Haematopoiesis

Question 1

What does blood plasma contain?

Answer 1

• Water
• Small organic compounds (eg glucose) and electrolytes (sg. Sodium)
• Proteins: Albumin, Globulins (α, β, γ), Fibrinogen – involved in clotting

Question 2

What type of cells give rise to all blood cells and where are they found?

Answer 2

Haemopoietic stem cells (HSCs) in the bone marrow give rise to all haemopoietic cell lineages

Question 3

What are the general stages of haematopoiesis?

Answer 3

1) Proliferation – mitosis, making more cells
2) Differentiation – which lineage will the cell go down?
3) Maturation – after a cell has committed to being a certain type, it will develop

These processes overlap.

The process is dependent on glycoprotein growth factors produced mainly by bone stromal cells – exceptions being erythropoietin (kidneys) and thrombopoietin (liver).

Question 4

List the different types of potency from most potent to least potent

Answer 4

Totipotent cells can differentiate into any cell type, including embryonic and extraembryonic

Pluripotent cells can differentiate into any cell type of the embryo

Multipotent cells can differentiate into several different, but related cell types

Oligopotent cells can differentiate into a small number of very closely related cell types

Unipotent cells can produce more cells of identical cell type

Question 5

What cell types can arise from the common myeloid progenitor?

Answer 5

• Megakaryocyte
• Erythrocyte
• Mast cell
• Myeloblast

Question 6

What cell type can arise from a megakaryocyte?

Answer 6

thrombocytes

Question 7

What cell type can arise from myeloblasts?

Answer 7

• Basophil (granulocyte)
• Neutrophil (granulocyte)
• Eosinophil (granulocyte)
• Monocyte -> Macrophage

Question 8

What cell type can arise from the common lymphoid progenitor?

Answer 8

• Natural killer cell

- Small lymphocyte

Question 9

What cell types can arise from the small lymphocyte?

Answer 9

• T lymphocyte

- B lymphocyte -> plasma cell

Question 10

Describe the characteristics of the 3 types of granulocytes

Answer 10

Neutrophils are phagocytic, with lytic enzymes within granules, including peroxidase and lysozyme - very effective in killing ingested bacteria

Eosinophils are most important in defence against larger parasites

Basophils are non-phagocytic and release active substances from their granules

Question 11

Describe the differences between monocytes and macrophages

Answer 11

Monocytes circulate in the blood

Macrophages are formed by differentiation of monocytes are 5-10x bigger and found in the tissues

Macrophages ingest small pathogens and other material by phagocytosis

Question 12

Describe the stages in thrombopoiesis

Answer 12

Thrombopoiesis = production of platelets

Megakaryoblast → Promegakaryocyte
→ Megakaryocyte → Thrombocytes (Platelets)

Megakaryocytes in the bone marrow are situated adjacent to blood sinusoids.
Segments of megakaryocyte cytoplasm protrude into the blood sinusoids.
The blood flow splits off cytoplasmic fragments, which become platelets.
Platelets circulate in the blood for 7 -10 days.
40% are located in the spleen.

Question 13

What is leukocytosis?

Answer 13

High white cell count

Question 14

What is leukopenia?

Answer 14

Low white cell count

Question 15

What is lymphocytosis?

Answer 15

High lymphocyte count

Question 16

What is lymphocytopenia?

Answer 16

Low lymphocyte count

Question 17

What is neutrophilia?

Answer 17

High neutrophil count

Question 18

What is neutropenia?

Answer 18

Low neutrophil count

Question 19

What is thrombocytosis?

Answer 19

High platelet count

Question 20

What is thrombocytopenia?

Answer 20

Low platelet count

Question 21

Describe erythropoiesis

Answer 21

Proerythroblast → Erythroblast → Reticulocyte → Erythrocyte

Question 22

What are the 4 characteristics of erythrocyte maturation?

Answer 22

1) Decrease in cell size
2) Haemoglobin production
3) Loss of organelles (inc. nucleus)
4) Acquisition of biconcave disc shape

It is controlled by erythropoietin (EPO) and requires Iron, Folic acid and Vitamin B12

Question 23

What is the purpose of the biconcave shape in erythrocytes?

Answer 23

1) Maximises surface area
2) Minimises distance from surface
3) Increases flexibility

Structural proteins to maintain shape

Simplified internal structure (lack organelles)

Simplified metabolism

Question 24

What vitamins etc. are required for erythropoiesis and why?

Answer 24

Folic acid (B9), Cobalamin (B12) and Intrinsic factor are required for DNA synthesis

Vitamin B6 and Iron are needed to make the globin chains and haem for haemoglobin synthesis

Question 25

What can cause megaloblastic/pernicious anaemia?

Answer 25

Folic acid (folate; vitamin B9) is required for DNA synthesis and therefore cellular proliferation Cobalamin (vitamin B12) is involved in the recycling of folic acid Lack of either can lead to megaloblastic anaemia, although plentiful folic acid can ameliorate the effects of vitamin B12 deficiency ``` Intrinsic Factor (IF) is a glycoprotein produced by the parietal cells of the stomach. It binds to vitamin B12 and is essential for it’s absorption in the ileum. Lack of Intrinsic Factor, most often due to an autoimmune response to parietal cells, leads to pernicious anaemia (megaloblastic anaemia) ```

Question 26

Where in the body are folic acid and cobalamin absorbed and how long are they stored for?

Answer 26

``` Folic acid (B9) is absorbed in the duodenum and jejunum. Normal stores of folic acid last about 3-7 months. Folic acid deficiency can arise from inadequate intake, malabsorption, increased demand, drugs (e.g. alcohol). ``` Cobalamin (B12) is absorbed in the terminal ileum. Normal stores of cobalamin last about 3-4 years. Cobalamin deficiency is usually due to malabsorption (rarely inadequate intake).

Question 27

Name some inherited disorders of the globin chains

Answer 27

α or β thalassemia, sickle cell anaemia

Question 28

How are haem groups synthesised?

Answer 28

Synthesis of haem groups occurs by a metabolic pathway, with steps in the mitochondria and cytoplasm. Vitamin B6 is an essential co-enzyme in this pathway

Question 29

What are inherited disorders in heme synthesis called?

Answer 29

Porphyrias

Question 30

Where is iron stored?

Answer 30

Most of the absorbed iron is transported to the bone marrow where it is used to make haem. The remainder is stored in the liver and spleen or used by other tissue cells in enzymatic processes. Iron absorption is regulated by the hormone hepcidin, which is released by the liver when iron levels are too high. Hepcidin inhibits iron absorption by decreasing ferroportin activity on the basolateral membrane of intestinal epithelial cells.

Question 31

Define anaemia

Answer 31

A deficiency of red cells or haemoglobin in the blood

Question 32

Define macrocytic anaemia

Answer 32

Involves large erythrocytes, but in low number and/or with low Hb content per cell

Question 33

Define microcytic anaemia

Answer 33

Involves small erythrocytes and usually low Hb content per cell

Question 34

Define normocytic anaemia

Answer 34

Involves erythrocytes of normal size, but usually present in inadequate number

Question 35

Describe iron deficiency anaemia and its causes

Answer 35

Deficiency of iron leads to decreased amounts of haemoglobin; low levels of haemoglobin in turn decreases the production of RBCs Caused by blood loss, diet low in iron, poor absorption of iron

Question 36

Describe pernicious anaemia and B vitamin deficiency

Answer 36

RBCs do not develop as they normally would because of a lack of B vitamins (B9, B12), which leads to decreased production of RBCs Causes: Lack of intrinsic factor, diet low in B vitamins, decreased absorption of B vitamins

Question 37

Describe aplastic anaemia and its causes

Answer 37

Bone marrow is unable to produce enough blood cells; a life threatening condition Causes: Cancer therapy, exposure to toxic substances, autoimmune disorders, viral infections

Question 38

Describe haemolytic anaemia and its causes

Answer 38

RBCs are destroyed faster than the bone marrow can replace them Inherited causes include sickle cell and thalassemia

Question 39

Describe anaemia of chronic diseases and its causes

Answer 39

Various illnesses over a long time can reduce the production of RBCs Causes: Rheumatoid arthritis, kidney disease, diabetes, tuberculosis or HIV

Question 40

What is erythropoietin (EPO)?

Answer 40

Erythropoietin (EPO) is released by fibroblasts in the kidneys in response to cellular hypoxia and stimulates erythropoiesis in the bone marrow. It binds to a specific receptor on proerythroblasts / basophilic erythroblasts and promotes cell survival.

Question 41

What is thrombopoietin?

Answer 41

Thrombopoietin is produced in the liver and elsewhere and primarily stimulates the differentiation of megakaryocytes and thrombocytes (platelets). There is a negative feedback loop in which thrombocytes reduce thrombopoietin levels.