RODAK'S (6TH ED. | HEMATOPOIESIS) Flashcards by Henrie C. Cruz

What is the continuous, regulated process of renewal, proliferation, differentiation, and maturation of all blood cell lines?

Hematopoiesis

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What is the lifespan of mature RBCs?

120 days

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What is capable of self-renewal (i.e., replenishment) and directed differentiation into all required cell lineages?

Hematopoietic stem cell (HSC)

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Hematopoiesis in healthy adults is restricted primarily in what site?

Bone marrow

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What are the sites of hematopoiesis during fetal development?

Initiated in yolk sac -> progresses in aorta-gonad-mesonephros (AGM) region (mesoblastic phase) -> fetal liver (hepatic phase) -> bone marrow (medullary phase)

Yolk sac -> AGM (mesoblastic phase) -> fetal liver (hepatic phase) -> bone marrow (medullary phase)

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When does hematopoiesis begin?

Around the 19th day of embryonic development after fertilization

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What happens in the early embryonic development (in mesoblastic phase)?

Cells (from the mesoderm) migrate to the yolk sac -> some cells form primitive erythroblasts (in the central cavity of the yolk sac) and others form angioblasts (which surround the cavity of the yolk sac) -> form blood vessels

Cells migrate to yolk sac -> primitive erythroblasts (central cavity of yolk sac) | angioblasts -> blood vessels

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What is the action of angioblasts?

Surrounds the cavity of the yolk sac

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What are the (2) characteristics of primitive erythroblasts (in the central cavity of the yolk sac)?

Primitive
Transient

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What is the importance of primitive erythroblasts in early embryogenesis?

These are needed to produce hemoglobin

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What are the (3) types of hemoglobin produced in early embryogenesis?

Gower-1
Gower-2
Portland

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What is the difference between yolk sac hematopoiesis vs hematopoiesis that occurs later in the fetus and adult?

Yolk sac hematopoiesis occurs intravascularly

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What is the meaning of intravascular?

Within the developing blood vessels

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What is the major site of adult blood formation in the embryo?

Yolk sac

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What HSC can generate hematopoietic and endothelial cells in vitro?

Flk1 HSCs (separated from human umbilical cord blood)

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When does the hepatic phase of hematopoiesis start?

At 5 - 7 gestational weeks

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When does hematopoiesis in the fetal liver peak?

3rd month

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When does hematopoiesis in the fetal liver gradually decline?

After the 6th month

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When does hematopoiesis in the fetal liver retain minimal activity?

Until 1 - 2 weeks after birth

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What is the 1st fully developed organ in the fetus?

Thymus

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What is the major site of T cell production?

Thymus

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What are the (2) organs that produce B cells?

Kidney
Spleen

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At what phase does production of megakaryocytes begin?

Hepatic phase

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What is the action of spleen?

Gradually decreases granulocytic production and subsequently contributes solely to lymphopoiesis

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What is the **predominant** hgb during the **hepatic** phase?

**Fetal hemoglobin** (Hb F)

During the hepatic phase, Hb F is the predominant hgb but **detectable** levels of what hgb may be present?

**Adult hemoglobin** (Hb A)

What is the other term for **medullary** phase?

**Myeloid**

Why is hematopoiesis in the bone marrow termed as **medullary** hematopoiesis?

Because it occurs in the **medulla** (inner part) of the bone cavity

When does **medullary** hematopoiesis begin?

**4th** and **5th** month of fetal development

What are the (2) components that **migrate** into the core of the bone during the myeloid phase?

1. **HSCs** 2. **Mesenchymal cells**

What are **mesenchymal cells**?

Type of **embryonic tissue**

Mesenchymal cells differentiate into **structural** elements such as what (2) cells?

Stromal cells such as: 1. **Endothelial** cells 2. **Reticular adventitial** cells

What is the action of **mesenchymal** cells?

**Support** developing hematopoietic elements

What is the **myeloid-to-erythroid ratio** during the medullary phase?

**3:1** to **4:1**

What is the **normal** adult levels of myeloid-to-erythroid ratio?

**4:1**

At the end of **24 weeks** gestation, what site becomes the **primary** site of hematopoiesis?

**Bone marrow**

Measurable levels of what (5) components can be **detected** during the **medullary** phase?

1. **Erythropoietin** (EPO) 2. **Granulocyte colony-stimulating factor** (G-CSF) 3. **Granulocyte-macrophage colony-stimulating factor** (GM-CSF) 4. **Hb F** 5. **Hb A**

In **adults**, at what (5) organs is **hematopoietic tissue** located?

1. **Bone marrow** 2. **Lymph nodes** 3. **Spleen** 4. **Liver** 5. **Thymus**

The bone marrow contains what (4) **developing** components?

1. **Erythroid** cells 2. **Myeloid** cells 3. **Megakaryocytic** cells 4. **Lymphoid** cells

At what (2) sites does lymphoid **development** occur?

1. **Primary** lymphoid tissue 2. **Secondary** lymphoid tissue

**Primary** lymphoid tissue consists of what (2) organs?

1. **Bone marrow** 2. **Thymus**

What are the (2) components derived from the **bone marrow** and **thymus**?

1. **T** lymphocytes 2. **B** lymphocytes

What happens in the **secondary** lymphoid tissue?

Lymphoid cells **respond** to foreign antigens

What are the (3) components of **secondary** lymphoid tissue?

1. **Spleen** 2. **Lymph nodes** 3. **Mucosa-associated lymphoid tissue** (MALT)

What is one of the **largest** organs in the body?

**Bone marrow**

Where is **bone marrow** located?

Within the **cavities** of the cortical bones

What is the result of **resorption** of cartilage and endosteal bone?

Creates a **central space** within the bone

**Projections** of calcified bone is called as what?

**Trabeculae**

**Projections** of calcified bone **radiate** out from the bone cortex into the central space forming what and resembles what?

Forming a **three-dimensional matrix** resembling a **honeycomb**

What is the action of **trabeculae**?

Provide structural **support** for the developing blood cells that mature within the sea of interposed mature adipocytes

What are the (2) major components of a **normal** bone marrow?

1. **Red** marrow 2. **Yellow** marrow

What is the hematopoietically **active** marrow that is composed of developing blood cells and their progenitors?

**Red** marrow

What is the hematopoietically **inactive** marrow that is composed primarily of **adipocytes**, with undifferentiated mesenchymal cells and macrophages?

**Yellow** marrow

What are **adipocytes**?

**Fat cells**

During **infancy** and **early childhood**, all the bones in the body contain primarily what marrow?

**Red** (active) marrow

If during infancy and early childhood, all the bones primarily contain red marrow, what happens between **5 - 7** years old?

**Adipocytes** become more abundant and begin to **occupy** the spaces in the long bones previously dominated by active marrow

The process of **replacing** the active marrow by adipocytes (yellow marrow) during development is called as what?

**Retrogression**

What is the result of **retrogression**?

Restriction of active marrow in the adult marrow in the adult to the **sternum**, **vertebrae**, **scapulae**, **pelvis**, **ribs**, **skull**, and proximal portion of the **long bones**

What is the ratio of **red** and **yellow** marrow in adults? Why?

Red and yellow marrow are approximately **equal** because yellow marrow is **scattered** throughout the red marrow

**True or False** The ratio of the red marrow to the yellow marrow (i.e., the hematopoietic cells to the adipocytes), typically **increases** with age

False. The ratio of the red marrow to the yellow marrow (i.e., the hematopoietic cells to the adipocytes), typically **decreases** with age

What is the term for the **ratio** of red marrow to the yellow marrow (i.e., hematopoietic cells to the adipocytes)?

**Marrow cellularity**

**True or False** The ratio of red marrow to yellow marrow **increases** w/ age

False, the ratio of red marrow to yellow marrow **decreases** w/ age

**True or False** Yellow marrow is **not** capable of reverting back to active marrow

False, yellow marrow is **capable** of reverting back to active marrow

What are the (2) instances when yellow marrow is capable of **reverting** back to active marrow?

In cases of increased demand on the bone marrow such as in: 1. Excessive **blood loss** 2. **Hemolysis**

What are the (3) components of the **bone marrow**?

1. **Hematopoietic** cells 2. **Stromal** cells 3. **Blood vessels** i. **Arteries** ii. **Veins** iii. **Vascular sinuses**

Stromal cells **originate** from what?

**Mesenchymal** cells

Where does mesenchymal cells **migrate**?

**Central cavity** of the bone

**Stromal cells** include what (7) cells?

1. **Endothelial** cells 2. **Adipocytes** 3. **Macrophages** 4. **Lymphocytes** 5. **Osteoblasts** 6. **Osteoclasts** 7. **Reticular adventitial** cells

What are **reticular adventitial** cells?

**Fibroblasts**

What are the (2) characteristics of **endothelial** cells?

1. **Broad** 2. **Flat**

What are the (2) actions of **endothelial** cells?

1. Form a **single continuous layer** along the inner surface of the **arteries**, **veins**, and **vascular sinuses** 2. **Regulate** the flow of particles entering and leaving hematopoietic **spaces** in the vascular sinuses

What are the (2) characteristics of **adipocytes**?

1. **Large** 2. Has a **single fat vacuole**

What are the (2) actions of **adipocytes**?

1. Play a role in **regulating** the volume of the marrow in w/c **active** hematopoiesis occurs 2. Secrete **cytokines** or **growth factors**

What is the action of **cytokines** or **growth factors** secreted by adipocytes?

Positively stimulate **HSC** numbers and **bone homeostasis**

What is the action of **macrophage**?

**Phagocytosis**

What is the action of both **macrophages** and **lymphocytes**?

Secrete various **cytokines**

What is the action of **cytokines** secreted by both macrophages and lymphocytes?

**Regulate** hematopoiesis

Where are **macrophages** located?

Throughout the **marrow space**

What are the (5) cells that **produce** cytokines?

1. **Adipocytes** 2. **Macrophages** 3. **Lymphocytes** 4. **Endothelial** cells 5. **Reticular adventitial** cells

What are the **bone-forming** cells?

**Osteoblasts**

What are the **bone-resorbing** cells?

**Osteoclasts**

What are the (2) actions of **reticular adventitial** cells?

1. Form an **incomplete** layer of cells on the **abluminal** surface of vascular sinuses 2. Extend **long, reticular fibers** into the perivascular space that form a **supporting lattice** for the developing hematopoietic cells

What are the (2) actions of **stromal** cells?

1. Secrete a **semifluid extracellular matrix** 2. Plays a critical role in the **regulation** of hematopoietic stem and progenitor cell **survival** and **differentiation**

What is the action of the **semifluid extracellular matrix** secreted by stromal cells?

**Anchor** developing hematopoietic cells in the bone cavity

What are the (6) components of the **extracellular matrix** (secreted by stromal cells)?

1. **Fibronectin** 2. **Collagen** 3. **Laminin** 4. **Thrombospondin** 5. **Tenascin** 6. **Proteoglycans** i. **Hyaluronate** ii. **Heparan sulfate** iii. **Chondroitin sulfate** iv. **Dermatan**

The **red** marrow is composed of what?

**Hematopoietic** cells (arranged in extravascular cords)

Where are the cords (that compose the red marrow) **located**?

**Spaces** between vascular sinuses

What **supports** the cords (that compose the red marrow)?

Trabeculae of **spongy bone**

What are the (2) components that **separates** the cords (that compose the red marrow) from the lumen of vascular sinuses?

1. **Endothelial** cells 2. **Reticular adventitial** cells

Where does hematopoietic cells **develop**?

In specific **niches** within the cords (that compose the red marrow)

**True or False** Erythroid precursors or erythroblasts develop in small clusters, and the more mature forms are located adjacent to the outer surfaces of the vascular sinuses

True

What is found **surrounding** iron-laiden macrophages?

**Erythroblasts**

What are located **adjacent** to the **walls** of the **vascular sinuses**?

**Megakaryocytes**

What is the action of **megakaryocytes**?

Facilitates the **release** of **PLTs** into the lumen of the sinus

What are located **deep** within the **cords**?

**Immature myeloid (granulocytic)** cells (through the metamyelocyte stage)

RODAK'S (6TH ED. | HEMATOPOIESIS) Flashcards

(95 cards)