Session 6 Flashcards
What is atherosclerosis?
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is atheroma?
Thickening and hardening of arterial walls as a consequence of atherosclerosis
What is arteriosclerosis?
Thickening of the walls of arteries and arterioles
Arteriosclerosis is often as a result of… (2)
Hypertension
Diabetes mellitus
What causes the fatty streak that can be seen in atherosclerosis?
Lipid deposits in tunica intima
What appearance do fatty streaks take in atherosclerosis?
Yellow, slightly raised
Describe the appearance of a simple plaque in atherosclerosis
Raised yellow/white
Irregular outline
Widely distributed
What can be seen as a result of a ‘complicated plaque’ (4)
Calcification
Thrombosis
Haemorrhage into plaque
Aneurysm formation
List some common sisters of atherosclerosis (5)
Aorta (particularly abdominal aorta) Coronary arteries Carotid arteries Cerebral arteries Leg arteries
Name the different layers of an artery from inside to outside
Endothelium Sub-endothelial connective tissue (tunica intima) Internal elastic lamina Tunica media External elastic lamina Tunica adventitia
What early microscopic features might your see in atherosclerosis? (3)
Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid
What later microscopic features might you see in atherosclerosis? (4)
Fibrosis
Necrosis
Cholesterol clefts
Inflammatory cells
What further microscopic features (after early and later changes) might be seen in atherosclerosis? (4)
Disruption of internal elastic lamina
Damage extends into media
Ingrowth of blood vessels
Splitting/cracking of plaque
Name 4 potential clinical effects of atherosclerosis
Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease
Name two potential consequences of ischaemic heart disease as a result of atherosclerosis
MI
Angina
Name two potential consequences of cerebral ischaemia as a result of atherosclerosis
Transient ischaemic attack
Cerebral infarction
Give the colloquial name for a transient ischaemic attack
Give the colloquial name for a cerebral infarction
Mini-stroke
Stroke
Name a potential consequence of mesenteric ischaemia as a result of atherosclerosis
Ischaemic colitis
Name two potential consequences of peripheral vascular disease
Gangrene
Intermittent claudication
What is the main symptom of intermittent claudication
Pain in the calves when walking
What is a plaque?
A raised patch on or within the body resulting from local damage of deposition of material
E.g. Fatty deposit on an artery wall in atherosclerosis
List some predisposing factors for atherosclerosis
Age Gender Hyperlipidaemia Cigarette smoking Hypertension Diabetes Alcohol Infection Lack of exercise Obesity Soft water Oral contraceptives
How does age work as a predisposing factor for atherosclerosis?
Slowly progressive throughout adult life
How does gender work as a predisposing factor for atherosclerosis?
Women are generally protected before the menopause
How does hyperlipidaemia work as a predisposing factor for atherosclerosis?
High plasma cholesterol associated with atherosclerosis
Which lipoprotein is most significant in contributing to atherosclerosis?
Which lipoprotein is protective against hyperlipidaemia?
LDL
HDL
What is the most powerful risk factor for atherosclerosis/Ischaemic Heart Disease?
Cigarette smoking
> __ units a day of alcohol is associated with increased risk of IHD?
5
Is there genetic predisposition for the onset of atherosclerosis?
Yes
Name the 4 theories of atherosclerosis pathogenesis
Thrombogenic theory
Insudation theory
Monoclonal hypothesis
Reaction to injury hypothesis
Describe the thrombogenic theory of atherosclerosis pathogenesis
Describe the insudation theory of atherosclerosis pathogenesis
Plaques formed by repeated thrombi, with the lipid derived from thrombi and an overlying fibrous cap
Considered the role of endothelial injury/inflammation in the formation of atherosclerotic plaques. Stated that the plaque gained lipid from the circulating plasma.
Describe the monoclonal hypothesis of atherosclerosis pathogenesis
Hypercholesterolaemia leads to endothelial damage and as a result plaque formation. Injury increases permeability and allows platelet adhesion. Monocytes penetrate the endothelium. Smooth muscle cells proliferate and migrate.
How does the reaction to injury hypothesis further explain atherosclerosis pathogenesis?
Has a crucial role for smooth muscle proliferation with each plaque being composed of monoclonal smooth muscle cells
Name the 4 main processes involved in atherosclerosis
Thrombosis
Lipid accumulation
Production of extracellular matrix
Interactions between cell types
List 6 cells that are involved in atherosclerosis
Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes Neutrophils
Describe the role of endothelial cells in atherosclerosis
Important role in haemostasis
Have altered permeability to lipoproteins
Produce collagen
Stimulate proliferation/migration of smooth muscle cells
What role do platelets play in atherosclerosis?
Important role in haemostasis
Stimulate proliferation/migration of smooth muscle cells
How do platelets stimulate the proliferation/migration of smooth muscle cells?
Through the production of PDGF
What role do smooth muscle cells play in atherosclerosis?
Take up LDL and other lipid to become foam cells
Synthesise collagen and proteoglycans
What role do macrophages play in atherosclerosis?
Oxidise LDL
Take up lipids to become foam cells
Secrete proteases which modify the matrix
Stimulate the proliferation/migration of smooth muscle cells
What role do lymphocytes play in atherosclerosis?
Produce TNF which can affect lipoprotein metabolism
Stimulate proliferation/migration of smooth muscle cells
What do lymphocytes produce that can affect lipoprotein metabolism?
TNF
What role do neutrophils play in atherosclerosis?
Secrete proteases leading to continued local damage and inflammation
In a unifying hypothesis of atherosclerosis, endothelial injury occurs which is due to… (4)
Raised LDL
Toxins - e.g. Cigarette smoke
Hypertension
Haemodynamic stress
In a unifying hypothesis of atherosclerosis, endothelial injury occurs which causes… (3)
Platelet adhesion, PDGF release and smooth muscle cell proliferation/migration
Accumulation of lipid, LDL oxidation, uptake of lipid by smooth muscle cells/macrophages
Migration of monocytes into the intima
State two cells that can take up lipid in atherosclerosis
Smooth muscle cells
Macrophages
In atherosclerosis, stimulated smooth muscle cells produce…
Matrix material
What do foam cells secrete in atherosclerosis?
What does this result in? (2)
Cytokines
Further smooth muscle stimulation
Recruitment of other inflammatory cells
List 5 preventative measures of atherosclerosis
No smoking Reduced fat intake Treat hypertension Not too much alcohol Regular exercise Weight control
