7) Pathology of cardiovascular disease (CVD)

• Atherosclerosis is the accumulation of fatty material (consisting mainly of cholesterol, fibrous material and calcium) forming an atheroma or plaque beneath the endothelium.
• As the atheroma grows the artery thickens and loses its elasticity. The diameter of the lumen becomes reduced and blood flow becomes restricted resulting in increased blood pressure.
• Atherosclerosis is the root cause of various cardiovascular diseases (CVD) — angina, heart attack, stroke and peripheral vascular disease.
• Atheromas may rupture damaging the endothelium.

  The damage releases clotting factors that activate a cascade of reactions resulting in the conversion of the enzyme prothrombin to its active form thrombin.
• Thrombin causes molecules of the plasma protein fibrinogen to form threads of fibrin.
• The fibrin threads form a meshwork that clots the blood, seals the wound and provides a scaffold for the formation of scar tissue.
• The formation of a clot (thrombus) is referred to as thrombosis.
• In some cases, a thrombus may break loose forming an embolus that travels through the bloodstream until it blocks a blood vessel.
• A thrombosis in a coronary artery may lead to a myocardial infarction (MI), commonly known as a heart attack.

  A thrombosis in an artery in the brain may lead to a stroke.

  Cells are deprived of oxygen leading to death of the tissues.
• Peripheral vascular disease is narrowing of the arteries due to atherosclerosis of arteries other than those of the heart or brain.
• The arteries to the legs are most commonly affected.

  Pain is experienced in the leg muscles due to a limited supply of oxygen.
• A deep vein thrombosis (DVT) is a blood clot that forms in a deep vein, most commonly in the leg.

  This can break off and result in a pulmonary embolism in the lungs.
• Cholesterol is a type of lipid found in the cell membrane. It is also used to make the sex hormones — testosterone, oestrogen and progesterone.
• Cholesterol is synthesised by all cells, although 25% of total production takes place in the liver.

  A diet high in saturated fats or cholesterol causes an increase in cholesterol levels in the blood.
• HDL transports excess cholesterol from the body cells to the liver for elimination. This prevents accumulation of cholesterol in the blood.
• LDL transports cholesterol to body cells.
• Most cells have LDL receptors that take LDL into the cell, where it releases cholesterol
• Once a cell has sufficient cholesterol a negative feedback system inhibits the synthesis of new LDL receptors and LDL circulates in the blood, where it may deposit cholesterol in the arteries forming atheromas.
• A higher ratio of HDL to LDL will result in lower blood cholesterol and a reduced chance of atherosclerosis.
• Regular physical activity tends to raise HDL levels.
• Dietary changes aim to reduce the levels of total fat in the diet and to replace saturated with unsaturated fats.
• Drugs, such as statins, reduce blood cholesterol by inhibiting the synthesis of cholesterol by liver cells.