[HEMA-LEC] HEMATOPOIESIS

Hematopoiesis

Continuous, regulated process of blood cell production that includes cell renewal, proliferation, differentiation, and maturation

Hemostasis

Stoppage of bleeding

Fetal Hematopoiesis
Adult Hematopoiesis

Stages of Hematopoiesis

Mesoblastic/Yolk Sac/Mesenchymal Phase
Hepatic/Extramedullary Phase
Medullary/Myeloid Phase

Phases of Hematopoiesis

Yolk Sac of the human embryo

In the Mesenchymal Phase:

Chief Site of Mesenchymal Phase

19th day

In Mesenchymal Phase:

It starts as early as the ___ day of gestation.

Erythropoiesis

Production of only RBCs

2nd Week

In the Mesenchymal Phase:

Formation of blood islands
Mesodermal extraembryonic layer which remains active for 8 – 12 weeks

9th Week

In the Mesenchymal Phase:

Development of Primitive Erythroblast
During the first 3 months

Primitive Erythroblast

Precursor of red blood cell

Gower I
Gower II
Portland

Embryonic Forms of Hemoglobin Produces

2 Zeta Chains
2 Epsilon Chains

Composition of Gower I

2 Alpha Chains
2 Epsilon Chains

Composition of Gower II

2 Zeta Chains
2 Gamma Chains

Composition of Portland

NOTE: Hemoglobin has 4 sub-heme units which has 2 pairs of chains

NOTE: Hemoglobin has 4 sub-heme units which has 2 pairs of chains

Extramedullary

Term meaning outside the medulla of bone marrow

Liver

In Hepatic Phase:

Chief Site of Extramedullary Phase

3rd Month

In Hepatic Phase:

Yolk sac discontinues its role, fetal liver becomes active
Erythrocytes and granulocytes (neutrophils, eosinophils, and basophils) in production

By the end of 4th Month

In Hepatic Phase:

Primitive cells are disappearing, with an increase in the more definitive erythroblast, granulocytes, and megakaryocytes

Thymus

Responsible for T-Cell Production

Kidneys

Responsible for B-Cell Production

Spleen

Responsible for Granulocyte and B-Cell Production

Lymph Nodes

Responsible for Lymphocytes Production

Hb A or HB A1
Hb A2
Hb F

Fetal forms of hemoglobin produced

Hb A or HB A1

In Fetal forms of hemoglobin produced:

2 alpha chains, 2 beta chains
Main hemoglobin of addults

Hb A2

In Fetal forms of hemoglobin produced:

2 alpha chains, 2 delta chains

Hb F

In Fetal forms of hemoglobin produced:

2 alpha chains, 2 gamma chains
Most predominant
Main hemoglobin of babies

NOTE: Hepatic hematopoiesis declines during the last trimester

NOTE: Hepatic hematopoiesis declines during the last trimester

Medullary

Term meaning occurs inside the bone marrow

Bone Marrow

In Medullary Phase:

Chief site of Myeloid Phase

Between the 5th and 6th Month

In Medullary Phase:

Bone marrow becomes the primary site of hematopoiesis

NOTE: Hematopoiesis occurs in most bones but primarily in the Flat Bones

NOTE: Hematopoiesis occurs in most bones but primarily in the Flat Bones

Sternum

Flat bone that is the main site of production

Iliac Crest

Best site for collection of sample since there are no nerves around the area

Adult Hematopoietic Tissues

In Adult Hematopoietic Tissues:

Where hematopoiesis occurs

Primary Lymphoid Tissues (Bone Marrow and Thymus)
Secondary Lymphoid Tissues (Spleen, Lymph Nodes, and Gut-Associated Lymphoid Tissue)

Tissues where lymphoid development occurs

Bone Marrow

Primary Lymphoid Tissue that:

Responsible for B Cell Production

Thymus

Primary Lymphoid Tissue that:

Responsible for T-Cell Production

Secondary Lymphoid Tissues

Where lymphoid cells become competent

Bone Marrow

Primary hematopoietic tissue
Responsible for blood cell production and proliferation

Trephine Biopsy or Core Biopsy
Aspiration

Specimen collection procedure for Bone Marrow

Jamshidi Needle

Needle used in Trephine Biopsy or Core Biopsy

University of Illinois sternal needle

Needle used in Aspiration

Red Marrow
Yellow Marrow

Two types of Marrow

Red Marrow

Type of Marrow that:

Hematopoietically active marrow
Produces blood cells

Yellow Marrow

Type of Marrow that:

Hematopoietically inactive marrow composed primarily of adipocytes (fat cells)
The more we get older, our yellow marrow increases

Stromal Cells

Composition of the protective hematopoietic microenvironment

Marrow Cellularity

The ratio of red marrow to yellow marrow which is an indirect representation of marrow activity.

10-50% fat cells
40-60% hematopoietic cells

Percentage of Normocellular Marrow in Adults

100% hematopoietic cells

Percentage of Normocellular Marrow in Children under 2 years

Hypercellular/hyperplasia

Increase in on or more cell lines due to compensation

Hypocellular/hypoplasia

Loss of cellularity or incomplete development in one or more cell lines

Stem Cells
Progenitor Cell
Precursor Cells

3 Major Cell Types in Bone Marrow Hematopoiesis

Stem Cells

In 3 Major Cell Types in Bone Marrow Hematopoiesis:

Referred as the colony-fighting units-spleen (CFU-S)
Have the ability to differentiate in any cell lineage and capability of self-renewal
Progenitor of two major ancestral cell lines

Pluripotential or Multipotential cells

Another term for Stem Cells

Progenitor Cells

In 3 Major Cell Types in Bone Marrow Hematopoiesis:

Have the ability to differentiate to only one cell lineage (BFU-E, CFU-Eo, CFU-MEG, CFU-GM)

Committed or Unipotential Stem Cells

Another term for Progenitor Cells

Precursor Cells

In 3 Major Cell Types in Bone Marrow Hematopoiesis:

Include the blast forms (myeloblast, megakaryoblast, erythroblast)

Myeloid to Erythroid Ratio (M:E Ratio)

Numeric expression comparing the relative number of granulocytic precursors with the relative erythroid precursors in the BM.

Granulocytes to Erythrocytes Ratio

2:1 to 4:1 (Average is 3:1)

Normal M:E ratio

Liver

Organ that:

Synthesize various transport proteins
Store essential materials and vitamins
Conjugate and transport bilirubin
Eliminate substances via the bile
Contains Kupffer Cells

Porphyria

The Liver is often involved in blood-related diseases:

Bleeding eyes; photosensitive/afraid of light

Gaucher disease
Niemann-Pick disease
Tay-Sachs disease

The Liver is often involved in blood-related diseases:

Monocyte-macrophage storage diseases

Spleen

Largest lymphoid organ in the body
Site for removal of 90% of Senescent RBCs

White Pulp
Red Pulp
Marginal Zones

Composition of capsules in Spleen

Senescent RBCs

Old or aged RBCs that need to be removed

Culling

Cells are phagocytosed with subsequent degradation of cell organelles; “eaten whole”

Pitting

Splenic macrophages remove inclusions or damaged surface membrane from the circulating RBCs; “bitten”

Lymph Nodes

Organs of the lymphatic system located along the lymphatic capillaries that parallel, but are not part of, the circulatory system

Inguinal/groin
Axillary
Cervical
Supratrochlear area

Location of Superficial Lymph Nodes

Peyer’s patches in the small intestine
Mesenteric
Retroperitoneal

Location of Deep Lymph Nodes

Lymph

Fluid portion of blood that escapes into the connective tissue
Characterized by a low protein concentration and the absence of RBCs

Afferent Lymphatic Vessels
Efferent Lymphatic Vessels

Two (2) Types of Lymphatic Vessels:

Afferent Lymphatic Vessels

Lymphatic Vessel that:

Carries circulating lymph to the lymph nodes

Efferent lymphatic vessels

Lymphatic Vessel that:

Filtered lymph (by the lymph nodes) exits via lymphatic vessels

Thymus

Organ that is:

Originates from endodermal and mesenchymal tissue
Bi-lobed organ that is densely populated with precursors of lymphoid cells that migrated from the bone marrow
Is populated initially by lymphocytes from the yolk sac and the liver

Primitive Hematopoiesis

Blood cell production that occurs during the mesoblastic stage of development

Definitive Hematopoiesis

Begins during the fetal liver stage and continues through adult life

Till and McCulloch (1961)

Conducted a series of experiments in which they irradiated spleens and bone marrows of mice, creating a state of aplasia (the cells in the organ died)

[Stem Cell Theory]

7 to 8 days

In Stem Cell Theory:

Days wherein colonies of HSCs were seen in the Spleens of the irradiated mice

Colony Forming Units-Spleen (CFU-S)

In Stem Cell Theory:

Colonies that are capable of cell-renewal and cell-differentiation

Granulocyte, erythrocyte, megakaryocyte, monocyte
(common myeloid, only non-committed progenitor cell)

In Colony Forming Units:

CFU-GEMM

Erythrocyte

In Colony Forming Units:

CFU-E

Megakaryocyte

In Colony Forming Units:

CFU-Meg

Monocyte

In Colony Forming Units:

CFU-M

Granulocyte, Monocyte

In Colony Forming Units:

CFU-GM

Myeloid to Basophil

In Colony Forming Units:

CFU-BASO

Myeloid to Eosinophil

In Colony Forming Units:

CFU-EO

Myeloid to Neutrophil

In Colony Forming Units:

CFU-G

T Lymphocyte

In Colony Forming Units:

CFU-pre-T

B Lymphocyte

In Colony Forming Units:

CFU-pre-B

Monophyletic Theory

Suggests that all blood cells are derived from a single progenitor stem cell called a pluripotential stem cell

Most accepted theory

Polyphyletic theory

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

Self-Renewal
Differentiation
Reconstructing

Characteristics of Stem Cells

Stochastic model of hematopoiesis

Model of Hematopoiesis that says:

Hematopoiesis is a random process whereby the HSCs randomlycommits self-renewal or differentiation (Till and McCulloch)

Instructive model of hematopoiesis

Model of Hematopoiesis that says:

Microenvironment in the bone marrow determines whether the stem cell will self-renew or differentiate

Multilineage priming model

Model of Hematopoiesis that says:

HSCs receive signals from the hematopoietic inductive microenvironment t amplify or repress genes

Extrinsic Regulation

Regulation that:

Involves proliferation and differentiation signals (cytokines)

Intrinsic Regulation

Regulation that:

Involves genes

Cytokines and Growth Factors

A group of specific glycoproteins that regulate the proliferation, differentiation, and maturation of hematopoietic precursor cells