Atherosclerosis Flashcards
Define Atheroma
Accumulation of Intracellular and extracellular lipid in the intima and media of large/ medium sized arteries
Define Atherosclerosis
The thickening and hardening of arterial walls as a consequence of Atheroma
Define Arteriosclerosis
The thickening of the walls of arteries and arterioles, due to hypertension or Diabetus Mellitus
What 2 conditions are causes by Atherosclerosis, making it the biggest killer in the world?
MI
Stroke
Describe the 3 stages/ Macroscopic features of Atherosclerosis
- Fatty streak (Early stages);
- Lipid deposit in intima
- Yellow, slightly raised - Simple plaque;
- Raised yellow/ white
- Irregular outline
- Widely distributed
- Enlarge and coalesce - Complicated plaque (Other things happen);
- Ulceration (Fibrous cap eroded from underneath)
- Thrombosis
- Haemorrhage into plaque
- Calcification
- Aneurysm formation
Name the 5 most common sites of Atherosclerosis
Aorta (Especially abdominal) Coronary arteries Carotid arteries Cerebral arteries Leg arteries
What are the 3 early changes in Microscopic features of Atherosclerosis
Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid deposition
What are the 6 later changes in Microscopic features of Atherosclerosis
- Necrosis and fibrosis
- Cholesterol clefts
- Disruption of internal elastic lamina
- Damage extends into media
- Ingrowth of blood vessels from adventitia
- Plaque fissuring
What are cholesterol clefts?
What are the 3 basic components of a plaque?
Needle shaped clefts left in the plaque, after cholesterol crystals have been dissolved by solvents used in microscopy
- Cells (Macrophages, WBCs, smooth muscle cells)
- Intra and Extracellular lipid
- ECM (Collagen, Elastin, Proteoglycans)
What conditions are caused by Atherosclerosis at;
- Heart
- Brain
- Kidneys
- Legs
- Bowel
- Ischaemic heart disease
- Cerebral ischaemia
- kidneys- Abdominal Aortic Aneurysm
- Legs- Peripheral vascular disease
- Bowel- Mesenteric ischaemia
What are 5 outcomes of Ischaemic heart disease
Sudden death MI Angina Arrhythmia Cardiac failure
What are 3 outcomes of Cerebral Ischaemia
- Transient ischaemic attack (Mini stroke, resolves in <24h)
- Cerebral infarction (Stroke)
- Multi-Infarct dementia
What are 3 outcomes of Mesenteric Ischaemia
Ischaemic colitis
Malabsorption
Intestinal infarction
What are 2 outcomes of Peripheral Vascular Disease
Gangrene
Intermittent claudication
What are 2 outcomes of Abdominal Aortic Aneurysm in Kidneys
Hypertension
Renal failure
Identify 11 risk factors for Atherosclerosis
DISHH GAFAAG
Diabetes (-> Hypercholesterolaemia) Infection Smoking Hyperlipidaemia (High LDL) Hypertension
Gender
Age
Familial hyperlipidaemia
Alcohol consumption (Excess, small amounts protect)
Apolipoprotein E Genotype
Geography (Lower in Asia, South America, Africa)
How is gender a risk factor for atherosclerosis
What 3 organisms cause infection which may lead to atherosclerosis
Women are relatively protected before menopause
(Hormones?)
Chlamidyia pneumoniae
Helicobater pylori
Cytomegalovirus
Explain how genetics can make you more likely to get Atherosclerosis in 2 ways?
Variations in Apolipoprotein metabolism
Variations in Apolipoprotein receptors
What are the 3 theories of of how Atherosclerosis comes about?
- Thrombogenic Theory/ Encrustations Hypothesis
- Monoclonal Hypothesis
- Reaction to injury hypothesis/ Insudation Theory
Describe the Monoclonal Hypothesis
Each plaque is monoclonal, so plaques could be benign
Possibly Induced by virus/ cholesterol
Describe the Thrombogenic theory/ Encrustation hypothesis
Plaques are formed by repeated thrombi and lipid deposit is derived from the thrombi
Describe Reaction to injury hypothesis/ Insudation Theory
Atherosclerosis is chronic inflammation due to endothelial injury
Increased Permeability leads to;
- Monocytes penetrate endothelium
- Extracellular lipid deposition + Foam cells
- SMC proliferation
What 4 processes are involved in atherosclerosis
Thrombosis
Lipid accumulation
Production of intercellular matrix
Interactions between cell types
What 6 cells are involved in Atherosclerosis
Endothelial cells Platelets SMCs Macrophages Lymphocytes Neutrophils
What are 2 roles of Endothelial cells in Atherosclerosis?
- Produce collagen
- Stimulate proliferation and migration of SMCs
What are 2 roles of Smooth Muscle Cells in Atherosclerosis?
- Take up lipid to become Foam Cells
- Make collagen + proteoglycans
What are 3 roles of Macophages in Atherosclerosis?
- Take up lipids and LDL to become foam cells
- Stimulate Proliferation and migration of SMCs
- Modify matrix by secreting proteases
What is the role of Platelets in Atherosclerosis?
- Stimulate Proliferation and migration of SMCs
What is the role of Neutrophils in Atherosclerosis?
- Secrete proteases leading to continued local damage and inflammation
What are 2 roles of Lymphocytes in Atherosclerosis?
- TNF affect lipoprotein metabolism
- Stimulate SMC proliferation and migration
Outline Stage 1 of the Unifying Hypothesis
Endothelial injury due to;
- Raised LDL
- Toxins
- Hypertension
- Haemodynamic stress
Outline Stage 2 of the Unifying Hypothesis
Endothelial injury causes;
- Platelet adhesion
- SMC proliferation and migration
- Lipid insudation and LDL oxidation
- Lipid uptake by SMCs and Macrophages
- Monocyte accumulation in intima
Outline Stage 3 of the Unifying Hypothesis
- SMCs produce matrix material
- Foam cells secrete cytokines
Suggest 7 methods of prevention/ intervention of Atherosclerosis
- No smoking
- Reduce fat intake
- Treat hypertension
- Reasonable alcohol Intake
- Regular exercise/ weight control
- Treat Diabetes Mellitus
- Lipid lowering drugs (Statins)
Describe the cellular events leading to Atherosclerosis, in 5 steps
- Chronic endothelial injury (Hyperlipidaemia, Hypertension, Smoking) leads to Endothelial dysfunction
- Lipid+monocytes accumulate in intima, macrophages ingest lipid-> Foam cells
- Fatty streak: Foam cells make endothelium bulge, SMCs migration and proliferation
- Plaque grows, SMCs take up lipid, SMCs form a ‘roof’ over plaque and secrete collagen, elastin-> ‘fibrous cap’. Endothelium stretches-> Gaps in plaque that are filled by platelets
- Necrosis in centre of plaque, cholesterol released-> Cholestrol crystals, Blood vessels grow into plaque, Calcification
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