Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 30 Disorders of Blood Flow in the Systemic Circulation
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Endothelial Cells Controls the transfer of molecules across the vascular wall Control of platelet adhesion and blood clotting Modulation of blood flow and vascular resistance Metabolism of hormones Regulation of immune and inflammatory reactions Influence the growth of other cell types
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Endothelial Dysfunction Endothelial dysfunction describes potentially reversible changes in endothelial function that occur in response to environmental stimuli –Products that cause inflammation Cytokines, bacteria, viruses –Hemodynamic stresses –Lipid products –Hypoxia
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Smooth Muscle Cells Vasoconstriction or dilation of blood vessels –ANS regulation Sympathetic –Local regulation NO ECM and growth factor elaboration –Essential for healing –Contribute to pathologic processes
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Lipids Triglycerides –Used in energy metabolism Phospholipids –Important structural constituents of lipoproteins, blood clotting components, the myelin sheath, and cell membranes Cholesterol –Chemical activity similar to other lipid substances Hyperlipidemia –Elevated levels of one or all of the above
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Lipoproteins, Classified by Densities Chylomicrons Very–low-density lipoprotein (VLDL) –Carries large amounts of triglycerides Intermediate-density lipoprotein (IDL) Low-density lipoprotein (LDL) –Main carrier of cholesterol High-density lipoprotein (HDL) –50% protein
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Lipoprotein Receptors Membrane proteins that facilitate cellular uptake of LDL, VLDL, chylomicrons, and IDL proteins Genetic abnormality may result in elevated levels with no dietary influence
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypercholesterolemia Serum cholesterol levels –240 mg/dL or greater –Levels that could contribute to a heart attack, stroke, or other cardiovascular event associated with atherosclerosis Primary hypercholesterolemia describes elevated cholesterol levels that develop independent of other health problems or lifestyle behaviors. Secondary hypercholesterolemia is associated with other health problems and behaviors.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following is considered the “good” cholesterol. Discuss why in small groups. –A. Chylomicrons –B. Very–low-density lipoprotein (VLDL) –C. Intermediate-density lipoprotein (IDL) –D. Low-density lipoprotein (LDL) –E. High-density lipoprotein
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer E. High-density lipoprotein Rationale: Due to its function of taking cholesterol from the tissues and moving it to the liver for metabolic breakdown
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Pathology of the Arterial System Hypercholesterolemia Atherosclerosis Vasculitis Arterial disease of the extremities Arterial aneurysms
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms of Development of Atherosclerosis Types of Lesions Associated with Atherosclerosis –Fatty streaks Thin, flat yellow intimal discolorations that progressively enlarge –Fibrous atheromatous plaque The accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, and formation of scar tissue –Complicated lesion Contains hemorrhage, ulceration, and scar tissue deposits
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Major Risk Factors for Atherosclerosis Hypercholesterolemia Cigarette smoking Hypertension Family history of premature CHD in a first-degree relative Age (men ≥45 years; women ≥55 years) HDL cholesterol <40 mg/dL CRP levels Homocysteine levels
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Major Complications of Atherosclerosis Ischemic heart disease Stroke Peripheral vascular disease Clinical manifestations of atherosclerosis –Narrowing of the vessel and resulting ischemia –Vessel obstruction due to plaque hemorrhage or rupture –Thrombosis and formation of emboli –Aneurysm formation
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Specific Arterial Involvement in Atherosclerosis In larger vessels, the important complications are those of thrombus formation and weakening of the vessel wall. In medium-sized arteries, ischemia and infarction due to vessel occlusion are more common. Arteries supplying the heart, brain, kidneys, lower extremities, and small intestine are most frequently involved.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations of Atherosclerosis Narrowing of the vessel and production of ischemia Sudden vessel obstruction due to plaque hemorrhage or rupture Thrombosis and formation of emboli resulting from damage to the vessel endothelium Aneurysm formation due to weakening of the vessel wall
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Signs and Symptoms of Acute Arterial Occlusion Limb ischemia –Pain –Paresthesia –Motor weakness distal to the site of occlusion There is loss of peripheral pulses, cool skin, and pallor or cyanosis distal to the obstruction site.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Vasculitides Vasculitis, angiitis, and arteritis often are used interchangeably –Group I Systemic necrotizing vasculitides –Group II Hypersensitivity vasculitides –Group III Giant cell arteritis –Group IV Miscellaneous
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Arterial Disease of the Extremities Atherosclerotic occlusive disease –Sudden event that interrupts arterial flow to the affected tissues or organ Thromboangiitis obliterans –Inflammatory arterial disorder that causes thrombus formation Raynaud disease and phenomenon –Intense vasospasm of the arteries and arterioles in the fingers and, less often, the toes
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins The Seven “P”s of Acute Arterial Embolism 1.Pistol shot (acute onset) 2.Pallor 3.Polar (cold) 4.Pulselessness 5.Pain 6.Paresthesia 7.Paralysis
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Aneurysms Berry aneurysm –Most often found in the circle of Willis in the brain circulation –Consists of a small, spherical vessel dilation Fusiform and saccular aneurysms –Most often found in the thoracic and abdominal aorta –Characterized by gradual and progressive enlargement of the aorta
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Aneurysms (cont.) Dissecting aneurysm –Acute, life-threatening condition –Involves hemorrhage into the vessel wall with longitudinal tearing (dissection) of the vessel wall to form a blood-filled channel
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Circulation One way valves in large veins Limited contractility –Skeletal muscle pump Decreased driving pressure Thin-walled vessel
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Disorders of the Venous Circulation Produce congestion of the affected tissues Predispose to clot formation because of stagnation of flow and activation of the clotting system Types of disorders –Varicose veins Primary Secondary –Thrombophlebitis
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Virchow’s Triad Associated with Venous Thrombosis Stasis of blood Increased blood coagulability Vessel wall injury
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Risk Factors Associated with Venous Stasis Bed rest Immobility Spinal cord injury Acute myocardial infarction Congestive heart failure Shock Venous obstruction
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Insufficiency Deep vein thrombosis (DVT) –Causes deformity of the valve leaflets Valvular incompetence –Loss of unidirectional blood flow Combination of both conditions Stasis dermatitis Venous ulcers
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Which of the following is not a risk factor for atherosclerosis? –A. Hypercholesterolemia –B. Cigarette smoking –C. Hypertension –D. Venous stasis –E. Age (men ≥45 years; women ≥55 years) –F. HDL cholesterol <40 mg/dL
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer D. Venous stasis Rationale: Venous stasis is responsible for disorders in the venous system and is not related to atherosclerosis.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question DVTs may be the direct result of _______________. –A. smoking –B. hypersensitivity reaction –C. hypercholesterolemia –D. bed rest
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer D. Bed rest Rationale: Bed rest can cause DVT formation due to blood stasis and lack of skeletal muscle pumping.