Module 2 - Hematopoiesis [LECTURE]

Hematopoiesis is also known as?

Hemopoiesis

This is the process of blood cell production, differentiation, and development

Hematopoiesis

Hematopoiesis occurs in the?

Reticuloendothelial system (RES)

This suggests that each of the blood cell lineages is derived from its own unique stem cell

Polyphyletic Theory

This suggests that all blood cells are derived from a single progenitor stem cell (pluripotential stem cell system)

Monophylectic Theory

This is the most widely accepted theory among experimental hematologist

Monophylectic Theory

This is the foundation of the adult hematopoietic system

Hematopoietic Stem Cell

TRUE OR FALSE. Hematopoietic stem cell self-renews

TRUE

Hematopoietic Stem cell gives rise to different what?

Progeny

What are the types of Human Stem Cells?

Totipotential Stem Cells, Pluripotential Stem Cells, Multipotential Stem Cells

This is the most versatile type of stem cells

Totipotential Stem Cells

This is present few hours after ovum is fertilized

Totipotential Stem Cells

This is present several days after fertilization

Pluripotential Stem Cells

This is derived from pluripotential stem cell

Multipotential Stem Cells

Which of the human stem cell is limited to specific types of cell to form tissues

Multipotential Stem Cells

3 Phases of Hematopoiesis

Mesoblastic phase (Yolk-sac Phase), Hepatic phase, Medullary (Myeloid) phase

The start of mesoblastic phase

19th day after fertilization

End of Mesoblastic phase

2nd to 3rd month after fertilization

Site of mesoblastic phase

Yolk-sac, intravascularly

Product of Mesoblastic phase

Primitive erythroblasts

Globin Chains of Gower I in Mesoblastic phase

2 Epsilon; 2 Zeta

Globin Chains of Gower II in Mesoblastic phase

2 Epsilon; 2 Alpha

Globin Chains of Portland in Mesoblastic phase

2 Zeta; 2 Gamma

The start of hepatic phase

4 to 5 weeks after fertilization

The peak of hepatic phase

3rd month

Which of the phases remains active 1-2 weeks after birth

Hepatic phase

The primary site of Hepatic phase

Liver

The Secondary site of hepatic phase

Thymus, spleen, kidneys

The product of hepatic phase

RBC, and some other blood cells

Globin chains of Hemoglobin F in Hepatic phase

2 alpha; 2 gamma

Globin chains of Hemoglobin A1 in Hepatic phase

2 alpha; 2 beta

Globin chains of Hemoglobin A2 in Hepatic phase

2 alpha, 2 delta

What is the proportion among newborn in Hemoglobin A1

20%

What is the proportion among newborn in Hemoglobin A2

The start of medullary phase

5th to 6th month of development

The end of medullary phase

Throughout lifetime

The primary site of medullary phase

Bone marrow

The secondary site of medullary phase

Liver, spleen

The product of medullary phase

Cells of various lineages are seen

Globin chains of Hemoglobin A1 in Medullary phase

2 alpha; 2 beta

Globin chains of Hemoglobin A2 in Medullary phase

2 alpha; 2 delta

Types of Hematopoiesis

Medullary and Extramedullary Hematopoiesis

This is the blood and cell production within the bone marrow

Medullary Hematopoiesis

This begins in the 5th month of gestation and continuous throughout life

Medullary Hematopoiesis

Blood cell production mainly in the liver and spleen

Extramedullary Hematopoiesis

This occurs when bone marrow cannot meet the body requirements

Extramedullary Hematopoiesis

The primary site of hematopoiesis in an adult

Bone marrow

Major site of hematopoiesis during the hepatic period

Liver

Secondary site of hematopoiesis during the hepatic period

Spleen

Secondary lymphoid organ; involved in the maturation of T cells

Thymus

Secondary lymphoid organ; involved in the production of lymphocytes, filtration and removal of old and damaged cells

Lymph nodes

In humans, this is the bone marrow.

Bursa Equivalent Organ

In the _________, the bursa is the site of maturation of B cells

Fabricius bird

Composed of the monocytes and macrophages

Mononuclear Phagocyte System

Produce erythropoietin

Kidneys

Site of primitive erythropoiesis

Yolk sac

Bone marrow is composed of?

Red Bone Marrow and Yellow Bone Marrow

Red Bone Marrow can be found where?

Sternum, skull, vertebrae, scapula, ribs, pelvic bones, and proximal ends of long bones

This is composed of adipose tissue

Yellow Bone Marrow

Red-to-yellow bone marrow ratio before birth

100% red bone marrow

Red-to-yellow bone marrow ratio at birth

90:10

Red-to-yellow bone marrow ratio 19-20 years old

60:40

Red-to-yellow bone marrow ratio adulthood

50:50

Red-to-yellow bone marrow ratio 65 years old

40:60

The ratio of granulocytes to nucleated erythroid precursors

Myeloid-Erythroid Ratio

Myeloid-Erythroid Ratio for those who do not have disease (Normal)

2:1-4:1 (3:1)

Myeloid-Erythroid Ratio with infection

6:1

Myeloid-Erythroid Ratio with Leukemia

25:1

Myeloid-Erythroid Ratio with Myeloid hyperplasia

20:1

Myeloid-Erythroid Ratio with Myeloid hypoplasia

3:20

Myeloid-Erythroid Ratio with Erythroid hyperplasia

1:20

Myeloid-Erythroid Ratio with Erythroid hypoplasia

5:1

Normal cell development depends on the interaction of?

Pluripotent Stem Cell, Microenvironment, Hematopoietic Growth Factors

Cytokines are also known as?

Growth Factors

These are soluble proteins that have direct or indirect effects on hematopoiesis

Cytokines

Cytokines includes what?

Interleukins (IL), Lymphokines, Monokines, Interferons, Chemokines, Colony-Stimulating-Factors (CSF)

Origin of the growth factor M-CSF (CSF-1)

Endothelial cells, Fibroblasts, Macrophages, Placenta, T cells

This stimulates macrophage differentiation. Important for maintenance of mature monocyte functions

M-CSF (CSF-1)

Origin of the growth factor Erythropoietin

Kidney, Liver

This stimulates erythropoiesis. No effect on more primitive progenitors

Erythropoietin

Origin of the growth factor Interleukin 5 (IL-5)

T cells

Stimulates production of eosinophils. Induces terminal B-cell differentiation

Interleukin 5 (IL-5)

Origin of the growth factor G-CSF

Endothelial cells, macrophages, epithelial cells, fibroblasts, neutrophils

This stimulates production of neutrophils. Predominantly acts late in hierarchy of development with strong maturational effects

G-CSF

Origin of the growth factor GM-CSF

Endothelial cells, fibroblasts, macrophages, T cells, NK cells

This stimulates production of neutrophils, macrophages, eosinophils. Predominantly induces proliferation and differentiation of early myeloid progenitors

GM-CSF

Origin of the growth factor Interleukin 3 (IL-3) (multi-CSF)

T Cells and NK cells

Stimulates production of neutrophils, monocytes, eosinophils, basophils, and platelets. Predominantly induces proliferation and differentiation of early myeloid progenitors

Interleukin 3 (IL-3) (Multi-CSF)

Which of the Hematopoietic growth factors predominantly induces proliferation and differentiation of early myeloid progenitors

GM-CSF and Interleukin 3 (IL-3) (multi-CSF)

What are the Lineage-Specific Hematopoiesis

Erythropoiesis, Leukopoiesis, Megakaryopoiesis

What are the 3 Leukopoiesis

Granulopoiesis, Monopoiesis, Lymphopoiesis