IMED3001 Lecture Notes - Lecture 9: Dyslipidemia, Hyperlipidemia, Thrombophilia
26 Mar 2020
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ATHEROSCLEROSIS+HYPERTENSION
ATHEROSCLEROSIS:
• Disease of large and medium sized arteries
o Hardening of the arteries
• An artery wall thickens and hardens as a result
of build-up of fatty materials- FORMING
PLAQUES or ATHEROMAS
• Nomenclature:
o Arteriosclerosis: general term for
thickening and hardening of arteries for
any reason (there are other causes besides
atherosclerosis)
o Atherosclerosis: when an artery wall
thickens as a result of a build-up of fatty
material (atheroma/atheromatous
plaques)
o Atherogensis: the process of development
of atheromatous plaques
o Arteriolosclerosis: thickening and
hardening of arterioles (most often due to
hypertension of diabetes, NOT result of
atherosclerosis)
Why is it a problem?- Atherosclerosis:
• Arteries are blocked
o either PARTIALLY or completely
o Either SLOWLY or SUDDENLY
• Which reduces or completely stops the flow of
blood to the tissues that the artery supplies,
causing tissue damage
• Artery walls are weakened
• Predisposition to thrombus formation
• HOW BIG IS THE PROBLEM:
o Leading cause of death in the developed
world (mostly due to ischaemic heart
disease and stoke)
o Over half of the deaths per year in the US
are attributable to atherosclerosis
o Decrease in the mortality of IHD in
developed countries but on the rise in
developing countries
Major factors:
• Non-modifiable: increasing age, male, family Hx
• Modifiable: hyperlipidaemia (LDL vs HDL),
hypertension, cigarette smoking, diabetes
• Lesser/uncertain risk factors for atherosclerosis
o Up to 20% of cardiovascular events occur in
the absence of overt risk factors
• Other possible risk factors include
o Inflammation
o Hyperhomocystinaemia
o Metabolic syndrome (central obesity, insulin
resistance, hypertension, dyslipidaemia,
hypercoagulability, pro-inflammatory state)
o Lipoprotein a
o Haemostatic factors
o Other (inc. lack of exercise, “stress”, type A
personality, obesity)
• Multiple risk factors:
o Have additive effect
o 2 major risk factors increases risks of IHD by
4x
o 3 major risk factors increases risks of IHD by
7x
Causes of
Atherosclerosis:
• Endothelium dysfunction
• Dyslipidaemia
• Inflammatory and immunologic factors
• Plaque rupture
• Smoking
Response to injury hypothesis:
• It’s a chronic inflammatory response initiated
by injury of the endothelium
• Endothelial injury → inflammation →
fibroproliferative tissue response →
plaque formation in the tunica intima
1. Injury to the endothelium:
o Oxidised LDL cholesterol,
infectious agents (? In animals),
toxins (by products of cigarettes)
o Elevated blood sugar, elevated
homocysteine, haemodynamic
factors
2. Inflammation
o Injured EC develop surface
adhesion molecules to bind
monocytes and T-lymphocytes
o Monocytes migrate through the
endothelium and engulf lipids to
become foam cells
o T cells use cytokines to stimulate
monocytes, ECs and SM cells
3. Fibroproliferative response:
o SM cells migrate from the MEDIA OF THE
ARTERY into the intimia and produce CT
elements like collagen
Classification of Atherosclerotic Lesions:
• Fatty streak:
o Universal, develops in
childhood
o Can regress
o Not all fatty streaks
become atheromas
o Irreversible ones = fibrous atheromas or
fibrous tissues as they are scarring and
fibrosis has occurred and cannot be
reverse
Document Summary
Atherosclerosis: disease of large and medium sized arteries, hardening of the arteries, an artery wall thickens and hardens as a result of build-up of fatty materials- forming. Major factors: non-modifiable: increasing age, male, family hx, modifiable: hyperlipidaemia (ldl vs hdl), hypertension, cigarette smoking, diabetes. Lesser/uncertain risk factors for atherosclerosis: up to 20% of cardiovascular events occur in the absence of overt risk factors, other possible risk factors include. Atherosclerosis: endothelium dysfunction, dyslipidaemia, plaque rupture, smoking. It"s a chronic inflammatory response initiated by injury of the endothelium: which reduces or completely stops the flow of. In animals), toxins (by products of cigarettes: elevated blood sugar, elevated homocysteine, haemodynamic factors. Irreversible ones = fibrous atheromas or fibrous tissues as they are scarring and fibrosis has occurred and cannot be reverse: sm cells migrate from the media of the. Artery into the intimia and produce ct elements like collagen.
