wk 1 Flashcards
(138 cards)
1
Q
continuous, regulated process of blood cell
production
A
HEMATOPOIESIS
2
Q
- In healthy adults hematopoiesis is
restricted primarily to the
A
bone marrow.
3
Q
can be characterized as a select
distribution of embryonic cells in specific
sites that rapidly change during
development
A
HEMATOPOIETIC SYSTEM
4
Q
cell is capable of self-renewal (i.e.,
replenishment) and directed differentiation
into all required cell lineages.
A
HEMATOPOIETIC STEM
5
Q
- 19th day of embryonic development
A
MESOBLASTIC PHASE
6
Q
Some of the cells from primitive
erythroblasts in the central cavity of the yolk
sac
A
MESOBLASTIC PHASE
7
Q
MESOBLASTIC PHASE
A
19th day of embryonic development
- Cells from mesoderm migrate to the yolk
sac
- Some of the cells from primitive
erythroblasts in the central cavity of the yolk
sac
Primitive erythroblasts are important
Early embryonic development
- Produces hemoglobin needed for delivery of
oxygen to rapidly developing embryonic
tissues
● Cells of mesodermal origin also migrate to
the aorta-gonadmesonephros (AGM) region
and give rise to hematopoietic stem cells
(HSCs) for definitive or permanent adult
hematopoiesis
8
Q
only site of definitive hematopoiesis
during embryonic development.
A
AGM Region
9
Q
- 5 to 7 gestational weeks
A
HEPATIC PHASE
10
Q
clusters of developing erythroblasts,
granulocytes, and monocytes colonizing the
fetal liver, thymus, spleen, placenta, and
ultimately the bone marrow space in the
final medullary phase.
A
HEPATIC PHASE
11
Q
- Developing erythroblasts signal the
beginning of definitive hematopoiesis
with decline inprimitive hematopoiesis of
yolk sac - Lymphoid cells begin to appear
A
HEPATIC PHASE
12
Q
Occurs extravascularly, with the liver
remaining the major site of
hematopoiesis during the second trimester
of fetal life
A
HEPATIC PHASE
13
Q
Hematopoiesis in AGM region and yolk sac
disappear during this stage
A
HEPATIC PHASE
14
Q
peak and min activity iof hepatic hase
A
Hematopoiesis in fetal liver reaches its
peak by third month of fetal
development, gradually declines after
sixth month , retaining minimal activity until
1 to 2 weeks after birth
15
Q
Hematopoietic activity, especially myeloid
activity, is apparent during this stage
A
MEDULLARY PHASE
16
Q
14th and 15th month begins between fourth
and fifth month of fetal developme
A
MEDULLARY PHASE
17
Q
Myeloid-to-erythroid ratio gradually
approaches
A
3:1 to 4:1 (normal adult levels)
18
Q
By the end of ___________, bone
marrow becomes the primary site of
hematopoiesis
A
By the end of 24 weeks’ gestation, bone
marrow becomes the primary site of
hematopoiesis
19
Q
consists of the bone
marrow and thymus and is where T and B
lymphocytes are derived
A
Primary lymphoid tissue -
20
Q
where lymphoid
cells respond to foreign antigens, consists of the
spleen, lymph nodes, and mucosa-associated
lymphoid tissue
A
Secondary lymphoid tissue -
21
Q
- projections of calcified bone
A
TRABACULAE
22
Q
forming a three dimensional matrix
resembling a honeycomb
A
Trabeculae
23
Q
Two major componensts of normal marrow:
A
Red marrow
- active marrow
- composed of developing blood cells and
their progenitors
Yellow Marrow
- inactive marrow
- composed primarily of adipocytes (fat cells)
with undeffirentiated mesenchymel cells and
macrophages - scattered throughout the red marrow so that
in adults, there is approximately equal amounts of red and yellow marrow in these
areas - capable of reverting back to active marrow
in cases of increased demand on the bone
marrow, such as in excessive blood loss or
hemolysi
24
Q
WHEMNN - all
the bones in the body contain primarily red (active)
marrow
A
nfancy and Early Childhoood
25
adipocytes
become more abundant and begin to occupy the
spaces in the long bones previously dominated by
active marrow.
Between 5 and 7 years of age - a
26
rocess of replacing the active marrow by
adipocytes (yellow marrow) during
development
Retrogression
27
Bone Marrow Composition
STROMAL, HEMATOPOIOTIC, BV
28
reguation of hematopoietic system and
progenitor cell survival and differentiation
STROMAL CELL
29
they play a role in regulating the volume of
the marrow in which active hematopoiesis
occur
Adipocytes
30
ecrete cytokines or growth factors (may
positively stimulate HSC numbers and bone
homeostasis
ADIPOCYTE
31
form an incomplete layer of cells on the
abluminal surface of the vascular sinuses
Reticular Aventitial Cells
32
extend long, reticular fibers into the
perivascular space that form a supporting
lattice for the developing hematopoietic cells
Reticular Aventitial Cells
33
composed of the hematopoietic cells and
macrophages arranged in extravascular CORDS
RED MARROW
34
spaces between the vascular sinuses IN RED MARROW
CORD
35
spaces between the vascular sinuses.
CORDS
36
erythroid precursors
- develop in small clusters, and the more
mature forms are located adjacent to the
outer surfaces of the vascular sinuses.
Erythroblasts
37
adjacent to the walls of the vascular
sinuses
Megakaryotes
38
acilitates the release of platelets into the
lumen of the sinus
Megakaryotes
39
Immature myeloid (granulocytic) cells
LOC
- through the metamyelocyte stage are
located deep within the cords.
- As they mature, they move closer to the
vascular sinuses
40
Supplement nutrient and oxygen
requirements of the marrow
Periosteal arteries
41
Periosteal arteries
ENTER BLOODSTREAM VIA
FORAMINA
42
Arteriole branches that enter the inner lining
of cortical bone (endosteum) form sinusoids
endosteum (endosteal beds),
43
provides nutrients for
osseous bone and marrow
Periosteal arteries
44
Hematopoietic cells located in endosteal
bed receive their nutrients from
nutrient
arterY
45
form an extracellular matrix in the
niche to promote cell adhesion and regulate HSCs
through complex signaling networks involving
cytokines, adhesion molecules, and maintenance
proteins
Stromal cells
46
regulate migration of HSC to vascular
niche
CXCL12
47
major site of blood cell production during the
second trimester of fetal development
LIVER
48
major site of blood cell production during second trimester of fetal development
LIVER
49
hepatocytes have many
functions:
● Protein synthesis and degradation
● Coagulation factor synthesis
● Carbohydrate and lipid metabolism
● Drug and toxin clearance
● Iron recycling and storage
● Hemoglobin degradation, in which bilirubin
is conjugated and transported to small
intestine for eventual excretion
50
Lumen of sinusoids contains
Kupffer cells
that maintain contact with endothelial cell
lining
51
macrophages that remove senescent cells
and foreign debris from blood that circulates
through the liver
Kupffer cells
52
also secrete mediators that regulate protein
synthesis in hepatocytes
Kupffer cells
53
hereditary or acquired defects in the
enzymes
Porphyrias
54
nvolved in heme biosynthesis result in the
accumulation of the various intermediary
porphyrins that damage hepatocytes,
erythrocyte precursors, and other tissues
Porphyrias
55
iver increases the conjugation of bilirubin
and the storage of iron
Severe Hemolytic Anemia
56
Blood cell that produced when liver
maintains hematopoietic stem and
progenitor cells
Extramedullary hematopoiesis
57
The production is as a response to
infectious agents or in pathologic
myelofibrosis of the bone marro
Extramedullary hematopoiesis
58
Directly affected by storage diseases of
monocyte/macrophage (Kupffer) cells as a result of
enzyme deficiencies that cause hepatomegaly with
ultimate dysfunction of the liver
Extramedullary hematopoiesis
59
As blood enters the spleen, it may follow
one of two route
slow-transit pathway through the red pulp in which the RBCs pass circuitously through the
macrophagelined cords before
reaching the sinuses. Plasma freely enters the sinuses, but the RBCs have a more difficult time passing through the tiny openings created by the interendothelial junctions of adjacent endothelial cells
rapid-transit pathway, blood cells enter the splenic artery and passdirectly to the sinuses in the red pulp and continue to the venous system to exit the spleen When splenomegaly occurs, the spleen becomes enlarged and is palpable
60
occurs as a result of many
conditions, such as chronic
leukemias, inherited
membrane or enzyme
defects in RBCs,
hemoglobinopathies,
Hodgkin disease,
thalassemia, malaria, and the
myeloproliferative disorders
rapid-transit pathway
61
may be beneficial in cases of excessive destruction of RBCs, such as
autoimmune hemolytic anemia when treatment with corticosteroids does not effectively suppress hemolysis or in severe hereditary spherocytosis
Splenectomy
62
after splenectomy, platelet and leukocyte
counts
increase transiently
63
n sickle cell anemia, repeated splenic
infarcts caused by sickled RBCs trapped in
the small-vessel circulation of the spleen
cause tissue damage and necrosis, which
often results in
autosplenectomy
64
s an enlargement of the spleen resulting in
some degree of pancytopenia despite the
presence of a hyperactive bone marrow
Hypersplenism
65
LYMPH NODE
- located along the lymphatic capillaries that
parallel, but are not part of, the circulatory
system
- Bean-shaped structures (1 to 5 mm in
diameter) that occur in groups or chains at
various intervals along lymphatic vessels
- May be superficial or deep
66
Filters particulate matter, debris, and
bacteria" entering via lymph
LYMPH NODE
67
is the fluid portion of blood that
escapes into the connective tissue and is
characterized by a low protein concentration
and the absence of RBCs
Lymph
68
carry circulating lymph to the lymph nodes
Afferent lymphatic vessels
69
outer capsule forms ____- that radiate through the cortex and provide support for the macrophages and lymphocytes located in the node
IN LYMPH
`outer capsule forms trabeculae that
radiate through the cortex and provide
support for the macrophages and
lymphocytes located in the node
70
Located between the cortex and the
medulla is a region called the paracortex
71
PARACORTEX PREDOM CON OF
predominantly consists of plasma
cells and B cellspredominantly consists of plasma
cells and B cells
72
After antigenic stimulation, the cortical
region of some follicles develop foci of
activated B cell proliferation called
GERMINAL CENTER
73
Follicles with germinal centers are called
_____, while those without
are called _________
Follicles with germinal centers are called
secondary follicles, while those without
are called primary follicles
74
The medullary cords lie toward the ______. These cords consist
primarily of __________
The medullary cords lie toward the interior
of the lymph node. These cords consist
primarily of plasma cells and B cells
75
Functions of Lymph node
1. site of lymphocyte proliferation from the
germinal centers,
2. they are involved in the initiation of the
specific immune response to foreign
antigens
3. they filter particulate matter, debris, and
bacteria entering the lymph node via the
lymph
76
__ is when an increased number of
microbes enter the nodes, overwhelming
the macrophages and causing infection in
our lymph nodes
Adenitis
77
Thymus
- Originates from
endodermal and
mesenchymal tissue
78
populated initially by lymphocytes from the
yolk sac and the liver
Thymus
79
characterized by a blood supply
system that is unique in that it
consists only of capillaries
Cortex
80
Its function seems to be that of a
“waiting zone,” which is densely
populated with progenitor T cells
Cortex
81
Contains only 5% nature T
lymphocytes and seems to be a
holding zone OF MATURE T CELLS TILL NEEDED
MEDULLA
82
Size of thymus is related to (
age
83
Nondevelopment of the thymus during
gestation results in the
lack of formation of T
lymphocytes
84
Related manifestations seen in patients with
this condition are failure to thrive,
uncontrollable infections, and death in
infanc
THYMUS
85
s when blood
cell production that occurs during the
mesoblastic stage of developmen
Primitive hematopoiesis
86
egins during
the fetal liver stage and continues through
adult life
Definitive hematopoiesis
87
apable of self-renewal and the
production of differentiated progeny
CFU
88
represents what we now refer to as
committed myeloid progenitors or (CFU GEMM
- Colony-forming units–spleen (CFU-S)
89
capable of giving
rise to multiple lineages of blood
cells
- Colony-forming units–spleen (CFU-S)
90
Morphologically unrecognizable hematopoietic
progenitor cells can be divided into two major
types:
1. noncommitted or undifferentiated stem cells
2. multipotential and committed progenitor
cells
91
two theories describing the origin of
hematopoietic progenitor cells:
monophyletic
and polyphyletic theory
92
suggests that all blood cells are derived
from a single progenitor stem cell called a
pluripotent stem cell
The monophyletic theory
93
suggests that each of the blood cell
lineages is derived from its own unique
stem cell. T
polyphyletic theory
94
- Characteristics of stem cells:
1. capable of self-renewal,
2. give rise to differentiated progeny
3. able to reconstitute the
hematopoietic system of a lethally
irradiated host
95
- lineage-specific progenitor cells consists
1. common lymphoid progenitor,;
2. the common myeloid progenitor,
96
which proliferates and differentiates
into lymphocytes of T, B, and natural
killer lineages;
common lymphoid progenitor,
97
the
which proliferates and differentiates
into individual granulocytic,
erythrocytic, monocytic, and
megakaryocytic lineage
common myeloid progenitor,
98
HSCs are directed to one of three possible
fates:
1. self renewal
2. differentiation,
3. apoptosis.
99
When the HSC divides, it gives rise to
two
identical daughter cells:
100
Both daughter cells may follow the
path of differentiation, leaving the
stem cell pool (
symmetric division),
101
one daughter cell may return to the
stem cell pool and the other
daughter cell may follow the path of
differentiation (????????????????????
or undergo apoptosis
one daughter cell may return to the
stem cell pool and the other
daughter cell may follow the path of
differentiation (asymmetric division)
or undergo apoptosis
102
hypothesized that hematopoiesis is a
random process whereby the HSCs
randomly commits to self-renewal or
differentiation
Stochastic model of hematopoiesis
103
ater studies suggested that the
microenvironment in the bone marrow
determines whether the stem cell will
self-renew or differentiate
Instructive model of hematopoiesis).
104
suggests that HSCs receive signals from
the hematopoietic inductive
microenvironment to amplify or repress
genes associated with commitment to
multiple lineages that are expressed only at
low levels
Multilineage priming model
105
involves proliferation
and differentiation signals from specialized
niches located in the hematopoietic
inductive microenvironment via direct cell-to-cell or cellular-extracellular signaling
molecules
Extrinsic regulation
106
Some cytokines released from the hematopoietic
inductive microenvironment include factors that
regulate proliferation and differentiation:
such as stem cell factor (SCF),
thrombopoietin (TPO), and Flt3 ligand.
Intrinsic regulation involves genes such as
SCL (TAL1), which is expressed in cells in
the hemangioblast
107
a bipotential progenitor cell of mesodermal
origin that gives rise to hematopoietic and
endothelial lineages and GATA2, which is
expressed in later-appearing HSCs
Hemangioblast
108
regulatory signaling factors which allow
HSCs to respond to hematopoietic inductive
microenvironment factors, altering cell fate
Notch-1 and Notch-2,
109
As hematopoietic cells differentiate, they
take on various morphologic features
associated with maturation. These include
an overall decrease in cell size and a
decrease in the ratio of nucleus to
cytoplasm
Notch-1 and Notch-2,
110
When mitosis has occurred, the cell may
reenter the cycle or go into a resting phase,
termed G0 phase
111
calculated to
establish the percentage of cells in mitosis
in relation to the total number of cells
mitotic index
112
mitotic index can be affected by the
It can be affected by the duration of mitosis
and the length of the resting state
113
Normally, the mitotic index is approximately
Normally, the mitotic index is approximately
1% to 2%. An increased mitotic index
implies increased proliferation. An exception
to this rule is in the case of megaloblastic
anemia, in which mitosis is prolonged
114
The identification and origin of stem cells
can be determined by immunophenotypic
analysis using
flow cytometry
115
regulates the proliferation, differentiation,
and maturation of hematopoietic precursor
cells.
Cytokines
116
cytokined exert a _____ influence on stem cells and
progenitor cells with multilineage potentia
positivve
117
cytokines exert a ____influence on hematopoiesis
include transforming growth factor-β, tumor
necrosis factor-α, and the interferons
negative
118
Growth factors and hematopoietic precursor
cells
Growth factors prevent hematopoietic
precursor cells from dying by inhibiting
apoptosis (or programmed cell death); they
stimulate them to divide by decreasing the
transit time from G0 to G1 of the cell cycle;
and they regulate cell differentiation into the
various cell lineages
119
They have a high specificity for their target
cells and are active at low concentrations
COLONY-STIMULATING FACTORS
120
The names of the individual factors indicate
the predominant cell lines that respond to
their preSENCE
COLONY-STIMULATING FACTORS
121
The biologic activity of CSFs was first
identified by
their ability to induce
hematopoietic colony formation in semisolid
media.
122
Aka kit ligand, early-acting growth factor; its
receptor is kit
stem cell factor
123
cytoplasmic domain to induce a series of
signals that are sent via signal transduction
pathways to the nucleus of the HSC,
stimulating the cell to proliferate
kut
124
HSCs differentiate and mature, the
expression of KIT receptor
decreases
125
s also a receptor-type tyrosine-protein
kinase. KIT ligand and FLT3 ligand work
synergistically with IL-3, GM-CSF, and other
cytokines to promote early HSC proliferation
and differentiation
FLT3
126
regulates blood cell production by
controlling the production, differentiation,
and function of granulocytes and
macrophages
IL-3
127
nduces expression of specific genes that
stimulate HSC differentiation to the common
myeloid progenitor
GM-CSF
128
- Characteristics of interleukins:
1. They are proteins that exhibit
multiple biologic activities, such as
the regulation of autoimmune and
inflammatory reactions and
hematopoiesis.
2. They have synergistic interactions
with other cytokines.
3. They are part of interacting systems
with amplification potential.
4. They are effective at very low
concentrations
129
complex, regulated process for maintaining
adequate numbers of erythrocytes in the
peripheral blood
ERYTHROPOIESIS
130
gives rise to the earliest
identifiable colony of RBCs, called the
burst-forming unit–erythroid (BFU-E)
CFU-GEMM
131
produces a large multiclustered colony that
resembles a cluster of grapes containing
brightly colored hemoglobin
burst-forming unit–erythroid (BFU-E)
132
Stimulated by oxygen availability in kidney
- recruit CFU-E from the more primitive
BFU-E compartment, prevents apoptosis of
erythroid progenitors, and induces
hemoglobin synthesis
epo
133
leukopeiois category
2 Categories: myelopoiesis and
lymphopoiesis
134
timulates the proliferation and
differentiation of neutrophil and macrophage
colonies from the colony-forming unit–
granulocyte-monocyte
GM-CSF
135
timulate neutrophil differentiation and
monocyte differentiation
timulate neutrophil differentiation and
monocyte differentiation
136
stimulates the growth of granulocytes,
monocytes, megakaryocytes, and erythroid
cells.
IL-3
137
controls the production and release of
platelets
tpo/thrombopoitin
138
The __ is the main site of production of
TPO.
The liver is the main site of production of
TPO.
