Vascular Diseases:Vascular abnormalities cause clinical disease by two principal mechanisms:1. Narrowing or complete obstruction of the lumen by atherosclerosis or

thrombo-embolism respectively. 2. Weakening of the wall leading to dilation or rupture.

Normal:The basic constituents of the wall are:1. Endothelial cells.2. Smooth muscle cells.3. Extracellular matrix (ECM), including elastin, collagen and glycosaminoglycans.

The 3 concentric layers-intima, media and adventitia-are most clearly defined in the larger vessels particularly arteries. Arteries consist of:1. Intima.2. Internal elastic lamina.3. Media.4. External elastic lamina.5. Adventitia.

Congenital Anomalies:Mostly are important in surgery during which an unexpected vessel can be injured. The anomalies are rarely symtomatics except in the coronary tree. Among the anomalies which are pathologically important are:A. Arteriovenous fistula (AVF) is rare small abnormal

communications between arteries and veins. • Causes Developmental defects• Or produced from rupture of an arterial aneurysm into

adjacent vein, • Trauma (penetrating injuries) • Inflammatory necrosis of adjacent vessels.They may be of clinical significance becauseA. they short circuit blood from the arterial to the venous side

causing cardiac volume overload which lead to high output cardiac failure.

B. They can rupture causing hemorrhage especially in the brain.

2- Berry Aneurysms, are saccular congenital of unknown etiology seen in

smaller arteries of the brain especially in the circle of Willis:

a. Although the majority occur sporadically, genetic factors may be

important.

b. Cigarette smoking and hypertension are considered as predisposing

factors.

c. Although the aneurysms" are labeled as congenital, they are not present at

birth but develop over time owing to the underlying defect in the media.

d. Morphologically, they measure few millimeters up to 3cm. There is lack of

intimal elastic tissue and muscle fibers in the wall, which are replaced by

hyalinized tissue.

e. Rupture of the aneurysm leads to subarachnoid hemorrhage, most

frequent at the fifth decade and slightly more common in female. The

rupture is associated with acute increase in intracranial pressure.

f. In 20% of cases, multiple Berry aneurysms occur this type associated with

adult polycystic kidney diseases.

Atheromatous plaque

Consequences of Atheroscerosis

Consequences of coronary artery atherosclerosis (Ischemic Heart Diseases (IHD))

Hypertensive Vascular Disease:

It is a multifactorial disorder defined as sustained elevation of blood

pressure above 140/90 mmHg. According to this criterion about 25%

of populations are regarded as hypertensives. There are two types:

1. Essential (idiopathic) in 95% of cases.

2. Secondary due to some underlying cause :

a. Renal (glomerulonephritis, renal artery stenosis and polycystic

kidney diseases.

b. Endocrine (adrenocortical, pheochromocytoma, hyper and

hypothyroidism).

c. Cardiovascular (coarctation of aorta and polyarteritisnodosa).

d. Neurogenic (psychogenic, increase intracranial pressure).

Clinical features

Atherosclerosis can begin in childhood but is typically

asymptomatic for decades until it finally manifests as the following :

1. Insidious narrowing of vascular lumens (e.g. gangrene of the

lower leg because of stenosing atherosclerosis in the popliteal

artery).

2. Plaque rupture of superficial erosion followed by superimposed

thrombus causing sudden luminal occlusion (e.g. MI).

3. Vessel wall weakening followed by aneurysm formation.

4. Providing a source of thromboembolic

Pathogenesis, basically there is alteration in the relationship between cardiac output and peripheral vascular resistance. The major factors that determine blood pressure variation are:1. Age.2. Gender.3. Body mass index.4. Diet principally sodium intake. Kidneys play an important role in blood pressure regulation

through:1. Renin-angiotensin system.2. Vasodilators (prostaglandins, nitric oxide).3. Glomerular filtration.4. Natriuretic factors. Essential hypertension results from an interaction between genetic

and environmental factors include; stress, obesity, cigarette smoking, physical inactivity and heavy consumption of salt.

Morphology, there are two changes:

l. Hyaline arteriosclerosis.

a. Occur in elderly patients particularly those with mild

hypertension and diabetes.

b. The lesion probably reflect EC injury with plasma leakage

into arteriolar walls and ECM synthesis from SMCs.

c. Microscopically there is diffuse pink hyaline thickening.

 

2. Hyperplastic arteriolosclerosis :

d. Characteristic of malignant hypertension.

e. There is concentric laminated (onion skin) thickening

Aneurysms:

It is a localized dilatation of the vessel or heart wall. We have two

types:

1. True,

2. False.

Causes, include:

3. Atherosclerosis.

4. Congenital.

5. Trauma.

6. Infection (syphilis).

7. Inflammation.

Morphologically: there are 2 types

1.Saccular.

2.Fusiform.

Types and sites of Aneurysm

Abdominal aortic aneurysm (AAA):

Is a localized abnormal dilation of a blood vessel, it is due to

atherosclerosis, which may involve also the" common iliac

arteries, aortic arch and descending part of thoracic aorta.

 

Morphology, positioned between renal arteries origin and

bifurcation of aorta. It is either saccular or fusiform up to

15cm in diameter and 25cm in length.

There is an inflammatory AAA of unknown cause.

Mycotic AAA is a complicated atherosclerotic due to infection

by bacteria such as salmonella.

Pathogenesis, there are 2 theories:1. Genetic defects in connective tissue component leading to dissection

then to aneurysm.2. Recently attention was focused on altered balance of collagen

degradation and synthesis mediated by local inflammatory cells. So altered collagen could provide a susceptible substrate on which atherosclerosis or hypertension or both could act to weaken the wall.

Matrix-metalloproteinases produced by inflammatory cells cause proteolysis of the extracellular matrix proteins. A decreased level of tissue inhibitors of metalloproteinases has been reported in aortic aneurysm.

 Clinical course, the condition is rare before the age of 50 years and it

is more common in males. Symptoms appear in case there are: 3. Rupture, potentially fatal hemorrhage related to size.4. Obstruction of iliac, renal, mesenteric or vertebral vessels.5. Embolism.6. Pressure on adjacent structures (ureter, vertebra).7. Abdominal mass.

Treatment is by using stent grafts (expandable wire frame).

Syphilitic aneurysm:

Syphilitic obliterative endarteritis of the vasa vasorum of the thoracic

aorta leads to aneurysm which may involve aortic annulus.

 

Pathogenesis, obliterative endarteritis of adventitial vasa vasorum

causes patchy loss of medial elastic fibers and muscle cells followed

by inflammation and scarring that leads to weakening of the wall and

aneurysmal dilation. Involvement of the aortic annulus leads to aortic

valve incompetence and left ventricular hypertrophy.

 

Clinical course, there are several outcomes:

1. Pressure on mediastinal structures (lung, airways, esophagus,

recurrent laryngeal nerve, vertebrae and ribs).

2. Heart failure.

3. Rupture.

Aortic dissection:

Catastrophic illness characterized by dissection of blood

between and along the laminar planes of the media, with the

formation of a blood filled channel within the aortic wall which

often ruptures outward causing massive hemorrhage. Affecting 2

groups of patients:

1. More than 90% occur in men of 40-60 years of age who are

hypertensive.

2. In younger age group with systemic or localized abnormality

of connective tissue.

3. The condition may be iatrogenic as a complication of arterial

cannulation (diagnostic catheterization or cardiopulmonary

bypass).

4. Rarely may occur during pregnancy.

Morphology, there is intimal tear usually within 10cm of aortic

valve, which is either transverse or oblique, l-5cm in length.

Dissection extends proximally and distally. The hematoma is

located between the middle and outer thirds of the wall. It often

ruptures outward but sometimes into the lumen with second

distal tear. The most preexisting histologically detectable lesion

in the aortic wall is cystic medial degeneration.

Pathogenesis, the trigger for intimal tear and intramural aortic

hemorrhage is unknown in most cases. Once the tear has

occurred,

increased systemic blood pressure maintains progression of

the medial hematoma

Clinical course, there are 2 types:

1. Type A (proximal), more common involving either the

ascending portion only or both the ascending and the

descending aorta.

2. Type B (distal), starts distal to the subclavian artery origin.

Sudden excruciating chest pain radiating to the back and

moving downward is the common presenting feature. Most

common cause of death is rupture to pericardial, pleural or

peritoneal cavity. Currently 65-75% of patients will survive.

WHAT IS VASCULITIS?

Vasculitis is a clinicopathologic process characterized

by inflammation and damage to blood vessels (Fibrinoid

necrosis), leading to compromise of the vascular lumen resulting

in ischemia of the tissues supplied by the involved vessels.

VasculitisThe 2 most common mechanisms are:1. Microbiological infection.2. Immune-mediated.Less common mechanisms are:1. Physical injury (radiation).2. Chemical toxins.

Pathogenesis of immune-mediated vasculitides, include:1. Immune complex deposition.2. ANCA mediated (pauci immune).3. Antiendothelial antibody.

Classification, depends on:1. Size and anatomic site of the involved vessel.2. Histology.3. Clinical manifestation.

CLASSIFICATIONCLASSIFICATION

PRIMARY VASCULITIS SYNDROMES

PREDOMINANTLY LARGE VESSEL VASCULITIS GIANT CELL VASCULITIS

TAKAYASUS ARTERITIS

PREDOMINANTLY MEDIUM VESSEL VASCULITIS PAN

KAWASAKIS DISEASE

PREDOMINANTLY SMALL VESSEL VASCULITIS

ANCA +VE--- c-ANCA +VE-

WEGENERS GRANULOMATOSIS p-ANCA +VE

MICROSCOPIC POLYANGITIS CHURG – STRAUSS SYNDROME

ANCA -VE ESSENTIAL MIXED CRYOGLOBULINEMIA

HENOCH SCHONLEIN PURPURA IDIOPATHIC CUTANEOUS VASCULITIS

BECHETS SYNDROME

PATHOGENIC MECHANISMS OF VESSEL DAMAGE IN VASCULITIS SYNDROMES

PATHOGENIC IMMUNE COMPLEX FORMATION AND/OR DEPOSITION H S P H E PAT I T I S A S S O S I AT E D PA N

PRODUCTION OF ANTINEUTROPHILIC CYTOPLASMIC ANTIBODIES W E G E N E R S G R A N U L O M AT O S I S C H U R G S T R A U S S S Y N D R O M E M I C R O S C O P I C P O LYA N G I T I S

PATHOGENIC T LYMPHOCYTIC RESPONSES AND GRANULOMA FORMATION

GIANT CELL ARTERITIS TAKAYASUS ARTERITS WEGENERS GRANULOMATOSIS CHURG STRAUSS SYNDROME

•ROLE OF ANCA—ANTI NEUTROPHILIC CYTOPLASMIC ANTIBODIES-

•DEMONSTRATED BY IMMUNOFLORESCENT STUDY

•Abs directed against proteins in cytoplasmic granules of neutrophils and monocytes

•2 types:•c-ANCA against proteinase – 3

•wegeners granulomatosis– Sensitivity—90% in active ds

• --specifity– 95%

•p- ANCA against myeloperoxidase•MPA

•Churg Strauss syndrome•WG

ANCA

Giant cell arteritis

“Temporal arteritis”Granulomatous large-vessel vasculitisOlder than 50 yearsHeadache ( ‘‘sinus’’ headache )Fever, jaw or tongue claudication, and scalp tenderness Polymyalgia rheumatica ( 40-50%)Blindness from optic nerve ischemia (15- 20%) ,diplopia and ptosisLife-threatening aortic rupture or dissection

Giant cell arteritisNodularity, tenderness or absent pulsations of the temporal arteries and other involved vesselsESR usually increased.Temporal artery biopsy (TAB) : granulomatous inflammation of the media and adventitia, with histiocytes and mononuclear cells, giant cells, irregular fragmentation of the internal elastic lamina. positive 60-80%Contralateral TAB if first biopsy negativePrednisone at 40 to 60 mg/d

Takayasu arteritisGranulomatous large-vessel vasculitis

Affects aorta, its main branches, and pulmonary a.

Predominantly in young women

Headaches and dizziness

Vascular hypoperfusion :limb claudication, double vision Glucocorticoids

Wegener granulomatosis

Granulomatous, necrotizing, small and medium vessel

Involves upper,lower airways, and kidneys

Any age (40-55 yrs.) Men and women equally

Upper airways symptoms (recurrent or nonresolving sinusitis, nosebleeds, nasal crusting

Sinus pain, epistaxis, persistent otitis media, saddle nose deformity subglottic stenosis.

Single or multiple cavitating/noncavitating nodules or diffuse alveolar hemorrhage

Wegener granulomatosisMicroscopic hematuria, proteinuria, and rapidly progressive RF

Skin rash, migratory arthritis

Ocular involvement (scleritis, corneal ulceration)

Mononeuritis multiplex or CNS involvement

Risk of venous thrombosis (DVT,PE) mechanism unclear

ANCA ( 96%)

Lung biopsy yield 91% of cases

Renal biopsy:focal, segmental necrotizing, crescentic glomerulonephritis with few to no immune complexes

Microscopic polyangiitis

Nongranulomatous necrotizing small-vessel vasculitis,few or no immune deposits

More common in male , average age of onset is 50 years

Persistent cough with or without hemoptysis

Kidneys (79%), joints (65- 72%), skin (44- 58%),

Pulmonary pathology shows capillaritis

Renal histology is similar to WG

Severe disease (lung, kidney, or nerve)

Churg-Strauss syndromeasthma, fever, hypereosinophilia, systemic vasculitis

all ages but rare in children and adolescents and occurs equally between sexes

recurrent allergic rhinitis, difficult-to-treat asthma, nonresolving ‘‘pneumonia’’/pulmonary infiltrates, or persistent eosinophilia

Peripheral eosinophilia (absolute eosinophil usually>1500)

Increased ESR,CRP, and IgE level

ANCA positive 50% of cases (predominantly MPO-pANCA)

Histology: eosinophilic tissue infiltrates, extravascular ‘‘allergic’’ granulomas, and small-vessel necrotizing vasculitis

Polyarteritis nodosa

medium-vessel disease

Incidence 2- 9 per million annually

Men = women

constitutional symptoms, HT,musculoskeletal symptoms, symptoms from vasculitic involvement of nerves, GI tract , skin, heart, and nonglomerular renal vessels

suspected immunologic disease

Biopsy specimens : necrotizing inflammation involving medium-sized or small arteries,with abundant neutrophils, fibrinoid changes, disruption of the internal elastic lamina

Angiographic changes : microaneurysms ,stenoses, occlusion

Polyarteritis nodosa

severe life-threatening disease ( GI tract, heart, or CNS system): 2 mkd oral CYC and glucocorticoids

non–life or non–organ-threatening : glucocorticoids alone

Plasma exchange in severe cases

5-year survival rate with treatment 80%

Relapses are infrequent (8- 19%)

PAN-like vasculitis ass. with viral inf. eg. HBV, HCV, HIV

Rx with glucocorticoids , antiviral treatment , and plasma exchange induced remission 81% , relapse 10%

If clinical improvement , immunosuppression should be withdrawn while continuing antiviral treatment

KAWASAKIS DISEASE

Henoch-SchÖnlein purpurasmall-vessel vasculitis

predominantly affects children

suspected drug allergy or immunologic condition

Purpura (100%), arthritis (82%), abdominal pain (63%), GI bleeding (33%), and nephritis (40%)

Complication : intussusception

Recurrence occurs in up to 40% ( mostly first 3 months)

tissue Bx : leukocytoclastic vasculitis with IgA deposition in blood vessel walls

Typically self-limited

Thrombo Angiitis Obliterans (Buerger Disease):

Segmental thrombosing acute and chronic inflammation

of medium-sized and small arteries principally tibial and

radial arteries with secondarily involvement of the adjacent

veins and nerves. Starts in patients younger than 35 years in

most of the cases.

There is strong relationship to cigarette smoking, due to

rather

1.Direct toxicity, or

2.Hypersensitivity to some tobacco products.

Morphology, sharply segmental transmural acute and

chronic arteritis accompanied by thrombosis.

Primary Raynaud Phenomenon:

Paroxysmal pallor or cyanosis of the digits of the hands or

feet and infrequently the tips of the nose or ears owing to

cold-induced vasoconstriction of the digital arteries,

precapillary arterioles and cutaneouse artero-venous

shunts. Median age is 14 years. The course is benign.

Secondary Raynaud Phenomenon:

Arterial insufficiency of the extremities caused by various

conditions including SLE, systemic sclerosis, atherosclerosis

or Burger disease.

Veins and Lymphatics: Varicose Veins:Abnormally dilated, tortous veins produced by prolonged increased intraluminal pressure and loss of vessel wall support. The superficial veins of the legs are the main sites of involvement. People at risk are:1. Occupations with long period of standings.2. People older than 50 years.3. Obese individuals.4. Women with multiple pregnancies.5. Familial tendency (wall weakness). Morphology, the dilated veins are tortous, elongated and scarred, with thrombosis.

Clinical course,leg edema with stasis dermatitis. No embolism. Apart from legs, varices occur also at the lower end of esophagus and ano-rectum (hemorrhoids).

Thrombophlebitis and phlebothombosis:

In 90% of cases deep veins of the legs are involved.

Predisposing factors are:

1. Cardiac failure.

2. Neoplasia.

3. Pregnancy.

4. Obesity.

5. Postoperative state.

6. Prolonged bed rest.

7. Genetic hypercoagulability syndromes.

Clinically pain may be elicited by pressure over affected

veins. Pain on dorsiflexion (Homer sign). Pulmonary embolism is a

common and serious sequelae,-

Superior and Inferior Vena Caval Syndromes:

They are secondaries to compression or invasions by tumors.

Tumors of Vessels:

Benign tumors and tumor-like conditions:

1. Hemangiomas; Capillary. Cavernous. Pyogenic granuloma.

2. Lymphangiomas; Capillary. Cavernous.

3. Glomus tumor.

4. Vascular ectasias.

5. Reactive vascular proliferations.

Intermediate grade neoplasms:

6. Kaposi sarcoma.

7. Hemangioendothelioma.

Malignant neoplasms:

8. Angiosarcoma.

9. Hemangiopericytoma.

Morphological patterns of vascular tumors

1. Classically, benign vascular neoplasms are composed of well-

formed vascular channels lined by ECs,.

2. Frankly malignant tumors show few or poorly developed

vascular channels with solid, cellular, anaplastic endothelial

proliferation.

3. A few entities fall into an intermediate group.