Atheroma Flashcards
Define atherosclerosis
Thickening and hardening of arterial walls as a consequence of atheroma.
Define atheroma
Accumulation of intracellular and extracellular lipids in the intima and media of large and medium sized vessels
How do fatty streaks appear?
They are lipid deposits in the intima. They are yellowish and appear slightly raised.
What are simple plaques like?
Raised yellow/white, irregular outline, widely distributed, enlarge and coalesce
What are complicated plaques like?
They are formed in thrombosis. Haemorrhage into plaques. Can undergo calcification.
Where are common sites for atheroma formation?
Aorta (especially abdominal aorta) Coronary arteries Carotid arteries Cerebral arteries Leg arteries
How is a normal artery structured?
Endothelium, sub-endothelial connective tissue, internal elastic lamina, muscular media, external elastic lamina, adventitia
What are the early changes in atheroma formation?
Proliferation of smooth muscle cells, accumulation of foam cells, extracellular lipid
What are later changes of atheroma formation?
Fibrotic cap, necrosis, cholesterol clefts, disruption of internal elastic lamina, damage extending into media, ingrowth of blood vessels, plaque fissuring
What are the consequences of ischaemic heart disease?
Sudden death, myocardial infarction, angina pectoris - chest pain on exertion, arrhythmias, cardiac failure
What are consequences of cerebral ischaemia?
Transient ischaemic attack (“mini stroke”), cerebral infarction (stroke), multi-infarct dementia - small infarcts built up
What are the consequences of mesenteric ischaemia?
Ischaemic colitis, malabsorption, intestinal infection
What are the consequences of peripheral vascular disease?
Intermittent claudication, Leriche syndrome (iliac artery affected), ischaemic rest pain, gangrene
List a few risk factors for atherosclerosis
Hyperlipidaemia, cigarette smoking, age, gender (women protected before menopause), hypertension, diabetes mellitus, alcohol, infection
What is the thrombogenic theory?
Plaques are formed by repeated small thrombi
What is the insudation theory?
Endothelial injury, inflammation and increased permeability to lipids from plasma causes plaque formation
What does the reaction to injury hypothesis state?
Plaques form in result of endothelial injury. Injury increases permeability and allows platelet adhesion, monocytes penetrate endothelium, smooth muscle cells proliferate and migrate. (oxidised LDLs could be dangerous)
What does the monoclonal hypothesis state?
Smooth muscle cells play a crucial role in proliferation because each plaque is monoclonal.
What are the processes involved in atheroma formation?
Thrombosis, lipid accumulation, production of intercellular matrix and interactions between cell types
What are the cells involved in atheroma formation?
Endothelial cells, platelets, smooth muscle cells, macrophages, lymphocytes and neutrophils
What role do endothelial cells have?
They have an altered permeability to lipoproteins, secrete collagen, stimulation and proliferation of smooth muscle cells.
What role do smooth muscle cells have?
Take up LDL and other lipids to become foam cells. They synthesis collagen and proteoglycans.
What role do macrophages have?
They oxidise LDLs, take up lipids to become foam cells, secrete proteases which modify the matrix and stimulate proliferation of smooth muscle cells.
What role do lymphocytes have?
T lymphocytes can produce TNF which may affect lipoprotein metabolism. Also stimulate proliferation and migration of smooth muscle cells.
What roles do neutrophils play?
They secrete proteases leading to continued local damage and inflammation
What role do platelets play?
Key role in haemostasis. They stimulate proliferation and migration of smooth muscle cells (PDGF)
What causes endothelial injury?
Raised LDL, toxins, haemodynamic stress and hypertension
What does endothelial injury cause?
Platelet adhesion, PDGF release, smooth muscle cell proliferation and migration, insudation of lipids, LDL oxidation, uptake of lipids by smooth muscle cells and macrophages, migration of monocytes into the intima
What happens in the final stage of the unified theory of atheroma formation?
Stimulated smooth muscle cells produce matrix material, foam cells secrete cytokines causing further smooth muscle stimulation, recruitment of inflammatory cells
How can atheroma formation be prevented?
No smoking, reduce fat intake, treatment of hypertension, not too much alcohol, regular exercise (weight control)
What steps can be take in an intervention for someone with atheroma formation?
Stop smoking, modify diet, treat hypertension, treat diabetes, lipid lowering drugs.
What is angiotensin converting enzyme?
An enzyme which indirectly increases blood pressure by causing blood vessels to constrict. It does this by converting angiotensin I to angiotensin II, which constricts the vessels.
How might an abdominal aortic aneurysm cause death?
Haemorrhage into his abdomen, therefore loss of blood to vital organs causing shock and eventually death. Retroperitoneal (might tamponade) or intraperitoneal leakage of blood. Tamponade (compression).
Grey turner’s sign - bruising of flesh
What dietary factors influencing atherosclerosis?
High intake of fatty foods, cholesterol rich foods and alcohol. Smoking can also affect the likelihood of developing atheromas.
What is prostacyclin and what does it do?
Prostacyclin is a prostaglandin which prevents adhesion and aggregation of platelets to endothelium.
What does thrombomodulin do?
Thrombomodulin binds to any locally formed thrombin and this complex initiates the anti-coagulant effects of protein C and protein S
These molecules inhibit elements of the normal coagulation cascade
