Vascular Conditions NOTES PDF

BIOL 2292 – Dr. Melisa Hamilton Vascular Disorders 1  Outline – Vascular Conditions Blood Vessel Review Arterial Conditions Part 1 Arteriosclerosis Atherosclerosis Aneurysms Peripheral Artery Disease Vas...

BIOL 2292 – Dr. Melisa Hamilton Vascular Disorders 1  Outline – Vascular Conditions Blood Vessel Review Arterial Conditions Part 1 Arteriosclerosis Atherosclerosis Aneurysms Peripheral Artery Disease Vasculitis Raynaud syndrome Part 2 Venous Conditions Chronic venous insufficiency Varicose veins Thrombophlebitis and DVT 2 AP - Blood Vessel Review 3  Basic Blood Vessel Structure Blood vessels are made of 2 kinds of cells Endothelial cells line the lumen of the vessel Roles: coagulation, vasodilation/vasoconstriction, inflammation Form the tunica intima Smooth muscle cells wrap around the vessel Roles in vasodilation/vasoconstriction Form the tunica media Blood vessels also contain ECM Forms the tunica externa or adventitia Elastic connective tissue also wraps vessels and contains nerve fibres and vasa vasorum (slide 8) Ratio of smooth muscle to elastic connective tissue varies depending on blood vessel’s function 4 Basic Blood Vessel Structure Artery Vein LM x 60 5 6 Basic Structure of Arteries Arteries are under greater pressure than veins, so the walls are thicker Lining of lumen is 3 part structure 1. Tunica intima Innermost layer (in contact with blood) is endothelium Sits on basement membrane made of glycoprotein Next is a layer of elastic tissue, the internal elastic lamina 7 Basic Structure of Arteries 2. Tunica media (the thickest layer) Made of elastic tissue and circularly-oriented smooth muscle Damage to these elastic fibres can lead to aneurysm Then there is another layer of elastic mesh, the external elastic lamina 3. Tunica adventitia Loose connective tissue 8 Vasa vasorum Vasa (vessel) vasorum (of the vessels) The vasa vasorum are small blood vessels that are found primarily in large arteries (e.g., aorta) and large veins. Key points about the vasa vasorum: They nourish the outer layer of the blood vessel wall (tunica externa), particularly in vessels that are too thick to be nourished by diffusion from the blood flowing within the vessel itself. (CONTRAST) The inner layers receive nutrients from the blood inside the vessel. The presence of vasa vasorum is more noticeable in veins than in arteries because veins have thinner walls and lower oxygen content in the blood, requiring more external nourishment. The vasa vasorum maintains the health and function of large blood vessels. Damage or dysfunction in these vessels can contribute to conditions like atherosclerosis. 9 Arterial Wall Structure 10 Types of Arteries 1 There are 3 types of arteries 2 Differ slightly in structure, tunic media, and EMC due to local adaptations 1. Elastic arteries (“conducting arteries”) Biggest type in the body (e.g. aorta, pulmonary trunk) Have a lot of elastin in the walls Elasticity allows vessel to stretch due to sudden rush of blood and then return to original diameter, pushing blood forward With age, arteries lose elasticity and become dilated and tortuous 2. Muscular arteries (“distribution arteries”) Distribute blood throughout body  Most arteries are muscular arteries Tunica media contains more smooth muscle cells, and less elastin, than in elastic arteries and lumen is more narrow e.g. Brachial, carotid, femoral arteries  Regional blood flow and blood pressure is regulated through changes in lumen size by contraction of the smooth muscle (i.e. vasoconstriction and vasodilation) 3. Arterioles (“resistance vessels”  small arteries) Microscopic arteries that deliver blood to capillaries Single layer of endothelium wrapped in one or two layers of smooth muscle; no elastic tissue Play major role in regulation of tissue perfusion Dilate when oxygen levels drop, constrict due to signals from sympathetic nervous system Because degree of constriction/dilation affects systemic blood pressure, sometimes known as resistance vessels 11  Question: Would blood flow faster through a smaller or larger diameter blood vessel?? 12  Question: Would blood flow faster through a smaller or larger diameter blood vessel??  Blood flows faster through larger diameter vessels because they offer less resistance to flow.  Smaller vessels, the resistance to blood flow is much higher. 13  Capillary endothelial cells Capillaries The smallest blood vessels (about the diameter of a RBC ~7-8um) Endothelium with scattered smooth muscle cells, that support the endothelium and regulate blood flow Capillaries form branching network between an arteriole and a venule Venule: a very small vein that collects blood from the capillaries. Collectively they have a very large cross-sectional area Branching leads to drop in blood pressure across network The drop in pressure, slower blood flow, and thin capillary walls all enhance diffusion between blood and tissue Fluid carrying oxygen and nutrients crosses endothelial barrier Barrier is selective, preventing escape of large molecules 14 Capillaries Capillar y on a vs. Arteriole muscle Lung capillari es 15 Capillary Beds Metarterioles = branches off arteriole into capillary bed Turn into thoroughfare channel at the venule end of capillary bed. thoroughfare channel: continuation of the metarteriole that enables blood to bypass a capillary bed and flow directly into a venule, creating a vascular shunt. Precapillary sphincters contract and relax to control blood flow into capillary bed The blood flow from a metarteriole through capillaries and into a postcapillary venule is called the microcirculation 16 Veins Veins have larger lumens and less well organized walls than arteries Because of the lack of support, veins are susceptible to irregular dilation and compression Also easier for tumours to penetrate  Veins have a large capacity and act as a reserve; ~ 2/3 of blood is in the venous system  Low pressure system and reverse flow is prevented by valves 17 Endothelial Cells Transcytosis Fenestrations 18 Functions of Endothelial Cells Endothelial cells have an extensive variety of functions: Express antithrombotic heparin-like molecule, thrombomodulin, tissue plasminogen activator Synthesize prothrombotic von Willebrand factor, tissue factor, plasminogen activator inhibitor Secrete both vasoconstrictors and vasodilators to regulate blood flow Help guide inflammatory response through expression of cellular adhesion molecules and secretion of chemokines Secrete a variety of growth regulators, both stimulatory and inhibitory, for tissue repair and angiogenesis 19 Endothelial Cells by location Endothelial cell properties in capillary beds vary depending on organ In brain, endothelial cells joined by tight junctions that block proteins from crossing the Blood/brain barrier In other organs, junctions not as tight, so passage of some molecules is possible Solutes may move across endothelial cells through transcytosis (e.g. hormones) In some organs, endothelial cells are fenestrated (i.e. kidney) Fenestrated: one or more holes or openings, like windows 20 Endothelial Dysfunction Injury or inappropriate (improper or excessive) activation of endothelial cells underlies many vascular problems Impaired vasoreactivity Inappropriate increase in prothrombotic traits Increased expression of adhesion molecules for inflammatory cells All implicated in formation of thrombi, atherosclerosis, and other disorders Dysfunction may be rapid in onset or slow, rapidly reversible or slowly 21 Vascular Smooth Muscle Plays a role in vascular repair and dysfunction Smooth muscle cells are able to proliferate when stimulated and can produce ECM, collagen, elastin, proteoglycans, as well as GF and cytokines SMC dmg  migrate (normally in the tunica media)  proliferate into the tunica intima  contributes to the thickening of walls Smooth muscle can also cause vasoconstriction or dilation in response to physiological or pharmacological stimuli 22 A typical response to vascular injury 1. Endothelial loss or dysfunction results in intimal thickening via SM proliferation 1. Produces neointima (scar tissue) that is covered by migrating endothelium (similar to wound healing) 2. SM cells produce ECM (as would fibroblasts in epithelial wounds) 3. Causes permanent thickening of the intima (bc of the neointima/scar tissue) 4. If there is chronic or recurrent injury stenosis can occur. 1. Stenosis and sclerosis can happen together 23 A typical response to vascular injury 24  Question: What is the difference between stenosis and sclerosis? 25  Question: What is the difference between stenosis and sclerosis?  Stenosis: narrowing of a blood vessel, valve, or other tubular structure, which restricts blood flow. It is often caused by plaque buildup, scar tissue, or congenital defects.  Sclerosis: hardening/thickening, or stiffening of tissues, often due to abnormal tissue growth, calcium deposits, or fibrosis. In the case of arteries (arteriosclerosis), the walls of the vessels become stiff, making it harder for blood to flow through them.  "stenos" narrow or tight.  "scleros“ hard  "-osis" condition, ,state, abnormal state. 26 Vasospasm Excessive contraction of smooth muscle in arterial walls, leading to vasoconstriction  Can lead to tissue ischemia and necrosis  Normally relaxation is > contraction; if contraction is > relaxation = vasospasm Caused by an imbalance of vascular mediators. Vasocontraction occurs: If platelets release more thromboxane A2 or serotonin (vasoconstrictors) Thromboxane: type of prostaglandin that cause VC. Stimulates Platelet Aggregation (clumping) for blood clotting. If endothelial cells produce less prostacyclin and NO (Nitric oxide). prostacyclin and NO are vasodilators/relax SMC. Prostacyclin: types of Prostaglandin that promotes VD. fast-acting antiplatelet effects(inhibitor) and inflammatory mediator. Lowers BP + improves BF Atherosclerosis is associated with vasospasm Atherosclerotic endothelium is dysfunctional, producing less prostacyclin and NO. Can lead to Cerebral vasospasm  stroke Coronary vasospasm  angina, MI, death Vasospasm in the extremities can lead to cyanotic digits and loss of dexterity 27  Question: How could you treat vasospasm? 28  Question: How could you treat vasospasm?  methods that relax the smooth muscle of blood vessels to restore normal blood flow o Calcium channel blockers: These relax blood vessel walls and reduce spasms. o Beta-receptor antagonist (beta-blockers): Inhibit constriction o Nitrates: Used to dilate blood vessels and relieve spasm. o Antispasmodics: Medications that target and relax smooth muscles. o Increasing blood flow: Hydration, warming the affected area, or oxygen therapy can help increase blood flow and reduce vasospasm. o Surgical intervention: In severe cases, surgery may be needed to alleviate the spasm. 29 30 31 32 33 Arterial Conditions 34 Disease of Blood Vessels Arterial diseases cause more morbidity and mortality in the developed world than all other diseases combined Veins do not cause as much trouble Two main ways arteries cause problems: 1. Narrowed or completely blocked arterial lumen May be sudden or gradual 2. Weakening of arterial walls leading to aneurysms or rupture 35  Arteriosclerosis Arteriosclerosis  general term , refers to arterial wall thickening/hardening  loss of elasticity, reduced bloodflow. Three different subtypes: 1. Arteriolosclerosis, sclerosis of small arteries and arterioles 2. Moneckeberg medial sclerosis, calcification of the muscular arteries (media) in patients over 50 years. 1. typically without narrowing of the vessel or affecting blood flow. 3. Atherosclerosis is when plaques of inflammatory cells build up in vessel walls and protrude into the artery lumen  potential ischemia  MI or stroke. 36 Atherosclerosis (athero- “gruel- like”) The most common arterial disease Tunica exter Due to a build-up of inflammatory and smooth muscle cells, lipids, and connective tissue in the walls of arteries Lipid deposi Lesions are referred to as atherosclerotic (plaque) plaques or atheromas Creation and growth of a plaque generally Tunica medi takes decades (takes a long time) Coronary artery LM x 6 Gradually narrow the lumen of the affected blood vessel but may also rupture or form aneurysms Plaque deposit 37 in vessel wall What are the major problems these plaques cause Narrow lumen  reduced perfusion/ischemia  hypoxia  weakening of vessel  cell damage Clot/increased risk of thrombosis  embolus  aneurysms Decrease elasticity  reduce perfusion  weakening of smooth muscle  aneurysms or  increased BHP  leak vessels/weakening of smooth muscle  rupture 38  Atherosclerosis: Epidemiology About half of all deaths in Canada are attributable to atherosclerosis Via stroke, ischemic heart disease, myocardial infarction (MI), gangrene Evidence of arterial damage has been found in people as young as 1 year Earliest sign is presence of fatty streaks Visible, narrow, pale yellow longitudinal streaks on arterial walls Caused by the presence of foam cells (macrophages full of ingested lipids) Fatty streaks are not harmful (by age 10 everyone has fatty streaks in their aorta) Some may eventually become plaques, others do not 39 Risk Factors for Atherosclerosis 1. Serum cholesterol level (LDL-C) Very closely correlated with ischemic heart disease High cholesterol can be due to high dietary fat intake or to a defect in lipid metabolism (genetic) E.g. Familial hypercholesterolemia (difficulty processing lipds  increased LDL) Due to defective LDL receptor Mutation is autosomal dominant About 1/500 people heterozygous for the trait; 1/1,000,000 homozygous (much more severely affected) 2. Hypertension  damage to endothelial cells  inflammation response High blood pressure also correlates well with likelihood of MI Systolic BP > 140 mmHg (3x increase in risk compared to 120 mmHg or less) 3. Smoking  dose dependent Atherosclerosis is much, much worse among smokers Immune mediated disease Strongly associated with atherosclerotic (plaque) aortic aneurysms (stay tuned…) Dose-dependent (it’s never too late to quit smoking) Leads to MI, ischemic stroke, abdominal aortic aneurysm 40 Atherosclerotic Plaques Atherosclerotic plaques mainly form in elastic or large and medium muscular arteries Aorta, carotid, iliac (elastic) Coronary, popliteal (muscular) More tend to form in the abdominal aorta than in the thoracic aorta Also tend to form around openings to large vessels branching from the aorta (due to turbulence) What problems do these plaques cause? There are many (stay tuned for a detailed discussion, but for now…) Atherosclerotic narrowing can lead to blockages  ischemia Plaques can break down, releasing emboli…  ischemia Symptoms most often show up in heart, brain, kidneys, legs Myocardial or cerebral infarctions, aortic aneurysm, peripheral vascular diseases (e.g. gangrene), ischemia of specific organs 42 Atherosclerotic Plaques Plaque develops as thickening of arterial intima Individually, tend to be 0.3 to 1.5 cm in diameter Individual lesions may combine to form larger lesions Lesion bulges into blood vessel lumen Core of lesion is soft, yellowish Covered with white, fibrous cap L: lumen F: Fibrous cap C: Necrotic core (largely lipids) 43 Basic Plaque Structure Plaques have 3 main components: 1. Cells – SM, macrophages, other leukocytes (inflammation mediators) 2. Extracellular matrix (ECM) – collagen, elastic fibres, proteoglycans 3. Intra-, and extracellular lipids Different plaques have different proportions of the above components Cap is mainly cells and dense ECM (fibrous cap) Core of plaque often necrotic, with lipids (soft) Many become calcified Sufficient 44 Basic Plaque Structure 45 Atherosclerosis: Pathogenesis  response to chronic inflammation ‘Response to injury hypothesis’ Suggests that atherosclerosis is a chronic inflammatory response due to some triggering injury to endothelium (cannot function properly) Results in endothelial activation/dysfunction, increased permeability, increased adhesion of leukocytes, different proteins expressed by endothelial cells  inflammation response. Two big factors seem to be disturbances in blood flow (like hypertension) and hypercholesterolemia Note: Normal flow can also cause problems, anywhere blood flow is disrupted or slow E.g. Plaques commonly occur at openings to large blood vessels leading off the aorta, arterial branch points, and down the posterior wall of the abdominal aorta Plaques are rare in places where blood flow is smooth Inflammation contributes to the initiation progression, and complications associated with atherosclerosis. 46 Might be a test question. Review why. How does Uncontrolled hyperglycaemia lead to atherosclerosis Increases synthesis of cholesterol Damage to the vessels over time from the “sugar crystals” 1. Endothelial Dysfunction: High glucose levels damage the endothelial cells that line blood vessels. This damage makes the endothelium more permeable and prone to inflammation, reducing its ability to prevent substances like cholesterol from entering the arterial wall. 2. Inflammation: Hyperglycemia triggers an inflammatory response. The damaged endothelial cells release signals that attract white blood cells (monocytes). These monocytes enter the damaged vessel wall and transform into macrophages, which engulf oxidized LDL (bad cholesterol), forming foam cells. 3. Oxidized LDL Accumulation: Inside the vessel wall, oxidative stress caused by high blood sugar increases the production of reactive oxygen species (ROS). These ROS oxidize LDL cholesterol, and the oxidized LDL is engulfed by macrophages, leading to the formation of fatty streaks, the earliest form of atherosclerotic plaque. 4. Plaque Formation: The accumulation of foam cells leads to the development of plaque within the arterial wall. Over time, smooth muscle cells migrate into the plaque area, contributing to the formation of a fibrous cap that hardens the artery (sclerosis). 5. Advanced Glycation End Products (AGEs): AGEs, formed by excess sugar binding to proteins, further damage the blood vessel walls by stiffening them and promoting inflammation. AGEs also reduce the flexibility of blood vessels, contributing to the progression of atherosclerosis. 6. Narrowing of Arteries: As plaques grow, the artery narrows, restricting blood flow. This can lead to reduced oxygen supply to organs and tissues, increasing the risk of heart attacks or strokes. In summary, uncontrolled hyperglycemia causes a chain reaction of endothelial damage, inflammation, LDL oxidation, and plaque buildup, leading to the narrowing and hardening of arteries characteristic of atherosclerosis. 47 Atherosclerosis: Pathogenesis Flowchart ‘Response to injury hypothesis’  not linear. May happen at same time. 1. Endothelial injury 2. Accumulation of lipoproteins (LDL-C) 3. Monocyte adhesion and transformation to foam cells 4. Platelet adhesion 5. Factor release from platelets, macrophage, EC and SM 6. Smooth muscle proliferation and ECM production 7. Lipid accumulation outside of cells and within macrophage and SM 48 Inflammation plays a major role in atherosclerosis pathogenesis Inflammation contributes to the initiation, progression, and complications associated with atherosclerosis Inflammation starts and finishes the process  positive feedback Early in development of atherosclerotic lesion, endothelial cells begin expressing adhesion molecules which specifically target monocytes and T cells (CD4+ and CD8+) These cells play a role in plaque development 49 Inflammation plays a major role in atherosclerosis pathogenesis Monocytes enter blood vessel connective tissue and become macrophages Begin consuming lipoproteins (mainly LDLs), eventually becoming foam cells Leads to further expansion of plaque Also secrete various cytokines, recruiting more macrophages (positive feedback) Macrophages release ROS that cause further damage ROS rip electrons T cells also secrete cytokines, such as IFN-, which stimulate macrophages, endothelial cells and SMCs Once these cells get activated, they secrete growth factors which cause SMCs to proliferate, migrate to the intima of the vessel, and begin producing extracellular matrix This results in thickening of the blood vessel wall Now evidence that leukocytes may cause damage to endothelial cells, triggering additional inflammation/repair/plaque formation (positive feedback) 50 Pathogenesis 51 Plaque Formation 52 Lipid metabolism is key in plaque formation Since lipids are hydrophobic they do not dissolve in plasma very well and tend to re-enter the nearest cell Need to be modified for transport in blood  lipids bind to proteins Lipids are combined with proteins (apoproteins, A – E), forming lipoproteins Lipoproteins are water soluble and allow interaction with cell membrane receptors 53 Lipoproteins Four kinds of lipoproteins 1. Chylomicrons 2. Very-low-density lipoproteins (VLDL) 3. Low-density lipoproteins (LDL)  taken up by peripheral tissues (anywhere fat is delivered 4. High-density lipoproteins (HDL)  hepatocytes Lipoproteins can be exogenous or endogenous  Exogenous lipoproteins from diet 🞑Fatty acids/glycerol absorbed by small intestine and packaged as chylomicrons (very high triglyceride content) 🞑Pulled from circulation by receptors on endothelial cells in adipose tissue, muscle and others 🞑 Triglycerides removed and remnants travel to liver for final absorption  Endogenous lipoproteins are synthesized and secreted by the liver into blood 54 Endogenous Pathway VLDLs High in triglycerides and cholesterol Triglycerides gradually removed by various cells, changing the composition Become LDLs LDLs are roughly 25% protein, 5% triglycerides, 20% phospholipids, and 50% cholesterol Transport about 75% of total blood cholesterol Taken up by cells in various tissues – ovaries, adrenal cortex, smooth muscle, hepatocytes 55 Why LDLs are Dangerous If there are too many LDLs in circulation, they can be taken up by “unauthorized” tissues (e.g. arterial walls, liver) ROS from macrophages oxidizes the LDLs Smooth muscle cells and macrophages phagocytize oxidized LDLs in vast numbers Macrophages and SMCs become foam cells – cells filled with cholesterol which accumulates because it can’t be processed Oxidized LDLs also act as chemoattractants for more macrophages 56 Hypercholesteremia is a key driver is atherosclerosis, but why? (I changed title) Lipids in atherosclerotic plaques are mainly cholesterol or derivatives of cholesterol LDLs are found in foam cells in plaques People with familial hypercholesterolemia develop serious atherosclerotic disease by age 20 Studies of people with atherosclerosis show that most also have high levels of cholesterol Reducing blood cholesterol levels has been shown to slow progress of atherosclerosis, or even cause plaques to disappear 57 58 59 60 61 Plaques can cause a variety of problems Chronic narrowing of lumen (stenosis) slowly starves tissues  ischemia Reduction in blood flow will lead to atrophy of cells/organs Acute blockage of an artery will cause ischemic necrosis in the “downstream” tissue Myocardial infarction, stroke, gangrene Growth, rupture, or repair of plaque can weaken artery wall, leading to aneurysm  (which can suddenly rupture  cardiovascular disaster) Common in abdominal aorta 62  Plaques can cause a variety of problems 1. Mural (“wall”) thrombi can form along the edge of the plaque 2. Plaque projecting into lumen disrupts smooth flow of blood 3. Resulting turbulence slows flow, allowing formation of thrombi 4. Turbulence may also strip away endothelial cells, exposing underlying basement membrane 5. Leads to thrombosis 63 Plaques can cause a variety of problems Lumenal surface of plaque can be damaged 1. As plaque ages, lumenal surface becomes covered with fibrous cap  2. Necrosis beneath can lead to rupture of cap  3. Rupture, ulceration, or erosion can lead to: Formation of thrombus Thrombus will further narrow or block vessel Thrombus may be incorporated into plaque (enlarging it) Release of emboli Thrombus or parts of thrombus may break off (thromboemboli) blocking smaller arteries Cholesterol emboli can be released from ruptured plaques May get bleeding/hemorrhage into plaque Through either a hole in fibrous cap, or through small blood vessels that form in the plaque Can cause expansion and possibly rupture of the plaque 64 Plaques can cause a variety of problems * stable plaques can be better but What causes a plaque to be disrupted? Age – time/growth/inflammation Changes in BP through adrenergic stimulation can increase physical stress leading to rupture Emotional stress can also contribute to plaque disruption Interestingly, between 6am-noon has the highest risk of MI, linked to adrenergic changes associated with waking and rising 65 Plaques can cause a variety of problems Eek!! 66 Plaque Progression and Consequences 67 Atherosclerosis RF, DX Risk factors: Abnormal cholesterol, high blood pressure, uncontrolled diabetes, smoking, obesity, family history, unhealthy diet, genetics Diabetes  increased glucose causes vessel damage Smoking to diet  increase in lipoproteins Diagnosis: Physical exam, ECG, exercise stress test, angiography (look into vessels) Not always detectable – plaque can rupture and cause artery occlusion very quickly, without prior narrowing Prevention***** Up to 90% of cardiovascular disease may be preventable if risk factors are avoided! Healthy diet, exercise, not smoking, maintaining normal weight 68 Atherosclerosis Treatment Medications Statins (lower LDL cholesterol levels by inhibiting cholesterol synthesis and increasing LDL uptake by the liver and removing from the blood) Changes exo/endogenous LDL metabolism at the liver  causing liver to take up more LDLs. Antihypertensives Antithrombotics (e.g. aspirin) Surgery to reduce effects of (downstream) ischemia in specific arteries. Vascular bypass surgery, angioplasty (may involve stents) Heart specific: Percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy **Anti inflammatory (high risk) potentially but they can cause problems. Bc Atherosclerosis is immune mediated But anti inflammatory has a bunch of risks Potentially used in combination with other meds/surgery. 69 Peripheral Artery Disease (PAD) Caused by narrowing of arteries (other than in the heart or brain) Most common in the legs, but can also involve the arms, neck, or kidneys Causes arterial insufficiency – diagnosed by ankle-brachial index (ABI) < 0.9 Symptoms include: Intermittent claudication (most common) muscle pain during activity, resolved at rest  hypoxia issue  movement uses oxygen,  rest replenishes O2 Pale or bluish skin (cyanosis) Cold skin Skin ulcers due to necrosis Abnormal hair or nail growth on affected limb Pain during activity Or can be asymptomatic Risk factors same as those for atherosclerosis (because atherosclerosis is the most common mechanism!) What are those risk factors?? Increase cholesterol, hypertension, smoking Complications include gangrene (which may require amputation), infection, coronary artery disease or stroke DX with ABI  Ankle-brachial index (bp around arm and ankle  should have a 1:1 ratio) ABI of less than 95% of cases show a transverse tear in the tunica intima and media Possible pathogenesis: Hypertension  Mechanical injury/ischemic injury  Medial weakness  Tear  Medial hematoma/hemorrhage 82 83 Aortic Dissection  Once tear is started, propagation of the dissection is very rapid (i.e. seconds)  May progress into adjoining blood vessels  External wall of aneurysm is thin, and easily ruptured  Leads to massive internal hemorrhage and death  Sometimes aneurysm breaks back into aorta further along, creating 2 channels for flow Main symptom is sudden, ripping anterior chest pain May be misdiagnosed as MI If person hypotensive (hypovolemic/hemorrhagic shock), indicates a hemorrhage If manage to make it to surgery, prospects are good With surgery, mortality < 20% Would have to already be hospitalized at time of onset  Very quick death 84 Syphilitic Aneurysms Can arise during tertiary syphilis Inflammatory response to Treponema bacteria causes chronic inflammation of the tunica adventitia of large arteries (most common in the aorta) o Restricts blood flow in the vaso vasorum (vessel within a vessel), which causes ischemia of the tunica media  Necrosis  weakening o Vaso vasorum doesn’t need its own blood supply bc it’s close to the nutrition supple of oxygen o That’s why it’s only in the large arteries o Results in weakening and destruction of the arterial wall  dilation  aneurysm Flow chart  Restricts blood flow in vaso vasorum  ischemia of tunica media  Necrosis  weakening + destruction of arterial wall  dilation  aneurysm 85 86 87 88 89 90 Vasculitis General group of disorders characterized by inflammation and necrosis of blood vessels (both arteries and veins) Caused by excessive/inappropriate immune attack on blood vessels (can be non-infectious or infectious), chronic damage May begin when immune complexes or anti-endothelial cell antibodies are deposited on endothelium Remember hypersensitivities? Some evidence that viruses can trigger immune attack  Results in inflammatory attack of blood vessels  PAD Look into hypersensitivities 91 Vasculitis There are over 20 recognized types. Classified according to the cause, the location, the type of vessel, or the size of vessel Clinical features and signs and systems are dependent on which vascular bed (location) is affected Fever, malaise, myalgia, and arthralgias are common  inflammation How could you diagnose this? Evidence of inflammation CBC – differential If they have leukopenia C reactive protein test Increase ESR  erythrocyte sedimentation rate  if they settle faster means more inflammation is present? Why Biopsy, angiogram What treatments would be useful? Anti-inflammatory  to cause immunosuppression  corticosteroids Infection  Antibiotics, antivirals 92 Raynaud Syndrome: Episodes of excessive signals triggering vasoconstriction of digital arteries and arterioles Episodes of excessive vasoconstriction of digital arteries and arterioles Fingers most common, sometimes toes Occasionally nose, ears, or lips Digits turn white and then blue; numbness or pain can occur; when blood flow is restored, digits turn red and burning can occur 93 Raynaud Syndrome/buerger disease Primary: 3-5% of people, women more affected than men (mb genetics) Due to exaggerated central and local vasomotor response to cold or emotional stress (sympathetic nervous system) Secondary: (upstream issue. Not vessel issue) Occurs due to another condition that causes vascular insufficiency of the extremities E.g. Autoimmune diseases (scleroderma, SLE), prolonged vibration, smoking, thromboangitis obliterans, or atherosclerosis Treatment: Avoid triggering factors (ie cold temperatures, stimulants (ie caffeine, nicotine), etc) Why does caffeine trigger episodes Too much caffeine may trigger excessive vasocontraction of the extremities 94 Venous Conditions Chronic venous insufficiency Varicose Veins Thrombophlebitis and DVT (previously covered) Note: Veins are not adapted to receive blood at high pressure Functions: Return blood against gravity Inhibit backflow  failure of valves/backflow  pooling of blood  edema 95  Chronic Venous Insufficiency Blood pools in the veins causing increased intraluminal pressure and stress on venous walls Results in decreased venous return Most often affects the legs bc gravity Caused by dysfunctional venous valves due to: DVT Superficial vein thrombosis  backflow Phlebitis May-Thurner syndrome – compression of left common iliac vein by overlying right common iliac artery  Manifestations:  Swelling (edema), pain, pruritus, hyperpigmentation  May lead to varicose veins, ulcer formation, contact and stasis dermatitis  Treatments: (best option depends on severity)  Include manual compression, leg elevation (tilting bed), surgery to remove or replace veins 96 Varicose Veins (Varicosities) Abnormally dilated, tortuous superficial veins The result of prolonged intraluminal pressure and loss of vessel wall support Typically occur in the legs but can also occur in other regions of the lower body  gravity Vulva Scrotum (varicocele) Anus (hemorrhoids) Typically asymptomatic but can cause pain and/or superficial thrombophlebitis  Very common, affect ~30% of people, 4x more common in women  Risk factors include pregnancy, obesity, lack of exercise, long periods of standing, family history  Treatment & Prognosis:  Compression stockings, weight loss, exercise, elevating the legs  Endovenous laser treatment, radiofrequency ablation, foam sclerotherapy 97 Thrombophlebitis and DVT Thrombophlebitis or phlebothrombosis Inflammation of the vein caused by a thrombus As previously discussed… Ultrasonographic image showing thrombosis of the great saphenous vein. 98 99 100 101 102