Hematopoiesis
Cortex
- "waiting zone" OF THYMUS
Cytoplasmic maturation
- Decrease / loss of basophilia - Increase in the proportion of cytoplasm - Cytoplasmic granules - Elaboration of Hgb for RBC
Intrinsic regulation
- Involves genes such as SCL (TAL 1), w/c is expressed in cells in the hemangioblast, and GATA 2, w/c is expressed in later-appearing HSCs
Extrinsic regulation
- Involves proliferation & differentiation signals f ro m s p e c i a l i ze d n i c h e s via direct cell-to-cell extracellular signaling molecules
liver
Capable of extramedullary hematopoietic production in case of bone marrow shutdown
Endothelial cells
Cells along the wall of marrow. Regulate the flow of particles entering and leaving hematopoietic spaces in the vascular sinuses.
1. Capable of self-renewal 2. Give rise to differentiated progeny 3. Able to reconstitute the hematopoietic system of a lethally irradiated host
Characteristics of Stem Cells
periarteriolar lymphatic sheath, or PALS.
Aggregates of T lymphocytes surround arteries that pass through these germinal centers, forming a region called the
Stromal cells
originate from ___. include endothelial cells, adipocytes (fat cells), macrophages and lymphocytes, osteoblasts, osteoclasts, and reticular adventitial cells (fibroblasts).
hematopoietic inductive microenvironment, or niche,
plays an important role in nurturing and protecting HSCs and regulating a balance among their quiescence, self-renewal, and differentiation
primitive erythroblasts
predominant cell in the 9th week of fetal lfe
primitive erythroblasts
produce hemoglobin needed for delivery of oxygen to rapidly developing embryonic tissues
periosteal arteries
provide nutrients for the osseous bone and the marrow.
pitting
splenic macrophages remove inclusions or damaged surface membrane from the circulating RBCs.
white pulp
splenic tissue which consists of lymphocytes, macrophages and dendritic cells
hepatocytes
structural units of liver
multilineage priming model
suggests that HSCs receive low-level signals from the hematopoietic inductive microenvironment to amplify or repress genes associated with commitment to multiple lineages.
polyphyletic theory /Dualistic Theory
suggests that each of the blood cell lineages is derived from its own unique stem cell.
nutrient artery
supplies blood only to the marrow.
fetal hemoglobin (Hb F) adult hemoglobin (Hb A, A2)
During the hepatic phase, ___ is the predominant hemoglobin, but detectable levels of ___ may be present
bone foramina.
The nutrient and oxygen requirements of the marrow are supplied by the nutrient and periosteal arteries, which enter via the __
physiologic need
The determining factor controlling the rate of production is
niche
The hematopoietic cells develop in specific ___ within the cords
retrogression
The process of replacing the active marrow by adipocytes (yellow marrow) during development is called
350 mL/min.
The spleen has a rich blood supply receiving approximately
committed myeloid progenitors or colony-forming unit- granulocyte, erythrocyte, monocyte, and megakaryocyte (CFUGEMM).
These cells are capable of giving rise to multiple lineages of blood cells.
mitotic index
calculated to establish the percentage of cells in mitosis in relation to the total number of cells.
Adventitial cells
capable of contraction to allow mature cells to pass through the basement membrane
Porphyria
defects in heme & iron metabolism. result in the accumulation of porphyrins that damage hepatocytes
Adenitis
inflammation of lymph node
Instructive model
microenvironment in the bone marrow determines whether the HSC will self-renew or differentiate
3:1
myeloid-to-erythroid ratio Indicates the readily available cells
1-2% increased proliferation
normal mitotic index increased index means
Thymus (T-Cells) kidney and spleen
the first fully developed organ in the fetus, becomes the major site of __ cell production, whereas the ___ produce B cells.
yolk sac
the major site of adult blood formation in the embryo.
Primitive Cells - hemocytoblast,hemohistioblast, hemopoietic reticulum cell, lymphoidocytes
undifferentiated mesenchymal cells that can produce only blood cells other term: 4
Monophyletic Theory / Unitarian
- most widely accepted theory; all cells came f r o m a s i n g l e p r o g e n i t o r c e l l (pluripotential)
Stem cell
- one in which the daughter cells of the cell division are IDENTICAL in appearance and potential to the mother cell
Homoplastic
- young cells in BM undergo mitotic division
Heteroplastic
- young cells in BM undergo mitotic division and multiplication
splenomegaly Hypersplenism
-the spleen becomes enlarged and is palpable -enlargement of the spleen resulting in some degree of pancytopenia despite the presence of a hyperactive bone marrow.
6th month
BM becomes the primary site of hematopoiesis.
central longitudinal vein,
Blood exits the marrow via the
3 2.5 1.5
Bone marrow (per kg daily) produces __ billion RBCs __ billion platelets __ billion granulocytes
bone marrow
By the end of 24 weeks' gestation, the ___ becomes the primary site of hematopoiesis
KIT ligand, FLT3 ligand, IL-1, IL-3, IL-6, IL-11, GM-CSF
Cytokines • Positive effect-
1. Interleukins (Ils) 2. Lymphokines 3. Monokines 4. Interferons 5. Chemokines 6. Colony-stimulating factors
Cytokines 6
Transforming growth factor-β - Tumor necrosis factor-α - Interferons
Cytokines Negative effect
Go to G1
Cytokines Stimulate the dying precursor cells to divide by decreasing the transit from
yolk sac -aorta-gonad mesonephros (AGM) region -fetal liver -bone marrow
During fetal development, the restricted, sequential distribution of cells initiates in the ___ and then progresses in the ___ (mesoblastic phase), ___ (hepatic phase), and finally resides in the __ (medullary phase).
Thymus
Efficient, well-developed organ at birth; but decreases at later ages, then begins to atrophy (old age)
1 per 1000
HSCs exist in the marrow in the ratio of __ per __ nucleated blood cells.
hepatic phase
Hematopoiesis in the aorta-gonad-mesonephros region and the yolk sac disappear during this stage
formation, development, and specialization
Hematopoiesis result in the _, __, __ of all of the functional blood cells that are released from the bone marrow to the circulation.
nutrient artery
Hematopoietic cells located in the endosteal bed receive their nutrients from the
Bone Thymus Spleen Liver Lymph nodes
In adults, hematopoietic tissue is located in the
bone marrow
In healthy adults hematopoiesis is restricted primarily to the __
red
Infancy and early childhood: BM consists primarily of __BM.
AGM region
It is believed that hematopoietic stem cells arise here
spleen
It is vital but not essential for life - functions as an indiscriminate filter of the circulating blood.
osteoblasts, osteoclasts, endothelial cells, mesenchymal stem cells, adipocytes and macrophages
Key stromal cells thought to support HSCs in bone marrow niches include
19th
Mesoblastic Phase is considered to begin around the ____ day of embryonic development after fertilization.
symmetric division assymetric division
Path of Differentiation of HSC -leaving the stem cell pool. -return to the stem cell pool
Cytokines
Prevent hematopoietic precursor cells from dying by inhibiting apoptosis
Dyspoiesis
Profound defect in the maturation of the formed elements
Primitive cells
Progenitor cells
trabeculae
Projections of calcified bone that provide structural support for the developing blood cells.
red pulp
This creates a sponge-like matrix that functions as a filter for blood passing through the region in spleen
stochastic model of hematopoiesis
Till and McCulloch proposed that hematopoiesis is a random process whereby the HSC randomly commits to selfrenewal or differentiation.
excessive blood loss or hemolysis
Yellow marrow is capable of reverting back to active marrow in cases of increased demand on the bone marrow, such as in
intravascularly,
Yolk sac hematopoiesis differs from hematopoiesis that occurs in the fetus and the adult bec it occurs
5-7 years old
adipocytes become more abundant and begin to occupy the spaces in the long bones previously dominated by active marrow
Cytokines
are a diverse group of soluble proteins that have direct and indirect effects on hematopoietic cells.
Osteoblasts osteoclasts
are bone-forming cells bone-resorbing cells.
Adipocytes cytokines or growth factors
are large cells with a single fat vacuole; they play a role in regulating the volume of the marrow in which active hematopoiesis occurs. They also secrete
Thymus
area of maturation of T cell
red bone marrow
assumes chief role in myeloid phase
Lymph Nodes
bean-shaped structures located along the lymphatic capillaries
culling
cells are phagocytized with subsequent degradation of cell organelles,
• CD 33 & CD 38 = • CD 10 and CD 38 = • CD 7 = • CD 19 =
committed MYELOID progenitors committed LYMPHOID progenitors T lymphoid progenitor cells & NK B lymphoid progenitors
Primary lymphoid tissues
consists of the bone marrow and thymus and is where T and B lymphocytesare derived.
Extravascular cords
contains all of the developing blood cell lineages, stem cell, progenitor cell, adventitial cell and macrophage
Lymph
fluid portion of blood that escapes into the connective tissue and is characterized by a low protein concentration and the absence of RBCs
Stromal cells
form an extracellular matrix in the niche to promote cell adhesion
marginal zone
forms a reticular meshwork containing blood vessels, macrophages, memory B cells, and CD41 T cells.
angioblast
give rise to blood vessel
2nd month
granulocyte and megakaryocyte prod
Myeloid phase/medullary stage 5th month
hematopoiesis begins in the bone marrow cavity. Month
extramedullary hematopoiesis
hematopoiesis outside bone marrow (e.g., liver spleen)
Extravascular cords trabeculae
hematopoietic cells and macrophages are arranged in here. Located between __ of spongy bones
red marrow
hematopoietically active marrow consisting of the developing blood cells and their progenitors
yellow marrow
hematopoietically inactive marrow composed primarily of adipocytes (fat cells), with undifferentiated mesenchymal cells and macrophages.
Gower 1, Gower 2, Portland
hemoglobin produced by primitive erythroblast
4-5 AOG
hepatic phase happens at
3rd month
hepatic phase peak
Hematopoiesis
is a continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation, and maturation.
red pulp
is composed primarily of vascular sinuses separated by cordscords of Billroth
spleen
is the largest lymphoid organ in the body
hematopoietic microenvironment
it is responsible for providing semifluid matrix which serves as an anchor for the developing hematopoietic cells
Nuclear Maturation
loss of nucleoli, decrease in the diameter of the nucleus, condensation of nuclear chromatin,possible change in the shape of the nucleus, and possible loss of the nucleus
CD 38 HLA-Drlow
loss of stemness
4th month
lymphocyte production month
Kupffer cells
macrophages that remove senescent cells and foreign debris from the blood that circulates through the liver;
liver, spleen
major site of hematopoiesis during the second trimester of fetal life.
hematopoietic growth factors or cytokines
regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells.
G0 phase
resting phase
liver
sequesters mebrane damaged RBCs and eliminates them from the circulation
spleen - 30%
serves as a storage site for platelets. __% of the total platelet count is sequestered in the spleen
Liver
serves as the major site of blood cell production during the second trimester of fetal development.
Secondary lymphoid tissue
where lymphoid cells respond to foreign antigens, (MATURATION) consists of the spleen, lymph nodes, and mucosa-associated lymphoid tissue.
mesenchymal cells
which are a type of embryonic tissue, differentiate into structural elements that support the developing blood cells.
myeloid progenitor
which proliferates and differentiates into individual granulocytic, erythrocytic, monocytic, and megakaryocytic lineages.
lymphoid progenitor
which proliferates and differentiates into T, B, and natural killer lymphocyte
Asynchronism
• Characterized by different rates of maturation of the different parts of the cell producing cells that are atypical or bizarre but whose external structure is easily recognized as that of normal cell
Synchronism
• Characterized by simultaneous changes or transformation of the individual components of the cell
culture assays (CFUs) -methylcellulose transplantation to animals
• In vitro : - Semi-solid media (___) • In vivo: __