Atherosclerosis, Thrombosis and Embolism PDF

Atherosclerosis, Thrombosis and Embolism PAT2121 Olaf Woods The circulatory system Wiggers diagram  Arteriosclerosis Thickening, hardening and loss of elasticity of the walls of arteries Gradually restricts the blood flow t...

Atherosclerosis, Thrombosis and Embolism PAT2121 Olaf Woods The circulatory system Wiggers diagram  Arteriosclerosis Thickening, hardening and loss of elasticity of the walls of arteries Gradually restricts the blood flow to one's organs and tissues Commonest cause is atherosclerosis Prime disorder leading to death and morbidity in West 20 - 50% of all deaths are due to atherosclerosis and its complications, half being myocardial infarction  Atherosclerosis What is atherosclerosis?  Atherosclerosis What is atherosclerosis? An intimal-based lesion composed of a fibrous cap and an atheromatous cap. The constituents of the plaque include smooth muscle cells, extracellular matrices, inflammatory cells, lipids and necrotic debris.  Atherosclerosis Basic Lesion of Atheroma Fatty deposits in wall of arteries, called plaques Lesions start as fatty streaks, in childhood Progress to intimal plaques (cholesterol covered by a fibrous cap) Finally complicated atheroma with calcium deposits in plaque  Atheromatous Plaques Lipid (LDL) present in: – macrophages (from blood monocytes) – smooth muscle cells from media – extracellularly - cholesterol crystals Fat turns into amorphous (no shape) mass of lipid and debris Inflammatory cells infiltrate the plaque Damaged wall becomes thin and is later calcified  Arteriosclerosis (Atherosclerosis) large & medium sized arteries: arteriosclerosis – elastic arteries - aorta, iliac arteries – muscular arteries - coronary, carotid, cerebral arteries, arteries to lower extremities small arteries: arteriosclerosis arterioles: arteriolosclerosis – commonly occurs in diabetes mellitus and hypertension  Atherosclerosis Effects: Stenosis (narrowing) of arteries Leads to poor blood flow to tissues resulting in ischaemia (imbalance between the supply and demand for blood flow) Occlusion (complete blockage) of artery causes death of tissue supplied Death of tissue due to absence of blood is called infarction Progression of atherosclerosis to late complications Vulnerable versus Stable plaque Histology of atherosclerosis  Pathogenesis of Atheroma Response to injury hypothesis Formation of plaque is response to some form of low grade injury to the endothelium Injury can be due to – haemodynamic stresses – hypertension – toxic effects of LDL Injury to endothelium allows plasma lipoproteins in the blood to enter the wall of the artery and to be engulfed, first by macrophages and later by smooth muscle cells Pathogenesis of Atheroma Risk factors  Risk factors What is meant by modifiable and non- modifiable risk factors?  Risk factors What is meant by modifiable and non- modifiable risk factors? In modifiable risk factors it means that you can take measures to change them, whereas in non-modifiable risk factors it means they cannot be changed.  Risk factors Mention some non-modifiable risk factors.  Risk factors Mention some non-modifiable risk factors. – Age – Male gender – Family history of hyperlipidaemia – Race (e.g., African-Americans)  Risk factors Mention some modifiable risk factors.  Risk factors Mention some modifiable risk factors. – High blood pressure – Diabetes mellitus – Smoking – Hyperlipidaemia – Obesity – Excess alcohol – Sedentary life – Stress and depression – Trauma  Hyperlipidaemia Blood contains lipoproteins (fats complexed with protein) 5 main classes: – Chylomicrons (mainly triglycerides) – VLDL ( = very low density lipoproteins) – IDL ( = intermediate density lipoproteins) – LDL ( = low density lipoproteins – cholesterol) – HDL ( = high density lipoproteins) High levels of blood cholesterol are associated with a high mortality from IHD (ischaemic heart disease) Triglycerides and cholesterol from diet and endogenous (internal) metabolism  Hyperlipidaemia Genetic and acquired disorders that affect pathways of lipid metabolism Poor function results in hyperlipidaemia (high lipid levels in the blood) Primary hyperlipidaemias genetic predisposition – AD or – more commonly polygenic high risk of developing atherosclerosis develop xanthomas (deposition of yellowish cholesterol-rich material that can appear anywhere in the body) treat with low cholesterol diet and drugs to control lipid levels Secondary hyperlipidaemias more common secondary to diabetes, renal disease, alcoholism, treatment with corticosteroids and hypothyroidism predispose to atheroma, often severe and premature  Consequences of atheroma Ischaemia – due to reduction of blood flow Infarction – due to occlusion of blood vessels by atheroma by bleeding in a plaque [fall in blood pressure also leads to infarction] Thrombosis – with embolisation as a complication Aneurysm formation – due to weakening of the vessel wall  ISCHAEMIA Stenosis (narrowing) of arteries results in poor blood flow (ischaemia) 75% stenosis is the critical lesion  ISCHAEMIA & INFARCTION Coronary artery Stenosis (incomplete blockage) by atheroma and its complications leads to ischaemia of the heart, called Ischaemic Heart Disease (IHD) Complete blockage leads to myocardial infarction  ISCHAEMIA & INFARCTION Coronary artery  ISCHAEMIA & INFARCTION Coronary artery  ISCHAEMIA & INFARCTION Coronary artery  ISCHAEMIA & INFARCTION Coronary artery Transmural infarct in the posterior wall of the left ventricle  ISCHAEMIA & INFARCTION Coronary artery Posterior left ventricular transmural infarct  ISCHAEMIA & INFARCTION Coronary artery After 24 hours  ISCHAEMIA & INFARCTION Coronary artery At 3 months  ISCHAEMIA & INFARCTION Cerebral artery Total blockage leads to cerebral (brain) infarction  ISCHAEMIA & INFARCTION Acute intestinal obstruction  THROMBOSIS A thrombus is – a blood clot – that occurs inside blood vessels (arteries and veins) – in a living person Thrombus formation (thrombosis) is due to activation of coagulation system, to form a mesh of platelets and fibrin, to plug defects in a vessel  THROMBOSIS Coronary thrombosis THROMBOSIS  THROMBOSIS In normal vessels, excessive thrombosis is prevented by physiological mechanisms that lyse the clot (fibrinolysis) Pathological thrombosis depends on three components, first emphasised by Rudolph Virchow, a German pathologist – endothelial dysfunction or injury – hemodynamic changes – hypercoagulability  THROMBOSIS Pathological thrombosis - Virchow’s triad: Endothelial injury – direct injury in trauma and inflammation – haemodynamic stresses in vessels with atheroma Alterations in blood flow – turbulence - hypertension – stasis – immobility / prolonged bed rest after trauma, operations / myocardial infarction Hypercoagulability – disorders of coagulation - deficiency of protein C (a major physiological anticoagulant) or S – prothrombin mutations  THROMBOSIS Sites - all vessels: Arteries in coronary arteries – usually occlusive mural thrombi in aorta or aneurysm Veins in deep veins of the calf muscles Heart in poorly contracting chambers – abnormal rhythm or infarction on damaged heart valves Myocardial Infarction - Mural Thrombus  Outcome of THROMBOSIS Dissolution or lysis by fibrinolytic system Propagation by enlargement Organization by growth of granulation tissue from the vessel wall and recanalization of organized thrombus with a new channel for the blood Embolism when fragments break off and are carried in the circulation to other vessels Complete organization of thromboembolus with recanalization  EMBOLISM An embolus is any material within a blood vessel that is carried by the blood to a site distant from its point of origin 99% of emboli arise from a thrombus Rare forms include: – atheroma from plaques in a vessel – fat and bone marrow in fractures – foreign bodies (bullets) – air or nitrogen in diving – fragments of a tumour Can carry infected material  Arterial Embolism Emboli travel through the systemic circulation to lodge in: Legs and feet (commonest) Brain Heart Bowel Kidney Spleen Other sites  Arterial Embolism An embolized fragment of an atrial myxoma at the iliac bifurcation (a tumor embolus)  Arterial Embolism 80-85% arise from thrombi in heart ventricle over an area of infarction In mitral valve disease, thrombus in left atrium may give rise to emboli In bacterial endocarditis, emboli arise from the cardiac vegetations on the damaged valves 15-20% arise from plaques of atheroma in an artery, e.g. emboli from atheroma in the carotid artery enter the cerebral circulation, causing TIA  Pulmonary Embolism The most common preventable cause of death in hospital patients 95% of all pulmonary emboli arise in thrombi in the large veins of the lower legs – in the deep veins of the calf muscles (DVT) – or the pelvic veins  Pulmonary Embolism Emboli travel from right side of the heart to the pulmonary trunk Large blockage causes sudden death Small emboli not symptomatic Pulmonary infarction (death of lung tissue) if smaller vessels are obstructed and if there is an increase in venous pressure Thank you