Atheroma (Wed 25th)

Question 1

Can you list the risk factors and epidemiology of atheroma?

Answer 1

Age – middle to late.
Sex – Males.
Western countries (USA, Europe, Russia, Australia, New Zealand)
Immigrants to these countries.

Potentially Modifiable Risk Factors
Hyperlipidemia  – HDL/LDL
Hypertension.
Smoking.
Diabetes.
Obesity.

Non Modifiable RF
Age – middle to late.
Sex – males. 
Family history.
Genetic

Question 2

Define atheroma

Answer 2

Deposits of fibrous tissue and lipid on arterial walls. Atheroma = Atheromatosis = Atherosclerosis
All arteries larger than 1 mm diameter can be affected. Maximum atheroma occurs at sites of haemodynamic stress (high blood flow)
e.g. bifurcations: the point at which division into two branches occurs

Question 3

What are the main clinical effects of atheroma?

Answer 3

Atheroma causes ischaemic heart disease and myocardial infarction.
Vascular consequences:
1. Aneurysm- blood filled balloon like bulge in a blood vessel. The commonest site for aneurysm is the infrarenal abdominal aorta. The patient with a ruptured aneurysm presents with severe abdominal or back pain, and is often shocked due to blood loss (hypovolemia). This is a surgical emergency, and grafting is required.
2. Luminal narrowing results in ischaemia if severe enough (75%). An example is chest pain on exertion due to narrowing of the coronary arteries (angina).
3. Luminal occlusion is due to thrombosis or embolism.
This will often result in infarction of the part served.
An example is myocardial infarction due to thrombosis of a coronary artery.

Organ consequences:
1. HEART
If atheroma causes narrowing, chest pain/angina
If atheroma causes occlusion (blockage) myocardial infarction.
2. BRAIN
Narrowing = CHRONIC ISCHAEMIC DEMENTIA
Occlusion = INFARCTION
3. LEG
Narrowing= CLAUDICATION  (calf pain)
Occlusion= GANGRENE
4. BOWEL
Narrowing= CHRONIC ISCHAEMIC COLITIS  (abdominal pain , bloody diarrhoea)
Occlusion= ACUTE ISCHAEMIC ENTEROCOLITIS (bowel necrosis)
5. KIDNEY
Narrowing= RENAL ATROPHY= hypertension
Occlusion= RENAL INFARCTION

Question 4

Can you describe the mechanisms involved in the development of atheroma?

Answer 4

There are six stages:
1) Foam Cells: Smooth muscle of endothelial thickens to adapt to high BP. 1st decade
2) Fatty Streak Develops: On the wall of the artery lipid laden histioctyes accumulates. 1st decade
3) Intermediate Lesion: pool of extracellular lipids forms. 3rd decade
4) Now we have atheroma, the extracellular lipid forms a core and the intracellular lipids form the outside.
5) Now have fibroatheroma, fibrous thickening. Smooth muscle cells migrate from the media and proliferate.
Fibrosis develops around the lipid, and forms a cap over the lesion.
6) Have a complicated lesion: there is a rupture, heamotoma (a solid swelling of clotted blood within the tissues.) The plaque may undergo calcification, visible on X-ray. Inflammation associated with the plaque destroys the media which undergoes fibrosis, and is weakened.

Injury to the endothelium triggers monocyte adhesion, a loosening of endothelial cell junctions, and migration of monocytes beneath the endolthelium where they differentiate into macrophages. The more permeable endothelium also permits LDL to enter the intima of the artery, and macrophages begin engulfing the LDL by phagocytosis. After macrophages become laden with lipid from ingesting LDL, they are referred to as “foam cells,” and collections of these create fatty streaks.
T-lymphocytes, which are also in the intima. They secrete cytokines that eventually induce smooth muscle cells to migrate from the media to the intima. These smooth muscle cells also begin to proliferate under the influence of growth factors. Over time there is a progressive accumulation of lipid and smooth muscle cells in the intima, and eventually the growing lesion begins to raise the endothelium and encroach on the lumen of the artery.

Endothelial cells INJURY = DYSFUNCTION
Inflammation= T LYMPH/ MONOCYTES
Fibroblasts (vascular wall)= PROLIFERATION AND FIBROSIS
Lipid (LDL cholesterol)= POOLING

Question 5

Difference thrombosis/ blood clot

Answer 5

Thrombosis: solid mass of blood constituents in vascular system, in life.
FIBRIN: Polymer
PLATELETS: tiny compared to red blood cell.
Entrapped RBCs and serum.

Blood clot: Clotting means coagulation, It can occur within or outside the vascular system, In life or post mortem

Question 6

RF Thrombosis

Answer 6

1) endothelial damage
2) abnormal blood flow
3) hypercoagulability
primary/genetic susceptibility
secondary/ aquired: prolonged bed rest

Question 7

Sudden Cardiac Death

Answer 7

in children: myocarditis and coranary artery anomolies
in adults:
in adults: atheroma with acute thrombosis or atheroma with stable plaque