Arterial Pathophysiology PDF

Arterial Pathophysiology SONO/VASC 112 – VASCUL AR FUNDAMENTALS Cardiovascular Disease Morbidity ◦80 million people in US with some form of CVD Mortality ◦>630,000 deaths each year - ~1 of every 4 deaths ◦ ~380,000 due to coronary heart disease (+additional deaths due to other causes such as h...

Arterial Pathophysiology SONO/VASC 112 – VASCUL AR FUNDAMENTALS Cardiovascular Disease Morbidity ◦80 million people in US with some form of CVD Mortality ◦>630,000 deaths each year - ~1 of every 4 deaths ◦ ~380,000 due to coronary heart disease (+additional deaths due to other causes such as heart failure, congenital disease, valve disorders, etc.) ◦ ~140,000 due to stroke (795,000 strokes per year) ◦ >13,000 due to peripheral arterial disease Cardiovascular Disease Economic cost ◦Direct and indirect medical costs ◦ $200 BILLION each year ◦Lost productivity Psychological cost ◦Debilitation ◦Loss of loved ones Arterial Pathology Atherosclerosis obliterans (ASO) Thrombosis (preceded by ASO) Thrombo-emboli Aneurysm ◦ AAA ◦ Popliteal Other disorders ◦ Arteritis ◦ Vasospastic ◦ Mechanical/Obstructional  Cross section view, plaque development Artery wall Atherosclerosis plaque Ultrasound color Doppler Ultrasound image plaque Normal artery residual lumen Definitions Arteriosclerosis ◦ Hardening (loss of elasticity) and thickening of the walls of arteries ◦ Atherosclerosis ◦ Calcification of arterial walls ◦ Thickening of muscular walls from chronically elevated blood pressure Atherosclerosis ◦ Fatty deposits within the vessel wall ◦ A progressive disease characterized by thickening and hardening of the arterial intima Atherogenesis Intimal accumulation of macrophages and smooth muscle cells Proliferation of intimal smooth muscle cells Production and accumulation of extracellular material in intima Accumulation of lipids (cholesterol) in cells and extracellular matrix 1. Early Atherosclerotic disease Endothelial injury (due to increase in LDL, hypercholesterolemia, etc.) ◦ Initiating event ◦ Attract and activate macrophage Deposition of LDL into intima Recruitment of lymphocytes, monocytes Initial Injury Causes alteration in metabolism of endothelial cells ◦ Increased permeability ◦ Secretion of procoagulants ◦ Stimulation of endothelial cell reproduction ◦ Secretion of vasoactive substances and growth factors Altered endothelial cell attracts macrophages and causes platelet adhesion Early Atherosclerotic Disease Role of endothelial cells ◦ Secrete growth factors ◦ Secrete vasoactive agents Role of platelets ◦ Secrete growth factors ◦ Adhesion-aggregation reaction ◦ Secrete vasoactive agents  2. Inflammatory process Monocytes in intima become macrophages Role of macrophage ◦ Secrete growth factors ◦ Scavenge cholesterol Growth factors attract smooth muscle cells and cause them to proliferate Macrophages penetrate endothelium and accumulate lipids - become foam cells “Fatty streak” appears Macrophages Oxidized LDL’s and chemoattractants in subendothelial space Fatty Streak Earliest manifestation, often seen in children Characterized by the accumulation of foam cells Lesions are flat or slightly raised “yellow” streaks oriented in the direction of flow Nonobstructive and subclinical 3. Atheroma Thickening Migration/proliferation of smooth muscle cells from media Neovasculature supplies plaque, feeds LDL and macrophages Fibrous Plaque ◦ Myointimal cells ◦ Proliferate ◦ Secrete matrix ◦ Form fibrous cap ◦ Loss of endothelium Start as focalized lesions  Proportion of LDL/HDL increases 5:1 Monocyte migration into subendothelial space Foam cells Migration of smooth muscle cells Atheroma Characteristic of more advanced disease A mass of extracellular cholesterol and foam cells surrounded by a fibrous connective tissue cap ◦ Fatty plaque ◦ Soft, lipid rich pool of extracellular cholesterol ◦ Most likely to ulcerate and embolize ◦ Fibrofatty plaque ◦ Solid, composed mainly of collagen and smooth muscle  4. Advanced Atherosclerosis Central core of macrophage foam cells Extracellular lipid deposits Cell necrosis Scar tissue formation (fibrosis) Macrophage lysis Intraplaque hemorrhage Rupture of fibrous cap Plaque ulceration Thrombus formation Embolization Calcification  Fibromuscular cap (ruptured) Blood, fibrin, platelets released when cap ruptures Cholesterol crystals Ruptured vaso vasorum Atherosclerosis Development While atherosclerosis is a diffuse disease, plaques typically are focal Common locations are bifurcations and branch points ◦ Carotid bifurcation (carotid bulb/proximal ICA) ◦ Aortic bifurcation into CIA’s ◦ Distal SFA (in adductor canal) **Most common site of atherosclerotic develop in the LE’s ◦ Common femoral bifurcation into SFA, PFA ◦ UE’s – Subclavian artery origin Clinical Aspects of Peripheral Arterial Disease Pathophysiology ◦ When a large artery is obstructed, blood flow into and blood pressure in smaller arteries is reduced ◦ If oxygen demand of tissues exceeds ability of arteries to supply oxygenated blood, ischemia results ◦ An approximately 50% reduction in vessel diameter is required before there is clinically significant reduction in blood flow ◦ Amount of ischemia depends upon extent of collateral blood supply Clinical Aspects of Peripheral Arterial Disease Intermittent Claudication ◦ AKA: Functional limb ischemia ◦ Aching, cramp-like squeezing pain that occurs after a certain amount of exercise and is relieved by rest ◦ Blood flow is normal in resting limb but cannot be increased in response to exercise ◦ Pain is always experienced in a functional muscle group ◦ It is reproducibly precipitated by a consistent amount of exercise ◦ It is promptly relieved by stopping the exercise Clinical Aspects of Peripheral Arterial Disease Ischemic Rest Pain ◦ Persistent, severe ache or gnawing pain ◦ Often occurs at night and persists for hours at a time ◦ First occurs when the foot is elevated; usually localized in digits/foot ◦ Can often be relieved by dangling foot or walking ◦ This condition implies that blood flow to the foot is below that necessary to meet normal metabolism (severe ischemia and sensory nerve damage) ◦ If left untreated, it generally leads to tissue necrosis (gangrene) Clinical Aspects of Peripheral Arterial Disease Pain of ischemic neuropathy ◦ Occurs late in the course of the disease ◦ Pain is associated with the distribution of sensory nerve fibers in the extremity Coldness and cold sensitivity ◦ Persons with occlusive disease often complain of coolness in the extremities ◦ The foot may be cold to touch ◦ More sensitive to exposure to cold Clinical Aspects of Peripheral Arterial Disease Impaired arterial pulsations ◦ Diminished or even loss of palpable pulse is a common finding in occlusive disease ◦ Particularly in the foot Color changes ◦ The ischemic extremity is often pale or cyanotic, particularly when elevated (elevation pallor) ◦ Color may return when extremity is lowered (dependent rubor) Clinical Aspects of Peripheral Arterial Disease Ulceration and gangrene ◦ Lesions may occur spontaneously or be induced by trauma ◦ Ulcers develop on tips of digits and between toes; often occur in places where shoes rub ◦ Secondary infections can lead to abscess formation and gangrene in the extremity ◦ Gangrene is a black, foul-smelling area of necrotic tissue, adjacent to living tissue Skin changes ◦ Thickened and deformed nails ◦ Loss of hair on extremity Classification of Lower Extremity Atherosclerosis Stage 1 Pathological changes in arteries Patient asymptomatic May have decreased pedal pulses With exercise a mild decrease in ankle pressure Stage 2 Intermittent claudication Asymptomatic at rest Intermittent claudication Significant decease in ankle pressure during and following exercise. Stage 3 Rest pain Stage 4 Presence of trophic lesions Non-healing wounds on feet/toes Ulceration Tissue necrosis, gangrene Other Causes of Extremity Pain Osteoarthritis ◦ Amount of exercise is variable ◦ Does not disappear promptly with rest ◦ Varies in severity day to day Neurospinal compression ◦ Numbing weakness that also occurs with standing ◦ Not relieved by stopping activity ◦ Relief requires assumption of a specific body position Other Causes of Extremity Pain Venous Disease ◦ Pain occurs with dependency ◦ Relieved by elevation Diabetic Neuritis ◦ Difficult to differentiate from ischemic pain because they have associated vascular disease Epidemiology of Atherosclerosis Major risk factors Minor risk factors ◦ Hyperlipidemia ◦ Obesity ◦ Smoking ◦ Sedentary lifestyle ◦ Hypertension ◦ Stress ◦ Gender ◦ Diabetes mellitus ◦ Age Hyperlipidemia Elevation in lipid content in blood Hypercholesterolemia (total cholesterol) ◦ >265 mg/dl = five times risk ◦ 160/95 have greater than 5 times the risk of clinically significant atherosclerosis than normotensive (BP 250 mg/dl Smoker Diastolic BP >90 mmHg ◦ Having all three with up risk 82% Sequelae of Atherosclerosis Stenosis ◦ Narrowing of arterial lumen ◦ Reduced compliance ◦ Reduced perfusion (ischemia)  50% or greater diameter stenosis is “hemodynamically significant” Velocity increase turbulence & Variables: pressure drop * Length of stenosis * Flow volume Hemodynamics of Arterial Disease Stenoses account for most abnormal energy losses in the arterial system. Most energy losses are due to changes in vessel radius. ◦ Small change in radius results in large changes in resistance/viscous energy losses (Poiseuille law). Inertial energy losses occur at the entrance and exit of a stenosis. ◦ Most at exit due to turbulence Hemodynamics of Arterial Disease Figure 5-11. Energy losses across a stenosis. Hemodynamics of Arterial Disease Critical stenosis ◦ Degree of narrowing at which pressure and flow begin to be affected ◦ Typically occurs when cross-sectional area has been reduced by 75% (diameter reduction of 50%) ◦ May be reached sooner in high-flow, low-resistance system Hemodynamics of Arterial Disease Collateral vessels ◦ Preexisting pathways that enlarge with a stenosis of occlusion ◦ Main mechanism to compensate for stenosis ◦ Helps reduce resistance at stenotic area, providing an alternate pathway for blood to reach distal vascular bed Collateral Arteries Figure 5-12. Collateral arteries including stem arteries, midzone collaterals, and reentry arteries. Sequelae of Atherosclerosis Occlusion ◦ Gradual ◦ Supply and demand (symptoms occur with use) ◦ Collateral circulation ◦ New blood vessels take over supply ◦ Sudden ◦ Intraplaque hemorrhage ◦ Thrombus formation (blood clot on top of plaque) ◦ Arterial muscle spasm Sequelae of Atherosclerosis Embolism ◦ Thrombus ◦ Plaque ulceration Aneurysm ◦ “Bulge” in artery from high pressure on weakened arterial wall Plaque regression ◦ Plaque may improve if risk factors are controlled Exercise Flow volume increases to lower extremity vascular beds The volume can increase by 5-10 times that of resting volume Hemodynamics of Arterial Disease Effects of exercise ◦ Exercise increases blood flow to at least three to five times resting values in normal limbs. ◦ With mild to moderate disease, blood flow is not able to increase this much. ◦ As a result, patients who are asymptomatic at rest become symptomatic after exercise. ◦ Additionally, blood pressure distal to an arterial lesion will decrease; exercise exacerbates this. Resting Popliteal a. Flow 151 ml/min Post Exercise Popliteal artery flow 734 ml/min  Acute Arterial Disease Sudden cessation of blood flow to an extremity Intrinsic obstruction ◦ Formation of a thrombus ◦ Impaction of a thrombotic embolus ◦ Impaction of an atheromatous embolus ◦ Catheter induced thrombus  Acute Arterial Disease Extrinsic obstruction ◦ Blunt and penetrating injury ◦ Intimal tear/dissection ◦ Proximity injury ◦ Compression by a neoplastic mass ◦ Venous outflow blockage (uncommon)  Acute Arterial Disease If collateral circulation is not well developed, acute ischemia occurs Muscle necrosis and irreversible changes occur within 4 to 6 hours Clinical manifestations/symptoms ◦ Six P’s Pain Paralysis Paresthesia Pallor Pulselessness Poikilothermia  Aneurysmal Disease An abnormal dilation in the wall of an artery Causes ◦ Complication of atherosclerosis ◦ Congenital defects ◦ Infection (syphilis) ◦ Trauma ◦ Iatrogenic (caused by medical procedure)  True Aneurysm Develops due to a defect in the tunic media of the artery wall ◦ The artery wall dilates but remains intact ◦ Fusiform Aneurysm ◦ A circumferential dilation, the wall balloons out on all sides ◦ More commonly associated with atherosclerosis Fusiform Aneurysm  True Aneurysm Saccular Aneurysm ◦ A sac like out pouching of one side of the arterial wall ◦ Remains connected to the arterial lumen ◦ More associated with infection of congenital development  False Aneurysm (Pseudoaneurysm) A rupture in the wall of the artery Results in a loss of blood from the artery Blood flows out of the wound and clots in the tissues The wall of the aneurysm is thrombus  Common Sites True aneurysms are most likely found ◦ Abdominal aorta (below level of renal arteries) ◦ Thoracic aorta ◦ Popliteal artery  Clinical Manifestations Frequently asymptomatic – often an incidental finding in a vascular exam as a palpable, pulsatile mass Rupture of the aneurysm is often catastrophic and associated with a poor prognosis The aneurysm is a site for thrombus formation ◦ Thrombus lines the wall of the aneurysm and can be source of thromboemboli  Arterial Pathology Thrombo-emboli Blue Toe Syndrome True (Fusiform) Aneurysm Pseudoaneurysm Dissection (Dissecting Aneurysm) The separation of the layers of the arterial wall by a column of blood The vascular separation creates a false arterial lumen which communicates with the true lumen via a tear in the intima The dissection usually extends along one side of the artery The dissection may re-enter the true artery lumen or it may terminate Can partially or totally occlude any vessel in the path of the dissection by separating the vessel orifice from the true lumen Dissections Dissection Arteritis Inflammation and damage to arterial walls Common types ◦ Giant cell (temporal)arteritis ◦ Takayasu’s arteritis ◦ Thromboangiitis obliterans (Buerger’s Disease) ◦ Polyarteritis nodosa ◦ Kawasaki Disease Giant Cell Arteritis AKA: temporal arteritis Inflammation of the arterial wall that primarily affects the thoracic aorta, large branches of the aorta and extracranial branches of the carotid arteries (arteries containing significant amounts of elastic tissue) Intimal layer is markedly thickened, with concentric narrowing and occlusion of the lumen May be localized, multifocal or widespread Giant Cell Arteritis Women more affected than men Mean age of onset is 70 years About 40 – 60% of patients have polymyalgia rheumatica (pain and stiffness in proximal muscles without weakness or atrophy) Giant Cell Arteritis Clinical manifestations/symptoms ◦ Headaches ◦ Visual disturbances ◦ Temporal artery tenderness ◦ Pain in jaw muscles with chewing ◦ Fever, weight loss, malaise ◦ Fatigue ◦ ESR and C-reactive protein are typically elevated Diagnosis is clinical with confirmation by biopsy Takayasu’s Arteritis Inflammatory disease affecting the aorta, its branches and pulmonary arteries Etiology/cause is unknown; may be related to immune response May cause arterial stenosis, occlusion, or aneurysms Rare disease ◦ More common in women and Asians ◦ Young onset (15 – 30 years) Takayasu’s Arteritis Clinical manifestations/symptoms ◦ Systemic phase ◦ Signs & symptoms of inflammatory illness ◦ Fever, fatigue, weight loss ◦ Non-specific aches and pains ◦ Tenderness over affected vessels ◦ Elevated ESR Takayasu’s Arteritis ◦ Occlusive phase ◦ Symptoms related to stenosis/occlusion of the vessels ◦ Claudication ◦ Stroke symptoms ◦ Pulselessness ◦ Bruits Diagnosis is clinical with confirmation by angiogram or MRI Thromboangiitis Obliterans AKA: Buerger’s Disease Inflammatory condition affecting small and medium sized arteries of upper and lower extremity Produces varying degrees of obstruction Inflammation is often accompanied by thrombosis, fibrosis and scarring More common in men, ages 20 – 40 Almost always associated with smoking More common in Asian rather than Western countries Thromboangiitis Obliterans Clinical manifestations/symptoms ◦ Associated with stenosis or occlusion of vessels ◦ Hands or feet may be pale, red or bluish ◦ Hands or feet may be cold; cold sensitivity ◦ Pain in the hands and feet ◦ Acute, severe ◦ Burning or tingling ◦ Often occurring at rest ◦ Intermittent claudication ◦ Skin changes or ulcers on hands or feet Thromboangiitis Obliterans Arteriospastic Disorders Raynaud’s Syndrome ◦ Only one typically evaluated by the vascular lab Acrocyanosis Livedo reticularis Cold hypersensitivity Raynaud’s Syndrome An episode of constriction of small arteries or arterioles in the extremities resulting in characteristic color changes in the digits (usually fingers) This occurs in response to exposure to cold or emotional stress Attacks are usually completed in 30 to 60 minutes but may last until the person rewarms hands Raynaud’s Syndrome Color changes ◦ Pallor (white) – loss of color due to arterial spasm; capillary blood flow is decreased ◦ Cyanosis (blue) – Capillaries dilate, oxygen extraction from the blood is increased ◦ Rubor (red) – Reactive hyperemia, reflex vasodilation restores blood flow Raynaud’s Syndrome Epidemiology Studies have shown that up to 30% of women and 25% of men report a history of Raynaud’s type symptoms 70% of persons seeking treatment are women Incidence is higher in cold environments Occupational incidence ◦ Pneumatic drill (jack hammer) operators ◦ Cold storage and food processor workers Raynaud’s Syndrome Pathophysiology Obstructive Raynaud’s ◦ Secondary Raynaud’s; Raynaud’s Phenomenon ◦ Pre-existing arterial occlusive disease in palmar and/or digital arteries ◦ The greater the amount of occlusion, the more pronounced the incidence of Raynaud’s Raynaud’s Syndrome Pathophysiology Vasospastic Raynaud’s ◦ Primary Raynaud’s; Raynaud’s Disease ◦ Normal blood flow in digits at room temperature ◦ Heightened physiological response to cold exposure ◦ Idiopathic – don’t really know the cause Raynaud’s Syndrome Clinical Manifestations Mild pain Numbness Ischemic digital ulceration in obstructive Raynaud’s