Haematpoiesis :) - 3.2

How does the location of the production of blood change?

• foetus blood → yolk sac (0-2months), liver/spleen (2-7months), bone marrow (5-9months)

• Infants → All bones contain blood cell producing bone marrow.

• During childhood → the red marrow is replaced by fat to form yellow marrow.

• Adulthood → 70% of red marrow is located in pelvis, vertebrae, sternum.

• EXTRAMEDULLARY haematopoiesis → production of blood outside the body

In what bones does haematopoiesis occur the most in?

Most:

1. Pelvis

2. Sternum

3. Ribs

4. Head of femur/uterus

How do we know where the bone marrow is?

PET scans

Uses a glucose dye; F-18 fluorodeoxyglucose

Highlights high glucose using areas such as the brain, kidneys, cancer cells or active bone marrow

Name some key facts of red marrow

Red Marrow

• cancellous (spongey part of bone)

• In flat bones, vertebrae, head of bones.

• Produces most blood cells

• Rich blood supply

• Risk of bleeding with fractures

Name 2 key facts about yellow marrow

Yellow Marrow

• Founding long bones

• Produce some WBCs

What type cf cells will you find in the bone marrow ?

What is the total haematopoietic cell production per day in the body ?

3.7 × 10^11 cells per day

How many haematopoietic cells are destroyed/ replaced per second?

4 Million!!!

How much can the production of haematopoietic cells during blood loss/fighting infection ?

10-20 x

What are the steps in blood cell production (haematopoiesis)?

Bone marrow → stem cell → proliferation → myeloid/ lymphoid progenitor → committed precursor → immature cells →mature blood cell

1. Blood cells are derived from the bone marrow this process is called haematopoiesis.

2. Start: Multipotent stem cell

3. Divides (proliferates): into 2 cells. One replaces the stem cell and the other differentiates.

4. Lineage: They either become a oligopotent myeloid or lymphoid progenitor and continue down this lineage.

5. Further differentiation: In the bone marrow to become blast cells (immature).

6. Maturation:

• Myeloid → granulocytes, monocytes/macrophages, megakaryocytes (platelets), Erythrocytes

• Lymphoid → T-cells, B-cells, NK cells

This is another diagram that shows haematopoiesis what do the following stand for:

1. CFU

2. CFU GEMM

3. BFU-E

1. CFU → colony forming unit (a colony of cells are generated from one progenitor cell0

2. CFU GEMM → CFU that can make myeloid cells (granulocytes, erythrocytes, monocytes, megakaryocytes [platelets])

What are CD (cluster of differentiation) proteins ?

• Cell surface molecules that are free used fro the identification og blood cells.

• Can be used to dentist cells at different stages of haematopoiesis.

• Using monoclonal antibodies

What are the CDs of the following blood component:

1. Stem cells

2. ALL WBC + platelets

3. Granulocytes

4. Monocytes

5. T - lymphocytes

6. B-lymphocytes

7. Platelets

8. Eryrobalasts

ERYTHROPOIEIS

Production of RBCs and the maturation over 7 days in the bone marrow

Why can’t RBCs mitose?

They are ANUCLEATE - they don’t contain nuclei

What are the stages of RBC production?

1. Proerythrobasts in bone marrow.

2. Differentiate into ERYTHROBLAST in bone marrow.

3. Reduce in size, produce haemoglobin, lose nuclei.

4. Reticulocytes: immature RBCs, anucleate, mature in the blood over 7 days

5. Mature erythrocytes (RBCs) live in the blood 120 days.

6. Haemolysis in spleen (destruction).

What is one molecule needed foe erythropoiesis?

IRON (for Hb)

• Recycled from destroyed RBCs

• Fond in meats and vegetables

How is Iron stored in the body ?

• In RBCs

• In liver as ferritin

How many years or Iron is stored in males and females ?

• Females: 2.7 years

• Males: 5 years

How is Iron moved from storage into use ?

• Enters through absorbtion and stored in the liver as ferritin.

• Moves into the blood and bind to tranferrin

• Then become function, when delivered to the Hb

What is the percentage of iron in the following component:

1. Body (liver, spleen, muscles)

2. Function (bound to Hb)

1. Body → 30% = 2g

2. Functional → 65% = 2-4g

What food have high levels of Iron ?

• Tuna

• Beef steak

• Baked beans

• Apricots

• Eggs

• Sunflower seeds

Why is vitamin B12 needed for RBS production ?

• For DNA synthesis from production of RBCs

• Absorbed in the ileum , this requires intrinsic factors!

• Pernicious anaemia → autoimmune condition that destroys these instructions factors

• Stored in the liver (2-5years worth)

Why is Folate needed for erythropoiesis ?

• Needed for DNA synthesis.

• Absorbed in the jejunum.

• Stored in the liver 3-4 months

CLINICAL LINK: What can B12/Folate deficiencies cause ?

• macrocytic anaemia

How much folate do u need daily ?

200 - 250 micrograms per day

• Found in uncooked greens

• Orange and bananas

• Deficiency can cause anaemia in months

• Need more during pregnancy, lactation, and when ne has inflammatory disease.

How does hypoxia effect the production of RBCs?

Erythropoietin - hormone produced by the kidneys that stimulates production of RBCs

What happens at destruction of RBCs (haemolysis)?

• RBCs circulate for 120days before being destroyed.

• Destroyed by the spleen/liver when flexibility is lot.

• Iron is recycled to the bone marrow

• Protein (globin) recycled.

• Haem is recycled into bilirubin

• Liver coverts the bilirubin into a water soluble form

• It’s excreted as part of the urine as urbilinogen

• Excreted as bile also (stercobilin makes faeces brown)

CLINICAL: What condition can link to not functional destruction of RBBs?

• Jaundice

• Gall stones

Haematopoiesis Homeostasis

A continuous process where production is equal to loss

What are the life span of the following cells:

• Erythrocytes

• Netrophils

• T-cells

• Platelets

What is the total haematopoietic cell production in the body. ?

• 3.7 × 10^11 cells per day

• 4 million destroyed/ replaced per second

What does the commitment (differentiation) of projector cell depend on?

• growth factors

• Cytokines

Where are haematopoietic growth factors produced ?

• Stromal cell in the bone marrow

• Apart from:

Erythropoietin: synthesised by the kidneys

Thrombopoietin: synthesised by the liver

The growth factors often work in synergy (combinations).

On growth factor may induce the production onanother

Negatively regulating growth factors also exist