Haemopoiesis

Question 0

Where are blood cells produced? What is the difference in the distribution of this organ in childhood and adulthood?

Answer 0

Bone marrow (by progenitor stem cells - haemocytoblasts)

Child: extensive distribution (need to produce a lot of RBCs in a small amount of bone)

Adult: limited distribution (central only e.g. pelvis, sternum, skull, ribs, vertebrae)

Question 1

What are the survival times for red blood cells, platelets, neutrophils, and lymphocytes?

Answer 1

Red blood cells = 120 days

Platelets = 10 days

Neutrophils = 2-4 days

Lymphocytes = 1 days (apart from memory cells - years)

Question 2

Which cytokines stimulate the development of what blood cells?

Answer 2

Erythropoietin = stimulate RBC production

Thrombopoietin = stimulate platelet production

Granulocyte-colony stimulating factor = stimulate basophil & neutrophil production

Granulocyte-macrophage colony stimulating factor = stimulate neutrophils, eosinophils, basophils, monocytes, and erythrocytes

Interleukins = stimulate lymphoid cells

Tumour necrosis factor = causes apoptosis of tumours

Question 3

How and where do you biopsy bone marrow?

Answer 3

Trephine biopsy

Take core from iliac crest

Question 4

How can you measure RBCs?

Answer 4

Red cell count

Haemoglobin

Mean corpuscular volume (size of each RBC)

Question 5

Outline the formation of different myeloid blood cells.

Answer 5

Myeloid progenitor —> Mast cells, Erythrocyte, Megakaryocyte, Myeloblast

Megakaryocyte —> Thrombocytes

Myeloblast —> Basophils, Neutrophils, Eosinophils, Monocytes

Monocyte —> Macrophage

Question 6

Outline the formation of lymphoid blood cells.

Answer 6

Lymphoid progenitor cells —> Small lymphocytes, Natural killer cells

Small lymphocyte —> B-lymphocytes, T-lymphocytes

B-lymphocyte —> Plasma cells

T-lymphocyte —> CD4+ helper cells, CD8+ suppressor cells

Question 7

Describe the important structural features of erythrocytes.

Answer 7

Biconcave disc

Globin chains protect haem molecule from oxidation, confer solubility, and permit variation in O2 affinity (by allowing a change in conformation)

Ankyrin anchors spectrin to cell membrane

+ actin & adducin & bands 3 and 4.1 & glycophorin

Question 8

Describe the functions of erythrocytes.

Answer 8

• Deliver O2 to all tissues and CO2 to the lungs
• Carry Hb
• Maintain Hb in its reduced state
• Maintain osmotic equilibrium
• Generate ATP (for O2 exchange)

Question 9

Give an example of a RBC disorder caused by defects in the cytoskeleton of the RBC membrane.

Answer 9

Hereditary spherocytosis = depletion of spectrin (~50%) —> rounded cells less resistant to lysis —> haemolysis —> haemolytic anaemia
(most commonly due to ankyrin defect)

Hereditary elliptocytosis = spectrin unable to form heterotetramers —> fragile ellipsoid cells —> haemolytic anaemia

Question 10

What metabolic pathways can take place in RBCs?

Answer 10

• glucose metabolised to lactate (generates ATP) (as no mitochondria are present)
• G-6-P metabolised to generate NADPH (protection against reactive oxygen species/prevents Heinz bodies formation)

Question 11

How is erythropoiesis regulated?

Answer 11

Interstitial peritubular kidney cells detect low pO2

Increase in erythropoietin synthesis

Increase in maturation and release of RBCs from bone marrow

Increase in haemoglobin

Increase in pO2

Decrease in erythropoietin synthesis

Question 12

How is haemoglobin metabolised?

Answer 12

Haem —> Bilirubin (liver)

Bilirubin —> Gall bladder —> Bile duct —> Small intestine —> Large intestine —> Stercobilin

Bilirubin —> Kidney —> Urobilinogen

Question 13

How are platelets formed?

Answer 13

Megakaryocytes produce platelets (cell fragments, therefore no nucleus) by increasing in cell size and replicating DNA, and platelets then bud from the cytoplasm.

Thromopoietin controls platelet production

Most platelets stored in spleen

Question 14

What are the functions of platelets?

Answer 14

• adhesion to connective tissue
• aggregation with other platelets (hence keep agitated when stored)
• phospholipid membrane forms Ca2+ bridges with Gla domains of clotting factors

Question 15

What are the three main components of platelet structure?

Answer 15

Alpha granules (glycoproteins) 
Glycoprotein receptors (help clotting factors and other platelets bind to the phospholipid membrane)
Dense bodies

Question 16

Summarise platelet adhesion and aggregation to damaged vessel walls.

Answer 16

Damage to vessel wall —> exposure of von Willebrand’s factor receptor —> platelets adhere (platelet plug)

Release of ADP from granules —> glycoprotein receptors exposed —> aggregation of platelets/clotting factors

Question 17

Outline the action of neutrophils at wound sites.

Answer 17

Neutrophils adhere to blood vessel wall near to damaged cell when stimulated by activating substances released from bacteria and damages tissues

Neutrophils cross the plasma membrane by diapedesis when stimulated by histamine (sign of inflammation)

Neutrophil phagocytoses bacteria that have entered the wound site, and digests the bacteria using lysozymes

Question 18

What is the reticuloendothelial system?

Answer 18

Immune system containing phagocytic cells (e.g. monocytes, macrophages, Kupffer cells, microglial cells, histiocytes) which identify and mount an appropriate immune response to foreign antibodies

Blood —> spleen & liver
ECF —> lymphatic system —> lymph nodes

Question 19

When are different myeloid cells active?

Answer 19

Neutrophils = active in bacterial infection

Eosinophils = mediate hypersensitivity reactions e.g. asthma, skin inflammation

Basophils = allergic reactions

Question 20

Outline the function of B-lymphocytes.

Answer 20

Humoral immunity = action of antibodies against antigens in the tissues

Express antigen-specific immunoglobulins and transform into plasmablasts (become plasma cells in the bone marrow and produce immunoglobulins) or memory cells (by interacting with T-cells)

Question 21

Outline the function of T-lymphocytes.

Answer 21

Cellular immunity = activation of phagocytes, T-lymphocytes, and cytokines in response to an antigen (no antibodies involved)

Migrate to thymus and undergo T-cell receptor rearrangement to recognise immunoglobulins

• CD4+ helper cells = induce proliferation of T & B cells and activate marophages
• CD8+ suppressor cells = cytotoxic activity and induces apoptosis

Question 22

Outline the functions of natural killer cells.

Answer 22

Have membrane-receptors for antigen-antibody complexes presented to them by B-cells

Recognise self (histiocompatibility antigens) and kill non-self cell lines by lysis

Kill viruses and tumour cells

Part of innate immune system