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SBL > WBC, Thymus, LN, and Spleen > Flashcards

WBC, Thymus, LN, and Spleen Flashcards

1
Q

Myeloid tissues

A

bone marrow and cells derived from it such as red cells platelets, granulocytes, and monocytes

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2
Q

Lymphoid tissues

A

thymus, lymph node, spleen

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3
Q

Origin of formed elements of blood

A

hematopoietic stem cells

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4
Q

What two properties of HSCs are required for the maintenance of hematopoiesis?

A

pluripotency and capacity for self-renewal

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5
Q

IL-5 triggers the production of which type of mature cell

A

eosinophil

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6
Q

Thrombopoietin triggers the production of which type of mature cell

A

megakaryocyte

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7
Q

Ertythropoietin triggers the production of which type of mature cell

A

Erythrocyte

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8
Q

Embryonic lineage of HSCs

A

mesonephros, migrates to liver and eventually bone marrow

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9
Q

Three main types of leukocytes

A

monocytes, granulocytes, lymphocytes

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10
Q

Normal WBC count

A

4.8 - 10.8 x10^3/uL

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11
Q

Normal granulocytes

A

40-70%

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12
Q

Normal RBC

A

4.3-5 in men, 3.5-5 in women x10^6

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13
Q

Normal platelets

A

150-450x10^3/uL

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14
Q

Lymphocyte percentage at birth

A

30%

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15
Q

Lymphocyte percentage 4-6mo

A

60%

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16
Q

Lymphocyte percentage 4 years

A

50%

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17
Q

Lymphocyte percentage by 6 years

A

40%

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18
Q

Lymphocyte percentage by 8 years

A

30%

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19
Q

Why are older persons more at risk for decreased immunologic capability?

A

dysregulation of T lymphocyte function, perhaps due to thymic atrophy

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20
Q

Neutrophil count

A

2-7x10^9, 40-80%

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21
Q

Lymphocytes count

A

1-3x10^9, 20-40%

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22
Q

Monocytes count

A

0.2-1.0x10^9, 2-10%

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23
Q

Eosinophil count

A

0.02-0.5x10^9, 1-6%

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24
Q

Basophil count

A

0.02-0.1x10^9, <1-2%

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25
Q

Definition of sinusoid

A

vascular structure, capillary with fenestrated endothelium with greatly enlarged diameter and tortuous path

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26
Q

How are senescent platelets eliminated?

A

phagocytosis in the spleen

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27
Q

Lifespan of circulating platelets

A

7-10 days

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28
Q

RBC progenitors are regulated by what hormone?

A

erythropoietin

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29
Q

What happens to EPO levels when hgb falls below 10gm/dL

A

increases logarithmically

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30
Q

What percentage of the red cell population do reticulocytes make up?

A

~2%

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31
Q

How are senescent red cells removed?

A

phagocytosis that line sinusoids of splenic red pulp, iron content is recycled

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32
Q

Where does a monocyte differentiate?

A

in tissues

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33
Q

What is the precursor cell of a macrophage?

A

monocyte

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34
Q

Percent of lymphocyte population that are CD4

A

32-56%

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35
Q

Percent of lymphocyte population that are CD8

A

17-40%

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36
Q

Percent of lymphocyte population that are B cells

A

4-20%

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37
Q

Percent of lymphocyte population that are NK cells

A

4-18%

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38
Q

What is Hct a measure of?

A

red cell mass, RBCs as % of blood volume

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39
Q

Major blood proteins

A

albumin, globulins, fibrinogen

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40
Q

Function of albumin

A

create and maintain oncotic pressure, transport insoluble molecules

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41
Q

function of globulins

A

disparate functions and major immunologic role

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42
Q

Function of fibrinogen

A

blood coag

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43
Q

Proliferative white cell disorder

A

expansion of leukocytes

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44
Q

Leukopenia

A

deficiency of leukocytes

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45
Q

Types of proliferative disorders

A

reactive and neoplastic

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46
Q

Diseases associated with lymphopenia

A

HIV, chronic inflammation, acute viral infections

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47
Q

Cause of neutropenia/agranulocytosis

A

inadequate production or increased destruction due to aplastic anemia, drug suppression, congenital conditions, immunologic mediated injury, splenomegaly, and increased peripheral utilization

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48
Q

Clinical features of neutropenia

A

malaise, chills, fever, marked weakness and fatigability, increased infections

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49
Q

Excessive destruction of neutrophils may cause what morphological changes in the bone marrow

A

hypercellularity due to a compensatory increase in granulocytic precursors

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50
Q

Infections commonly seen in agranulocytosis

A

ulcerating necrotizing lesions, invasive infections in lung, kidney, urinary tract, Candida and Aspergillus infections

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51
Q

Leukocytosis

A

increase in number of white cells in the blood

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52
Q

What influences the peripheral blood leukocyte count?

A

amount of production in the marrow, rate of release from marrow stores, proportion of cells adherent to vessel walls at any time, rate of extravasation

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53
Q

What things may increase WBC production in bone marrow?

A

chronic infection or inflammation, paraneoplastic or myeloproliferative disorders

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54
Q

What things may cause an increased release of WBC from marrow stores?

A

endotoxemia, infection, hypoxia

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55
Q

What things may cause decreased margination of WBC?

A

exercise, catecholamines

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56
Q

What may caused decreased extravasation of WBC into tissues?

A

glucocorticoids

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57
Q

What types of white cells tend to respond to acute bacterial infections?

A

neutrophils

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58
Q

What type of white cells tend to respond to allergic or autoimmune disorders?

A

Eosinophils

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59
Q

What types of white cells tend to respond to myeloproliferative diseases?

A

basophils

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60
Q

What type of white cells tend to respond to chronic infections and autoimmune disorders?

A

monocytes

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61
Q

What type of white cells tend to respond to viral infections?

A

lymphocytes

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62
Q

Cells that respond to B. pertussis

A

lymphocytes

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63
Q

Morphologic changes seen in sepsis or severe inflammatory disorders

A

toxic granulations, Döhle bodies (dilated ER), and cytoplasmic vacuoles

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64
Q

Lymphadenitis

A

enlarged, inflamed lymph nodes

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65
Q

Follicular hyperplasia

A

large germinal centers surrounded by a collar of small resting naive B cells

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66
Q

Paracortical hyperplasia

A

stimulated by T-cell mediated response, hypertrophy, presence of immunoblasts

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67
Q

sinus histiocytosis

A

increase in number and size of cells that line lymphatic sinusoids

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68
Q

cells activated in hemphagocytic lymphohistiocytosis

A

macrophages and CD8+ t cells

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69
Q

HLH defined labs

A

anemia, thrombocytopenia, high ferritin, soluble IL-2, elevated LFTs and triglyceride levels

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70
Q

acute myeloid leukemia

A

immature progenitor cells accumulate in bone marrow

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71
Q

myelodysplastic syndromes

A

infective hematopoiesis and peripheral blood cytopenias

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72
Q

chronic myeloproliferative disorders

A

increased production of terminally differentiated myeloid elements leads to elevated peripheral blood counts

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73
Q

What do conventional dendritic cells produce?

A

IL-12, IL-6, TNF, chemokines

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74
Q

What do plasmacytoid dendritic cells produce?

A

IFN-alpha

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75
Q

Etiologic factors in white cell neoplasia

A

chromosomal translocations, genetic factors, viruses, chronic inflammation, iatrogenic factors, smoking

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76
Q

Why are proto-oncogenes often activated in lymphoid cells?

A

errors during ag-receptor gene rearrangement and diversification

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77
Q

Carcinomas arise from…

A

squamous epithelium, glandular epithelium

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78
Q

Sarcomas arise from…

A

mesenchyme

79
Q

How does the presence of oncoproteins affect cell growth and maturation?

A

blocks normal maturation, turns on pro-growth signaling pathways, protects the cell from apoptosis

80
Q

Definition of differentiation

A

degree to which a neoplasm resembles tissue from which it arises or is derived

81
Q

Is tumor vascularity a general feature of lymphomas and leukemias?

A

No!

82
Q

Is differentiation a useful tool in determining severity of hematologic neoplasias?

A

No

83
Q

Function of B lymphocyte

A

neutralization of microbe, phagocytosis, complement activation

84
Q

Function of helper T lymphocyte

A

activation of macrophages, inflammation, activation of T and B lymphocytes

85
Q

Function of cytotoxic T lymphocyte

A

killing of infected cell

86
Q

Function of regulatory T lymphocyte

A

suppression of immune response

87
Q

Function of NK cell

A

killing of infected cell

88
Q

Role of Th1 cells

A

IFN-gamma, IL-2, TNF-beta to activate macrophages

89
Q

Role of Th2 cells

A

produce IL-4, IL-5, IL-10, and IL-13; ab production, activate eosinophils, inhibit macrophages

90
Q

Role of Th17 cells

A

produce IL-17

91
Q

High endothelial venules

A

specialized blood vessels which support migration of lymphocytes from blood to lymphoid organs

92
Q

CA associated with HTLV-1

A

adult t-cell leukemia/lymphoma

93
Q

CA associated with EBV

A

Burkitt lymphoma, HL, NK neoplasms, B cell lymphoma

94
Q

CA associated with HHV-8

A

Kaposi’s sarcoma, B cell lymphoma

95
Q

Leukemia

A

neoplasms that present with widespread involvement of the bone marrow and peripheral blood

96
Q

Lymphoma

A

proliferations that arise as discreet tissue masses

97
Q

Initial clinical presentation of most lymphomas

A

enlarged, non-tender lymph nodes

98
Q

Most common plasma cell neoplasm

A

multiple myeloma

99
Q

5 categories of lymphoid neoplasms

A

precursor b-cell neoplasms, peripheral b-cell neoplasms, precursor t-cell neoplasms, peripheral t-cell and NK-cell neoplasms, hodgkin’s lymphoma

100
Q

How are reactive and malignant proliferations distinguished from one another?

A

malignant - monoclonal population

reactive - polyclonal population

101
Q

Origin of most lymphoid neoplasms

A

B-cell

102
Q

Spread of HL vs. NHL

A

HL spread is orderly, while NHL spreads widely in a less predictable fashion

103
Q

Neoplasms of immature B and T cells

A

B-ALL, T-ALL

104
Q

Neoplasms of mature B cells

A

Burkitt lymphoma, diffuse large B cell lymphoma, extranodal margin zone lymphoma, follicular lymphoma, hairy cell leukemia, mantle cell lymphoma, multiple myeloma, SLL/CLL

105
Q

Neoplasms of mature T cells or NK cells

A

Adult T-cell leukemia, peripheral t-cell lymphoma, anaplastic large cell lymphoma, extra-nodal NK/T-cell lymphoma, mycosis fungoides, lymphocytic leukemia

106
Q

Most frequent site of primary extranodal lymphoma

A

GI tract

107
Q

Extranodal lymphoma

A

involves sites other than lymph nodes, spleen, thymus, pharyngeal lymphatic ring (HL spleen involvement is considered nodal)

108
Q

Most common CA of children

A

ALL

109
Q

High risk groups for ALL

A

white or hispanic ethnicity, male>female, peak incidence at age 3 (B-ALL) or adolescence (T-ALL)

110
Q

Typical T-ALL genotype

A

NOTCH1 gain-of-function mutation

111
Q

Typical B-ALL genotype

A

t(12;21)

112
Q

Favorable ALL prognostic factors

A

age 2-10, low wbc count, hyperdiploidy, trisomies of 4, 7, or 10, t(12;21)

113
Q

Unfavorable ALL prognostic factors

A

under age 2, adolescent or adult, blasts>100,000

114
Q

Most common Leukemia of adults in western world

A

chronic lymphocytic leukemia

115
Q

Unfavorable CLL/SLL prognostic factors

A

presence of deletions 11q and 17p, lack of somatic hypermutation, ZAP-70 expression, NOTCH1 mutation

116
Q

Richter Syndrome

A

transformation of CLL to diffuse large b cell lymphoma

117
Q

Follicular lymphoma genotype

A

t(14;18), involves BCL2

118
Q

Most common form of NHL

A

Diffuse large B-cell lymphoma

119
Q

Frequent pathogenic event in DLBCL

A

dysregulation of BCL6

120
Q

Potential genomic translocation in DLBCL

A

t(14;18)

121
Q

Immunodeficiency-associated LBCL

A

occurs in setting of sever T-cell immunodeficiency, B cells infected with EBV

122
Q

Primary effusion lymphoma

A

pleural or ascitic effusion, contain clonal IgH gene rearrangements, often infected with KSHV/HHV-8

123
Q

Translocation in burkitt lymphoma

A

MYC translocation on C8, upregulates Warburg effect

124
Q

Primary virus responsible for Burkitt lymphoma

A

EBV

125
Q

Most common plasma neoplasma

A

Myeloma

126
Q

Bence-Jones proteins

A

free light chains excreted in the urine

127
Q

Rearrangements of what locus are responsible for oncogenes in multiple myeloma

A

IgH

128
Q

Major pathologic feature of multiple myeloma

A

bone resorption and destruction

129
Q

What causes the rouleaux formation in multiple myeloma

A

high level of M proteins

130
Q

How is multiple myeloma definitively diagnosed?

A

bone marrow examination contains >30% plasma cells with considerable atypia, >3gm/dL Ig and >6mg/dL of urinary Bence-Jones proteins

131
Q

Solitary myeloma

A

solitary lesion presents in bone or soft tissue, modest elevations of M proteins

132
Q

Smoldering myeloma

A

plasma cells make up 10-30% of bone marrow, M protein is >3gm/dL, but pts unsymptomatic

133
Q

Monoclonal Gammopathy of Uncertain Significance

A

pts asymptomatic, M protein <3gm/dL; may progress to multiple myeloma

134
Q

Most common excess M protein in multiple myeloma

A

IgA and IgG3

135
Q

Waldenström macroglobulinemia

A

hyperviscosity syndrome caused by increase IgM

136
Q

Genetic change in lymphoblasmacytic lymphoma

A

MYD88 mutation

137
Q

Hyperviscosity syndrome

A

increase in blood viscosity resulting in retinopathy, neurologic sxs, and spontaneous bleeding

138
Q

Mantle Cell Lymphoma translocation

A

t(11;14), involves IgH locus and cyclin D1 locus leading to an overexpression of cyclin D1

139
Q

Important/Distinguishing characteristics of lymphomas that occur at extranodal sites

A

arise within tissues involved in chronic inflammation, remain localized for prolonged periods of time, regree is inciting agent is eradicated

140
Q

Genomic mutation in hairy cell leukemias

A

BRAF

141
Q

Genetic mutation in Anaplastic large cell lymphoma (ALK positive)

A

ALK gene rearrangement on chromosome 2p23

142
Q

Adult T-cell leukemia

A

neoplasm of CD4+ T-cells infected with HTLV-1, occurs where virus is endemic

143
Q

Mycosis fungoides

A

tumor of CD4 that homes to the skin

144
Q

Large granular lymphocytic leukemia

A

large lymphocytes with abundant blue cytoplasm and scant azurophilic granules; neutropenia and anemia are common

145
Q

Extranodal NK/T-Cell lymphoma

A

associated with EBV, surrounds small vessels leading to ischemic necrosis; typically presents as NP mass

146
Q

Nodular sclerosis HL

A

65-70% of cases, lower cervical and supraclavicular cites, frequent mediastinal involvement

147
Q

Mixed cellularity HL

A

20-25% of cases. RS cells abundant, mostly infected by EBV, systemic symptoms and advanced tumor stage

148
Q

Lymphocyte-rich HL

A

uncommon, 40% of cases associated with EBV

149
Q

Lymphocyte depletion HL

A

least common form, >90% EBV involvement, predominate in elderly and people with HIV

150
Q

Lymphocyte predominance HL

A

CD30-, L&H cells rather than RS cells, resembles large B cell lymphoma

151
Q

Activated TF in HL

A

NF-kB

152
Q

Reed-Sterberg cell morphology

A

large cell with multiple nuclei or a single nucleus with multiple lobes, with a large inclusion-like nucleolus

153
Q

Nodular sclerosis HL morphology

A

lacunar variant RS cells and deposition of collagen that divide LN into circumscribed nodules

154
Q

Mixed cellularity HL morphology

A

diagnostic RS and mononuclear variants, heterogenous cell infiltrate

155
Q

Lymphocyte rich type HL morphology

A

reactive lymphocytes make up vast majority of cell infiltrate, mononuclear variants, RS cells

156
Q

Lymphocyte depletion type HL morphology

A

abundance of RS cells

157
Q

Lymphocyte predominance HL morphology

A

L&H cells, eosinophils and plasma cells are usually scant or absent

158
Q

immunophenotype L&H cells

A

CD20 and BCL6

159
Q

typical spread of HL

A

nodal, splenic, hepatic, marrow and other tissues

160
Q

Stage I HL/NHL

A

involvement of single LN region or extralymphatic organ

161
Q

Stage II HL/NHL

A

involvement of two or more LN regions on same side of diaphragm

162
Q

Stage III HL/NHL

A

involvement of LN regions on both sides of diaphragm with or without extralymphatic involvement

163
Q

Stage IV HL/NHL

A

diffuse involvement of one or more extralymphatic organ

164
Q

Cell origin of myeloid neoplasia

A

hematopoietic progenitor cells

165
Q

Three overarching categories of myeloid neoplasia

A

Acute myeloid leukemias, myelodysplatic syndromes, myeloproliferative disorders

166
Q

Manifestations of myeloid neoplasms are dependent on…

A

position of transformed cell within hierarchy of progenitors, effect of transforming events on differentiation

167
Q

Four major subtypes of AML

A

AML with genetic aberrations, AML with MDS-like features, therapy related AML, NOS AML

168
Q

Favorable genetic aberrations AML

A

t(8;21), inv(16), t(15;17)

169
Q

Poor genetic aberrations AML

A

t(11q23;v)

170
Q

Genetic aberrations in AML cells cause what down stream effects?

A

activation of growth factor pathways, mutations in cohesin and IDH1/IDH2, p53 errors

171
Q

Pseudo-Pelger-Hüet cells

A

neutrophils with only two nuclear lobes commonly observed in MDS

172
Q

Common pathogenic feature of meyloproliferative disorders

A

presence of mutated, constitutively activated tyrosine kinase

173
Q

Common features of MPD

A

increased proliferative drive, extramedullary hematopoiesis, progresses to marrow fibrosis and peripheral blood cytopenias, transformation to acute leukemias

174
Q

Genetic aberration of CML

A

BCR-ABL gene created from t(9;22), philadelphia chromosome

175
Q

Genetic aberration of polycythemia vera

A

JAK2 point mutation

176
Q

PCV EPO levels

A

most cases are significantly suppressed

177
Q

Hallmark of primary myelofibrosis

A

development of obliterative marrow fibrosis by non-neoplastic fibroblasts

178
Q

What cytokine growth factors are typically produced by abnormal megakaryocytes in primary myelofibrosis?

A

PDGF, TGF-B

179
Q

Hand-Schuller-Christian triad

A

calvarial bone defects, diabetes insipidus, exophthalmos

180
Q

Four major functions of the spleen

A

removal of unwanted elements, major secondary organ of the immune system(ab production), source of hematopoietic cells, sequesters a portion of the formed blood elements

181
Q

Common symptoms associated with splenomegaly

A

LUQ mass, GI/abd discomfort, anemia, leukopenia, thrombocytopenia

182
Q

Reasons for congestive splenomegaly

A

systemic or central venous congestion, cirrhosis of the liver, obstruction of extrahepatic portal or splenic vein

183
Q

Causes of splenic infarcts

A

cardiac emboli, sickle cell disease, infectious endocarditis

184
Q

Outcome of reduced splenic function?

A

Increased risk of infections with encapsulated bacteria

185
Q

DiGeorge syndrome

A

thymic hypoplasia or agenesis accompanied by parathyroid developmental failures, 22q11 deletion

186
Q

Thymic follicular hyperplasia

A

appearance of B-cell germinal centers in thymus

187
Q

Thymoma

A

tumor of thymic epithelial cells

188
Q

Cause of thymoma symptoms

A

impingement on mediastinal structurs, often present in pts with myasthenia gravis

189
Q

Types of thymomas

A

cytologically benign and non-invasive, cytologically benign but invasive, cytologically malignant

190
Q

Most common variant of malignant thymic carcinoma

A

squamous cell carcinomas

191
Q

Noninvasive thymoma morphology

A

medullary-type epithelial cells or mixture of medullary and cortical type epithelial cells

192
Q

Invasive thymoma morphology

A

epithelial cells with abundant cytoplasm and rounded vesicular nuclei

193
Q

Lymphoepithelioma morphology

A

lymphocytic infiltrates intrinsic to epithelial neoplastic component

SBL (21 decks)

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