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
2
Q
Lymphoid tissues
A
thymus, lymph node, spleen
3
Q
Origin of formed elements of blood
A
hematopoietic stem cells
4
Q
What two properties of HSCs are required for the maintenance of hematopoiesis?
A
pluripotency and capacity for self-renewal
5
Q
IL-5 triggers the production of which type of mature cell
A
eosinophil
6
Q
Thrombopoietin triggers the production of which type of mature cell
A
megakaryocyte
7
Q
Ertythropoietin triggers the production of which type of mature cell
A
Erythrocyte
8
Q
Embryonic lineage of HSCs
A
mesonephros, migrates to liver and eventually bone marrow
9
Q
Three main types of leukocytes
A
monocytes, granulocytes, lymphocytes
10
Q
Normal WBC count
A
4.8 - 10.8 x10^3/uL
11
Q
Normal granulocytes
A
40-70%
12
Q
Normal RBC
A
4.3-5 in men, 3.5-5 in women x10^6
13
Q
Normal platelets
A
150-450x10^3/uL
14
Q
Lymphocyte percentage at birth
A
30%
15
Q
Lymphocyte percentage 4-6mo
A
60%
16
Q
Lymphocyte percentage 4 years
A
50%
17
Q
Lymphocyte percentage by 6 years
A
40%
18
Q
Lymphocyte percentage by 8 years
A
30%
19
Q
Why are older persons more at risk for decreased immunologic capability?
A
dysregulation of T lymphocyte function, perhaps due to thymic atrophy
20
Q
Neutrophil count
A
2-7x10^9, 40-80%
21
Q
Lymphocytes count
A
1-3x10^9, 20-40%
22
Q
Monocytes count
A
0.2-1.0x10^9, 2-10%
23
Q
Eosinophil count
A
0.02-0.5x10^9, 1-6%
24
Q
Basophil count
A
0.02-0.1x10^9, <1-2%
25
Definition of sinusoid
vascular structure, capillary with fenestrated endothelium with greatly enlarged diameter and tortuous path
26
How are senescent platelets eliminated?
phagocytosis in the spleen
27
Lifespan of circulating platelets
7-10 days
28
RBC progenitors are regulated by what hormone?
erythropoietin
29
What happens to EPO levels when hgb falls below 10gm/dL
increases logarithmically
30
What percentage of the red cell population do reticulocytes make up?
~2%
31
How are senescent red cells removed?
phagocytosis that line sinusoids of splenic red pulp, iron content is recycled
32
Where does a monocyte differentiate?
in tissues
33
What is the precursor cell of a macrophage?
monocyte
34
Percent of lymphocyte population that are CD4
32-56%
35
Percent of lymphocyte population that are CD8
17-40%
36
Percent of lymphocyte population that are B cells
4-20%
37
Percent of lymphocyte population that are NK cells
4-18%
38
What is Hct a measure of?
red cell mass, RBCs as % of blood volume
39
Major blood proteins
albumin, globulins, fibrinogen
40
Function of albumin
create and maintain oncotic pressure, transport insoluble molecules
41
function of globulins
disparate functions and major immunologic role
42
Function of fibrinogen
blood coag
43
Proliferative white cell disorder
expansion of leukocytes
44
Leukopenia
deficiency of leukocytes
45
Types of proliferative disorders
reactive and neoplastic
46
Diseases associated with lymphopenia
HIV, chronic inflammation, acute viral infections
47
Cause of neutropenia/agranulocytosis
inadequate production or increased destruction due to aplastic anemia, drug suppression, congenital conditions, immunologic mediated injury, splenomegaly, and increased peripheral utilization
48
Clinical features of neutropenia
malaise, chills, fever, marked weakness and fatigability, increased infections
49
Excessive destruction of neutrophils may cause what morphological changes in the bone marrow
hypercellularity due to a compensatory increase in granulocytic precursors
50
Infections commonly seen in agranulocytosis
ulcerating necrotizing lesions, invasive infections in lung, kidney, urinary tract, Candida and Aspergillus infections
51
Leukocytosis
increase in number of white cells in the blood
52
What influences the peripheral blood leukocyte count?
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
53
What things may increase WBC production in bone marrow?
chronic infection or inflammation, paraneoplastic or myeloproliferative disorders
54
What things may cause an increased release of WBC from marrow stores?
endotoxemia, infection, hypoxia
55
What things may cause decreased margination of WBC?
exercise, catecholamines
56
What may caused decreased extravasation of WBC into tissues?
glucocorticoids
57
What types of white cells tend to respond to acute bacterial infections?
neutrophils
58
What type of white cells tend to respond to allergic or autoimmune disorders?
Eosinophils
59
What types of white cells tend to respond to myeloproliferative diseases?
basophils
60
What type of white cells tend to respond to chronic infections and autoimmune disorders?
monocytes
61
What type of white cells tend to respond to viral infections?
lymphocytes
62
Cells that respond to B. pertussis
lymphocytes
63
Morphologic changes seen in sepsis or severe inflammatory disorders
toxic granulations, Döhle bodies (dilated ER), and cytoplasmic vacuoles
64
Lymphadenitis
enlarged, inflamed lymph nodes
65
Follicular hyperplasia
large germinal centers surrounded by a collar of small resting naive B cells
66
Paracortical hyperplasia
stimulated by T-cell mediated response, hypertrophy, presence of immunoblasts
67
sinus histiocytosis
increase in number and size of cells that line lymphatic sinusoids
68
cells activated in hemphagocytic lymphohistiocytosis
macrophages and CD8+ t cells
69
HLH defined labs
anemia, thrombocytopenia, high ferritin, soluble IL-2, elevated LFTs and triglyceride levels
70
acute myeloid leukemia
immature progenitor cells accumulate in bone marrow
71
myelodysplastic syndromes
infective hematopoiesis and peripheral blood cytopenias
72
chronic myeloproliferative disorders
increased production of terminally differentiated myeloid elements leads to elevated peripheral blood counts
73
What do conventional dendritic cells produce?
IL-12, IL-6, TNF, chemokines
74
What do plasmacytoid dendritic cells produce?
IFN-alpha
75
Etiologic factors in white cell neoplasia
chromosomal translocations, genetic factors, viruses, chronic inflammation, iatrogenic factors, smoking
76
Why are proto-oncogenes often activated in lymphoid cells?
errors during ag-receptor gene rearrangement and diversification
77
Carcinomas arise from...
squamous epithelium, glandular epithelium
78
Sarcomas arise from...
mesenchyme
79
How does the presence of oncoproteins affect cell growth and maturation?
blocks normal maturation, turns on pro-growth signaling pathways, protects the cell from apoptosis
80
Definition of differentiation
degree to which a neoplasm resembles tissue from which it arises or is derived
81
Is tumor vascularity a general feature of lymphomas and leukemias?
No!
82
Is differentiation a useful tool in determining severity of hematologic neoplasias?
No
83
Function of B lymphocyte
neutralization of microbe, phagocytosis, complement activation
84
Function of helper T lymphocyte
activation of macrophages, inflammation, activation of T and B lymphocytes
85
Function of cytotoxic T lymphocyte
killing of infected cell
86
Function of regulatory T lymphocyte
suppression of immune response
87
Function of NK cell
killing of infected cell
88
Role of Th1 cells
IFN-gamma, IL-2, TNF-beta to activate macrophages
89
Role of Th2 cells
produce IL-4, IL-5, IL-10, and IL-13; ab production, activate eosinophils, inhibit macrophages
90
Role of Th17 cells
produce IL-17
91
High endothelial venules
specialized blood vessels which support migration of lymphocytes from blood to lymphoid organs
92
CA associated with HTLV-1
adult t-cell leukemia/lymphoma
93
CA associated with EBV
Burkitt lymphoma, HL, NK neoplasms, B cell lymphoma
94
CA associated with HHV-8
Kaposi's sarcoma, B cell lymphoma
95
Leukemia
neoplasms that present with widespread involvement of the bone marrow and peripheral blood
96
Lymphoma
proliferations that arise as discreet tissue masses
97
Initial clinical presentation of most lymphomas
enlarged, non-tender lymph nodes
98
Most common plasma cell neoplasm
multiple myeloma
99
5 categories of lymphoid neoplasms
precursor b-cell neoplasms, peripheral b-cell neoplasms, precursor t-cell neoplasms, peripheral t-cell and NK-cell neoplasms, hodgkin's lymphoma
100
How are reactive and malignant proliferations distinguished from one another?
malignant - monoclonal population
| reactive - polyclonal population
101
Origin of most lymphoid neoplasms
B-cell
102
Spread of HL vs. NHL
HL spread is orderly, while NHL spreads widely in a less predictable fashion
103
Neoplasms of immature B and T cells
B-ALL, T-ALL
104
Neoplasms of mature B cells
Burkitt lymphoma, diffuse large B cell lymphoma, extranodal margin zone lymphoma, follicular lymphoma, hairy cell leukemia, mantle cell lymphoma, multiple myeloma, SLL/CLL
105
Neoplasms of mature T cells or NK cells
Adult T-cell leukemia, peripheral t-cell lymphoma, anaplastic large cell lymphoma, extra-nodal NK/T-cell lymphoma, mycosis fungoides, lymphocytic leukemia
106
Most frequent site of primary extranodal lymphoma
GI tract
107
Extranodal lymphoma
involves sites other than lymph nodes, spleen, thymus, pharyngeal lymphatic ring (HL spleen involvement is considered nodal)
108
Most common CA of children
ALL
109
High risk groups for ALL
white or hispanic ethnicity, male>female, peak incidence at age 3 (B-ALL) or adolescence (T-ALL)
110
Typical T-ALL genotype
NOTCH1 gain-of-function mutation
111
Typical B-ALL genotype
t(12;21)
112
Favorable ALL prognostic factors
age 2-10, low wbc count, hyperdiploidy, trisomies of 4, 7, or 10, t(12;21)
113
Unfavorable ALL prognostic factors
under age 2, adolescent or adult, blasts>100,000
114
Most common Leukemia of adults in western world
chronic lymphocytic leukemia
115
Unfavorable CLL/SLL prognostic factors
presence of deletions 11q and 17p, lack of somatic hypermutation, ZAP-70 expression, NOTCH1 mutation
116
Richter Syndrome
transformation of CLL to diffuse large b cell lymphoma
117
Follicular lymphoma genotype
t(14;18), involves BCL2
118
Most common form of NHL
Diffuse large B-cell lymphoma
119
Frequent pathogenic event in DLBCL
dysregulation of BCL6
120
Potential genomic translocation in DLBCL
t(14;18)
121
Immunodeficiency-associated LBCL
occurs in setting of sever T-cell immunodeficiency, B cells infected with EBV
122
Primary effusion lymphoma
pleural or ascitic effusion, contain clonal IgH gene rearrangements, often infected with KSHV/HHV-8
123
Translocation in burkitt lymphoma
MYC translocation on C8, upregulates Warburg effect
124
Primary virus responsible for Burkitt lymphoma
EBV
125
Most common plasma neoplasma
Myeloma
126
Bence-Jones proteins
free light chains excreted in the urine
127
Rearrangements of what locus are responsible for oncogenes in multiple myeloma
IgH
128
Major pathologic feature of multiple myeloma
bone resorption and destruction
129
What causes the rouleaux formation in multiple myeloma
high level of M proteins
130
How is multiple myeloma definitively diagnosed?
bone marrow examination contains >30% plasma cells with considerable atypia, >3gm/dL Ig and >6mg/dL of urinary Bence-Jones proteins
131
Solitary myeloma
solitary lesion presents in bone or soft tissue, modest elevations of M proteins
132
Smoldering myeloma
plasma cells make up 10-30% of bone marrow, M protein is >3gm/dL, but pts unsymptomatic
133
Monoclonal Gammopathy of Uncertain Significance
pts asymptomatic, M protein <3gm/dL; may progress to multiple myeloma
134
Most common excess M protein in multiple myeloma
IgA and IgG3
135
Waldenström macroglobulinemia
hyperviscosity syndrome caused by increase IgM
136
Genetic change in lymphoblasmacytic lymphoma
MYD88 mutation
137
Hyperviscosity syndrome
increase in blood viscosity resulting in retinopathy, neurologic sxs, and spontaneous bleeding
138
Mantle Cell Lymphoma translocation
t(11;14), involves IgH locus and cyclin D1 locus leading to an overexpression of cyclin D1
139
Important/Distinguishing characteristics of lymphomas that occur at extranodal sites
arise within tissues involved in chronic inflammation, remain localized for prolonged periods of time, regree is inciting agent is eradicated
140
Genomic mutation in hairy cell leukemias
BRAF
141
Genetic mutation in Anaplastic large cell lymphoma (ALK positive)
ALK gene rearrangement on chromosome 2p23
142
Adult T-cell leukemia
neoplasm of CD4+ T-cells infected with HTLV-1, occurs where virus is endemic
143
Mycosis fungoides
tumor of CD4 that homes to the skin
144
Large granular lymphocytic leukemia
large lymphocytes with abundant blue cytoplasm and scant azurophilic granules; neutropenia and anemia are common
145
Extranodal NK/T-Cell lymphoma
associated with EBV, surrounds small vessels leading to ischemic necrosis; typically presents as NP mass
146
Nodular sclerosis HL
65-70% of cases, lower cervical and supraclavicular cites, frequent mediastinal involvement
147
Mixed cellularity HL
20-25% of cases. RS cells abundant, mostly infected by EBV, systemic symptoms and advanced tumor stage
148
Lymphocyte-rich HL
uncommon, 40% of cases associated with EBV
149
Lymphocyte depletion HL
least common form, >90% EBV involvement, predominate in elderly and people with HIV
150
Lymphocyte predominance HL
CD30-, L&H cells rather than RS cells, resembles large B cell lymphoma
151
Activated TF in HL
NF-kB
152
Reed-Sterberg cell morphology
large cell with multiple nuclei or a single nucleus with multiple lobes, with a large inclusion-like nucleolus
153
Nodular sclerosis HL morphology
lacunar variant RS cells and deposition of collagen that divide LN into circumscribed nodules
154
Mixed cellularity HL morphology
diagnostic RS and mononuclear variants, heterogenous cell infiltrate
155
Lymphocyte rich type HL morphology
reactive lymphocytes make up vast majority of cell infiltrate, mononuclear variants, RS cells
156
Lymphocyte depletion type HL morphology
abundance of RS cells
157
Lymphocyte predominance HL morphology
L&H cells, eosinophils and plasma cells are usually scant or absent
158
immunophenotype L&H cells
CD20 and BCL6
159
typical spread of HL
nodal, splenic, hepatic, marrow and other tissues
160
Stage I HL/NHL
involvement of single LN region or extralymphatic organ
161
Stage II HL/NHL
involvement of two or more LN regions on same side of diaphragm
162
Stage III HL/NHL
involvement of LN regions on both sides of diaphragm with or without extralymphatic involvement
163
Stage IV HL/NHL
diffuse involvement of one or more extralymphatic organ
164
Cell origin of myeloid neoplasia
hematopoietic progenitor cells
165
Three overarching categories of myeloid neoplasia
Acute myeloid leukemias, myelodysplatic syndromes, myeloproliferative disorders
166
Manifestations of myeloid neoplasms are dependent on...
position of transformed cell within hierarchy of progenitors, effect of transforming events on differentiation
167
Four major subtypes of AML
AML with genetic aberrations, AML with MDS-like features, therapy related AML, NOS AML
168
Favorable genetic aberrations AML
t(8;21), inv(16), t(15;17)
169
Poor genetic aberrations AML
t(11q23;v)
170
Genetic aberrations in AML cells cause what down stream effects?
activation of growth factor pathways, mutations in cohesin and IDH1/IDH2, p53 errors
171
Pseudo-Pelger-Hüet cells
neutrophils with only two nuclear lobes commonly observed in MDS
172
Common pathogenic feature of meyloproliferative disorders
presence of mutated, constitutively activated tyrosine kinase
173
Common features of MPD
increased proliferative drive, extramedullary hematopoiesis, progresses to marrow fibrosis and peripheral blood cytopenias, transformation to acute leukemias
174
Genetic aberration of CML
BCR-ABL gene created from t(9;22), philadelphia chromosome
175
Genetic aberration of polycythemia vera
JAK2 point mutation
176
PCV EPO levels
most cases are significantly suppressed
177
Hallmark of primary myelofibrosis
development of obliterative marrow fibrosis by non-neoplastic fibroblasts
178
What cytokine growth factors are typically produced by abnormal megakaryocytes in primary myelofibrosis?
PDGF, TGF-B
179
Hand-Schuller-Christian triad
calvarial bone defects, diabetes insipidus, exophthalmos
180
Four major functions of the spleen
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
Common symptoms associated with splenomegaly
LUQ mass, GI/abd discomfort, anemia, leukopenia, thrombocytopenia
182
Reasons for congestive splenomegaly
systemic or central venous congestion, cirrhosis of the liver, obstruction of extrahepatic portal or splenic vein
183
Causes of splenic infarcts
cardiac emboli, sickle cell disease, infectious endocarditis
184
Outcome of reduced splenic function?
Increased risk of infections with encapsulated bacteria
185
DiGeorge syndrome
thymic hypoplasia or agenesis accompanied by parathyroid developmental failures, 22q11 deletion
186
Thymic follicular hyperplasia
appearance of B-cell germinal centers in thymus
187
Thymoma
tumor of thymic epithelial cells
188
Cause of thymoma symptoms
impingement on mediastinal structurs, often present in pts with myasthenia gravis
189
Types of thymomas
cytologically benign and non-invasive, cytologically benign but invasive, cytologically malignant
190
Most common variant of malignant thymic carcinoma
squamous cell carcinomas
191
Noninvasive thymoma morphology
medullary-type epithelial cells or mixture of medullary and cortical type epithelial cells
192
Invasive thymoma morphology
epithelial cells with abundant cytoplasm and rounded vesicular nuclei
193
Lymphoepithelioma morphology
lymphocytic infiltrates intrinsic to epithelial neoplastic component
