1 Vascular and Lymphatic System Pathology

2 Blood Flow Systemic blood flow is a circuit : Systemic blood flow is a circuit : Heart → Arteries → Arterioles → Capillaries → Venules → Veins → Heart Heart → Arteries → Arterioles → Capillaries → Venules → Veins → Heart Artery – any vessels that carries blood away from the heart. Artery – any vessels that carries blood away from the heart. Vein – any vessels that carries blood toward the heart Vein – any vessels that carries blood toward the heart

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4 Structure of blood vessels Tunica intima Tunica intima –Endothelium and connective tissue Tunica media Tunica media –Smooth muscle and elastic tissue Tunica externa or tunica adventitia Tunica externa or tunica adventitia –Connective and elastic tissue

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7 Arteries Large arteries are elastic (conducting) arteries – pressure reservoirs Large arteries are elastic (conducting) arteries – pressure reservoirs Medium arteries are muscular (distributing) arteries – more smooth muscle Medium arteries are muscular (distributing) arteries – more smooth muscle Contraction or relaxation of muscle changes the size of the lumen, and so controls the blood pressure in the vessel. Contraction or relaxation of muscle changes the size of the lumen, and so controls the blood pressure in the vessel.

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9 Capillaries Only a single layer of endothelium and a basement membrane Only a single layer of endothelium and a basement membrane Connect arterioles and venules Connect arterioles and venules Functional part of system Functional part of system True capillaries begin at a precapillary sphincter which controls blood flow through the capillary True capillaries begin at a precapillary sphincter which controls blood flow through the capillary

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11 Veins Relatively thin; less elastic Relatively thin; less elastic Larger in diameter than arteries Larger in diameter than arteries Have valves to prevent backflow of blood Have valves to prevent backflow of blood Flow to heart is assisted by contraction of skeletal muscles Flow to heart is assisted by contraction of skeletal muscles

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15 Control of systemic circulation Nervous control – innervated by sympathetic nervous system ONLY Nervous control – innervated by sympathetic nervous system ONLY Cardiac control center (primarily in medulla oblongata) Cardiac control center (primarily in medulla oblongata) Heart has both Sympathetic and Parasympathetic innervations. Heart has both Sympathetic and Parasympathetic innervations.

16 Baroreceptors and chemoreceptors: Baroreceptors and chemoreceptors: –Monitor pressure –Monitor blood levels of O 2, CO 2 and H + –Send information to cardiovascular center, which responds

17 Compliance The increase in volume a vessel can accommodate for a given increase in pressure. The increase in volume a vessel can accommodate for a given increase in pressure. –Depends on the ratio of elastic fibers to muscle fibers in the vessel wall. Elastic arteries more compliant than muscular arteries Elastic arteries more compliant than muscular arteries Veins more compliant than either artery (blood reservoirs) Veins more compliant than either artery (blood reservoirs) Decreased compliance suggests an increased stiffness of vessel wall. Decreased compliance suggests an increased stiffness of vessel wall. Determines the vessel’s response to changes in pressure. Determines the vessel’s response to changes in pressure.

18 Blood pressure Mean arterial pressure is the average in pressure in the arteries throughout the cardiac cycle. Mean arterial pressure is the average in pressure in the arteries throughout the cardiac cycle. Depends on the compliance of the arteries and the amount of blood in the arterial system. Depends on the compliance of the arteries and the amount of blood in the arterial system.

19 Blood pressure BP = Cardiac Output * Total Peripheral Resistance BP = Cardiac Output * Total Peripheral Resistance

20 Lymphatic System A vascular system that runs “parallel” to the blood vascular system A vascular system that runs “parallel” to the blood vascular system Flow does not circulate – begins in tissue Flow does not circulate – begins in tissue Returns to venous system at subclavian veins Returns to venous system at subclavian veins Fluid in vessels is lymph – mostly water and proteins Fluid in vessels is lymph – mostly water and proteins Interstitial fluid → lymphatic capillaries → lymphatic vessels → lymphatic trunks → lymphatic ducts Interstitial fluid → lymphatic capillaries → lymphatic vessels → lymphatic trunks → lymphatic ducts

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23 Lymph nodes Lie along lymphatic vessels Lie along lymphatic vessels Contain lymphocytes that filter lymph and eliminate microbes/damaged cells/ toxins Contain lymphocytes that filter lymph and eliminate microbes/damaged cells/ toxins Biological filtration Biological filtration

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25 Diseases of Arteries and Veins Thrombus- “clotting” in an unbroken vessel Thrombus- “clotting” in an unbroken vessel –Maintains a point of attachment –Organized differently than a clot –usually due to damage to endothelium and exposure of collagen in the basement membrane

26 Arterial thrombus Forms where blood is moving rapidly – see alternating lines of platelets and red cells trapped in fibrin Forms where blood is moving rapidly – see alternating lines of platelets and red cells trapped in fibrin Lines of Zahn Lines of Zahn

27 Venous thrombus Forms differently due to decreased blood flow Forms differently due to decreased blood flow Mixed region at site of attachment Mixed region at site of attachment More blood clotting forms a downstream red cap More blood clotting forms a downstream red cap

28 Factors that predispose to thrombosis Endothelial damage Endothelial damage –Bacterial damage –Damage to the myocardium –Wear and tear – hemodynamic stress Hypertension increases this Hypertension increases this Arteriosclerosis Arteriosclerosis –Inflammation –Tumors and irritation by their products

29 Factors that predispose to thrombosis Flow abnormalities Flow abnormalities –Increases platelet contact with endothelium –Reduction in flow: Arterial: Arterial: –Cardiac damage and decreased pumping action –Increased blood viscosity Venous: Venous: –Physical inactivity –Varicose veins

30 –Turbulence: Damaged heart valves Damaged heart valves Congenital heart defects Congenital heart defects Compression of the vessel Compression of the vessel Weakened arterial wall - aneurysm Weakened arterial wall - aneurysm

31 Other Causes Aging Aging Immobilization Immobilization Injury to vessel endothelium Injury to vessel endothelium Increased clotting response Increased clotting responseEffects: Decreased venous emptying Decreased venous emptying Increased venous pressures Increased venous pressures Edema Edema Pain Pain

32 Sequelae of Thrombosis 1 Resolution – Anticoagulation system Fibrolytic system Moderate exercise increases thrombus resolution

33 2 Organization The thrombus is digested by phagocytes and replaced by connective tissue – incorporating the thrombus into the vessel wall. May recanalize – small channels open up and restore blood flow

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35 3 Propagation – Thrombus extends further down the vessel, usually a vein. Initial thrombus acts as a site for further platelet adherence.

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37 4 Infarction – an infarct is an area of necrosis caused by ischemia and hypoxia. More common in arteries than veins due to blood flow patterns Collateral circulation and anastomosis prevent infarction

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39 Embolism – obstruction of vessel by matter circulating in blood stream –Matter could be fat, air, infant’s cells, in addition to pieces of clot – thromboemboli –Thromboemoboli from the venous system tend to end up in the: lungs and liver

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41 Treatment Anticoagulants Anticoagulants Fibrinolytics – t-Pas Fibrinolytics – t-Pas Prophylactic aspirin therapy Prophylactic aspirin therapy

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43 Arterial Occlusions Arteriosclerosis – abnormal thickening and hardening of the arterial walls Arteriosclerosis – abnormal thickening and hardening of the arterial walls –Smooth muscle cells and collagen fibers migrate into the tunica intima, causing stiffening and thickening, narrowing the lumen –Can exacerbate high blood pressure, and cause weakening and outpouching of vessel walls

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45 Atherosclerosis A form of arteriosclerosis where soft deposits of intra-arterial fat and fibrin harden over time – atheroma A form of arteriosclerosis where soft deposits of intra-arterial fat and fibrin harden over time – atheroma May see build up in skin – Xanthoma or arcus in cornea. May see build up in skin – Xanthoma or arcus in cornea. In general, patients suffer few symptoms unless > 60 % of blood supply is blocked In general, patients suffer few symptoms unless > 60 % of blood supply is blocked

46 Progressive over years Progressive over years –Starts with some injury to endothelium Smoking, hypertension, hyperlipidemia, diabetes, autoimmune disease, and infection Smoking, hypertension, hyperlipidemia, diabetes, autoimmune disease, and infection –Inflammation, release of enzymes by macrophages causes oxidation of LDL, which is then consumed by macrophages – foam cells – accumulate to form fatty streaks –Fatty streaks of lipid material appear first as yellow streaks and spots –Smooth muscle cells proliferate, and migrate over the streak forming a fibrous plaque

47 Fibrous plaque results in necrosis of underlying tissue and narrowing of lumen Fibrous plaque results in necrosis of underlying tissue and narrowing of lumen Inflammation can result in ulceration and rupture of the plaque, resulting in platelet adherence to the lesion = complicated lesion Inflammation can result in ulceration and rupture of the plaque, resulting in platelet adherence to the lesion = complicated lesion Can result in rapid thrombus formation with complete vessel occlusion → tissue ischemia and infarction Can result in rapid thrombus formation with complete vessel occlusion → tissue ischemia and infarction

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50 Clinical manifestations Signs and symptoms of inadequate perfusion – TIAs, often associated with exercise or stress Signs and symptoms of inadequate perfusion – TIAs, often associated with exercise or stress When lesion becomes complicated, can result in tissue infarction When lesion becomes complicated, can result in tissue infarction –Coronary artery disease – myocardial ischemia –In brain – major cause of stroke

51 Treatment Exercise Exercise Smoking cessation Smoking cessation Control of hypertension and/ or diabetes Control of hypertension and/ or diabetes Reduce LDL cholesterol by diet or medication or both Reduce LDL cholesterol by diet or medication or both

52 Other arterial problems Aneurism – dilation in the arterial wall Aneurism – dilation in the arterial wall Most arise in aorta or major branches as a result of atherosclerotic wall damage Most arise in aorta or major branches as a result of atherosclerotic wall damage Males over 50 at greatest risk for aortic aneurysms Males over 50 at greatest risk for aortic aneurysms Disturbs blood flow, predisposing to thrombus formation - can release thromoemboli Disturbs blood flow, predisposing to thrombus formation - can release thromoemboli

53 Asymptomatic until rupture Asymptomatic until rupture –Embolism –Death Treatment by surgical repair Treatment by surgical repair Aortic Dissection –bleeding into vessel wall, separating vessel layers Aortic Dissection –bleeding into vessel wall, separating vessel layers –Men in y.o. age group with hypertension –Younger persons with connective tissue disease or congenital defects –Presents with pain – life threatening

54 Systemic Hypertension A consistent increase in arterial blood pressure caused by increased Cardiac output or increased peripheral resistance or both A consistent increase in arterial blood pressure caused by increased Cardiac output or increased peripheral resistance or both Leads to damage of vessel walls Leads to damage of vessel walls If arteries constrict over a long time with increased pressure in vessel, the wall becomes thicker to withstand the stress. If arteries constrict over a long time with increased pressure in vessel, the wall becomes thicker to withstand the stress. Results in narrowing of arterial lumen Results in narrowing of arterial lumen Leads to inflammatory response Leads to inflammatory response

55 Causes one in eight deaths worldwide Causes one in eight deaths worldwide Third leading cause of death in the world Third leading cause of death in the world Affects 50 million Americans Affects 50 million Americans

56 Primary hypertension Also called essential or idiopathic hypertension Also called essential or idiopathic hypertension % of all cases % of all cases No specific cause identified No specific cause identified Can happen with retention of sodium and water → increased blood volume. Can happen with retention of sodium and water → increased blood volume. Also low dietary potassium, calcium and magnesium intakes Also low dietary potassium, calcium and magnesium intakes

57 Other risk factors Smoking Smoking –Nicotine is a vasoconstrictor Greater than 3 alcoholic drinks/ day Greater than 3 alcoholic drinks/ day –2-4 drinks / week lowers blood pressure

58 Suspected causes Interaction of genetics and environment Interaction of genetics and environment Overactivity of sympathetic nervous system Overactivity of sympathetic nervous system Overactivity of renin / angiotensin/ aldosterone system Overactivity of renin / angiotensin/ aldosterone system Salt and water retention by kidneys Salt and water retention by kidneys And others And others

59 Secondary hypertension Caused by a systemic disease process that raises peripheral resistance or cardiac output = % of cases. Caused by a systemic disease process that raises peripheral resistance or cardiac output = % of cases. Renal vascular disease Renal vascular disease Adrenocortical tumors Adrenocortical tumors Adrenomedullary tumors Adrenomedullary tumors Drugs ( oral contraceptives, corticosteroids, antihistamines) Drugs ( oral contraceptives, corticosteroids, antihistamines)

60 Complicated hypertension Sustained primary hypertension that damages the structure and function of the vessels themselves. Sustained primary hypertension that damages the structure and function of the vessels themselves. Commonly affects heart, aorta, kidneys, eyes, brain, and lower extremities (target-organ damage). Commonly affects heart, aorta, kidneys, eyes, brain, and lower extremities (target-organ damage).

61 Clinical manifestations None in early stages other than elevated BP None in early stages other than elevated BP Some individuals never have symptoms; others become very ill and die Some individuals never have symptoms; others become very ill and die

62 Treatment Modification of life style Modification of life style Drugs Drugs –Diuretics, beta-blockers, angiotensin converting enzyme inhibitor Compliance is often difficult – patients stop taking medication when they feel better – can get rebound effects Compliance is often difficult – patients stop taking medication when they feel better – can get rebound effects

63 Venous Disorders Varicose veins – dilations, can lead to valvular insufficiency Varicose veins – dilations, can lead to valvular insufficiency Can occur in superficial veins (saphenous) or deep veins Can occur in superficial veins (saphenous) or deep veins Causes of secondary varicose veins: Causes of secondary varicose veins: –Deep vein thrombosis –Congenital defects and pressure on abdominal veins

65 Treatment Prevention – little can be done after valves become incompetent Prevention – little can be done after valves become incompetent Avoid stressors, such as standing for long periods Avoid stressors, such as standing for long periods Elastic support stockings Elastic support stockings Sclerotherapy – injections of drugs to induce fibrosis of vessel Sclerotherapy – injections of drugs to induce fibrosis of vessel Surgical removal - but only when deep vein are open. Surgical removal - but only when deep vein are open.