Unit 6

Question 1

How does the site of erythropoiesis change through life?

Answer 1

Early weeks - yolk sac
Middle trimester - mainly liver (some in spleen and LNs)
Last month of gestation and after birth - bone marrow

Question 2

How does IL-3 act on the bone marrow?

Answer 2

Promotes growth and reproduction of nearly all types of committed stem cells

Question 3

What is the developmental journey of a RBC?

Answer 3

MHSC => CFU-S => CFU-B => CFU-E => pro erythroblast => basophil erythroblast => polychromatophil erythroblast => orthochromatic erythroblast => reticulocyte => erythrocyte

Question 4

Which RBC precursor is the first to contain haemoglobin?

Answer 4

Polychromatophil erythroblast

Question 5

After release from the marrow, how long does it take a reticulocyte to mature?

Answer 5

1-2 days

Question 6

Where is EPO produced?

Answer 6

90% kidneys
10% liver

Question 7

What are the steps for EPO production?

Answer 7

Renal hypoxia => increased tissue HIF-1 - transcription factor for hypoxia-inducible genes
HIF-1 binds hypoxia response element in EPO gene, inducing transcription and EPO synthesis

Question 8

How can non-renal hypoxia stimulate RBC production?

Answer 8

Norepinephrine, epinephrine and several prostaglandins stimulate EPO production

Question 9

How does EPO increase RBC count?

Answer 9

Stimulates production of pro erythroblasts from stem cells, and increases rate of maturation

Question 10

What is needed for final maturation of RBCs?

Answer 10

Vitamin B12 and folic acid

Question 11

What molecules are needed for haemoglobin formation? Describe the steps

Answer 11

2 x succinyl-CoA (from Kreb’s cycle)
2 x glycine
Combine to form pyrrole
4 x pyrrole combine => protoporphyrin IX
Combines with Fe => heme
Heme combines with globin

Question 12

How many oxygen molecules can one haemoglobin molecule bind?

Answer 12

4

Question 13

Describe iron transport and metabolism

Answer 13

pg 444, F 33-7

Question 14

How and where is iron absorbed?

Answer 14

All of small intestine
Liver secretes apotransferrin in bile - combines => transferrin
Complex absorbed by pinocytosis

Question 15

How do the lysosomes of macrophages and neutrophils differ?

Answer 15

Macrophage lysosomes contain lipases - capable of digesting thick lipid membranes

Question 16

What cytokines play dominant roles in the control of the macrophage response to inflammation?

Answer 16

TNF, IL-1, GM-CSF, C-CSF, M-CSF

Question 17

What are the components of the innate immune system?

Answer 17

Phagocytosis
Destruction of swallowed organisms by stomach acid/digestive secretions
The skin
Presence of lysozyme, basic polypeptides, complement and NK lymphocytes in the blood

Question 18

What are the requirements for a substance to be antigenic?

Answer 18

Large molecular weight
Must have regularly recurring molecular groups - epitopes

Question 19

Where are lymphocytes processed?

Answer 19

T - thymus
B - liver then bone marrow

Question 20

Where is IL-1 produced and what is it’s role?

Answer 20

Macrophages
Promotes growth and reproduction of lymphocytes

Question 21

Which antibody class is associated with the primary response to an antigen?

Answer 21

IgM

Question 22

What component of the complement cascade activates phagocytosis?

Answer 22

C3b

Question 23

What complement factors are responsible for lysis of invading organisms?

Answer 23

C5b6789

Question 24

What complement factors are responsible for initiating chemotaxis of neutrophils and macrophages?

Answer 24

C5a

Question 25

What complement components activate mast cells and basophils?

Answer 25

C3a, C$a abd C5a

Question 26

What are the 7 effects of the compliment cascade?

Answer 26

1 - opsonisation and phagocytosis 2 - lysis 3 - agglutination 4 - neutralisation 5 - chemotaxis 6 - mast cell/basophil activation 7 - inflammation

Question 27

What are the 3 major types of antigen presenting cells? Which cells respond to them?

Answer 27

Macrophages, B lymphocytes and dendritic cells T lymphocytes

Question 28

How do APCs present antigen?

Answer 28

On MHCs

Question 29

What are the two types of MHC and what id their purpose?

Answer 29

MHC I - present to cytotoxic T cells MHC II - present to T-helper cells

Question 30

What are the most numerous T cells?

Answer 30

T helper cells

Question 31

What T cell is CD4+?

Answer 31

T helper cell

Question 32

What lymphokine stimulates growth and proliferation of cytotoxic and regulatory T cells?

Answer 32

IL-2

Question 33

Which lymphokines stimulate the B-cell response?

Answer 33

IL-4, 5 and 6

Question 34

What T cell is CD8+?

Answer 34

Cytotoxic T cell

Question 35

How to cytotoxic T cells exert their effect?

Answer 35

Secrete hole-forming proteins - perforins Release cytotoxic substances into the attacked cell

Question 36

What are the mechanisms causing vascular constriction after trauma to a blood vessel?

Answer 36

Local myogenic spasm Local autacoid factors (including thromboxane A2 from platelets Nervous reflexes

Question 37

What is found in the platelet cytoplasm?

Answer 37

1 - actin, myosin and thrombosthenin 2 - ER and Golgi apparatus 3 - mitochondria 4 - enzyme systems for prostaglandin synthesis 5 - fibrin-stabilising factor 6 - growth factor

Question 38

What components make up the platelet surface membrane? What are their function?

Answer 38

Glycoproteins - repulse adherence to normal endothelium but adhere to injured areas Phospholipids - role in activating clotting

Question 39

What is the half life of a circulating platelet?

Answer 39

8-12 days

Question 40

What happens to platelets following contact with a damaged vascular surface?

Answer 40

Swell and assume irregular form with multiple protruding pseudopods Contractile proteins contract and release granules Become 'sticky' - adhere to collagen and vWF Secrete ADP, PAF and thromboxane-A2

Question 41

What are the possible sequelae following blood clot formation?

Answer 41

Invasion by fibroblasts and connective tissue formation Dissolution

Question 42

What are the three essential steps to clotting?

Answer 42

Following vessel damage there is a cascade of chemical reactions, resulting in the formation of prothrombin activator This catalyses the conversion of prothrombin to thrombin This converts fibrinogen into fibrin

Question 43

What is factor I?

Answer 43

Fibrinogen

Question 44

What is factor II?

Answer 44

Prothrombin

Question 45

What is factor III?

Answer 45

Tissue factor

Question 46

What is factor IV?

Answer 46

Calcium

Question 47

Where is prothrombin formed?

Answer 47

Liver

Question 48

Where is fibrinogen formed?

Answer 48

Liver

Question 49

What activates fibrin stabilising factor?

Answer 49

Thrombin

Question 50

Briefly describe the extrinsic pathway

Answer 50

Tissue factor (FIII) released from traumatised tissue Complexes with FVII, in the presence of calcium activated FX Xa complexes with V to form prothrombin activator

Question 51

Briefly describe the intrinsic pathway

Answer 51

Blood trauma causes activation of FXII and release of platelet phospholipids Activates FXI Activates FIX Activates FX (alongside FVIII, FIII and platelet phospholipids)

Question 52

What is needed for the activation of FXI?

Answer 52

FXIIa High-molecular weight kininogen Accelerated by prekallikrein

Question 53

Which steps of the coagulation cascade are dependent on calcium?

Answer 53

All except first 2 steps of intrinsic pathway

Question 54

Which clotting pathway is fastest?

Answer 54

Extrinsic

Question 55

What factors prevent blood clotting in the normal vascular system?

Answer 55

Endothelial factors 1 - smoothness of endothelial cell surface 2 - layer of glycocalyx on the endothelium 3 - thrombomodulin - binds thrombin 4 - production of prostacyclin and NO by norma intact endothelial cells Blood-based factors Fibrin fibres ATIII Heparin (not normally significant)

Question 56

What is heparin's action?

Answer 56

Binds to ATIII and increases activity 100-1000x Removes thrombin and FIX-XIIa

Question 57

What are the vitamin K-dependent factors?

Answer 57

II, VII, IX, X, protein C

Question 58

Where is vita normally produced?

Answer 58

Intestine

Question 59

How does liver disease cause vit K deficiency?

Answer 59

Lack of bile prevents adequate fat digestion and depresses vitK absorption