atherosclerosis

Question 1

what is atherosclerosis

Answer 1

the hardening and narrowing of the blood vessels

Question 2

how does atherosclerosis affect the heart and vascular system

Answer 2

• if the vessels become blocked this then reduces blood flow, causing ischemia
• cells may die leading to necrosis which can lead to an MI

Question 3

what are the layers to the blood vessels (inner to outer)

Answer 3

1. endothelial layer
2. tunica intima
3. tunica media (smooth muscle)
4. tunica adventitia

Question 4

what are some key features of the endothelial layer

Answer 4

• has tight junctions
• usually smooth
• low levels of adhesion molecules
• is an active layer

Question 5

what are the different stages of plaque formation called

Answer 5

1. fatty streaks
2. plaque formation
3. plaque growth
4. plaque rupture
5. clotting

Question 6

how does plaque formation progress

Answer 6

1. fatty streaks build up in the intima
2. this then starts to build up and begins to bulge
3. increase in growth not through the lumen but there is a decrease in lumen size
4. when the plaque becomes unstable it then ruptures the endothelium and begins to leak into the lumen
5. this then triggers the clotting cascade

Question 7

symptoms of plaque build up in the carotid arteries

Answer 7

• reduced blood flow to the brain
• increased risk of stroke
• asymptomatic until a rupture occurs

Question 8

symptoms of plaque build up in the coronary vessels

Answer 8

• reduced flow of blood supplying to the heart
• intermittent angina in initial stages until complete occlusion

Question 9

symptoms of plaque build up in peripheral vasculature

Answer 9

• reduction of blood flow to extremities
• common blockages in the legs
• cramping and tissue discolouration

Question 10

how are lipids metabolised

Answer 10

1. bile salts and lipase break down lipids
2. monoglycerides and fatty acids absorbed into cells
3. these are then formed into chylomicrons to release into the blood stream
4. chylomicrons are too large to be absorbed into peripheral tissue but when they contact lipase in the vessel walls they care broken down and fatty acids are released

Question 11

what are chylomicrons

Answer 11

digested fats to carry lipids into the bloodstream. produced by intestinal epithelial cells

Question 12

what does LDL do

Answer 12

transports lipids to cholesterol to where it is neede

Question 13

what does HDL do

Answer 13

it is transported back to the liver when the cells no longer need it

Question 14

stages of liver LDL synthesis

Answer 14

1. liver cells synthesis VLDL release into vessels
2. lipase in vessel walls removes triglycerides
3. fatty acids and monoglycerides are taken up by tissue
4. IDLs return to the liver
5. IDLs are altered into LDLs by removing triglycerides
6. LDL is taken up by receptors on peripheral tissues
7. LDL is broken down and cholesterol used to synthesise plasma membranes
8. Excess cholesterol released and absorbed by HDLs
9. HDLs taken up by liver and cholesterol are extracted
10. Cholesterol use in LDL synthesis. HDL is recycled into the bloodstream
    - (cycle then joins in at point 5)

Question 15

what happens when there is too much LDL

Answer 15

the build up of LDL will sit around and then build up to form plaque

Question 16

what causes LDL to build up in the vessles

Answer 16

injury, causing damage to the vessel walls.

Question 17

stages of LDL build up tiggering plaque growth

Answer 17

1. endothelial injury allows LDL into the vessel walls
2. this builds up into fatty streaks and can become oxidised
3. macrophages recognises the Ox-LDL through scavenger and Toll like receptors
4. Ox-LDL is then phagocytosed
5. Pro-inflammatory cytokines are released by the macrophages and endothelial cells
6. inflammation upregulates the adhesion molecules on the vessel lumen, recruiting monocytes and T cells into the tissue
   - (more inflammation means more damage which then means more LDL build up)

Question 18

stages of inflammation leading to plaque growth

Answer 18

1. recruited T cells and Th1 secrete INFy which enhances macrophage phagocytosis
2. this cause inflammatory cytokine release which perpetuates inflammation
3. growth factors are also released by the macrophages to stimulate the smooth muscle cells proliferation and migration into the intima
4. macrophages become full of Ox-LDL and turn into foam cells
5. some macrophages undergo apoptosis releasing the lipids and forming swollen necrotic core
6. the smooth muscle cell proliferation causes them to migrate into the intima
7. MMPs are more inflammatory cytokines are released and collagen is deposited forming a stable plaque
8. any cells that become necrotic explode causing another inflammatory response

Question 19

stages of plaque rupture causing clotting

Answer 19

1. plaque continues to grow as foam cells and smooth muscle cells accumulate
2. small vessels grow into the plaque as it expands, helping its growth
3. changes in composition of smooth muscle and collagen leads to weaker cap and the plaque can rupture
4. interior of the plaque is exposed the clotting cascade is activated
5. platelets bind to the extracellular matric and clotting cascade is activated
6. clots may the break off and cause a thrombus

Question 20

stages of clot forming a thrombus

Answer 20

1. exposed extracellular matrix activates von Willebrand factor bound to collagen
2. platelets and erythrocytes gather and platelet receptors interact with vWF and adhesion molecules
3. platelets release their granule contents to recruit more platelets
4. the clotting cascade results in prothrombin activation which cleaves thrombin to make fibrin
5. fibrin forms a mesh over the erythrocytes and platelets forming a stable clot

Question 21

what are the clotting cascade pathways

Answer 21

• intrinsic pathway
• extrinsic pathway

Question 22

what is the main outcome of the clotting cascade

Answer 22

• the activation of thrombin
• fibrin - which when activated cross links the platelet plug to make a stable clot

Question 23

what are risk factors for artherosclerosis

Answer 23

• age
• obesity
• hypertension
• stress
• diabetes
• smoking