MoD S7 - Atheroma Flashcards

Question

How is apolipoprotein E related to atheroma development?

Answer 1

Genetic variations in Apo E are associated with changes in LDL levels Polymorphisms of the genes involved lead to at least 6 phenotypes These phenotypes can be used as risk markers for atheroma

Answer 2

Genetically determined abnormalities of lipoproteins These lead to early development of atheroma Associated physical signs include: - Corneal Arcus (ring around the cornea) - Tendon xanthomas (cholesterol rich lipid deposition in tendons) - Xanthelasma (raised deposits of fat around the eyes/eyelids)

Answer 3

Thrombogenic theory Insudation theory Monoclonal hypothesis Reaction to injury hypothesis Can be collected to form the 'Unified theory'

Answer 4

Thrombogenic: - Plaques formed by repeated thrombi sticking to the arterial wall - Then somehow becoming associated with lipid - A cap then forms over the thrombus - This is repeated over and over as the plaques grow Insudation: - Some method of endothelial injury - This leads to inflammation - This increases the permeability of the vessel wall to lipids allowing lipids into the vessel wall from the plasma

Answer 5

Plaques form in response to endothelial injury Hyperlipidaemia leads to the endothelial damage Injury increases permeability and allows platelet adhesion Monocytes penetrate into endothelium and become foam cells Smooth muscle cells proliferate and migrate Later suggested that: - Endothelial injury was so subtle as to be undetectable visually - Oxidised LDL may be what is damaging the endothelium

Answer 6

Smooth muscle cell proliferation is crucial Each plaque is monoclonal Each plaque might therefore represent a benign tumour due to abnormal growth control Also a viral aetiology suggested

Answer 7

Thrombosis Lipid accumulation Production of intercellular matrix Interactions between cell types

Answer 8

``` Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes Neutrophils ```

Answer 9

Key role in haemostasis (pro and anti coagulant effects) Their permeability to lipoproteins is altered They secrete collagen (major structural protein in the plaques, may be abnormal in atheroma) Stimulate the proliferation and migration of smooth muscle cells

Answer 10

Key role in haemostasis Stimulation of proliferation and migration of smooth muscle cells via platelet derived growth factor

Answer 11

Proliferate and migrate Take up LDL and other lipids and become foam cells Synthesise collagen and proteoglycans (for the intercellular matrix that may be abnormal in atheroma)

Answer 12

Oxidise LDL Take up lipids and become foam cells Secrete proteases which modify matrix (can have an effect on plaque stability/rupture/fissure) Stimulate the proliferation and migration of smooth muscle cells

Answer 13

Produce TNF that may affect lipoprotein metabolism Stimulate proliferation and migration of smooth muscle cells

Answer 14

Secrete proteases leading to continued local damage and inflammation, which then in turn may lead to atheroma Proteases can also modify the proteins of the intercellular matrix affecting the stability of the plaque (more likely to rupture/fissure)

Answer 15

Subtle endothelial injury due to: - Raised LDL - Toxins (E.g. Cigarette smoke) - Hypertension - Haemodynamic stress This injury leads to: - Platelet adhesion, platelet derived growth factor release and subsequent smooth muscle cell proliferation and migration - Insudation of lipid, LDL oxidation, uptake of lipid by smooth muscle cells and macrophages - Migration of monocytes into intima Stimulated smooth muscle cells then produce matrix material Foam cells secrete cytokines causing: - Further smooth muscle cell stimulation - Recruitment of other inflammatory cells

Answer 16

``` No smoking Reduce fat intake Treat hypertension Limit alcohol Regular exercise/weight control ``` However some people will still develop atheroma even if they adhere to all these points

Answer 17

``` Stop smoking Modify diet Treating hypertension (if present) Treating diabetes (if present) Lipid lowering drugs (statins) ```

Answer 18

Unsaturated fats that will raise levels of LDL in the blood are going to increase the chance of developing atherosclerosis if eaten in excess

Answer 19

Reduce unsaturated fat intake Eat a balanced diet, include more fruits and vegetables, lean protein sources Limit cholesterol intake Limit total fat and calorie intake Reduce salt intake

Answer 20

Genetic (E.g. Familial hypercholesterolaemia) Geographical - Less common in the mediterranean (diet) Ethnicity - CHD more common in Asians

Answer 21

``` Smoking Gender (More prevalent in males) Hypertension (increased endothelial damage) Diabetes mellitus (increased IHD risk) Alcohol (>5 units/day) Infection (E.g. helicobacter pylori) ```