2. Hematopoiesis
● a continuous, regulated process of blood cell production that
includes cell renewal, proliferation, differentiation, and maturation.
● In healthy adults hematopoiesis is restricted primarily to the bone
marrow.
● During fetal development, the restricted, sequential distribution of
cells initiates in the yolk sac and then progresses in the aorta-gonad
mesonephros (AGM) region (mesoblastic phase), then to the fetal
liver (hepatic phase), and finally resides in the bone marrow
(medullary phase).
2
3. HEMATOPOIETIC DEVELOPMENT
1. Mesoblastic Phase
● begin around the nineteenth day of embryonic development after
fertilization
● Early in embryonic development, cells from the mesoderm
migrate to the yolk sac.
● hemoglobin (Gower-1, Gower-2, and Portland) needed for
delivery of oxygen to rapidly developing embryonic tissues.
● yolk sac is the major site of adult blood formation in the embryo.
3
4. HEMATOPOIETIC DEVELOPMENT
2. Hepatic Phase
● begins at 5 to 7 gestational weeks and is characterized by
recognizable 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.
● The developing erythroblasts signal the beginning of
definitive hematopoiesis with a decline in primitive
hematopoiesis of the yolk sac.
● lymphoid cells begin to appear
4
5. HEMATOPOIETIC DEVELOPMENT
● occurs extravascularly, with the liver is the major site of
hematopoiesis during the second trimester of fetal life.
● liver reaches its peak by the third month of fetal
development, then gradually declines after the sixth month.
● The thymus, the first fully developed organ in the fetus,
becomes the major site of T cell production, whereas the
kidney and spleen produce B cells.
● Production of megakaryocytes
● fetal hemoglobin (Hb F) is the predominant hemoglobin.
5
6. HEMATOPOIETIC DEVELOPMENT
● detectable levels of adult hemoglobin (Hb A) may be present.
3. Medullary (Myeloid) Phase
● Prior to the fifth month of fetal development, hematopoiesis
begins in the bone marrow cavity.
● it occurs in the medulla or inner part of the bone.
● The major active site: Bone Marrow
● HSCs and mesenchymal cells migrate into the core of the
bone.
6
7. ● myeloid activity, is apparent during this stage of development,
and the myeloid-to-erythroid ratio gradually approaches 3:1
(adult levels)
● By the end of 24 weeks’ gestation, the bone marrow becomes
the primary site of hematopoiesis
● erythropoietin (EPO), granulocyte colony stimulating factor
(G-CSF), granulocyte-macrophage colony stimulating factor
(GM-CSF), and hemoglobins F and A can be detected
7
8. ADULT HEMATOPOIETIC TISSUE
● In adults, hematopoietic tissue is located in the bone marrow, lymph
nodes, spleen, liver, and thymus.
● Primary lymphoid tissue consists of the bone marrow and thymus
and is where T and B lymphocytes are derived. Secondary lymphoid
tissue, where lymphoid cells respond to foreign antigens, consists of
the spleen, lymph nodes, and mucosa-associated lymphoid tissue.
● Only active sites are pelvis, vertebrae, ribs, sternum, skull. Shafts of
long bones filled with fat. Fatty marrow may be reactivated to
compensate for anemia. Liver & spleen may be reactivated
(extramedullary hematopoiesis) if bone marrow fails to keep up with
demand.
8
9. Erythropoiesis
9
● Process of making red blood cells
● Develop from identifiable progenitors:
a. Burst-forming unit colony (BFU-E)
b. Colony- forming unit - erythroid (CFU-E)
● Stimulated by:
a. EPO
b. Hypoxia
c. Hormones: Testosterone & TSH
10. Leukopoiesis
10
● Leukopoiesis can be divided into two major
categories: myelopoiesis and lymphopoiesis
● Factors that promote differentiation of the
CFU-GEMM into neutrophils, monocytes,
eosinophils, and basophils include GM-CSF,
G-CSF, macrophage colony-stimulating, factor
(M-CSF), IL-3, IL-5, IL-11, and KIT ligand.
11. 11
● GM-CSF stimulates the proliferation and differentiation of
neutrophil and macrophage colonies from the colony-forming
unit–granulocyte-monocyte.
● G-CSF and M-CSF stimulate neutrophil differentiation and
monocyte differentiation from the colony forming
unit–granulocyte and colony-forming unit–monocyte
● IL-3 is a multilineage stimulating factor that stimulates the
growth of granulocytes, monocytes, megakaryocytes, and
erythroid cells.
● Eosinophils require GM-CSF, IL-5, and IL-3 for
differentiation.
12. 12
● for basophil differentiation are IL-3 and KIT ligand.
Megakaryopoiesis
● The stimulating hormonal factor TPO (also known as
MPL ligand), along with IL-11, controls the production
and release of platelets.
● The liver is the main site of production of TPO.
