Transcript Document
The disorder of local circulation Dr. Philip S.L. Beh Email: [email protected] Lecture Outline Overview and revisit basic concepts Circulatory system Structure of blood vessels Components of blood Oedema Generalised Local Effects on Brain and Lungs Hemostasis – Normal physiological response Thrombosis – Abnormal pathological response Other forms of obstruction Infarction – Abnormal pathological outcome Overview and Revisit Circulatory System Structure of blood vessels Components of Blood Circulatory System – Pump Blood Vessels – Pipes Heart Artery, Vein, Capillary Lymphatics – Drainage pipes Properties of circulatory system Ensure smooth and adequate flow of blood. Delivers nutrients and oxygen Removes waste and carbon dioxide Properties of arteries Aorta Comes off the heart Sustains high blood pressures Elastic but rigid wall Arteries Lower blood pressures Often have muscular wall and can contract Structure of artery Taken from www.sirinet.net/~jgjohnso/ circulation.html Properties of veins Thin wall Some have valves to prevent back-flow of blood Weak ability to contract even if there are muscle fibers in the wall. Dependant on “pumping action of surrounding muscles – particularly of the limbs. Structure of vein Taken from www.sirinet.net/~jgjohnso/ circulation.html Properties of capillary bed Very thin wall often only one cell-thick and can change to allow blood to pass through into the interstitial space. Taken from Underwood – General and Systemic Pathology Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Properties of lymphatic channels Tube-like Numerous valves Drains fluid back to blood-stream – passes through at least one lymph-node. Present in all tissues except CNS, Eyeballs, Internal Ear, Epidermis of the skin, cartilage and bone. Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Systemic circulation vs. Pulmonary circulation Taken from Robbins Pathologic Basis of Disease Schematic of lymphatic channels Taken from Colour Atlas of Anatomy – Roden, Yokochi and Lutjen-Drecoll Components of Blood – proteins, electrolytes and water Cells – red blood cells, white blood cells and platelets. Plasma Disorders of the Circulatory System Congestion Hemostasis Thrombosis Emboli Other obstruction Ischaemia and infarction Congestion Distension of blood vessels May be an active or passive process Reversible condition Oedema Oedema Water compartments Movement of water between the compartments Causes of oedema Pulmonary oedema Cerebral oedema Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Underwood – General and Systemic Pathology Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanisms of Disease Taken from Guyton & Hall – Human Physiology and Mechanis ms of Disease Taken from Underwood – General and Systemic Pathology Taken from Underwood – General and Systemic Pathology Taken from Underwood – General and Systemic Pathology Taken from Sternberg`s HISTOLOGY for PATHOLOGISTS Taken from Sternberg`s HISTOLOGY for PATHOLOGISTS Taken from Colour Atlas of Anatomy – Roden, Yokochi and Lutjen-Drecoll Taken from Colour Atlas of Anatomy – Roden, Yokochi and Lutjen- Taken from Colour Atlas of Anatomy – Roden, Yokochi and Lutjen-Drecoll Taken from Colour Atlas of Anatomy – Roden, Yokochi and LutjenDrecoll Hemostasis Diagram from Robbins Pathologic Basis of Diseases Platelet adhesion to von Willebrand’s factor Diagram from Robbins Pathologic Basis of Diseases Hemostasis – Adhesion and Recruitment Diagram from Robbins Pathologic Basis of Diseases Hemostasis – Thrombin activation Diagram from Robbins Pathologic Basis of Diseases Diagram from Robbins Pathologic Basis of Diseases Hemostasis - Plug Diagram from Robbins Pathologic Basis of Diseases Opposing actions Diagram from Robbins Pathologic Basis of Diseases Thrombosis Definition – a blood clot. Thrombosis – a pathological process whereby there is formation of a blood clot in uninjured vasculature or after relatively minor injury. Thrombus Definition – A detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin. Embolus Virchow’s Triad Pathogenesis of a Thrombus Endothelial injury Abnormal blood flow Hypercoagulability • Primary (genetic) • Secondary (acquired) ENDOTHELIAL INJURY THROMBOSIS ABNORMAL BLOOD FLOW HYPERCOAGULABILITY Endothelial Injury Dominant factor Sufficient as the sole factor Examples include Myocardial infarction Ulcerated atheromatous plaques Hemodynamic injury such as hypertension, turbulent flow over heart valves Endotoxins, inflammation, etc Abnormal Blood Flow Turbulence in arterial flow as a result of changes in the diameter of the vessel leading to nonlaminar flow, resulting in:-. Platelet coming into contact with endothelium. Prevent dilution by fresh flowing blood of activated clotting factors. Retard inflow of clotting factor inhibitors. Promote endothelial cell activation predisposing to local thrombosis. Hypercoagulability Alteration of the coagulation pathway that predisposes to thrombosis Higher viscosity of blood changing the flow dynamics of blood Fate of a Thrombus Diagram from Robbins Pathologic Basis of Diseases Fate of a Thrombus The thrombus may propagate The thrombus may become organised and recanalised The thrombus may become organised and incorporated into the wall of the vessel The thrombus may be resolved completely The thrombus may dislodge and become an embolus or emboli Propagation of Thrombus Classification of Thrombi Anatomical Cardiac Arterial Venous Capillary Morphological Pale (platelet thrombus) Red (RBC thrombus) Mixed (intermittent layers) Renal Artery Thrombus Iliac Artery Thrombosis of the descending aorta extending from the origins of the renal arteries down to the iliac vessels A mixed thrombus Pale thrombus Red thrombus Venous Thrombosis Two distinct types Phlebothrombosis – predisposes to thromboemboli to lungs Thrombophlebitis – unusual to have associated pulmonary thromboemboli Effects of Thrombosis Dependent on location and degree of vascular occlusion. Effects also dependent on the availability of collateral blood supply and susceptibility of area of supply to interruption of blood supply. Demand Supply Taken from www.ecureme.com/atlas/ ata/Renal_Artery_Steno... Taken from Underwood – General and Systemic Pathology Other obstruction Atherosclerosis Embolism Others Congenital Mechanical Chemical Iatrogenic Schematic of atherosclerosis Concepts of atherogenesis Hyperlipideamia, Hypertension, Smoking, Homocysteine, Hemodynamic factors, etc Endothelium (E) Subendothelial space Smooth muscle layer (S) Endothelial Injury/Dysfunction Adventitia Taken from Robbins Pathologic Basis of Disease Concepts of atherogenesis Circulating platelets adhere to endothelial surface Leukocyte adhesion Leukocyte migration Taken from Robbins Pathologic Basis of Disease Concepts of atherogenesis Endothelial Permeability increased LDL, VLDL and leukocyte accumulation Ingestion of oxidised LDL by leukocyte (Foamy macrophage) Smooth muscle migration Taken from Robbins Pathologic Basis of Disease Concepts of atherogenesis Gross appearance of fatty streaking Macrophage and smooth muscles engulfing more and more LDL Arrival of lymphocyte Taken from Robbins Pathologic Basis of Disease Concepts of atherogenesis Smooth muscle proliferation and accumulating extracellular collagen and fatty deposits Effects of atherosclerosis Hardening of the wall, Loss of elasticity Obstruction of lumen Aneurysm Rupture Markedly atheromatous Advanced atheromatous and calcified aorta with degeneration and thrombus saddle at the calcification with thrombus iliac bifurcation. at iliac bifurcation Cerebrovascular Disease Intracerebral haemorrhage with rupture of the haemorrhage into the lateral ventricle of the brain. This lesion is likely to result in hemiplegia and could also be fatal if the brain haemorrhage and swelling cannot be controlled. Types of embolism Pulmonary Air Fat Amniotic Septic Tumour Others fluid Emboli Pulmonary Fat thromboemboli emboli Marrow emboli Air emboli Amniotic fluid emboli Others – foreign bodies e.g. glass, metal fragments (even occasionally bullets), etc. Phlebothrombosis Phlebothrombosis Pulmonary Thromboembolism Probably the most common form of embolism. Emboli derived from thrombosis of deep veins of the lower limbs. Predisposing factors include prolonged immobility, dehydration, etc. Fat Embolism Commonly found at autopsies Often associated with injuries to adipose tissues, long bones and stressful states May be quite asymptomatic Can however lead to extensive occlusion of vessels leading to hemorrhagic infarcts Marrow Embolism Often seen together with fat embolism in particular following fractures of long bones. Also quite commonly found after fractures of ribs during cardiopulmonary resuscitation. Air-embolism Associated with “high-pressure” activities or work, e.g.. Scuba diving, compression chamber workers, etc Gases are dissolved in the blood at high pressures, sudden decompression allows the gases to form bubbles within the vascular system, leading to obstruction Air-embolism When large quantities of gases/air collects in the right heart (usually more than 100 ml), the pumping action of the heart together with the blood plasma and air/gas mixture will lead to frothing and obstruction to the blood flow and death. Amniotic Fluid Embolism Associated with high mortality. Contents of the fetal amniotic sac is forced into the maternal circulation often during induced labour. The squames and other material in the amniotic fluid is believed to lead to an anaphylactic type reaction with resultant disseminated intravascular coagulopathy and death due to shock. Embolism – other forms A variety of material may give rise to emboli, e.g. Foreign objects such as glass, bullets, etc. Tumor and bacteria may give rise to tumor and septic emboli. Effects of embolisation Identical to those of thrombosis and governed by similar factors. Effects of embolism Dependant on extent of disruption to the local circulation and susceptibility of the target organ or tissue to such disruption. Fate of a Thrombus Diagram from Robbins Pathologic Basis of Diseases Tissues supplied by end-arteries without significant collateral supplies will be the most susceptible. Obstruction of blood supply leads to ischemia which when prolonged leads to necrosis and atrophy. Where there is reperfusion after ischemic necrosis the tissues will show a hemorrhagic necrosis. Where there is infection by Clostridia (gram positive bacilli), gangrene sets in. Ischaemia Transient Insufficient blood supply Infarction Cell death due to prolonged ischaemia Irreversible Mural thrombus of the left ventricle commonly seen after transmural infarction Occlusive thrombus or emboli of cerebral artery leading to hemorrhagic infarct of internal capsule region Chronic insufficient blood supply leading to atrophy Patchy areas of gangrene of left foot Bilateral gangrene of feet. Wedged shaped area of infarct of the liver Hemorrhagic infarcts of small bowels Coil of thromboemboli of the pulmonary trunk Saddle thrombus of the pulmonary trunk Often leads to sudden death. Pulmonary thrombus – organised Hemorrhagic infarcts of the lung Fat emboli stained red Fat embolism involving glomeruli of kidney Marrow emboli Amniotic fluid emboli (squames) Tumor embolus References & Hall – Human Physiology and Mechanisms of Disease – 6th Edition Guyton Section IV – Chapters 13 Section V – Chapters 20 – Pathologic Basis of Disease – 5th Edition Robbins Chapter 1V