Mechanism of atheroma and infarction (Physiology)

♡ Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, leading to restriction of the circulation and a risk of thrombosis

♡ Obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue

♡ Lipoproteins transfer fats around the body, so they are available to be taken up by the cells via receptor mediated endocytosis

♡ The lipids carried by LDLs include cholesterol, phospholipids, and triglycerides

♡ Mediated by low density lipoprotein (LDL), angiotensin II and various inflammatory substances

♡ Carotid arteries

♡ Circle of Willis

♡ Coronary arteries

♡ Iliac arteries

♡ Aorta

Activation of Endothelial Cells:

Inflammatory triggers activate arterial endothelial cells.

Oxidized LDL particles, stimulated by necrotic cell debris and free radicals, contribute to this activation.

Expression of Inflammatory Signals:

Activated endothelial cells express cytokines and adhesion molecules in response to LDL and inflammation.

Monocyte Adhesion and Migration:

Circulating monocytes bind to the activated endothelium.

These monocytes express adhesion molecules and migrate into the intimal layer.

Differentiation and Mediator Release:

Monocytes differentiate into macrophages within the tissue.

Macrophages release inflammatory mediators, leading to an immune response in the affected area.

1)

-Macrophages begin to accumulate LDL from the circulation and become foam cells

2)

-Activated foam cells release other growth factors which cause smooth muscle cells to leave the medial layer and cross the internal elastic lamina entering the intima

3)

-The activated smooth muscle cells also release growth factors and may also begin synthesising collagen and elastin in the intima layer

1)

-Smooth muscle cells accumulate LDL becoming a second type of foam cell, but they continue to make extracellular matrix of elastin and collagen which forms a fibrous plaque

2)

-Cells underneath this plaque become oxygen starved they begin to undergo apoptosis and release their fat which forms a globule of fat that is now accumulating in the intima, known as the lipid core

3)

-The dying cells release matrix metalloproteases and other enzymes which can break down the fibrous matrix towards the edge of the plaque leaving a large lipid core covered by a thinner fibrous plaque.

Atheroma

-These are visible on a CT scan

♡ The role of calcium deposits remains uncertain, there have been arguments that calcification may actually stabilise the plaque

♡ Calcium may be a bad thing, but paradoxically a lot of calcium deposits rather than a few could be a slight advantage.

♡ If the central core becomes too large, plaque rupture can occur and the sub-endothelium is exposed. The endothelium is normally an anticoagulant surface

♡ Collagen forms a very good bases for clotting along with other proteins and factors in the intima

♡ This gives us a procoagulant surface in an artery

e.g. Myocardial infarction

-Commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle

e.g. Ischaemic stroke

-In this case obstruction due to an embolus from elsewhere in the body (usually carotid artery) blocking blood supply to part of the brain

-Other types of ischaemic strokes occur

e.g. Aortic aneurysm

-Cause weakness in the wall of the aorta and increase the risk of aortic rupture

-When rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur

♡ Particularly cardiac and carotid arteries. Anything downstream from arterial occlusion becomes starved of oxygen

♡ The reduced blood flow can lead to symptoms such as angina on exercise

♡ A thrombus becoming detached can block the cardiac arteries (MI)or cerebral arteries (stroke) and cause death or serious damage very quickly.

♡ We tend to think of it as happening in the legs, but here an occlusion doesn’t cut off the oxygen supply

♡ It will cause pain and swelling, as hydraulic pressure causes oedema

♡ However, a thrombus may detach and return to the right side of the heart and could enter the pulmonary circulation causing a pulmonary embolism

♡ Acute cardiac failure

♡ Conduction problems – arrhythmia

♡ Papillary damage – valve dysfunction

♡ Mural thrombosis - stroke

♡ Wall rupture

♡ Chronic heart failure – myocardial scarring

♡ Thrombus at carotid plaque rupture travels into smaller cerebral vessels

♡ 85% from carotid atheroma rupture, 15% from stasis in left atrium due to arrhythmia

♡ Due to hypoperfusion, loss of blood pressure (e.g. heartfailure, haemorrhage, shock), or aneurysm rupture andbleeding in the brain