BLOOD VESSELS

Dr Vinay H S
M.D

BLOOD PRESSURE

Systolic (wnl 120, Htn > 140) Myocardial contractility Arterial elasticity Peripheral resistance (arteriolar tone) Diastolic (wnl 80, Htn > 90) Arterial elasticity Peripheral resistance (arteriolar tone) Pulse Pressure The pressure difference between the systolic and diastolic pressures is the pressure change to create the pulse (Measure of arterial compliance)

CONSEQUENCES OF VASCULAR DISEASE

Narrowing and obstruction of the vessel lumen Progressively - by atherosclerosis Precipitously - by thrombosis/embolism tissue atrophy or infarction
Weakening of vessel wall Dilation, dissection, or rupture

CONGENITAL ANOMALIES
1.

Anomalous /Variations (unexpected location of vessels)

2.

Berry aneurysms (saccular)

Vascular out-pouchings Due to congenital wall weakness Location- Cerebral vessels May rupture suddenly

3.

Arterio-venous (AV) fistulas

Abnormal communications b/w arteries and veins Etiology Congenital Acquired (eg; Dialysis patients, Penetrating knife injury, rupture of aneurysm) Pagets disease of bone Potential complications High output heart failure: Large AV fistulas reduce systemic resistance & bypass microcirculation increases VR to heart Risk of rupture & hemorrhage: especially in brain

HYPERTENSION

1.

Sustained increase in diastolic BP > 90 mmHg and/or a systolic BP >140 mmHg Idiopathic (Essential) primary HTN (95%) Secondary Hypertension (5%) - due to secondary causes: Renal disease Acute glomerulonephritis, chronic renal disease, Polycystic disease; Renal artery stenosis, Renal Vasculitis, renin-producing tumors

2. Endocrine Adreno-cortical hyperfunction: Cushing syndrome, Primary aldosteronism, Congenital adrenal hyperplasia, Licorice ingestion Drugs: Estrogen( including PIH, Oral contraceptives), Glucocorticoids, MAO inhibitors. Pheochromocytoma, acromegaly, hypothyroidism (myxedema), hyperthyroidism (thyrotoxicosis) 3. Cardiovascular Coarctation of aorta, Polyarteritis nodosa (or other vasculitis)

Factors influencing development of HTN

Genetic defects Increases sodium concentration in SMCs of peripheral resistance arterioles Sodium opens calcium channels Increased smooth muscle contraction increase in TPR Reduced renal sodium excretion Sodium retention increase in ECF volume increases CO increases TPR Activation of RAA system increases CO and TPR

Increased sympathetic nervous system activity Most important increases TPR

Medications Decongestants NSAIDS (block vasodilator effect of PG) Estrogen (increase angiotensinogen synthesis in liver)
Environmental factors Can modify genetic determinants Stress, obesity, smoking, physical inactivity, and heavy consumption of salt

CLINICAL MANIFESTATIONS

Asymptomatic Symptomatic Morning headaches that subside before noon, blurred vision, sweating & chest pain Signs Hypertensive retinopathy Increased amplitude of point of maximal impulse (PMI) from LVH & S4

Heart Concentric LV hypertrophy; CCF, MI Blood vessels Accelerated atherosclerosis Aneurysm, rupture, dissection Brain Intra-cerebral hemorrhage Kidney Chronic renal failure

VASCULAR PATHOLOGY

Hyaline arteriosclerosis

Hyperplastic arteriosclerosis (Onion skinning)

MALIGNANT (ACCELERATED) HYPERTENSION

Markedly elevated BP (systolic > 200 & diastolic > 120 mm Hg) causing end-organ damage Headache and dramatic elevations of BP, which get worse as time goes by.

Medical emergency Untreated patients die within 2 yrs from renal failure, intracerebral hemorrhage or CHF. Fundoscopy examination Retinal hemorrhages, exudates, papilledema

MORPHOLOGY

Kidney - Petechial hemorrhages (Flea-bitten appearance) Microscopy -Hyperplastic arteriosclerosis (onion skin) -Necrotizing arteriolitis (Fibrinoid necrosis of vessel walls)

ARTERIOSCLEROSIS (HARDENING OF ARTERIES)

Thickening & loss of elasticity of arterial walls 3 patterns Atherosclerosis Hypertensive arteriolosclerosis Monckebergs medial calcific sclerosis

ATHEROSCLEROSIS

A form of arteriosclerosis of the intima of large blood vessels characterized by formation of fibro fatty plaques called atheroma

Common site (In decreasing order) Abdominal aorta Coronary artery Popliteal artery Descending thoracic aorta Internal carotid artery Circle of Willis

RISK FACTORS FOR ATHEROSCLEROSIS

MAJOR Non-modifiable Increasing age Male gender Family history Genetic abn. LESSER, UNCERTAIN, OR NONQUANTITATED Obesity Physical inactivity Stress ("type A" personality) Postmenopausal estrogen deficiency

High carbohydrate intake Potentially Controllable

Hyperlipidemia Hypertension Cigarette smoking Diabetes Lipoprotein Lp(a) Hardened (trans)unsaturated fat intake Chlamydia pneumoniae

PATHOGENESIS

Response to injury hypothesis Initial injury to endothelium: Chronic inflammatory response of arterial wall Lesion progression: Interaction between Modified lipoproteins Monocyte-derived macrophages T lymphocytes Normal arterial wall cellular constituents

Components: Endothelial injury Role of lipids Role of inflammation Endothelial injury with endothelial dysfunction Leads to Increased permeability, leukocyte adhesion, thrombotic potential

Role of lipids
Hyperlipidemia increases oxygen free radicals & destroys NO (endothelial-relaxing factor) Accumulation of lipoproteins (LDL)& Oxidized LDL - Ingested by macrophages via scavenger receptor foam cells - Increases monocyte accumulation in lesions - Stimulates release of growth factors and cytokines - Cytotoxic to ECs and SMCs

Role of inflammation Adhesion of blood monogiytes (and other WBCs) to endothelium Migration into intima Transform into macrophages and foam cells Adhesion of platelets

Role of smooth muscle Migration of SMCs from mediaintima Factors released by activated platelets, macrophages, or vascular cells Proliferation of smooth muscle cells in intima Deposition of ECM accumulation of collagen & proteoglycans Fatty streak mature fibro-fatty atheroma with growth of lesions

CELLULAR INTERACTIONS IN ATHEROSCLEROSIS

Gross views of atherosclerosis in the aorta. A, Mild atherosclerosis composed of fibrous plaques, one of which is denoted by the arrow. B, Severe disease with diffuse and complicated lesions.

MICROSCOPY

Major components Cells- SMCs, macrophages, WBCs (lymphocytes) ECM- Collagen, elastic fibers, proteoglycans Lipid Fibrous cap Covered by endothelium Smooth muscle cells, ECM Macrophages, T-lymphocytes Necrotic Core Lipid, cholesterol clefts, cell debris, foam cells, fibrin, thrombus

COMPLICATIONS
Rupture, ulceration, or erosion Hemorrhage Hematoma expand plaque / induce plaque rupture Superimposed thrombosis On disrupted lesions (rupture, ulceration, erosion, or hemorrhage) occlude lumen Aneurysmal dilation weakness and rupture

Primary pathogenesis of IHD or MI CNS disease- TIA, stroke, atrophy

Peripheral vascular disease

-

Claudication or amputation of an extremity

Kidney failure
-

Reno-vascular hypertension or kidney infarction

Aneurysms Gastro-intestinal disease

- Mesenteric angina, bowel infarction, ischemic strictures

Monckebergs arteriosclerosis: Calcification of media of small & medium sized vessels in persons > 50 yrs Clinically insignificant degenerative disease Sites: Femoral, tibial, radial, ulnar and genital arteries

Microscopy: Deposits of calcium salts in the media; No inflammatory reaction seen

ANEURYSM

Localized abnormal dilation of a blood vessel or wall of heart Causes Weakened vessel wall due to Congenital defect (Marfan's syndrome, Ehlers-Danlos syndrome) Acquired : - Atherosclerosis - Systemic disease (Hypertension) - Infection - Trauma

Most common etiology In ascending aorta Dissecting aortic aneurysm extending proximally Hypertension In distal aorta (thoracic & abdominal) and in extremities Atherosclerosis

Types Saccular (spherical) Fusiform (spindle shaped) Dissecting aneurysms Complications Enlarge and rupture Thrombosis and embolism Erosion/compression of surrounding structures

ABDOMINAL AORTIC ANEURYSMS

Due to atherosclerosis Sites Abdominal aorta, below renal arteries Lack of vasa vasorum below renal artery orifices Cause Intrinsic/acquired defect in structural components of wall Age > 50 years Sex- M:F- 5:1

Symptoms Asymptomatic or a pulsatile mass Mid-abd to lower back pain Signs Abdominal bruit on auscultation (50%) Complication Rupture (Most common) C/F- Abrupt severe back pain; BP Lab diagnosis Abdominal USG- Gold standard

Syphilitic aneurysm: Tertiary stage of syphilis Obliterative endarteritis of vasa vasorum & aortitis Site- Thoracic aorta Gross Tree barking- Intimal roughening Complications Rupture Aortic insufficiency Narrowing of coronary ostia Mycotic abdominal aortic aneurysms: Microorganisms, especially Salmonella gastroenteritis

BERRY ANEURYSM

Site Cerebral artery at bifurcations of Circle of Willis Anterior communicating artery with ACA Cause Congenital (absence of internal elastic lamina & muscular wall) Associated with PCKD (10-15%) Coarctation of aorta (Increased pressure in cerebral vessels)

C/F Headache, stiff neck (meningeal irritation) & death Gross Saccular, 5-10 mm to > 3 cm; may be multiple Complication Rupture subarachnoid hemorrhage

AORTIC DISSECTION
Entry of blood from vessel lumen enters an intimal tear & dissects through layers of media Etiology Degeneration (cystic medial necrosis) of tunica media Loss of elastic and smooth muscle fibers

Predisposing factors:

Hypertension Marfans syndrome (fibrillin defect) Ehler-Danlos syndrome (collagen defect) Pregnancy (ed plasma volume) Cu deficiency (cofactor in lysyl oxidase)

Coarctation of aorta (wall stress)

Trauma

There is a tear (arrow) located 7 cm above the aortic valve and proximal to the great vessels in this aorta with marked atherosclerosis. This is an aortic dissection.

Blood is pushing apart the media of the aorta. When an intimal tear occurs.

Proximal (type A) lesions Dissections within 1st 10 cm of proximal aorta (ascending aorta) Most common; most dangerous

Type B lesions Dissections that do not involve ascending aorta Begin below sub-clavian artery Less common; better prognosis

Blood is pushing apart the media of the aorta. When an intimal tear occurs.

Symptoms Severe tearing pain Acute onset chest pain; radiates to back May compress & obstruct aortic branches (eg. renal or coronary arteries) Labs Chest X-ray- mediastinal widening Increased aortic diameter Retrograde arteriography Gold standard test
- CT- Scan

NON INFECTIOUS VASCULITIS

The main immunological mechanisms that initiate noninfectious vasculitis are (1) immune complex deposition, (2) antineutrophil cytoplasmic antibodies, and (3) anti-endothelial cell antibodies.

Giant Cell Arteritis (GCA) Takayasu Arteritis Polyarteritis Nodosa Kawasaki Disease Microscopic Polyangiitis Wegener Granulomatosis Thromboangiitis Obliterans (Buerger) Vasculitis with other disorders

GIANT CELL ARTERITIS (TEMPORAL ARTERITIS)

Most common vasculitis in elderly individuals Site of involvement - Affects large to small arteries - Usually branches of carotid artery (temporal & extracranial branches) Epidemiology - Females > males - Primarily affects elderly population (> 50 years) - Associated with HLA- class II

Distribution of disease - Cranial arteries- temporal, facial, ophthalmic - Aortic arch- giant cells aortitis (uncommon)
-

Etiology ? autoimmune reaction to elastic fibers in vessel wall

Clinical features: - Throbbing unilateral headache - Jaw claudication / Facial pain - Visual disturbances (Ophthalmic artery occlusion)

 Morphology: - Nodular thickenings with reduction of lumen - Segmental granulomatous vasculitis with multinucleate giant cells - Fragmentation of internal elastic lamina - Intimal fibrosis with luminal narrowing

ESR- High Temporal arterial biopsy (2-3 cm) -Positive in 60% cases Treatment Corticosteroids and anti-inflammatory agents Prognosis - Treated- dramatic response to steroids - Untreated- blindness due to occlusion of ophthalmic artery

TAKAYASU ARTERITIS (PULSELESS DISEASE)

Ocular disturbances Marked weakening of pulses in upper extremities Epidemiology Most common in Asia Young and middle-aged women (15-45 years) Distribution of disease Medium sized to large arteries Aortic arch and major branches Etiology Unknown

Pathology Vasculitis Transmural thickening of aorta with narrowing of lumina Gross Narrowing of orifices Irregular fibrous thickening of wall Microscopy Granulomatous vasculitis Massive intimal fibrosis

Clinical presentation: Fever Arthritis Night sweats Myalgia Skin nodules Ocular disturbances Visual defects, retinal hemorrhages, total blindness Weaker pulses in UL Coldness or numbness of fingers

Variable course Rapid progression Quiescent stage within 1-2 years Sequelae Collagenous fibrosis involving all layers, especially intima Aortic valve insufficiency Due to involvement of aortic root leading to dilation Myocardial infarction Due to a narrowing of the coronary ostia

Diagnosis Distinctions among active giant cell lesions of aorta are based largely on age of patient Most giant cell lesions of aorta in young patients are designated Takayasu arteritis

POLYARTERITIS NODOSA (PAN)

Necrotizing immune vasculitis Epidemiology Young adults Male> female Distribution of disease Systemic necrotizing vasculitis Any organ Except Lung Kidney, heart, liver, GIT Small & medium sized muscular arteries

Cause Immune complex deposition (type III hypersensitivity) Associated conditions HBV antigenemia (30-50%) Hypersensitivity to drugs i.v amphetamines Lesions are in different stages of development (acute or healing stage) Frequently only part of vessel is involved Nodosa Focal aneurysm formation

Symptoms - Fever, weight loss, malaise - Hematuria, renal failure hypertension - Abdominal pain, diarrhea, GI bleeding - Myalgia and arthralgia

Signs - Micro-aneurysms - Pericarditis, myocarditis, palpable purpura

Segmental necrotizing vasculitis 3 stages Acute lesions - Fibrinoid necrosis and neutrophils Healing lesions - Fibroblast proliferation Healed lesions - Nodular fibrosis & loss of internal elastic lamina

Fibrinoid necrosis

Complications: - Thrombosis and infarction - Multiple aneurysms (kidneys, heart, GIT) Diagnosis - Arteriography - Arterial biopsy - Biopsy of palpable nodules in skin or organ Prognosis - Untreated- fatal in most cases - Treated- 90% long term remission rate

KAWASAKI DISEASE

Epidemiology Commonly affects infants and young children (age<4) Japan, Hawaii, and US mainland Distribution of disease Large, medium-sized, and small arteries Coronary artery commonly affected Etiology- Possible viral Clinical features Fever Conjunctivitis; erythema and erosions of oral mucosa

- Skin rash - Generalized maculopapular

-

Lymphadenopathy

Pathology Acute necrotizing vasculitis of small/medium-sized vessels Weakened vascular wall may undergo aneurysm formation Complications Thrombosis, aneurysm, and myocardial infarction Prognosis Self-limited course Mortality rate: 1-2% due to rupture of a coronary aneurysm or coronary thrombosis

MICROSCOPIC POLYANGITIS(LEUCOCYTOCLASTIC VASCULITIS)

Organs affected Post-capillary venules, mostly skin palpable purpura Can affect internal organs & tissues Pathogenesis Immune complex deposition, Type III hypersensitivity P-ANCA positive Causes Drugs: penicillin, sulfonamides Bacterial: hemolytic Streptococcal Ag, Hepatitis B Ag
C/F: Hemoptysis, Hematuria, Proteinuria and cutaneous purpura

HYPERSENSITIVITY VASCULITIS (LEUCOCYTOCLASTIC VASCULITIS)

Microscopically: Fibrinoid necrosis of vascular wall Extravasation of RBCs Nuclear dust from neutrophil breakdown Inflammation is at same stage in all vessels

CHURG-STRAUSS SYNDROME
Small-vessel necrotizing vasculitis classically associated with - Asthma, - Allergic rhinitis, - Lung infiltrates, - Peripheral hypereosinophilia, and - Extravascular necrotizing granulomas Also called Allergic granulomatosis and angiitis Etiology remains obscure

Clinical features: Cutaneous involvement (palpable purpura), gastrointestinal tract bleeding, and renal disease are major association. Cardiomyopathy(60%). Microscopic appearance: Vascular lesions can be histologically similar to polyarteritis nodosa or microscopic polyangiitis but are also characteristically accompanied by granulomas and eosinophils Diagnosis: ANCAs (mostly MPO-ANCAs) are present

WEGENER'S GRANULOMATOSIS

Epidemiology Rare Males > females Age Peak incidence 40-60 yrs Distribution of disease Focal necrotizing vasculitis with granulomas Classically involves nose, sinuses, lungs & kidneys Small size arteries & veins

Classic triad

- Acute necrotizing Granuloma - Granulomatous vasculitis - Necrotizing glomerulonephritis

Clinical features

- Cough, dyspnea, hemoptysis - Chronic sinusitis - Perforation of nasal septum - Otitis media - Mastoiditis - Hematuria

Microscopy - Fibrinoid necrosis - Neutrophils - Granulomas Lab findings - C-ANCA - Autoantibody against proteinase 3 - Correlates with disease activity - Urine examination

BUERGERS DISEASE(THROMBOANGITIS OBLITERANS)

Age: 25-50 years

Etiology: Cigarette smoking

Site

Radial & tibial arteries; adjacent nerves & veins

C/F Intermittent claudication Superficial nodular phlebitis Raynauds phenomenon May lead to distal gangrene

Pathology Thrombosis, organization, recanalization Micro-abscess Granulomas Fibrosis of vascular bundle

RAYNAUDS PHENOMENON & DISEASE

Raynauds phenomenon Arterial insufficiency of digital vessels in response to cold or increased emotion TAO Takayasus arteritis Cryoglobulinemia Ergot poisoning Thoracic outlet syndrome Cold agglutinin disease CREST Syndrome

Clinical features Young woman Episodic small artery vasospasm in extremities, nose or ears Blanching and cyanosis of fingers or toes Precipitated by cold temperature/emotions No underlying disease or pathology

HENOCH-SCHONLEIN PURPURA

Immune vasculitis Usually occurs in children following URTI Most common vasculitis in children IgA-C3 immunocomplexes deposit in vessel wall IgA nephropathy (Bergers disease) may be part of the systemic complex

Palpable purpura Lower extremities, buttocks Polyarthritis Abdominal pain Sometimes with melena Renal disease Hematuria

VARICOSE VEINS
Abnormally lengthened, and tortuous veins Sites Superficial saphenous veins Distal esophagus in portal HT Anorectal region Left testicle Primary varicose veins - Due to valvular incompetence & weakened vessel walls - Positive family or occupational history

Secondary varicose veins - Due to valve damage from previous thrombophlebitis or DVT

Epidemiology Females > males 15% of US population

Predisposing factors Long standing Long automobile/airplane rides Age >50 years Obesity Pregnancy

Clinical features Edema, pain, thrombosis, stasis, dermatitis and ulcerations

Complications - Phlebothrombosis - Stasis dermatitis - Ulcerations - Vulnerability to injury - Poorly healing wounds and infections that may become chronic varicose ulcers - Embolism or other serious complications very rare

CLASSIFICATION OF VASCULAR TUMORS AND TUMOR-LIKE CONDITIONS

Benign Neoplasms, Developmental and Acquired Conditions Hemangioma (Capillary / Cavernous) Pyogenic granuloma (lobular capillary hemangioma) Lymphangioma- Capillary/ Cavernous (cystic) Glomus tumor Spider telangiectasia (arterial spider) Hereditary hemorrhagic telangiectasis (Osler-WeberRendu disease)

Intermediate-Grade Neoplasms

Kaposi sarcoma Hemangioendothelioma

Malignant Neoplasms

Angiosarcoma Hemangiopericytoma

HEMANGIOMAS
Incidence Extremely common, benign vascular tumors 7% of all benign tumors in infancy and childhood Clinical features Site- skin, mucous membranes, or internal organs May spontaneously regress Malignant transformation occurs rarely if at all Major types Capillary hemangioma Cavernous hemangioma

CAPILLARY HEMANGIOMA
Most common Strawberry type" of capillary hemangioma (juvenile hemangioma) skin of newborns grows rapidly first few months, fades during 1-3 years, usually regresses by age 7 Gross few mm-several cm in diameter, bright red - blue; flat/elevated

Microscopy Lobulated aggregates of closely packed, thin-walled capillaries lined by a flattened endothelium Separated by scant connective tissue stroma

Microscopy

- Lobulated aggregates of closely packed, thinwalled capillaries lined by a flattened endothelium - Separated by scant connective tissue stroma

CAVERNOUS HEMANGIOMA

- Less common - Usually larger, more frequently involve deep structures( Liver and Spleen) - May be locally destructive Grossly and show no tendency to Red-blue, soft, spongy mass regress, many require surgery. 1-2 cm diameter

Histology: - Large, cavernous vascular spaces - Partly or completely filled with blood - Separated by a scant connective tissue stroma

PYOGENIC GRANULOMA (LOBULAR CAPILLARY HEMANGIOMA)

Type of capillary hemangioma Skin and gingival /oral mucosa Clinical features Past H/O trauma Rapid growth in a few weeks H/O bleeding & ulceration May recur Granuloma gravidarum Variant in gingiva; found in 1% of pregnant women; regresses post delivery

Hereditary hemorrhagic telangiectasia(Vascular ectasia): - AD inheritance - Malformations composed of dilated capillaries and veins - Present from birth - Site: skin, oral mucosal membrane, GIT, Respiratory tract and urinary tract. - C/F: Epistaxis, G.I bleeds, Haematuria

Bacillary angiomatosis: - Vascular proliferation due to oppurtunistic infection in immunocompromised individuals - Bartonella henselae - modified silver (Warthin-Starry) stain of clusters of tangled bacilli (black).

Other tumors
Hemangioblastomas Associated with von HippelLindau disease Multiple tumors involving the cerebellum, brain stem, spinal cord, and retina
Glomus tumor (Glomangioma) Benign but extremely painful tumor Origin Modified smooth muscle cells of glomus body(thermoregulation) Site Distal portion of digits, especially under fingernails

KAPOSI SARCOMA

Low grade malignant tumor of endothelial cells Associated with Kaposi-sarcoma-associated virus (HHV8)

Chronic (Classic or European) KS: Clinical features - Red purple skin plaques on lower extremities - Slowly spread to viscera in 10% patients

- Not

associated with HIV, but homosexuals are at increased

risk. Asymptomatic, localized to skin and subcutaneous tissue Clinical course Locally persistent, with remissions. Transplant-associated KS (Immunosuppressionassociated KS): Clinical features Aggressive Site- LN, mucosa and viscera (50% cases) Skin lesions may be absent

Clinical course May regress with reduction of immunosuppression Organ or internal involvement is usually fatal. Lymphadenopathic(African or endemic KS): African children (especially Bantu children of South Africa) and young men Clinical features Localized or generalized lymphadenopathy Skin lesions are sparse

AIDS associated form: Epidemiology Most common AIDS-associated cancer in US Most common in homosexual male AIDS patients Clinical features Aggressive form with widespread visceral dissemination No site of predilection Clinical course Usually responsive to treatment ; rarely causes death

Gross: Multiple, red-purple patches, plaques or nodules May be confined to skin or it may disseminate Microscopy: Proliferation of spindle-shaped endothelial cells; Slit-like vascular spaces; Extra-vasated RBCs

Hemangioendothelioma Vascular neoplasms Behavior intermediate b/w hemangiomas and angiosarcomas Hemangiopericytoma Staghorn" vascular pattern

Angiosarcomas (Hemangiosarcoma) Highly malignant - Liver angiosarcomasassociated carcinogensPolyvinyl chloride, arsenic, thorotrast - Radiation, foreign material inside the body

References: Robbins and Cotran Pathologic basis of Disease 8th edition.

Acknowledgements:

Dr Ronnie Coutinho (Guidance) Dr Suneet Kumar

Thank you