Cellular Components of Blood: Development and Function

Question 1

What composes plasma?

Answer 1

• Plasma if the yellow/straw coloured liquid portion of blood (non-clotted) - Keeps cells in suspension - 92% water - 7% plasma proteins (albumin, fibrinogen, prothrombin) - 1% other substances - electrolytes, nutrients, hormones, gases, waste products. - Serum is plasma devoid of clotting factors (achieved by drawing blood in the absence of an anti-coagulant).

Question 2

What is serum?

Answer 2

Serum is centrifuged blood to remove cellular components. Anti-coagulanted blood yields plasma containing fibrinogen and no clotting factors.

Question 3

Where does haematopoeisis occur most commonly throughout a human lifespan?

Answer 3

• Bone marrow only becomes major producer of RBC about half-way through lifetimes.
• Blood cells regulated by environment by stromal cells.

Question 4

Which types of white blood cells are found in tissues?

Answer 4

• Mast cells
• Dendritic cells
• Macrophages

Macrophages and Dendritic cells come from monocytes.

Question 5

Memorise the diagramatic overview of all blood cell progenitors.

Answer 5

Question 6

How is haematopoiesis regulated?

Answer 6

Production of blood and immune cells is tightly controlled by cytokines and growth factors.

EPO - erythropoietin.

TPO - thrombopoeitin

IL - Interlukin

G-CSF - Granulocyte Colony Stimulating Factor

GM-CSF - Granulocyte Macrophage Colony Stimulating Factor

SCF - Stromal Cell Factor

Question 7

Explain the process of Erythropoiesis

Answer 7

• Erythropoiesis is the process of RBC formation.
• Occurs in the bone marrow.
• Body produces approximately 2.5x10^6 RBC every second.

Hypoxia is detected by kidney cells.

Kidney releases EPO into blood.

Erythropoiesis is regulated by EPO binding to erythropoietin kinase receptor on progenitor cells.

Question 8

Describe the structure of Haemoglobin (Hb).

Answer 8

• 2 identical alpha chains & 2 identical beta chains. Each chain is associated with a Heme molecule.
• Fe molecule in centre
• Porphyrin ring linked to Iron as a co-factor
• Every RBC has around 280 million haemoglobin molecules and each haemoglobin molecule can carry 4 02.

Question 9

What is the lifespan of Red Blood Cells?

Answer 9

120 days.

Question 10

How are erythrocytes recycled?

Answer 10

• Aged cells are removed by macrophages of the spleen.
• Haemoglobin is seperated into Iron and Porphyrin ring.
• Iron transported to bone marrow via transferrin for new RBC production
• Porphyrin ring excreted via digestive or urinary tract.

(Bilirubin - Urine, Biliverdin - faeces)

Question 11

What is the lifespan of platelets?

Answer 11

7-10 days

Question 12

What is the process of platelet production?

Answer 12

• Magakaryocyte (contains 64 copies of DNA)
• Megakaryocytes can produce around 5000 platelets, which occurs through its budding off mechanism. Membrane will extend but platelets will fragment off.
• Thrombocytes are regulated by thrombopoeitein (TPO), produced by the liver and kidneys.
• They secrete PDGF in regulating blood vessels.

Question 13

What are the five cardinal signs of inflammation?

Answer 13

• Pain
• Heat
• Redness
• Swelling
• Loss of Functioning

Question 14

What’s wierd about natural killer cells?

Answer 14

They are part of the innate immune response despite being part of lymphoid progenitor.

They have a relatively long life (around 14 days). They are essential for killing virally infected cells and comrpomise around 15% of WBCs.

Question 15

What are the characteristics and functions of Neutrophils?

Answer 15

• Lifespan: 5.4 days
• 60-70% phagocytic
• Initiate inflammatory process.

Question 16

What are the characteristics and functions of Eosinophils?

Answer 16

Lifespan: 2-5 days

2-5% of WBC

Phagocytic - protection against helminths.

Question 17

What are the characteristics and functions of Basophils?

Answer 17

• Lifespan: 1-2 days
• 0.2% of WBC
• Involved in allergic reactions

Question 18

What are the characteristics and functions of monocytes?

Answer 18

Lifespan: 1-7 days

2-10% of WBC phagocytic

Question 19

What is polycythemia vera and how would you test for it?

Answer 19

Neoplasm in which the bone marrow makes too many red blood cells.

• It may also result in overproduction of white blood cells and platelets.

Question 20

What is Polycythemia vera and what causes it?

Answer 20

• Increased haemoglobin, PCV and RBC numbers
• 95% of cases due to mutation in the gene encoding the cell signalling Janus Kinase 2 (JAK2)
• Complications of PV include thrombosis and haemorrhage

Mutation in gene V617F (valine to phenylalanine mutation) results in constitutive activation of EPO/TPO receptors even in absence of EPO.

Question 21

What is essential thrombocythaemia (another type of Polycythaemia)

Answer 21

• Normal Hb and WBC levels but increased platelet counts.
• Complications include thromboembolic events.
• JAK2 mutation present in 50% of all cases.

Question 22

What is Myelofibrosis/myelosclerosis? (another polycythemia)

Answer 22

• Elevated WBC and platelet count
• 25% of cases preceded by PV
• 50% of cases have a JAK2 mutation.

Question 23

What treatment options are available for those with Polycythaemia vera?

Answer 23

Aims to maintain normal blood count

Venesection - removal of blood (about a 1 pint)

Chemotherapy -

Chemotherapy can suppress immune system in low doses, maybe that’s how it works? Through inhibition of IL-2? Look this shit up?

Question 24

What are the most common systems for grouping blood?

Answer 24

ABO and Rhesus

Question 25

What are A and B antigens?

Answer 25

Present on red cell membrane glycoproteins and glycolipids. The major carriers of A and B on red cells are the abundant N-glycosylated glycoproteins, the anion exchanger (band 3) and the glucose transporter (GLUT1). Glycosyltransferase structure is encoded by different genes **_Type A: N-acetylgalactoaminyltransferase_** **_Type B: galactotransferase_** **_Type O (H): no transferase_**

Question 26

What is present on type A red blood cells?

Answer 26

N-acetylgalactoaminyltransferase

Question 27

How can Rhesus Disease develop?

Answer 27

Two genes encode this blood group: - Most important is D - Why is D antigen important? - Because it is capabale of resulting in Rhesus disease.

Question 28

Explain the Rh blood group system

Answer 28

- 5 major Rh antigens - D, C, E, c and e - most immunogenic is D. - Encoded by two genes: RHD and RHCE - Individuals can be homozygous for RHD (2 copies) or hemizygous (1 copy). - All express D antigen on RBC - Individuals where RHD is deleted have no expression of D antigen. - Individuals are RhD+ or RhD- - No anti-D antibodies present in blood

Question 29

How does Rhesus disease manifest?

Answer 29

- 85% of population - Range in effect: mild anaemia of newborn to intrauterine death 18 weeks after gestation - HDN is relatively rare - alleviated through routine antenatal serology and administration of Anti-D therapy - Anti-D immunoglobulin will bind and neutralise any RhD+ cells preventing the development of maternal antibodies.

Question 30

Which blood group would make you a universal recipient and a universal donor?

Answer 30

Question 31

Explain the process of agglutination.

Answer 31

Agglutination is an immune response factilitated by antibody-antigen interactions. Agglutination is detrimental in vivo. This is not coagulation

Question 32

Work out possible blood types of a baby based on mother and father's blood types. (or just memorise this diagram).

Answer 32