Blood Vessels 2024 PDF

DISEASES of the BLOOD VESSELS Ali Pourian [email protected]  01 STRUCTURE AND FUNCTION  Blood Vessels Composition and Types Basic Composition: Three main components: Extracellular Matrix (ECM): Structural support – composed of fibrin and connective tissue Smooth M...

DISEASES of the BLOOD VESSELS Ali Pourian [email protected]  01 STRUCTURE AND FUNCTION  Blood Vessels Composition and Types Basic Composition: Three main components: Extracellular Matrix (ECM): Structural support – composed of fibrin and connective tissue Smooth Muscle Cells (SMCs) Controls contraction and relaxation of the vessel walls Influence blood flow and pressure. Endothelial Cells (ECs): Line the inner surface of blood vessels Maintains vascular health - inflammation and blood clotting  Blood Vessels Composition and Types Vessel Structure: three concentric layers: Intima: Inner layer composed of single layer of endothelial cells. It is separated from the media by the internal elastic lamina. Media: Middle layer is composed primarily of SMCs and ECM. Sometimes contains elastic fibers in elastic arteries (like the aorta). Separated from adventitia by external elastic lamina Adventitia: Outer layer made up of loose connective tissue, collagen fibers, and some elastin Provides structural integrity and support  Types of Blood Vessels - Arteries Large Elastic Arteries (aorta) High concentration of elastic fibers that allow them to expand and recoil Medium-Sized Muscular Arteries (coronary arteries): Composed mainly of SMCs Arteries regulate blood flow to organs through vasoconstriction and vasodilation. Small Arteries and Arterioles: MAIN REGULATOR OF BLOOD PRESSURE Resistance varies with the fourth power of vessel radius. Capillaries: Location of gas and nutrient Exchange Types of Blood Vessels - Veins Structure: Thin walled, larger-diameter vessels Less distinct layers Normally contains ~2/3 of blood Valves within veins prevent backflow and assist in venous return.  Lymphatic System Thin-walled endothelium-lined channels Drain lymph from tissues Transport fluid and cells to lymph nodes Continuous monitoring for infection Returns cells via blood stream via thoracic duct  02 Congenital Anomalies Artery Variants: 1-5% of the population 1) Berry Aneurysm 2) AV Fistula  Berry Aneurysm Definition: Thin-walled outpouching in the cerebral vessels Classically at branch points around circle of Willis Can spontaneously rupture - deadly TREATMENT: monitored or treated by clipping to prevent rupture ANEURYSM: an abnormal localized dilation of a blood vessel wall  Arteriovenous Fistula Abnormal connection between artery and vein without intervening capillary bed Most commonly are developmental May lead to high-output cardiac failure or organ ischemia TREATMENT: Some cases require surgery Used intentionally in hemodialysis FISTULA: an abnormal connection or passageway that forms between two organs, vessels, or spaces that are not normally connected  03 Hypertension 1) Blood Pressure Regulation 2) Hypertension Blood Pressure Determined by cardiac output and peripheral vascular resistance Hypotension (low blood pressure) leads to inadequate organ perfusion, organ dysfunction and tissue necrosis Hypertension (high blood pressure) causes vessel and organ damage and risk factor for atherosclerosis KIDNEYS Sodium Balance Regulates Na and water levels Renin Produced by renal juxtaglomerular cells Released in response to low blood pressure Leads to activation of angiotensin II ANGIOTENSIN II Causes vasoconstriction Stimulates release of aldosterone ALDOSTERONE Produced by adrenal gland Regulates Na and water levels  Blood Pressure Measurement Blood Pressure: Amount of pressure (force/area) that blood exerts on arterial walls Systolic Blood Pressure Measurement of pressure when heart is contracting 120 mmHg 80 mmHg Diastolic Blood Pressure Measurement of NORMAL = 120mmHg Renal failure Retinal hemorrhages  Hypertension Clinical Guidelines 2017 American College of Cardiology-American Heart Association guidelines: Hypertension defined as BP ≥ 130/80 Overall US prevalence: 46% (rate of control 46%)  Hypertension Clinical Guidelines Diagnosis made by at least 2 BP measurements on 2 separate occasions Back supported, legs uncrossed, feet on floor, measurement arm resting on table at heart level After patient has sat quietly for 5 minutes Automated devices take 2-6 measurements serially Allow attendant to place cuff and leave room Minimizes ‘white coat’ effect  Hypertension Management Stage 1 HTN without pre-existing conditions Implement lifestyle modifications with 3-6 month follow up Sodium intake < 1500mg per day, increased potassium intake Weight loss if overweight 90-150 minutes of aerobic or resistance exercise per week Moderation of alcohol intake DASH diet: fresh produce, whole grains, low-fat dairy products All other patients Lifestyle modifications plus pharmacologic therapy  4 drug classes reduce cardiovascular events: ACE inhibitors Angiotensin-receptor blockers Calcium-channel blockers Thiazide-type diuretics 3. Calcium- channel blockers 4. Thiazide- type diuretics 2. Angiotensin- receptor blockers 1. Angiotensin-converting-enzyme inhibitors  04 Atherosclerosis Arteriosclerosis - hardening of the arteries General term meaning arterial wall thickening and loss of elasticity Arteriolosclerosis – affects small arteries and arterioles Atherosclerosis – “gruel” and “hardening” SCERLOSIS: abnormal Most common and most important clinically thickening or hardening of Hardening from a atheromatous plaque tissue  Atherosclerosis – Big Picture Vascular injury leads to endothelial loss stimulating smooth growth, extracellular matrix synthesis and thickening of the vascular wall Characterized by intimal lesions called atheromas (or atherosclerotic plaques) Cause of coronary, cerebral and peripheral vascular disease  Atherosclerosis – Big Picture Plaques are raised lesions Plaques composed of soft friable lipid cores Lipids = cholesterol and necrotic debris Plaques enlarge Cause vascular obstruction and stenosis Can rupture resulting in thrombosis and sudden occlusion Thrombosis can break off and lead to emboli Weakens walls leading to aneurysm Atherosclerosis – Big Picture Areas affected Heart – coronary artery Angina, vomiting, feeling faint, myocardial infarction (~25% of all US deaths) Carotid artery Weakness, dysphagia, headaches, facial numbness, stroke Peripheral Vascular disease Weakening, erectile dysfunction, hair loss Kidney Increases renin/BP, hand/feet swelling Atherosclerosis Ubiquitous in higher income nations Increasing in lower-income countries – globalization of Western diets Africa, India, and Southeast Asia now exceeds US in coronary artery disease , Atherosclerosis – Risk Factors Constitutional (inherent, non-modifiable) Risk Factors Genetics: Family history most important independent risk factor for atherosclerosis Age: Death from ischemic heart disease increase with each Sex: Premenopausal women protected against atherosclerosis vs. age-matched men Estrogen? Postmenopausal women at equal or higher risk than men Atherosclerosis – Risk Factors Modifiable Risk Factors Hyperlipidemia, especially hypercholesterolemia Induces lesion in absence of other risk factors Low-density lipoprotein (LDL) Distributes cholesterol to peripheral tissue High density lipoprotein (HDL) Mobilizes cholesterol from developing and existing vascular plaques and transports them to liver for excretion Atherosclerosis – Risk Factors Modifiable Risk Factors Hyperlipidemia, especially hypercholesterolemia Low-density lipoprotein (LDL) “bad cholesterol” Elevated in high cholesterol diets Can be lowered with Dietary control Omega-3 fatty acids (fish oils) Statins: cholesterol-lowering drugs High density lipoprotein (HDL) ”good cholesterol” Lowered in obesity or with smoking Can be elevated with exercise  Atherosclerosis – Risk Factors Modifiable Risk Factors Hypertension: increases risk for IHD by 60% Cigarette smoking: prolonged smoking doubles risk Increases severity and risk in women Cessation reduces risk Diabetes – associated with increased levels of serum cholesterol Other minor factors Atherosclerosis – Pathogenesis How does the plaque form? The Response to Injury Hypothesis Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury Atherosclerosis – Pathogenesis How does the plaque form? The Response to Injury Hypothesis 1. Endothelial injury 2. Lipid Accumulation 3. Inflammatory Response 4. Formation of Fatty Streaks 5. Smooth Muscle Proliferation 6. Plaque Development 7. Plaque Stability and Rupture 8. Thrombosis Atherosclerosis Pathogenesis How does the plaque form? 1. Endothelial injury Causes: Hyperlipidemia Hypertension Smoking Diabetes Leads to Increased permeability Leukocyte adhesion Thrombosis EC injury leads to endothelial dysfunction Atherosclerosis Pathogenesis How does the plaque form? 2. Lipid accumulation Lipids (importantly LDL) permeate and accumulate in the intimal layer LDL becomes oxidized Attracts inflammation and immune cells Monocytes adhere and migrate into intima Atherosclerosis Pathogenesis How does the plaque form? 3. Inflammatory response Monocytes enter intimal layer and differentiate into macrophages Macrophages engulf oxidized LDL and become known as FOAM CELLS Smooth muscle cells migrate into media Atherosclerosis Pathogenesis How does the plaque form? 4. Formation of fatty streaks Accumulation of foam cells 5. Smooth muscle proliferation Proliferate in intimal layer Also take up lipids Contribute to fatty streak formation Atherosclerosis Pathogenesis How does the plaque form? 6. Plaque Development FIBROUS Foam cells PLAQUE CAP Smooth muscle cells Lipid Core This plaque consists of lipids, dead cells, and a mixture of inflammatory cells and extracellular matrix components.  Atherosclerosis Pathogenesis How does the plaque form? 7. Plaque Stability Atherosclerotic plaques can either be stable or unstable. Stable plaques have a thick fibrous cap, while unstable plaques have a thin cap and a large lipid core and are prone to rupture. When an unstable plaque ruptures, the underlying materials are exposed to the bloodstream, leading to platelet activation and the formation of a thrombus (blood clot).  Atherosclerosis Pathogenesis How does the plaque form? 8. Thrombosis If a thrombus forms, it can further narrow or completely occlude the artery, leading to reduced blood flow to the downstream tissues and potentially resulting in conditions such as: Angina (chest pain) Myocardial infarction (heart attack) Stroke Peripheral artery disease Summary Slide Atherosclerosis – Consequences  04 Vasculitis 1) Overview 2) Specific Diseases VASCULITIS OVERVIEW VASCULITIS Inflammation of blood vessels Mostly occurs in ARTERIES Two main causes of inflammation of blood vessels: Direct invasion of vascular walls by infectious pathogens IMMUNOLGIC (AUTO-IMMUNE) attack of the blood vessels CONSEQUENCES: Decreased blood flow Aneurysms Ischemic organs Inflammation cause Auto-immune Mechanism: DIRECT ATTACK Known as molecular mimicry B cells mistake human endothelial cell for a foreign pathogen Inflammation cause Auto-immune Mechanism: DIRECT ATTACK Known as molecular mimicry B cells mistake human endothelial cell for a foreign pathogen Endothelial cell layer destroyed OCCURS IN MEDIUM and LARGE VESSELS Inflammation Cause Autoimmune Mechanism: INDIRECT DAMAGE B cells attack other HUMAN cells Dead cells release free radicals which damage/kill endothelial cells OCCURS IN SMALL VESSLES  Vasculitis Mechanism Once damaged, ALL vasculitis follow same pattern: Collagen and tissue factor exposed Induces coagulation Repeated damage leads to fibrin deposition Blood vessels weakened Can lead to aneurysm  Overall Vasculitis Pattern: TRIGGER → VASCULITIS → COMPLICATION GENERAL SYMPTOMS SPECIFIC SYMPTOMS Fever Depends on WHERE it is occurring in Weight Loss the body and organ affected Fatigue Reduced blood flow Reduced vessel diameter (fibrosis) Blood clots (thrombosis) Organ ischemia VASCULITIS SPECIFIC DISEASES - Categorized by vessel size LARGE VESSEL VASCULITIS: 1. Giant Cell Arteritis 2. Takayasu Arteritis  Giant Cell Arteritis – large vessels Temporal Artery Most common vasculitis in - Headaches elderly in US and Europe Rare before age 50 Ophthalmic Artery - Vision complication Ocular symptoms: Most concerning Facial Artery Ischemia in eyes: Can - Claudication: Jaw cause diplopia or even pain on eating blindness Lab Values: increased Erythrocyte sediment rate Giant Cell Arteritis Giant Cell Arteritis Segmental Lesions Diagnosis: Long biopsy needed Treatment: corticosteroids Takayasu Arteritis – large vessels Head: Vision or neurologic Very similar to Giant cell vasculitis symptoms Common in Japan Women under age 40 “Pulseless” disease Upper Extremities: weak or no Histology: giant cells in inner elastic pulse lamina Lab Values: increased Erythrocyte sediment rate Treatment: corticosteroids MEDIUM VESSEL VASCULITIS: 1. Polyarteritis Nodosa 2. Buerger’s Disease 3. Kawasaki Disease Polyarteritis Nodosa – medium vessels Transmural inflammation – all 3 layers affected Leads to fibrosis of the vessel wall Wall weakened and leads to aneurysm Leads to multiple fibrotic aneurysms Looks like “string of beads” Polyarteritis Nodosa – medium vessels MEDIUM Vessels affected Renal arteries – hypertension Low blood flow = increases blood volume Mesenteric arteries – abdominal pain and GI bleeding Brain arteries – neurologic symptoms Skin arteries – skin lesions Treatment: Corticosteroids  Buerger’s Disease – medium vessels Aka: Thromboangiitis obliterans Clots in vessels supplying fingers and toes Risk factor: smoking Tobacco triggers autoimmune response Usually MEN, 20-40 years old  Buerger’s Disease – medium vessels Can lead to autoamputation of fingers or toes May require amputation Cessation of smoking may slow process, but disease process continues  Kawasaki Disease – medium vessels Usually affects 1-5 year olds Symptoms Conjunctivitis – red eyes Rash - skin Adenopathy (enlarged lymph nodes) Strawberry tongue Hands and Feet swollen (with rash) 5 or more days of high fever Not responsive to antipyretic Usually self-limiting Lasts 6-8 weeks IF NOT TREATED, risk of heart ischemia, myocardial infarction  Kawasaki Disease Treatment IVIG Antibody Decreases immune response Reduces inflammation Aspirin Reduces platelet adhesion SMALL VESSEL VASCULITIS: 1. Granulomatosis with Polyangiitis 2. Microscopic Polyangiitis  Small Vessel Vasculitis Affects arterioles, capillaries, venules ANCA is an auto-antibody (IgG type) Attacks neutrophils (not vessel anti-neutrophilic cytoplasmic antibody walls) ANCA Free radicals released and destroy vessel walls  Granulomatosis with Polyangiitis (GPA) AKA Wegener’s Granulomatosis Small Vessels Release cytoplasmic –ANCA (cANCA) cANCA attacks proteinase 3 in cytoplasm of neutrophils cytoplasmic anti-neutrophilic cytoplasmic antibody c-ANCA Leads to granulomas in vessel wall Granulomatosis with Polyangiitis – small vessels Areas Affected: Nasopharynx Chronic pain and sinusitis Bloody mucous from ulcers Saddle nose deformity Lungs Difficulty breathing Bloody cough from ulcers Kidneys Restricted blood to glomeruli – can lead to kidney failure ↓ urine production; ↑ BP Bloody urine Treatment Controlled by corticosteroids, cyclophosphamide  Microscopic Polyangiitis - Small Vessels VERY similar to GPA Key differences: No nasopharynx involvement DOES affect kidneys and lungs No granulomas PERINUCLEAR anti-neutrophilic cytoplasmic antibody No c-ANCA p-ANCA Releases – perinuclear ANCA (pANCA) Attacks myeloperoxidase TREATMENT Corticosteroids and cyclophosphamide Can relapse (same as GPA)  05 Aneurysms and Dissections Aneurysm Aneurysm: localized abnormal dilation of blood vessel or heart May be congenital or acquired Most common causes: hypertension and atherosclerosis Aneurysms may be saccular or fusiform Saccular aneurysm Spherical outpouchings involving portion of vessel wall Fusiform aneurysm Diffuse, circumferential dilations of long vascular segment True vs. Pseudo-aneurysm True aneurysm Involves all 3 layers of the blood vessel False aneurysm (pseudo-aneurysm) Breach in vascular wall leads to extravascular hematoma Extravascular blood surrounded by fibrous capsule Communicates with vascular space (“pulsating hematoma”) HEMATOMA: is a localized collection (big mass) of blood outside of blood vessels; usually due to the rupture of blood vessels Dissection Dissection: blood enters the wall of the artery Tear in the intima Blood enters the space between intima and media and ”channels” within vessel wall Media separates from adventitia Channel widens and elongates Adventitia remains intact but weakened  Aortic Dissection Definition: Laminar planes of media split apart and blood filled channel forms within aortic wall Causes: Atherosclerosis and Hypertension Symptoms: Chest pain, abdominal pain; mistaken for myocardial infarction Complications: Rupture most common cause of death Treatment: Depends on location and severity Surgery Anti-hypertensive medication  Abdominal Aortic Aneurysm Definition: Enlarged aorta: more than 1.5 times its normal diameter Causes: Atherosclerosis number one factor 1. Hypertension 2. Genetic Factors 3. Age and Sex: Men over the age of 65. 4. Smoking Symptoms: Abdominal Pain: Persistent, deep ache in the abdomen or back. Pulsating Sensation: A pulsating feeling near the navel. Leg Pain: Pain that radiates to the legs or buttocks.  Abdominal Aortic Aneurysm Complications RUPTURE: potentially fatal hemorrhage Treatment Surgery Pre-rupture: removal of aneurysm and replacement with synthetic graft Post-rupture: Emergency surgery; mortality rate of 50%  06 Vascular Tumors 1) Hemangioma 2) Pyogenic Granuloma 3) Kaposi’s sarcoma 4) Angiosarcoma  Hemangioma Definition: benign “tumor” of blood vessels; proliferation of endothelial cells Capillary Hemangioma: most common Formed by capillaries (small blood vessels) Appear as a red or purple mark on the skin Most common type Cavernous Hemangioma: Larger blood vessels and may extend deeper into the tissues. Raised, bluish masses; found in deeper tissues Most common “tumor” of infancy and childhood Infantile hemangioma (common): Becomes apparent within first few days/weeks/months of life Slow proliferation/growth over 6-12 months Spontaneous involution over 3-9 years Predilection for head and neck  Pyogenic Granuloma Definition: benign “tumor” of blood vessels; proliferation of endothelial cells TERRIBLE NAME! NOT PYOGENIC: does NOT produce purulent material (pus) NOT a GRANULOMA: does NOT have a focus of chronic inflammation surrounded by macrophages and multi- nucleated giant cells  Pyogenic Granuloma Definition: benign “tumor” of blood vessels; proliferation of endothelial cells Purple/red, rapidly growing nodule or papule occurring on skin or mucosa Predilection for head and neck Common on mucosal membranes 75% of oral cases on gingiva Treated by conservative excision “Pregnancy tumor” PG occurring during pregnancy (estrogen regulates angiogenic factors such as VEGF, NO) Involution/regression upon cessation to hormonal exposure  Kaposi Sarcoma Definition: vascular malignant neoplasm Caused by Human Herpes Virus – 8 (HHV-8) infection 4 clinical settings Classic Endemic African Transplant-associated AIDS-associated  Kaposi Sarcoma Most prevalent tumor among AIDS patients Incidence has decreased nearly 90% since introduction of anti-retroviral therapy Most patients die of other causes Oral involvement 60-70% of HIV/AIDS patients Presentation leads to AIDS diagnosis in ~20% 2-5% of non-epidemic cases  Angiosarcoma Definition: malignant endothelial neoplasm Primarily in older adults Locally invasive and readily metastasize 5-year survival rates approach 30%