cardiovascular pathology

Question 1

epidemiology of coronary heart disease

Answer 1

deaths from ischaemic heart disease have increased globally as high calorific intake

Question 2

modifiable risk factors

Answer 2

smoking, lipids intake, blood pressure, diabetes, obesity, sedentary lifestyle

Question 3

non-modifiable risk factors

Answer 3

age, sex, genetic background

Question 4

changes in epidemiology over last decade

Answer 4

reduced hyperlipidaemia (statin), reduced hypertension, increased obesity so increased diabetes

Question 5

atheroscleoris focality

Answer 5

at branching, turbulent flow so plaques more likely to form

Question 6

LDL deposition

Answer 6

deposit in subintimal space and binds to matrix proteoglycans - endothelium becomes leaky - inflammatory reaction

Question 7

progression

Answer 7

adaptive thickening - macrophage foam cells - preatheroma (EC lipid) - atheroma (core EC lipid) - fibroatheroma (fibrous thickening) - complicated lesion (fissure and haemotoma, thrombus; stratified); if fibrous thickening doesn’t happen enough fibres can crack apart, triggering thrombus, blocking artery - myocardial infarction; stenosis

Question 8

clinical interventions

Answer 8

secondary prevention, catheter based interventions, revascularisation surgery, treatment of heart failure

Question 9

main cell types

Answer 9

vascular endothelial cells (barrier function, leukocytes recruitment), platelets (thrombus generation, cytokine and growth factor release), monocyte-macrophages (metalloproteinases make firbous cap thinner), vascular smooth muscle cells (collagen so thicker fibrous cap), T lymphocytes

Question 10

LDL

Answer 10

cholesterol from liver to rest of body

Question 11

HDL

Answer 11

cholesterol from peripheral tissues back to liver

Question 12

oxidised LDL

Answer 12

highly inflammatory and toxic forms of LDL in vessel walls

Question 13

modification of LDLs in atheroclerosis

Answer 13

LDL leaks through endothelial barrier - binds to sticky matrix proteoglycans - oxidised LDL by free radicals - phagocytosed by macrophages (foam cells) - chronic inflammation

Question 14

familial hyperlipidemia

Answer 14

elevated cholesterol as failure to clear LDL from blood; xanthoma (skin) and foam cell (artery); if untreated myocardial infarction before 20

Question 15

scavenger LDL receptor

Answer 15

scavenger, not under feedback control, bind oxidised LDL in atheroclerosis; normal receptor under negative feedback by IC cholesterol (statins lower plasma cholesterol)

Question 16

macrophage scavenger receptors

Answer 16

A and B both bind to oxidised LDL, but also bind to dead cells (A: gram +ve, B: malaria parasites); inflammatory or homeostatic

Question 17

macrophage plaques

Answer 17

posess oxidative enzymes that generate free radicals - further oxidise lipoproteins (LDL) (positive feedback)

Question 18

enzymes

Answer 18

NADPH oxidase, myeloperoxidase

Question 19

phagocytose modified lipoproteins

Answer 19

become foam cells

Question 20

express cytokine mediators

Answer 20

recruit monocytes (positive feedback - self-perpetuating inflammation)

Question 21

cytokines

Answer 21

activate endothelial cell adhesion molecules; IL-1 (upregulates vascular cell adhesion molecule VCAM-1), VCAM-1 (mediates tight monocyte binding)

Question 22

chemokines

Answer 22

chemoattractant to monocytes; MCP-1 (binds to monocyte GPCR)

Question 23

express chemoattractants and growth factors for VSMC

Answer 23

wound healing; recruit smooth muscle cells and stimulate them to proliferate and deposit EC matrix SLIDE 26

Question 24

IHD

Answer 24

narrowing of coronary arteries cause ischaemia in heart muscle - progressive worsening as more O2 required but not available so more ischaemia - biggest cause