Red Cells

Question 1

1. where does haematopoiesis occur prenatally?
2. where does haematopoiesis occur postnatally in early years
3. where does haematopoiesis occur in adults?

Answer 1

1. yolk sac, then liver and spleen
2. bone marrow of tibia and fibula
3. bone marrow of vertebrae and pelvis

Question 2

1a. name the progenitors derived from the common myeloid progenitor
1b. name the cells derived from the above progenitors
2. name the cells derived from the common lymphoid progenitors
3. which progenitor gives rise to:
a) innate immune cells
b) adaptive immune cells

Answer 2

1a. megakaryocyte and erythroid progenitor.
granulocyte and macrophage progenitor
1b. megakaryocytes/platelets and erythrocytes
mast cells. basophils. eosinophils. neutrophils.
monocytes (monocytes give rise to macrophages and
dendritic cells)
2. B cells and T cells
3a. myeloid progenitors
3b. lymphoid progenitors

Question 3

1. How are the kidney’s involved in the regulation of erythropoiesis?
2. Where are aged/damaged red cells removed?
3. Describe the sequence of the breakdown of haemoglobin

Answer 3

1. they respond to hypoxia and release EPO into the blood. EPO then binds to the EPO receptor on progenitor cells and promotes erythropoiesis
2. by macrophages and the spleen
3. Hb is separated into iron and porphyrin ring. Iron is transported back to the bone marrow via transferrin. Porphyrin ring is excreted as bilirubin/biliverdin by digestive or urinary systems

Question 4

1. What is the name of platelet production?
2. From which cells are platelets formed from?
3. what factor regulates platelet production?

Answer 4

1. thrombopoiesis
2. megakaryocytes, a derivative of the common myeloid progenitor
3. TPO

Question 5

What is the general role of:

1. neutrophils
2. eosinophils
3. basophils
4. monocytes
5. natural killer cells

Answer 5

1. phagocytosis
2. phagocytosis
3. mediate immune reactions
4. phagocytosis. Also differentiate into tissue macrophages or dendritic cells
5. kill virally infected cells.

Question 6

1a. what is polycythaemia vera?
1b. complications?
2a. what is essential thrombocythaemia?
2b. complications?
3. what is myelofibrosis?
4. what gene are these conditions associated with and how?
5. name 3 treatments of these disorders

Answer 6

1a. an increase in Hb, haematocrit and RBC numbers
1b. thrombosis and haemorrhage
2a. an increase in platelets (with normal Hb and WBC numbers(
2b. thromboembolic events
3. elevated WBCs and Platelets
4. JAK2. This acts downstream of the EPO and TPO receptors. Mutations result in constitutive activation of the receptor, leading to excessive proliferation of erythroid, myeloid and megakaryocytic progenitor cells.
5. Venesection. Chemotherapy. Low dose aspirin to treat thrombotic episodes.

Question 7

1. what happens when serum from different ABO blood groups is mixed?

Answer 7

1. Agluttination

Question 8

1. what is anaemia?

2. name signs and symptoms of anaemia

Answer 8

1. a reduced number of RBCs or a decreased amount of Hb
2. pallor
   tachicardia
   glossitis (painful and swollen tongue)
   koilonchia (spoon nails)
   dark urinefatigue, lethargy
   weakness, dizziness, palpitations
   shortness of breath

Question 9

1. What does MCV stand for?
2. What does MCH stand for?
3. Name the 2 general aetiologies of anaemia

Answer 9

1. mean cell volume
2. mean cell hameoglobin
3. excessive destruction of mature red cells or inadequate production of red cells

Question 10

1. What is the name of the condition that specifically effects erythropoiesis?
2. name 3 causes of this condition (1)
3. what is the name of the condition that affects all blood cells production (haematopoiesis)

Answer 10

1. pure red cell aplasia
2. diamond-blackfan anaemia (congenital PRCA)
   primary PRCA - idiopathic
   secondary PRCA - due to exposure to pathogenic agents)
3. pancytopenia

Question 11

1. what is the name of the type of anaemia whereby functional erythrocytes are destroyed?
2. name the 2 general mechanisms that lead to this type of anaemia
3. name 2 examples of immune mediated anaemia
4. how can immune mediated anaemias be characterised by blood film?
5. name an example of a haemoglobinopathy

Answer 11

1. haemolytic anaemia
2. intrinsic - something intrinsically wrong with the erythrocyte so it is destroyed. e.g hameoglobinopathy
3. allo-immune haemolysis - e.g. rhesus disease
   auto-immune haemolytic anaemia - autoantibodies against erythrocytes. Can be idiopathic, secondary (due to lymphoproliferative disorders or other autoimmune disorders) or drug induced (drug binds to surface of RBC and act as antigen; eg. penicillin allergy)
4. schisocytes and polychromasia - fragments of erythrocytes and larger blue tinged reticulocytes
   nucelated erythrocytes
   spherocytes (small cells)
5. sickle cell anaemia

Question 12

1. what is sideroblastic anaemia?

2. how is B6, B12 and folate involved in the production of haem/erythrocytes (4 points)

Answer 12

1. anaemia caused by the failure of iron to be encorporated into haem. Caused by mutations in genes that regulate the expression of key enzymes involved in haem synthesis. A consequence is the formation of iron rich mitochondria, called sideroblasts; they surround the nucleus of erythrocyte precursors.
2. B6 is required by succinylcholine, which is involved in the formation of porphyrin.
   B12 acts as a co-enzyme for ALA synthase, which is involved in the formation of porphyrin
   B6 and B12 are required for enzymatic processes in the mitochondria
   B12 and folate are essential for the DNA synthesis in erythrocyte proliferation

Question 13

which anaemias are:

1. microcytic? (3)
2. normocytic? (2)
3. macrocytic? (2)

Answer 13

1. iron deficiency anaemia, anaemia of chronic inflammation and sideroblastic anaemia
2. haemolytic anaemia, anaemias of chronic disease
3. vitamin B12 deficiency. folic acid deficiency

Question 14

1. describe the mutation in sickle cell anaemia

2. what is thalassaemia?

Answer 14

1. a glu to val mutation in the Hb beta gene, results in the formation of HbS. Under hypoxic conditions, a hydrophobic patch is exposed, meaning that the Hb chains aggregate.
2. a haemoglobinopathy resulting from mutations in the alpha or beta globulin chain. Common in people of African or Mediterranean ethnicity.

Question 15

1. what is contained in the alpha granules of platelets? (4)
2. what is contained in dense granules of platelets? (3)
3. what is the function of von willebrand factor? (3)
4. what do platelets possess receptors for? (4)

Answer 15

1. adhesive proteins such as fibrinogen, fibronectin and von Willebrand factor
   platelet specific proteins such as PDGF
   membrane proteins - GPIIaIIIb, GPIb/IX/V
   alpha granule specific proteins such as P selectin

2. vasoconstrictive agents such as serotonin
platelet agonists (ATP, ADP)
Ca and Mg

3. acts as a stabiliser for factor III - protects it from degradation and localises it to the site of platelet plug formation
   binds to platelet surface glycoproteins, and to components of connective tissue of subendothelium, providing the link between platelets and damaged vessels.
4. agonists such as ADP, thrombin and thromboxane A2
   GPIb/IX/V complex that interracts with vWF
   GPIIb-IIa complex - this complex interracts with vWF and provides a site for fibrinogen binding
   GPIa/IIa complex and GOVI - site for collagen interaction.

Question 16

1. describe the process of platelet adhesion
2. describe the process of platelet release reaction
3. describe the process of platelet aggregation

Answer 16

1. following vessel damage, platelets are exposed to the sub-endothelial layer (containing collagen) and vWF. Platelets adhere to exposed collagen and vWF.
   blood flow rolls the platelet along the subendothelium, promoting more associations
   firmer adhesion initiates platelet activation
2. platelets change shape and undergo degranulation
   aDP and thromboxane A2 activate nearby platelets (positive feedback)
   serotonin and thromboxane A2 act as vasoconstrictors
3. ADP causes other platelets in the area to become sticky. This causes them to adhere to the originally activated platelets. Eventually, the accumulation and attachment of large numbers of platelets form a platelet plug

Question 17

1. what is the extrinsic pathway triggered by?
2. what is the intrinsic pathway triggered by?
3. how do both pathways converge?
4. describe the extrinsic pathway
5. describe the intrinsic pathway
6. Describe the common pathway.

Answer 17

1. triggered by trauma
2. triggered by internal damage to vessel wall (e.g. atherosclerosis)
3. both activate factor X which proceeds to the common pathway
4. tissue factor (factor III) leaks from cells into bloodstream. In presence of Ca, it forms a complex with factor VII that activates factor X
5. contact with collagen fibres activates clotting factor XII, which begins a sequence of reactions involving factors XI, IX and VIII to activate factor X
6. n the presence of Ca, clotting factor X combines with clotting factor V to produce prothrombinase.
   prothrombinase catalyses the conversion of prothrombin to thrombin. thrombin converts fibrinogen to fibrin
   thrombin also activates factor XIII which strengthens and stabilises the fibrin threads

Question 18

what clotting factors are deficient in the following:

1. haemophillia A
2. haemophillia B

Answer 18

1. VIII
2. IX
   * both intrinsic pathway