. What is the treatment?

Back 354

1. PBG deaminase
2. 4x PBG -[PBG deaminase]-> HMB
3. PBG and d-ALA
4. IV hematin

Front 355

1. Deficiency of PBG deaminase is associated with what condition?
2. What molecules build up?
3. What should be avoided?
4. What is the treatment?

Back 355

1. AIP
2. PBG and d-ALA
3. drugs, steroids, dietary changes, inducers of d-ALA synthase
4. IV hematin

Front 356

1. What is the deficient enzyme of CEP?
2. What step of heme synthesis is affected?
3. What molecules build up?
4. What is the treatment?

Back 356

1. Uroporphyrinogen III cosynthase
2. HMB -[Uroporphyrinogen III cosynthase]-> Uroporphyrinogen III
3. Uroporphyrinogen I and Coproporphyrinogen I
4. Transferrin suppresses defective erythropoiesis, IV hematin

Front 357

1. Deficiency of Uroporphyrinogen III cosynthase is associated with what condition?
2. What step of heme synthesis is affected?
3. What molecules build up?
4. What is the treatment?

Back 357

1. CEP
2. HMB -[Uroporphyrinogen III cosynthase]-> Uroporphyrinogen III
3. Uroporphyrinogen I and Coporporphyrinogen I
4. Transferrin suppresses defective erythropoiesis, IV hematin

Front 358

What does a right shifted O2 saturation curve reflect?

Back 358

Decreased affinity

Front 359

What is the effect of increased temperature on the O2 saturation curve?

Back 359

Right shift, decreased affinity

Front 360

What is the effect of decreased pH (increased [H⁺]) on the O2 saturation curve?

Back 360

Right shift, decreased affinity

Front 361

What is the effect of no DPG on the O2 saturation curve?

Back 361

Left shift, increased affinity (fetal Hb)

Front 362

Which HAART drugs induce CYP3A4?

Back 362

nNRTIs
Efavirenz

Front 363

What are the symptoms of cinchonism?

Back 363

flushing
sweaty
tinnitus
dizziness
nausea
diarrhea

Front 364

What are the causes of microangiopathic hemolytic anemia?

Back 364

DIC
TTP
Vasculitis
Mechanical heart valves

Front 365

What is the cause of IIa VWD?

Back 365

Absence of HMW vWF mutimers

Front 366

Which leukemia is often the cause of ITP?

Back 366

CLL

Front 367

When are spur cells often visible?

Back 367

Cases of liver failure

Front 368

1. What are platelet concentrates used to treat?
2. What are they not used to treat?

Back 368

1. Thrombocytopenia
2. ITP

Front 369

What are FFP used to treat?

Back 369

Factor deficiencies

Front 370

When are target cells visible?

Back 370

Liver disease
thalassemia

Front 371

When are burr cells visible?

Back 371

Kidney disesae

Front 372

1. How many copies of Hb-a are there in a-thal minima?
2. What is the other name for this disease?

Back 372

1. 3
2. Thal-2

Front 373

1. How many copies of Hb-a are there in a-thal minor?
2. What is the other name for this disease?

Back 373

1. 2
2. Thal-1

Front 374

1. What is HbH?
2. What is the effect of HbH on the O2 dissociation curve?
3. In what disease is HbH seen?

Back 374

1. HbB₄
2. Major left shift (increased affinity)
3. HbH disease/a-Thal intermedia

Front 375

What is the mutation responsible for sickle cell anemia?

Back 375

AA6 of HbB: Glu-->Val

Front 376

What are the two reasons why NO is reduced in sickle cell anemia?

Back 376

1. RBCs are lysed and produce arginase, which degrades L-arginine. NO is produced from L-arginine.
2. Free heme binds to NO in the bloodstream

Front 377

What is contained within platelet primary granules?

Back 377

Sticky stuff

Front 378

What is contained within platelet dense granules?

Back 378

ATP, ADP, serotonin, calcium

Front 379

1. What platelet receptor does vWF bind to?
2. A lack of this receptor is known as what disease?

Back 379

1. GpIb/IX
2. Bernard-Soulier Syndrome

Front 380

1. What platelet receptor cross-links platelets with fibrin?
2. A lack of this receptor is known as what disease?

Back 380

1. GpIIb/IIIa
2. Glanzmann's thrombasthenia

Front 381

What is the cause of type IIb vWD?

Back 381

Lack of HMW vWF multimers and increased affinity for platelet gpIb

Front 382

What is the cause of type IIn?

Back 382

vWF variants have markedly decreased affinity for VIII, VIII is degraded.

Front 383

In which form of vWD will platelets be low?

Back 383

vWD IIb

Front 384

In which form of vWD will there be no FVIII?

Back 384

vWD IIn

Front 385

A lack of ADAMTS13 leads to what disorder?

Back 385

TTP

Front 386

What is gray platelet syndrome?

Back 386

Deficiency of alpha granules leads to lifelong mucocutaneous bleeding

Front 387

Low LDH levels in a sick cell patient often indicate what sort of disease progression?

Back 387

Pain crises

Front 388

Which chromosome is Hb-b on?

Back 388

Ch11

Front 389

What are the four mechanisms by which anemia of chronic disease occurs?

Back 389

1. Shortened RBC survival due to macrophage activation
2. Lactoferrin moves iron to macrophages and hepcidin causes retention in macrophages and decreased GI absorption of iron
3. Blunted EPO response by IL-1 and TNF-a
4. IFN-g inhibits CFU-E growth, IL-1 inhibits CFU-E growth, TNF-a decreases stem cell colony formation

Front 390

1. What is a normal PT time?
2. What is the criteria for abnormal PT?

Back 390

Normal: 12 seconds
Abnormal: >1.3

Front 391

1. What is a normal aPTT?
2. What is the criteria for abnormal aPTT?

Back 391

1. Normal: 35 seconds
2. Abnormal: >1.3

Front 392

1. What is a normal TT?
2. What is the criteria for abnormal TT?

Back 392

1. Normal: 30 seconds
2. Abnormal: >1.3

Front 393

1. What does a deficiency in ADAMTS13 cause?
2. What is the effect on platelets?

Back 393

TTP
Increased aggregation of platelets due to increased HMW-vWF

Front 394

Which will lead to a low bleeding time, TTP or ITP?

Back 394

ITP will have a normal bleeding time even though there are few platelets
TTP will have a prolonged bleeding time

Front 395

Which factors required for primary hemostasis will kidney failure lead to a deficiency of?

Back 395

vWF
Fibrinogen

Front 396

What will a deficiency of FXIII cause?

Back 396

Delayed bleeding since XIIIa is responsible for cross-linking fibrin

Front 397

What will a deficiency of FXII cause?

Back 397

Thrombotic disorder

Front 398

What will a deficiency of FXI cause?

Back 398

Bleeding related to trauma, more common in the Jewish population

Front 399

Factor V Leiden will lead to thrombosis in which vascular system?

Back 399

venous

Front 400

How is antiphospholipid characterized?
Why is it paradoxical?

Back 400

Lupus anticoagulant is an antibody inhibitor directed at membrane phospholipids which prolongs PTT and PT but leads to thrombosis.

Front 401

What differentiated liver disease from vitamin k deficiency?

Back 401

FV is low in liver disease, not vitamin K deficiency

Front 402

1. What is the cause of Tranmissable Spongiform Encephalopathy?
2. What is the name of the disease in humans?

Back 402

1. Prions
2. Creutzfeldt-Jacob Disease

Front 403

What are the three forms of Creutzfeldt-Jacob Disease?

Back 403

Spontaenous
Inherited (Prnp mutation)
Acquired (vCJD, iatrogenic, transfusion, eating infected brain tissue)

Front 404

1. What does the Prnp gene code for?
2. What is the normal characteristics of the protein product and its name?
3. What is the abnormal characteristics of the disease protein product and its name?

Back 404

1. PrP
2. PrP^C, many a-helices
3. PrP^SC, many b-sheets

Front 405

What is the structure of CMV?

Back 405

Enveloped, icosahedral, dsDNA genome herpesvirus

Front 406

How does CMV evade the immune system?

Back 406

Suppresses MHC I/II expression
Produces proteins which block NK attack
IL-10 downregulates Th1 response

Front 407

1. Describe the structure of West Nile Virus
2. What are the common, uncommon, and rare presentations of West Nile Virus?

Back 407

1. ss(+)RNA
2. 80% asymptomatic, 20% West Nile Fever, 1% neuroinvasive

Front 408

1. Describe the structure of West Nile Virus
2. How is West Nile Virus diagnosed?

Back 408

1. ss(+)RNA
2. WNV IgM/IgG antibodies in blood or CSF

Front 409

At what CD4 level does a person have AIDS?

Back 409

<200

Front 410

At what CD4 level does a person have symptomatic HIV disease?

Back 410

<500

Front 411

at what CD4 level does a person have PCP?

Back 411

<200

Front 412

At what CD4 level does a person get cryptococcus meningitis?

Back 412

<100

Front 413

At what CD4 level does a perso get toxoplasmosis or candidal esophagitis (disseminated cadidiasis)?

Back 413

<100

Front 414

At what CD4 level does a person get CMV retinitis?

Back 414

<50

Front 415

What are the most common pathogens which cause nosocomial pneumonia?

Back 415

S. aureus
P. aeruginosa

Front 416

What are the 4 most common Hospital-Acquired infections in order of increasing prevalence?

Back 416

1. UTI
2. Pneumonia
3. Central line associated blood infection
4. Surgical Site infection

Front 417

What are the most common pathogens which cause Central Line Associated Blood infections?

Back 417

Coagulase(-) Staph (epidermidis), S. aureus, Enterococci, Candida

Front 418

Which operations have the highest risk of Surgical Site infections?

Back 418

Colon, small bowel, gastric operations

Front 419

What are the most common pathogens which cause surgical site infections?

Back 419

S. aureus, Coagulase(-) staph, Enterococci, E. coli

Front 420

1. What is SIRS?
2. What is the clinical definiciont of SIRS?

Back 420

1. Systemic Inflammatory Response Syndrome
2. 2+ of the following:
-T >38C or &lt;36c>90bpm
-Resp >20
-WBC >12,000 or &lt;4000>10% bands

Front 421

1. What is the clinical definition of Sepsis?

Back 421

SIRS + Infection

Front 422

What is the clinical definition of severe sepsis?

Back 422

Sepsis (SIRS + infection)
Organ dysfunction
Hypoperfusion or hypotension (systolic &lt; 90mmHg)
May include lactic acidosis, oliguria, AMS, or aute lung injury

Front 423

What is the clinical definition of septic shock?

Back 423

Sepsis (SIRS + infection)
Hypotension despite fluid rescucitation

Front 424

1. What is the primary site of infection in sepsis?
2. Where does the infection often spread?

Back 424

1. Lung
2. Spread to blood and abdomen

Front 425

1. Which TLR recongizes LPS?
2. Which signalling molecules are released?

Back 425

1. TLR-4
2. TNF-a, IL-1

Front 426

Which is worse, warm shock or cold shock?

Back 426

Warm shock

Front 427

What is the supportive,
antimicrobial
Anti-inflammatory
anticoagulant
therapies of sepsis?

Back 427

1. Supportive care
--IV fluids
--supplemental O2/ventilation
2. Antimicrobial
--Broad spectrum initially
--Directed abx once organism ID'ed
3. Anti-inflammatory
--Low dose hydrocortisone in pts who don't respond to fluids+vasopressors
4. Anticoagulant
--Activated Protein C

Front 428

Describe the structure of EBV

Back 428

dsDNA herpesvirus

Front 429

What does EBNA2 gene do?

Back 429

Transforms B cells into immortal B cells

Front 430

What is the current antiviral treatment of EBV?

Back 430

None effective

Front 431

What mediates GVHD?

Back 431

Donor T cells

Front 432

Which graft sources are the lowest risk for histoincompatibility, which are the highest?

Back 432

(most risky) PBSC > BM > Cord Blood (least risky)

Front 433

Rank leukemias in order of easiest to cure with HSCT to hardest to cure.

Back 433

CML > AML > ALL

Front 434

What is the post-transplant immunosuppression regimen?

Back 434

Calcineurin inhibitor (cyclosporin or tacrolimus) + methotrexate or mycophenolate

Front 435

1. What is the most common viral infection after HSCT?
2. Why?

Back 435

1. CMV
2. CMV reactivates during immunosuppression

Front 436

Which myeloproliferative disorder leads to a shortened lifespan?

Back 436

Myelofibrosis

Front 437

What is the cure for myelofibrosis?

Back 437

Allogeneic stem cell transplant

Front 438

CD13 and CD33 are associated with which forms of leukemia?

Back 438

Myeloid

Front 439

CD5, CD7, and CD19 are associated with which forms of leukemia?

Back 439

Lymphoid

Front 440

What stain is used to identify ALL

Back 440

Periodic Acid Schiff

Front 441

1. What chromosomal abnormality is the best in childhood ALL?
2. What is the gene product?

Back 441

t(12;21) - TEL/AML-1

Front 442

What special precaution must be taken for ALL chemotherapy?

Back 442

CNS prophylaxis

Front 443

What are TDT and CD7 markers of?

Back 443

Immature T-lymphocytes

Front 444

How does Small Cell B lymphoma/CLL prognosis differ with ZAP 70?

Back 444

ZAP70+ is worse
ZAP70- is better

Front 445

1. t(11;14) is associated with what lymphoma?
2. What is the gene product?
3. What is the overall effect?

Back 445

1. Mantle Cell lymphoma
2. Bcl-1/Cyclin-D1
3. hyperproliferation

Front 446

1. t(8;14) is associated with what lymphoma?
2. What is the gene product?
3. What is the overall effect?

Back 446

1. Burkitt lymphoma
2. C-myc
3. Hyperproliferation

Front 447

A low power "starry sky" appearance is associated with what lymphoma?

Back 447

Burkitt lymphoma

Front 448

1. Bcl-6 point mutations or, rarely, t(3;14) are associated with what lymphoma?

Back 448

DLBCL

Front 449

What two chromosomal or genetic abnormalities are associated with DLBCL?

Back 449

Bcl-6
t(3;14)

Front 450

What is the treatment of DLBCL?

Back 450

CHOP+R

Front 451

What is the effect of Rituximab?

Back 451

MAB to CD20

Front 452

1. What lymphoma is associated with t(14;18)?
2. What is the gene product?
3. What is the overall effect?

Back 452

1. FCC
2. Bcl-2
3. antiapoptosis

Front 453

What lymphoma are butt cells associated with?

Back 453

FCC lymphoma

Front 454

1. Which lymphoma are clover leaf cells associated with?
2. What is the associated pathogen?

Back 454

1. Adult T Cell Lymphoma/Leukemia
2. HTLV-1

Front 455

1. What lymphoma is t(11;18) associated with?
2. What is the gene product?

Back 455

1. MALT lymphoma (advanced)
2. API2

Front 456

Which form of Hodgkin's lymphoma is most related to EBV?

Back 456

Mixed-cellularity HL

Front 457

t(4:14) is associated with what lymphoma?

Back 457

multiple myeloma

Front 458

1. Which thalassemia is prevalent among descendants of mediterranean families?
2. Which hemoglobins are elevated?

Back 458

1. beta-thalassemia
2. Hb F (a2g2), Hb A2 (a2d2)

Front 459

Which antigens are present on platelets?

Back 459

Human Platelet Antigen (HPA)
HLA Class I
Blood Group A and B antigens

Front 460

1. What is the function of gpVI?
2. What is the function of a2b1?

Back 460

1. Binds collagen
2. Is expressed by platelet and stabilizes binding

Front 461

What happens to platelets during cardiopulmonary bypass?

Back 461

The platelets are activated in the mechanical pump and are thereafter dysfunctional

Front 462

What is the effect of APC on PAI-1 and tPA/uPA?

Back 462

APC inhibits PAI-1, thus de-inhibiting tPA and uPA

Front 463

1. What does antithrombin+HMW heparin inhibit?
2. What does antithrombin+LMW heparin hinhibit?

Back 463

1. Thrombin
2. IXa, Xa

Front 464

What does HMW heparin+antithrombin inhibit?

Back 464

Thrombin

Front 465

What does LMW heparin+antithrombin inhibit?

Back 465

IX
Xa

Front 466

How is plasmin activity limited to the fibrin plug?

Back 466

Plasmin binds lysines on fibrin

Front 467

1. How is TAFI activated?
2. How does TAFI function?

Back 467

1. TAFI is activated by thrombin-thrombomodulin
2. TAFI removes terminal arginine and lysine residues from fibrin, preventing plasmin from binding

Front 468

What component must be present in an allergen to elicit an immediate hypersensitivity reaction (Type 1)?

Back 468

Protein

Front 469

Which interleukin mediates allergic asthma independently of IgE and eosinophils?

Back 469

IL-13

Front 470

What is the cause of Grave's disease?

Back 470

Antibody activates TSH receptor

Front 471

What is the cause of Myasthenia Gravis?

Back 471

Antibody inactivates AChR

Front 472

1. Which form of hypersensitivity is the tetanus toxoid booster reaction?
2. What is it called?

Back 472

1. Type III
2. Arthus reaction

Front 473

1. What are the symptoms of DiGeorge?
2. Which chromosome is fucked up?

Back 473

C - cardiac dysfunction
A - abnormal facies
T - thymic aplasia
C - cleft palate
H - hypocalcemia
del22q11.2

Front 474

Mutations in C5-C9 lead to a increased risk of infection with what organism?

Back 474

Neisseria spp.

Front 475

Mutations in the IFN-g receptor lead to an incresed risk of infection with what organism?

Back 475

Atypical mycobacteria

Front 476

Mutations in TLR3 receptor lead to an increased risk of infection which what organism?

Back 476

Herpes simplex encephalitis

Front 477

What 4 components mediate type I hypersensitivity reactions?

Back 477

Th2, IgE, Mast Cells, Eosinophils

Front 478

Which organisms are patients with CGD likely to be infected with?

Back 478

S. aureus
E. coli
Apsergillus
Candida

Front 479

What is the genetic defect of X-linked agammaglobulinemia?

Back 479

Defective Bruton's tyrosine kinase

Front 480

Defective Bruton's tyrosine kinase leads to which syndrome?

Back 480

X-linked agammaglobulinemia

Front 481

What is the genetic defect of X-linked HyperIgM?

Back 481

Defective CD40L on T cells leads to no class switching

Front 482

Defective CD40L on T cells leads to what syndrome? How?

Back 482

X-linked HyperIgM since an absence of CD40L on T cells means there can be no class switching

Front 483

What are the four types of rejection?

Back 483

Hyperacute
Acute vascular
Acute cellular
Chronic

Front 484

1. Describe hyperacute rejection
2. What is a cause of hyperacute rejection?

Back 484

Occurs within hours due to preformed antibodies, such as ABO mismatch

Front 485

1. Describe acute vascular rejection
2. What is a cause of acute vascular rejection?

Back 485

1. Occurs in days to weeks, presents with vasculitis
2. Recognition of endothelial antigens

Front 486

1. Describe acute cellular rejection
2. What is a cause of acute cellular rejection?

Back 486

1. Occurs in days to weeks, presents with parenchymal necrosis and lymphoid infiltration
2. Cytotoxic and delayed hypersensitivity response to alloantigens

Front 487

1. Describe chronic rejection
2. What is a cause of chronic rejection?

Back 487

1. Fibrosis of the organ
2. Cytokines released in response to alloantigens

Front 488

Myeloperoxidase deficiencies lead to impaired host defense to what organism?

Back 488

Candida

Front 489

What is Wiskott-Aldrich syndrome caused by?
What is Wiskott-Aldrich syndrome characterized by?

Back 489

1. Mutations in WAS protein, involved in cytoskeletal function, leads to decreased antibody production
2. Eczema, thrombocytopenia, immunodeficiency, bloody diarrhea

Front 490

What are the two effects of APC?

Back 490

1. Deactivate FV and FVIII
2. Deactivate PAI-1