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Guyton > Unit 6 > Flashcards

Unit 6 Flashcards

1
Q

How does the site of erythropoiesis change through life?

A

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

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2
Q

How does IL-3 act on the bone marrow?

A

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

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3
Q

What is the developmental journey of a RBC?

A

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

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4
Q

Which RBC precursor is the first to contain haemoglobin?

A

Polychromatophil erythroblast

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5
Q

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

A

1-2 days

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6
Q

Where is EPO produced?

A

90% kidneys
10% liver

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7
Q

What are the steps for EPO production?

A

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

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8
Q

How can non-renal hypoxia stimulate RBC production?

A

Norepinephrine, epinephrine and several prostaglandins stimulate EPO production

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9
Q

How does EPO increase RBC count?

A

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

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10
Q

What is needed for final maturation of RBCs?

A

Vitamin B12 and folic acid

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11
Q

What molecules are needed for haemoglobin formation? Describe the steps

A

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

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12
Q

How many oxygen molecules can one haemoglobin molecule bind?

A

4

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13
Q

Describe iron transport and metabolism

A

pg 444, F 33-7

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14
Q

How and where is iron absorbed?

A

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

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15
Q

How do the lysosomes of macrophages and neutrophils differ?

A

Macrophage lysosomes contain lipases - capable of digesting thick lipid membranes

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16
Q

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

A

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

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17
Q

What are the components of the innate immune system?

A

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

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18
Q

What are the requirements for a substance to be antigenic?

A

Large molecular weight
Must have regularly recurring molecular groups - epitopes

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19
Q

Where are lymphocytes processed?

A

T - thymus
B - liver then bone marrow

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20
Q

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

A

Macrophages
Promotes growth and reproduction of lymphocytes

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21
Q

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

A

IgM

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22
Q

What component of the complement cascade activates phagocytosis?

A

C3b

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23
Q

What complement factors are responsible for lysis of invading organisms?

A

C5b6789

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24
Q

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

A

C5a

25
Q

What complement components activate mast cells and basophils?

A

C3a, C$a abd C5a

26
Q

What are the 7 effects of the compliment cascade?

A

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

27
Q

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

A

Macrophages, B lymphocytes and dendritic cells
T lymphocytes

28
Q

How do APCs present antigen?

A

On MHCs

29
Q

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

A

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

30
Q

What are the most numerous T cells?

A

T helper cells

31
Q

What T cell is CD4+?

A

T helper cell

32
Q

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

A

IL-2

33
Q

Which lymphokines stimulate the B-cell response?

A

IL-4, 5 and 6

34
Q

What T cell is CD8+?

A

Cytotoxic T cell

35
Q

How to cytotoxic T cells exert their effect?

A

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

36
Q

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

A

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

37
Q

What is found in the platelet cytoplasm?

A

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

38
Q

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

A

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

39
Q

What is the half life of a circulating platelet?

A

8-12 days

40
Q

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

A

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

41
Q

What are the possible sequelae following blood clot formation?

A

Invasion by fibroblasts and connective tissue formation
Dissolution

42
Q

What are the three essential steps to clotting?

A

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

43
Q

What is factor I?

A

Fibrinogen

44
Q

What is factor II?

A

Prothrombin

45
Q

What is factor III?

A

Tissue factor

46
Q

What is factor IV?

A

Calcium

47
Q

Where is prothrombin formed?

A

Liver

48
Q

Where is fibrinogen formed?

A

Liver

49
Q

What activates fibrin stabilising factor?

A

Thrombin

50
Q

Briefly describe the extrinsic pathway

A

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

51
Q

Briefly describe the intrinsic pathway

A

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

52
Q

What is needed for the activation of FXI?

A

FXIIa
High-molecular weight kininogen
Accelerated by prekallikrein

53
Q

Which steps of the coagulation cascade are dependent on calcium?

A

All except first 2 steps of intrinsic pathway

54
Q

Which clotting pathway is fastest?

A

Extrinsic

55
Q

What factors prevent blood clotting in the normal vascular system?

A

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)

56
Q

What is heparin’s action?

A

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

57
Q

What are the vitamin K-dependent factors?

A

II, VII, IX, X, protein C

58
Q

Where is vita normally produced?

A

Intestine

59
Q

How does liver disease cause vit K deficiency?

A

Lack of bile prevents adequate fat digestion and depresses vitK absorption

Guyton (10 decks)

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