Transcript Blood Vesselsx

• Basic Constituents of walls of blood vessels
• Endothelial cells
• Smooth muscle cells
• Extracellular matrix
• Three concentric layers
• Intima
• Media
• Adventitia
• Three types of arteries
• Large, elastic
• Medium-sized , muscular
• Small arteries
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Arterioles- principle points of physiologic resistance to blood flow
Capillaries – thin wall, slow flow= ideal for exchange between blood and tissues
Venules – vascular leakage and leukocyte exudation occur preferentially
Veins –predisposed to irregular dilation, compression, easy penetration
Lymphatics –important pathway for disease dissemination
• Vasculogenesis – de novo formation of blood vessels during
embryogenesis
• Angiogenesis – neovascularization in mature organism
• Arteriogenesis – remodeling of existing arteries
• Developmental (berry) aneurysms
• Arteriovenous fistulas
• Fibromuscular dysplasia
• Endothelial Cells
• Weibel-Palade bodies – von Willebrand’s factor
• Endothelial cell properties and functions - Table 11-1
• Endothelial ativation vs dysfunction – Figure 11-2
• Vascular smooth muscle cells
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Proliferate when stimulated
Synthesize ECM
Elaborate growth factors and cytokines
Vasoconstriction or dilation
• Intimal thickening – a stereotypic response to vascular injury
• Vascular injury – with endothelial loss or even just dysfunction – stimulates
smooth muscle cell growth and associated matrix synthesis that thickens the
intima
• Neointimal smooth muscle cells divide but do not contract
• Healing response results in permanent intimal thickening
• Types and causes of hypertension – Table 11-2
• 95% is essential hypertension
• Complex, multifactorial disorder
• Interactions of mutations and polymorphisms at several loci that influence
blood pressure, with a variety of environmental factors
• Regulation of Blood Pressure – Figure 11-4
• Function of cardiac output and peripheral vascular resistance
• Malignant hypertension - >200/120 mmHg
• Retinal hemorrhages and exudates, +/- papilledema
• Renal failure
• Vascular pathology in hypertension
• Benign – hyaline arterioslerosis
• Malignant – hyperplastic asteriolosclerosis
• “onion-skinning”
• Necrotizing arteriolitis
• Arteriosclerosis
• Monckeberg medial sclerosis
• Atherosclerosis
• Epidemiology
• Pathogenesis of Atherosclerosis
• Endothelial Injury
• Smooth Muscle Proliferation – PDGF, FGF, TGF-alpha -> ECM production
• Overview
• Consequences of Atherosclerotic Disease
• Major risk factors
• Nonmodifiable
• Increasing age
• Male gender
• Family history
• Genetic abnormalities
• Modifiable
• Hyperlipidemia
• Hypertension
• Cigarette smoking
• Diabetes mellitus
• Additional risk factors
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Inflammation – CRP
Hyperhomocystinemia
Metabolic syndrome
Lipoprotein (a)
Factors affecting hemostasis
Other factors – Type A, etc
• Response-to-injury hypothesis
• Atherosclerosis is a chronic inflammatory and healing response of the
arterial wall to endothelial injury. Lesion progression occurs through the
interaction of modified lipoproteins, monocyte-derived macrophages, and
T-lymphocytes with the normal cellular constituents of the arterial wall.
• Endothelial injury -> Accumulation of lipoproteins -> monocyte adhesion
to the endothelium -> platelet adhesion -> factor release -> smooth
muscle recruitment, proliferation, and ECM production -> lipid
accumulation
• Endothelial dysfunction
• Hemodynamic disturbances
• Nonturbulent laminar flow leads to athero-protection
• Lipids
• Cholesterol and cholesterol esters
• Oxygen free radical production
• Oxidized LDL - cytotoxic
• Inflammation – Dysfunctional endothelial cells express adhesion molecules
for leukocytes
• Infection – Herpesvirus, CMV, C. pneumoniae detected in plaques
• Fatty streaks
• Earliest lesions
• Lipid-filled foamy macrophages
• Atherosclerotic plaque
• Components
• Superficial fibrous cap – Smooth muscle cells and collagen
• “Shoulder” – beneath and to the side – macrophages, T cells, smooth
muscle
cells
• Necrotic core – lipid, debris from dead cells, foam cells, fibrin, variable organized
thrombus, plasma proteins
• Periphery – neovascularization
• Calcification
• Clinically important changes
• Rupture, ulceration, erosion -> thrombosis
• Hemorrhage into a plaque
• Atheroembolism
• Aneurysm
• Major consequences
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Myocardial infarction
Cerebral infarction
Aortic aneurysms
Peripheral vascular disease
• Principal outcomes depend on:
• Size of the involved vessels – smaller vessels can become occluded
compromising the distal blood supply
• Relative stability of the plaque itself – ruptured plaques can cause
embolism causing distal vessel obstruction or acute thrombosis
• Degree of degeneration of the arterial wall – aneurysm formation with
rupture and/or thrombosis
• Atherosclerotic stenosis
• Early stages – outward remodeling of the media tends to preserve lumen
diameter
• Critical stenosis – usually around 70% - symptoms start
• Chronically diminished blood supply
• Mesenteric occlusion and bowel ischemia
• Chronic IHD
• Ischemic encephalopathy
• Intermittent claudication
• Acute plaque changes
• Rupture/fissuring – exposing highly thrombogenic plaque constituents
• Erosion/ulceration – exposing the thrombogenic subendothelial basement
membrane to blood
• Hemorrhage into the atheroma – expanding its volume
• Precipitating lesion in patients who develop MI and other acute coronary
syndromes is not necessarily a severely stenotic and hemodynamically
significant lesion before its acute change
• Events that trigger acute changes
• Intrinsic – plaque structure and composition
• Extrinsic – blood pressure and platelet reactivity
• Vulnerable plaque vs stable plaque
• Thrombosis – potent activator of multiple growth-related signals
in smooth muscle cells leading to growth of atherosclerotic
lesions
• Vasoconstriction – compromises lumen size and increases local
mechanical forces
• Stimulated by circulating adrenergic agonists, locally released platelet
contents, impaired secretion of endothelial relaxing factors( NO)
• Abdominal Aortic Aneurysm
• Thoracic Aortic Aneurysm
• Aortic Dissection
• Aneurysm = localized abnormal dilation of a blood vessel or
the heart
• Types
• True aneurysm – involves an intact attenuated arterial wall of thinned
ventricular wall of the heart
• False (pseudo-) aneurysm – defect in the vascular wall leading to an
extravascular hematoma that freely communicates with the intravascular
space
• Dissection – blood enters the arterial wall itself as a hematoma dissecting
between the layers
• Saccular – spherical outpouchings
• Fusiform – diffuse, circumferential dilation of a long vascular segment
• Pathogenesis
• Structure or function of the connective tissue within the vascular wall is
compromised
• The intrinsic quality of the vascular wall connective tissue is poor
• E.g. Marfan syndrome – defect in synthesis of fibrillin
• E.g. Loeys-Dietz syndorme – abnormalities in elastin and collagen I
and II
• E.g. Ehlers-Danlos syndrome – Defective type III collagen
• Scurvy – altered collagen cross-linking
• Pathogenesis
• The balance of collagen degradation and synthesis is altered by local
inflammatory infiltrates and the destructive proteolytic enzymes they
produce - MMP
• The vascular wall is weakened through the loss of smooth muscle cells or
the inappropriate synthesis of noncollagenous or nonelastic ECM
• Two most important disorders that predispose to aortic aneurysms are
atherosclerosis and hypertension
• Other - trauma, vasculitis, congenital defects, infections (mycotic)
• Abdominal aortic aneurysm
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Increased age
Males
Smokers
Clinical consequences
• Rupture into the peritoneal cavity or retroperitoneal tissues with
massive potentially fatal hemorrhage- rate of rupture related to size
• Obstruction of a branch vessel resulting in ischemic injury of
downstream tissues
• Embolism from atheroma or mural thrombus
• Impingement on an adjacent structure
• Presentation as an abdominal mass
• Thoracic aortic aneurysms
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Hypertension
Marfan, etc
Syphilis
Clinical presentation
• Encroachment on mediastinal structures
• Respiratory difficulties
• Difficulty in swallowing
• Persistent cough
• Pain caused by erosion of the bone
• Cardiac disease – aortic valve or coronary ostia involvement
• Rupture
• Aortic dissection
• Blood splays apart the laminar planes of the media to form a blood-filled channel
within the aortic wall
• Occurs principally in two groups
• Pressure-related mechanical injury and/or ischemic injury
• Clinical features
• Men aged 40-60 with antecedent hypertension
• Younger patients with abnormalities affecting the connective tissue
• Classification – Figure 11-21
• Type A – more common, proximal (DeBakey I and II)
• Type B – distal lesions not involving the ascending part, usually distal to the
subclavian (Debakey III)
• Excurciating pain beginning in the anterior chest, radiating to the back, and
moving downward
• The most common cause of death is rupture of the dissection outward into the
pericardial, pleural, or peritoneal cavities
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Noninfectious Vasculitis
Giant-Cell (Temporal) Arteritis
Takayasu Arteritis
Polyarteritis Nodosa
Kawasaki Disease
Microscopic Polyangiitis
Churg-Strauss Syndrome
Wegener Granulomatosis
Thromboangiitis Obliterans (Buerger Disease)
Vasculitis Associated with other Disorders
Infectious Vasculitis
• Vasculitis = vessel wall inflammation
• Classification – Table 11-4
• Two most common
Immune-mediated
Direct-invasion by infectious pathogens
• Clinical features
• Depend on the vascular bed involved
• Constitutional signs and symptoms
• Three main mechanisms
• Immune complex deposition
• Drug hypersensitivity – serum sickness
• Viral infections – polyarteritis nodosa
• Pauci-immune
• Antineutrophil cytoplasmic antibodies (ANCAs)
• Circulating antibodies that react with neutrophil cytoplasmic antigens
• Anti-myeloperoxidase (MPO-ANCA) – formerly called perinuclear (pANCA) – microscopic polyangiitis and Churg-Strauss
• Anti-proteinase-3 (PR3-ANCA) –formerly called cytoplasmic ( cANCA) – Wegener granulomatosis
• Anti-endothelial cell antibodies – Kawasaki disease
• Most common form of vasculitis among elderly in US and Europe
• Granulomatous inflammation of arteries in the head
• Fever, weight loss, fatigue, facial pain, headache, tender,
superficial temporal artery, ocular symptoms
• Segmental nodular intimal thickening, medial granulomatous
inflammation, elastic lamina fragmentation, T cell and
macrophage infiltration, multinucleated giant cells
• Granulomatous vasculitis
• Ocular disturbances and marked weakening of pulses in the
upper extremities (pulseless disease)
• Transmural fibrous thickening of the aorta particularly the aortic
arch and great vessels, severe luminal narrowing of the great
vessels
• Under 50 – Takayasu
• Over 50 – Giant-cell aortitis
• Initial symptoms – non-specific – fatigue, weight loss, fever
• Systemic vasculitis of small or medium-sized muscular arteries,
typically involving renal and visceral but sparing pulmonary
• 30% have chronic hepatitis B with HBsAg-HbsAb complexes in
affected vessels
• Classic idiopathic –segmental transmural necrotizing
inflammation. Weakens the wall, impaired perfusion
• Malaise, fever, weight loss, hypertension, abdominal pain and
melena, diffuse muscular aches and pains, peripheral neuritis
• Leading cause of acquired heart disease in children
• Acute, febrile, usually self-limited illness associated with arteritis
affecting large to medium-sized, and even small vessels
• Predilection for coronary artery involvement – leading to
aneurysms, rupture and acute MI
• Also known as mucocutaneous lymph node syndrome
• Conjunctival and oral erythema and erosion, edema of hands
and feet, erythema of the palms and soles, desquamative rash,
cervical lymph node enlargement
• IVIG and aspirin
• Necrotizing vasculitis generally affecting capillaries, arterioles,
and venules
• Also called hypersensitivity or leukocytoclastic vasculitis
• Necrotizing glomerulonephritis and pulmonary capillaritis
• Allergic granulomatosis and angiitis
• Small vessel necrotizing vasculitis associated with asthma,
allergic rhinitis, lung infiltrates, peripheral eosinophilia, and
extravascular necrotizing granulomas
• Acute necrotizing granulomas of the upper respiratory tract
• Necrotizing or granulomatous vasculitis of the lungs and upper
respiratory tract
• Renal disease, often foal necrotizing, often crescentic GN
• Segmental, thrombosing, acute and chronic inflammationof
medium-sized and small arteries principally tibial and radial
arteries
• Almost exclusively associated with smoking
• Superficial nodular phlebitis, cold sensitivity of Raynaud type,
instep claudication, severe pain even at rest, chronic ulcerations
• Exaggerated vasoconstriction of the digital arteries and
arterioles
• Red, white, blue changes – proximal vasodilation, central
vasoconstriction, distal cyanosis
• Primary - 3-5% general population, usually young woman
• Secondary – e.g. SLE, Buerger,scleroderma
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Varicose Veins
Thrombophlebitis and Phlebothrombosis
Superior and Inferior Vena Caval Syndromes
Lymphangitis and Lymphedema
Varicose veins = Abnormally dilated, tortuous veins produced by
prolonged, increased intraluminal pressure and loss of
vessel wall support
10-20% men, 25-33% woman, obesity, pregnancy, familial
Stasis, congestion, edema, pain, thrombosis, stasis dermatitis,
varicose ulceration
Portal hypertension -> esophageal varices, hemorrhoids, caput
medusa
• Deep leg veins are the site of 90%
• Others – periprostatic venous plexus, pelvic venous plexus, large
skull veins, dural sinuses, portal vein
• Prolonged immobilization resulting in decreased blood flow
through the veins is the most important predisposing factor
• Systemic hypercoagulability
• Trousseau sign – migratory thrombophlebitis in cancer
• Homan sign may or may not be present
• Pulmonary embolism is a serious complication of DVT and in
many cases is the first manifestation
• Superior Vena Cava – neoplasms that compress or invade the
SVC leading to marked dilation of the veins of the head, neck,
and arms and cyanosis (bronchogenic carcinoma or mediastinal
lymphoma)
• Inferior Vena Cava – Neoplasms that invade or compress or by
thrombus leading to marked lower extremity edema, distension
of the superficial collateral veins of the lower abdomen,
massive proteinuria (hepatocellular carcinoma or renal cell
carcinoma)
• Lymphangitis – acute inflammation elicited when bacterial
infections spread into the lymphatics, most common Group A
beta-hemolytic strep, red painful streaks, enlargement of lymph
nodes
• Lymphedema
• Primary – simple congenital lymphedema or Milroy disease
(heredofamilial congenital lymphedema)
• Secondary – tumors, surgical procedures involving nodes, irradiation
filiarisis, post-inflammatory thrombosis and scarring
• Peau d’orange
• Chylous ascites, thorax, pericardium caused by rupture of dilated
lymphatics
• Benign Tumors and Tumor-like Conditions
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Hemangiomas
Lymphangiomas
Glomus Tumor (Glomangioma)
Vascular Ectasias
Bacillary Angiomatosis
• Intermediate-Grade (Borderline) Tumors
• Kaposi Sarcoma
• Hemangioendothelioma
• Malignant Tumors
• Angiosarcoma
• Hemangiopericytoma
• Hemangioma – very common, increased numbers of normal or
abnormal blood vessels filled with blood
• Capillary hemangioma – most common variant, skin, subcutaneous tissues,
mucous membranes, liver, spleen, kidney
• Cavernous hemangioma – Large, dilated channels, less well circumscribed,
more frequently involve deep structures, von Hippel-Lindau disease
• Pyogenic granuloma – Rapidly growing pedunculated red nodule, bleeds
easily, often ulcerated , pregnancy tumor, associated with trauma,
proliferating capillaries, inflammation, exuberant granulation -like tissue
• Lymphangiomas
• Simple (capiilary)
• Caverous (cystic hygromas) – neck and axilla of children, Turner syndrome
• Glomus tumor (glomangioma)
• Very painful, modified smooth muscle cells of the glomus body
• Distal portion of the digitd, especially under the fingernails
• Vascular ectasias
• Nevus flammeus – “birthmark”, port wine stain – Sturge-Weber syndrome
• Spider telangiectasia – high estrogen
• Hereditary hemorrhagic telangiectasia ( Osler-Weber-Rendu disease)
• Bacillary angiomatosis –
• Vascular proliferation resulting from an opportunistic infection
• Kaposi sarcoma
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Chronic KS
Lymphadenopathic KS (African or endemic)
Transplant- associated KS
AIDS-associated KS (epidemic)
HHV-8
Red to purple macules, raised plaques, nodules
• Hemangioendothelioma
• Angioplasty and Endovascular Stents
• Vascular Replacement
• Act like a vascular injury leading to stenosis, etc