HEMATOPOIESIS

HEMATOPOIESIS

continuous and regulated process of blood cell production

HEMATOPOIESIS

this process results in formation, development, & specialization of all functional blood cells (RBCs, WBCs, & Platelets)

HEMATOPOIESIS

can be characterized as a select distribution of embryonic cells in specific sites that rapidly change during development

• Cell Renewal

• Proliferation

• Differentiation

• Maturation

Function of Hematopoiesis

Bone Marrow

In healthy adults, hematopoiesis is restricted primarily in which organ?

MESOBLASTIC PHASE

Chief site (responsible for the production of cells): “Embryonic Yolk Sac”

MESOBLASTIC PHASE

it is early in the embryonic development where cells from the Mesoderm, migrate to the Yolk sac

MESOBLASTIC PHASE

The hematopoietic stage begins as early as 19th day of gestation [we are starting to produce cells; erythroblasts that are important in the production of hemoglobin

Globin content

In order to know how to classify/differentiate these types of hemoglobin, you need to check their?

Embryonic Hemoglobin

present only on the mesoblastic phase or the embryonic life

• Gower 1

• Gower 2

• Portland Hemoglobin

Types of Embryonic Hemoglobin

Gower 1

Globin contents present: 2 epsilon chains & 2 Zera chains

Gower 2

Globin contents present: 2 alpha chains & 2 epsilon chains

Portland Hemoglobin

Globin contents present: 2 Zeta chains & 2 gamma chains

MESOBLASTIC PHASE

this phase occurs INTRAVASCULARLY, wherein it is within the developing blood vessels

MESOBLASTIC PHASE

the yolk sac could remain active up to the 8th or the 12th week of gestation

HEPATIC PHASE

this phase begins at 5-7 gestational weeks

HEPATIC PHASE

it could reach its peak/highest production on the 3rd month of pregnancy (roughly 12 weeks)

HEPATIC PHASE

it is where the yolk sac has totally discontinued its role in Hematopoiesis

HEPATIC PHASE

this phase ends or it will gradually decline after the 6th month period of gestation, where there will be a transition & replacement once again

HEPATIC PHASE

it is characterized by recognizable clusters of developing

• Erythroblasts

• Granulocytes

• Monocytes

HEPATIC PHASE

presence of Lymphoid cells & the evidences of Megakaryopoiesis as WBCs (Granulocytes, Monocytes, Lymphocytes) & Platelets

HEPATIC PHASE

Chief Site: Liver

- The clusters of cells colonizes the Fetal liver & other Reticuloendothelial System (RES) organs

HEPATIC PHASE

Other Active Sites: Spleen, Kidneys, and Thymus

• Occurs Extravascularly

1. HbF

2. HbA

   • HbA 1

   • HbA 2

   • 1-2% HbF

Hemoglobin present in the HEPATIC PHASE

HEMOGLOBIN F OR FETAL HEMOGLOBIN (HbF)

the predominant hemoglobin for this stage (while the fetus is still inside the womb)

HEMOGLOBIN F OR FETAL HEMOGLOBIN (HbF)

globin contents present: 2 Alpha chains & 2 Gamma chain

HEMOGLOBIN A OR ADULT HEMOGLOBIN (HbA)

The most abundant hemoglobin amongst adults

Hemoglobin A1 (HbA 1)

predominant HbA

• roughly 95% of our hemoglobin

Hemoglobin A1 (HbA 1)

contents present: 2 Alpha chains & 2 Beta chains

Hemoglobin A2 (HbA2)

roughly 2-3% of our hemoglobin

Hemoglobin A2 (HbA2)

globin contents present: 2 Alpha chains & 2 Delta

MEDULLARY PHASE

This phase begins at the 5th-6th month of gestation

• prior to the 5th month of pregnancy, Hematopoiesis then starts to begin in the Bone marrow cavity

MEDULLARY PHASE

when reaching the 5th month, this transition is called as, ‘Medullary Hematopoiesis,’ because it occurs in the medulla or the inner part of the bone

MEDULLARY PHASE

By the end of the 24th week of gestation, the bone marrow is then considered as the ‘Main Site for Hematopoiesis’ & will persist all throughout our life

MEDULLARY PHASE

According to studies, in the bone marrow during this phase, Hematopoietic Stem Cells (HSCs) become present, along with Mesenchymal cells, & migrate into the core of the body

MEDULLARY PHASE

Measurable levels of growth factors: are present during this phase & are needed to make sure that the stem cells will commit themselves in the production of a specific cell

MEDULLARY PHASE

This phase also referred to as ‘Myeloid Stage’

MEDULLARY PHASE

This phase occurs generally in most of the bones, wherein among adults, the principal source production are the Flat bones - Ex. Sternum, Ribs, Pelvis

24th week

week when the bone marrow is then considered as the ‘Main Site for Hematopoiesis’ & will persist all throughout our life

Hematopoietic Stem Cells (HSCs)

they are responsible for the development & production of the blood cells

HEMATOPOIETIC TISSUE

Responsible for the synthesis or production of blood cells

HEMATOPOIETIC TISSUE

it is where Lymphoid Development occurs

Primary Lymphoid tissue

Refers to the Bone Marrow & Thymus

Thymus

(produces T-cells)

Bone Marrow

(produces B- cells)

Bone Marrow

when you reach the Medullary stage, it will then further contain the developing cells (RBCs, WBCs, Megakaryocytes for platelet production, & Lymphoid cells for lymphocyte production)

Secondary Lymphoid tissue

where lymphoid cells respond to foreign bodies & antigens

Secondary Lymphoid tissue

it is comprised of Spleen, Lymph nodes, and other Lymphoid tissues (e.g. Mucosa-associated lymphoid tissue or MALT)

BONE MARROW

Main responsible organ/site for Hematopoiesis

BONE MARROW

Develops in the embryo by the hollowing-out of the skeletal bones, forming a Central Cavity

• it is not the bone itself, but it is the soft tissue inside the bone cavity (central cavity)

BONE MARROW

It contains Hematopoietic cells, Stromal cells, & Blood vessels (e.g. Arteries, Veins, Vascular sinuses)

proliferation & production of blood cells

Main Function of Bone Marrow

Hematopoietic Cells

give rise to the primitive and undifferentiated cell, or the Hematopoietic Stem Cells (HSCs)

Stromal cells

play an important role in the microenvironment of our hematopoietic tissue to produce the cells [endothelial cells, macrophages, etc.]

YELLOW BONE MARROW

Cellular

YELLOW BONE MARROW

it is inactive, which meant that it is not capable of producing out blood cells

RED BONE MARROW

‘active’

RED BONE MARROW

it consists of the developing cells & progenitors, that produces the mature ones

RED BONE MARROW

it is composed of Hematopoietic cells [developed in specific niches within the cords of the bone marrow] & Macrophages that are arranged in Extravascular cords

• 100% red (birth)

5-7 years old

age when Adipocytes become more present or dominant, & later then occupies the spaces in our Long bones

• Production if Blood Cells

• Iron Storage

• B-cell Development

Main functions of Bone Marrow

Normocellular

normal bone marrow in a stained smear there is 30-70% Hematopoietic cells (including the mature & immature forms)

Hypercellular (Hyperplasia)

Abnormal INCREASE in the production of cells

Hypercellular (Hyperplasia)

there is more than 70% Hematopoietic cells

Hypocellular (Hypoplasia)

Abnormal DECREASE in the production of cells

Hypocellular (Hypoplasia)

there is less than 30% Hematopoietic Cells

Aplastic (Aplasia)

there is very few or a total absence of Hematopoietic cells

Aplastic (Aplasia)

due to this, there will be less RBCs to provide oxygen, less WBCs to protect the body from unwanted organisms, & less Platelets to help the body to form clots

Nutrient & Periosteal Arteries

they supply the nutrient & oxygen requirement of the bone marrow

Nutrient Artery

supplies blood ONLY for the bone marrow

Periosteal Artery

provides nutrients BOTH for the bone & for the bone marrow

Endosteal Bed

Hematopoietic cells that are located at the ____, receive their nutrients at the Nutrient artery

HEMATOPOEITIC MICROENVIRONMENT

it is sometimes referred to as ‘Hematopoietic Inductive Microenvironment (niches)

HEMATOPOEITIC MICROENVIRONMENT

it is needed to nurture & protect the Hematopoietic stem cells (HSCs)

HEMATOPOEITIC MICROENVIRONMENT

it is responsible for supplying Semifluid matrix (Stroma)

HEMATOPOEITIC MICROENVIRONMENT

it is used in order to balance in quiescence (inactive/dormant cells), and the self-renewal & differentiation of HSCs

Stroma

serves as an anchor for the developing hematopoietic cells

STROMAL CELLS

they play a critical role in the regulation of HSCs & progenitor cells, so they can survive & easily differentiated/distinguish as to their cell line (RBCs, WBCs, Platelets)

• Endothelial cells

• Adipocytes

• Macrophages

• Osteoblasts

• Osteoclasts

• Reticular Cells

The key stromal cells that support the HSCs in the bone marrow niches are

Endothelial cells

regulate the flow of particles, entering and leaving the hematopoietic spaces.

Adipocytes

essential for they secrete various steroids that influence erythropoiesis, maintain bone integrity and regulate the volume of bone marrow

Macrophages

important for phagocytosis and the removal of unwanted materials; essential for they secrete Cytokines, which later on regulate hematopoiesis

Osteoblasts

bone-forming cells; mistaken as plasma cells

Osteoclasts

bone-resorbing cells or bone destroying cells

Reticular Cells

support the vascular sinuses and hematopoietic cells

STROMAL CELLS

secrete semifluid extracellular matrix in order to anchor & protect the developing HSCs in the bone cavity

1. Fibronectin (FN)

2. Collagen

3. Laminin

4. Thrombospondin (TSPs)

5. Tenascin

6. Proteoglycans

This Matrix Is Made Up of the Following:

MYELOID TO ERYTHROID RATIO (M:E)

it is a numerical expression of comparing the relative number of Granulocyte precursors to the relative number of Erythrocyte precursors

• INFECTION

• LEUKEMIA

• MYELOID HYPERPLASIA

• MYELOID HYPOPLASIA

• ERYTHROID HYPERPLASIA

• ERYTHROID HYPOPLASIA

ABNORMAL M:E RATIO

• Macrophages

• Mast cells

• Osteoblasts

• Osteoclasts

OTHER NORMAL MARROW CELLS

Posterior Iliac crest

Preferred site in marrow specimen

anterior iliac crest, spinal processes, vertebral bodies, and sternum

Occasionally preferred sites

Jamshidi

Needle used for Trephine Biopsy: (gauge size: 11)

University of Illinois Sternal Needle

Needle used for aspiration:

EXTRAMEDULLARY HEMATOPOIESIS

it occurs whenever Hyperplasia of the bone marrow cannot meet the physiologic needs of the body

EXTRAMEDULLARY HEMATOPOIESIS

Even if this takes place, there should still be a production of cells

EXTRAMEDULLARY HEMATOPOIESIS

It is where other Reticuloendothelial Organs steps in:

A. Liver B. Spleen C. Lymph Nodes D. Thymus

LIVER

Provides the cells the different necessary proteins & essential minerals that are needed in the synthesis of the different substances for hematopoiesis, such as: 1. DNA 2. RNA

LIVER

The major site of cell production in the second trimester of fetal development