Pathology of Blood Vessels

Dr. Henny Sulastri, SpPA

Departement of Pathology Anatomic University of Sriwijaya/ dr. M Hoesin Central General Hospital

Normal Vessels
Vessel walls are organized into 3 concentric layers : Intima, media, adventitia. The vessels Arteries, veins, lymphatics. Arteries Based on size and structural features 3 basic type of arteries :

1. Large (elastic arteries ) ec. aorta 2. Medium-sized (muscular arteries) ec. Coronary, renal arteries. 3. Small arteries and arterioles, capillaries ( 2mm in diameter).

Veins have larger diameter, larger lumina,

thinner, less-well-organized walls, more prone to dilatation, compression, easy penetration by tumors and inflamatory processes.

Lymphatics thin-walled, endotheliumlined channels, contains mononuclear inflamatory cells and host of proteins.

The vascular wall. A, Cross from a muscular artery (eg. coronary artery). B, Histology showing an artery (A) and adjacent vein CV), with the elastic lamellae stained black (the arrow points to the arterial internal elastic lamina). Sources : BPD

Congenital Anomalies

Berry aneurysms in cerebral vessels. Arteriovenous fistulas. Fibromuscular dysplasia focal irregullar thickening of the walls of medium and large muscular arteries.

Vascular wall cells and Their response to injury

The main cellular components of blood vessel walls Endothelial Cells (ECs), Smooth Muscle Cells (SMCs). The integrated function of these cells is critical for vasculature to adapt to hemodynamic and biochemical stimuli.

Endothelial Cells (ECs) The endothelium is A macromolucular barrier A thromboresistant surface A modulator of vascular smooth muscle cell function A highly metabolic cell intimately involved in coagulation, inflammation and repair Functions maintaining vessel wall homeostasis and circulatory

Vascular Smooth Muscle (SMCs)

SMCs participate in both normal vascular and pathologic processes such as atherosclerosis. SMCs have capacity to proliferate when appropriately stimulated Can also synthesize ECM collagen, elastin, proteoglycans and elaborate growth factors and cytokines. Responsible for the vasoconstriction or dilatation in response to physiologic or pharmacologic stimuli.

Response of Vascular Wall Cells to Injury

Injury to the vessel wall results in stereotypic healing response, involving intimal expansion by proliferating SMCs and newly synthesized ECM. The recruitment and activation of the SMCs in this process involves signals from cells (ECs, plateles, macrophages), mediators and complement cascades. Excessive thickening of the intima can result in luminal stenosis that blocks vascular flow.

Arteriosclerosis
Means hardening of the arteries. Generic term arterial wall thickening and loss of elasticity. Three patterns : 1. Arteriolosclerosis affects small arteries and arterioles. 2. Monckeberg medial calcific sclerosis. 3. Atherosclerosis.

Arteriolosclerosis
Hyalin thickening or proliferative change of small arteries and arterioles especially in the kidneys and is ussually associated with hypertension or diabetes mellitus. Two variants : 1. Hyalin arteriolosclerosis hyalin thickening of arteriolar walls. In kidneys benign nephrosclerosis, associated with hypertension. 2. Hyperplastic arteriolosclerosis concentric laminatd, onion-skin thickenig of the arteriolar walls. In kidneys malignant nephrosclerosis associated with malignant hypertention

Hyaline Arteriolosclerosis

Homogeneous

pink hyaline thickening of the walls of arterioles The lessions reflect leakage of plasma components across vascular endothelium and excessive ECM production The major morphologic characteristic of benign nephrosclerosis causes diffuse impairment of renal blood supply, with loss of nephrons

Hyperplastic arteriolosclerosis

Related to more acute or severe elevations of blood pressure. Associated with onion-skin concentric, laminated thickening of the wall of arterioles with luminal narrowing The laminations consist SMCs and thickened, duplicated basement membrane In hypertension fibrinoid deposits, vessel wall necrosis (necrotizing arteriolitis) prominent in kidney

Monckeberg Arteriosclerosis Medial calcific sclerosis Degenerative calcification involved the media of medium-size muscular arteries Most typically radial and ulnar arteries Occur in older person (> 50yr ) Doesnt obstruct arterial flow because intima isnt involved. Macroscopic arteries are hard and dilated Microscopic The smooth muscle is focally replaced by pale, acellular, hyalinized materials Ring- like calcifications in the media of arteries Stiff,calcific pipestem arteries result May coexist with atherosclerosis.

Atherosclerosis
Characterized by intimal lesions called atheromas that protude into vascular lumina. Also called : atheromatous/ atherosclerotic

plaques.

Its consist : raised lession with soft, yellow, grumous core of lipid ( cholesterol, cholesterol esters) covered by a firm white fibrous cap. The plaques weaken the underlying media and can themselves rupture acute catastrophic vessel thrombosis. Causes morbidity and mortality

Risk Factors

Increasing age Cigarette smoking Hypertension Male sex Hyperlipidaemia Diabetes Mellitus

Pathogenesis Current concept of atherogenesis reaction to injury formulation. A chronic inflammatory response of the arterial wall to endothelial injury

maybe produced by hypercholesterolemia, mechanical injury, hypertension, immune mechanisms, toxins, or viruses or other infectious agents.

Hyperlipidemia may initiate endothelial injury, promote foam cell formation,act as chemotactic factor for monocytes, inhibit macrophage motility, or injure smooth muscle cells.

The processes : Entry of monocytes and lipid into subendothelium occurs, sometimes with platelet adhesion and aggregation at injury site. Mitogenic factors are released The growth factors induce proliferation and migration of smooth muscle cells into the intima with the production of connective tissue matrix proteins Monocytes and smooth muscle cells engulf lipid and contibute to the deposition of lipid into lesions.

The Natural History of Atherosclerosis

Atherosclerosis primarily affects elastic arteries : aorta, carotid, iliac arteries medium-sized muscular arteries : coronary, popliteal arteries In small arteries atheromas can gradually occlude lumina ischemic injury. In large arteries plaque destructive, encroaching subadjacent media, weakening affective vessel wall aneurysma rupture Atheromas can friable, fragmented atheroemboli into down-stream circulations

Clinical Features

The natural history, morphologic features, main pathogenic events, and clinical complications of atherosclerosis.

Morphology

Fatty streaks

lipid-filled

foam cells, not significant rised, not cause any disturbance in blood flow. Begin as multiple minute yellow, flat spots can coalescene into elongated streaks, 1cm or longer. Can appear in the aortas of infants younger than 1 yr Not all fatty streaks are destined to become advanced atherosclerotic lesions

Fatty streak collection of foam cells in the intima. A, Aorta with fatty streaks (arrows), associated largely with the octia of branch vessels. B, Photomicrograph of fatty streaks in rabbit

Atherosclerotic plaques
Intimal thickening and lipid accumulation, impinge in the lumen of artery. Grossly white to yellow, thrombosis is red brown. Vary in size : 0.3 to1.5 cm Lession are pathcy, eccentric In human abdominal aorta much more involved than thoracic aorta Atherosclerotic plaques have 3 principal components Cells, including SMCs, macrophage, T cells ECM, collagen, elastic fibers, proteoglycans Intracellular and extracellular lipid

1.
2. 3.

 Fibrous

cap composed of SMCs and relative

dense collagen The shoulder more cellular area containing macrophages, T cells, SMCs Necrotic core containing lipid, debris, foam cells, fibrin, thrombus, other plasma proteins The cholesterol content present as crystalline aggregates. Neovascularisation proliferating small blood vessels at the periphery of lession Plaques can progressive through cell death and degeneration, synthesis and degradation (remodeling), calcification

 Rupture, ulceration or erosion The luminal surface exposes bloodstream

to highly thrombogenic substances induced thrombus formation occlude lumen ischemia

Rupture of fibrous cap or thin-walled vessels in areas of neovascularization intra plaque hemorrhage, hematoma induce plaque rupture.

Hemorrhage

Plaque rupture can discharge debris into the blood stream producing microemboli

Atheroembolism

Weaknes of the vessel wall develop aneurysms that may rupture.

Aneurysm formation

The major conponents of a well-developed intimal atheromatous plaque overlying an intact media.

Cellular interactions in atherosclerosis. Hyperlipidemia and other risk factors are thought to cause endothelial injury, resulting in adhesion of platelets and monocytes and release of growth factors, including platelet-derived growth factor (PDGF), which lead to SMC miqration and proliferation foam cells of atheromatous pJaques are derived from both macrophages and SMCs

features of atheromatous plaque in the coronary artery. A, Overall architecture demonstrating fibrous cap (F) and a central necrotic ( lipid) core (C). The lumen (L) has been moderately narrowed. Note that a segment of the wall is plaque free (arrow). that there is an eccentric lesion. In this section, has been stained blue (Massons trichrome stain).

Complications

Ulceration and thrombosis Haemorrhage Calcification Aneurysm

Summary
Atherosclerosis is an intima-based lesion organized into a fibrous cap and an atheromatous (gruel-like) core and composed of SMCs, ECM, inflamatory cells, lipids and necrotic debris. Atherogenesis is driven by an interplay of inflammation and injury to vessel wall cells. Atherosclerotic plaques accrue slowly over decades but may acutely cause symptoms due to rupture, thrombosis,hemorrhage or embolization. Risk factor recognition and reduction can reduce the incidence and severity of atherosclerosisrelated disease.

Hypertensive Vascular Disease

1. 2.

Essential Hypertension Unknown etiology Exogenous factors determinants : Genetic factors family history,African lineage Environmental factors dietary sodium intake, stress, obesity,cigarette smoking, physical inactivity. Results retinal changes, left ventricular hypertrophy, cardiac failure, benign nephrosclerosis Predispose to ischemic heart disease or stroke

Secondary Hypertension Renal hypertenson disordered of renal parenchyma, unilateral renal artery stenosis Stimulation of the renin-angiotensin system Primary aldosteronism (Conn syndrome) Acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism Diabetes mellitus Coarctation of the aorta, toxemia of pregnancy, CNS disorders, drugs and chemicals

1. Renal Disease

2. Endocrine disorders

3. Others causes

Malignant hypertension

Can be a complications of essential or secondary hypertension. Increase in diastolic blood pressure, papiledema, left ventricular hypertrophy, left ventricular failure Renal changes of malignant nephrosclerosis rupture flea-bitten kidney, multiple pinpoint petechial hemorrhages on the kidney surface, large swollen kidneys, necrotizing arteriolitis and glomerulitis with fibrinoid necrosis & hyperplastic arteriolosclerosis.

Regulation of Blood Pressure

1. 2. 1.

2.

3.

Central players in blood pressure regulation: The kidney (primarily) Adrenal (secondary) The interaction as follow : The kidney influences peripheral resistance and sodium homeostasis through the reninangiotensin system When blood volume/pressure reduced kidney senses this as a decreased pressure in the afferent arterioles. The juxtaglomerular cells respond to reduced intraluminal pressures by releasing renin

4. Renin catabolizes plasma angiotensinogen to angiotensin I turn is converted to angiotensin II 5. The kidneys filter plasma containing salt to maintain homeostasis 6. The kidneys produces variety of vasorelaxant/ antihypertensive substances (prostaglandin, nitric oxide) 7. When renal excretory fg/ is impaired increased arterial pressure 8. Other tissues can also influence

Blood pressure variation and the renin-angiotensin system. Components of the systemic renin-angiotensin system

Vascular Pathology in Hypertension

1. 2.

Hypertension associated degenerative changes in the walls of large and medium arteries can potentiate both aortic dissection and cerebrovascular hemorrhage. Its also associated with 2 small of blood vessel disease : Hyaline arteriolosclerosis Hyperplastic arteriolosclerosis

Vascular pathology in hypertension. A, Hyaline arterioloscierosis. The arteriolar wall is hyalinized and the lumen is markedly narrowed. B, Hyperplastic arteriolosclerosis (onion-skinning) causing luminal obliteration (arrow)

Aneurysms

1. 2. 3. 4. 5. 6.

Localized abnormal dilatations of either arteries or veins Can erode adjacent structures or rupture. There are several different types : Atherosclerotic aneurysms occurs in descending (abdominal, aorta) Aneurysms due to cystic medial necrosis. Berry aneurysms Syphilitic aneurysm Dissecting aneurysm (dissecting hematoma) Arteriovenous fistula

Two most important causes of aortic aneurysms atherosclerosis and cystic medial degeneration of the arterial media. Others causes trauma, congenital defects, infections. Morphology Inflammatory : dense periaortic fibrosis containing abundant lymphoplasmacytic infiltrate with many macrophages often giant cells Mycotic : lodging of circulating microorganisms in the wall, suppuration destroys the media rapid dilatation and ruptur

Aneurysms. A. Normal vessel. B, True aneurysm, saccular type. The wall focally bulges outward C. True aneurysm. fusiform type. There is circumferential dilation of the vessel, without rupture D, False aneurysm. the wall ruptured, and there is a collection of blood (hematoma) that is bounded externarly byadherent extravascular tissues. E, Dissection. Blood has entered (dissected) the wall of the vessel and separated the layers.

Vasculitis Syndromes
Inflammatory and often necrotizing vascular lessions Occur in almost any organ and usually mediated by immune mechanisms, most often immune complex depositions. Frequent antigens in immune complexes include DNA, hepatitis B surface antigen and hepatitis C RNA

Polyarteritis Nodosa
Necrotizing immune-complex inflammation of small and medium sized arteries

aneurysmal nodules.

There is an association with hepatitis B viral infection in 30% of patients. Fever, weight loss, malaise, abdominal pain, headache, myalgia, hypertension Serum antibodies to neutrophilic myeloperoxidase (P-ANCAs)

Polyarteritis nodosa is seen in the following site :

Kidneys vasculitis in the arterioles and glomeruli cause most death Coronary arteries ischemic heart disease Musculoskeletal system myalgia , arthralgia, arthritis. GI tract nausea, vomiting, abdominal pain. CNS system or peripheral nervous system, the eye or skin.

Polyarteritis nodosa. There s segmental fibrinoid necros and thrombotic occlusion in the lumen of this small artery

Wagener granulomatosis
Unknown etiology Necrotizing granulomatous vasculitis of the small-medium sized vessels of the respiratory tract, kidneys and other organs Dominated clinically by respiratory tract signs and symptoms (paranasal sinuses & lungs), necrotizing glomerulonephritis. Granuloma formation with giant cell is dominant In most cases associated with circulating antineutrophils C -ANCA

Thromboangitis obliterans (Buerger disease)

An acute inflammation involving smallmedium sized arteries of the extremitas, extending to adjacent veins and nerves Jewish population and young men Results in painful ischemic disease gangrene Heavy cigarette smoking

Tbromboangiitis obliterans (Buerger disease). The lumen is occluded by a thrombus containing abscesses (arrow), and the vessel wall is infiltrated with leukocytes.

Raynaud disease
Recurrent vasospasm of small arteries and arterioles with resultant pallor or cyanosis, most often in the fingers and toes. In young and healthy women Raynaud phenomenon similar to Raynaud disease but is always secondary to an underlying disorder Most characteristically systemic SLE or progressive scleroderma.

Veins and Lymphatics

Varicose Veins Thrombophlebitis and Phlebothrombosis Superior and Inferior Vena Caval Syndromes Lympangitis and Lymphedema

Varicose Veins
Abnormally dilated, tortuous veins produced by prolonged, increased intramural pressure and loss of vessel wall support. Superficial veins of upper and lower leg Long periods of standing, long automobile, airplane rides. 10-20% of the general population Women> men

Morphology

dilated, tortuous, elongated, scarred with thinning at the points of maximal dilatation, valvular deformities (thickening, rolling,shortening of cups)

Microscopically variations in the thickness of

the vein wall, elastic tissue degeneration,phlebosclerosis

Varicose Veins of The Leg

Risk factor age, sex, heredity, posture, obesity Exhibit variations in wall thickness, patchy calcification, deformity of valves May lead ulcerations

Varicose Veins at Other Sites

1.

Hemorrhoids :
dilations of the veins of rectum and anal canal in anal sphincter. Constipation and pregnancy, often bleed.

2. Esophageal Varices In portal hypertension & liver cirrhosis 3. Variocele Palpable mass in scrotum

Thrombophlebitis and Phlebothrombosis

Inflammation and venous thrombosis Cardiac failure, neoplasia, pregnancy, obesity,prolonged bedrest or immobilization, post operative state, genetic hypercoagulability syndromes Edema distal to the occluded vein, dusky cyanosis, dilatation of superficial veins, heat, tenderness, redness, swelling.

Deep Veins Thrombosis

Principally affect leg veins Associated with prolonged bed rest Reduced cardiac output

Superior and Inferior Vena Caval Syndromes

Usually caused by neoplasms that compress or invade the superior vena cava, primary bronchogenic carcinoma or mediastinal lymphoma Neoplasm compress or penetrate the walls of the inferior vena cava or a thrombus from the femoral or iliac vein. Obstruction of the inferior vena cava causes marked edema of the legs, distention of the superficial collateral veins of lower abdomen. When renal veins are involved massive proteinuria.

Lymphangitis and Lympedema

Secondary processes develop in association with inflammation or cancer. Lymphangitis bacterial infections (group A Betahemolytic streptococi, viral ) Dilated, filled with exudate, extends to wall into the perilymphatic tissues Limphedema causes dilatation of lymphatics up to the points of obstruction, increases interstitial fluid, increased subcutaneous interstitial fibrous tissue, peau d orange appearance of the skin, skin ulcers

Vascular Tumors
Benign - Haemangiomas - Lymphangioma - Glomus tumor - Vascular ectasis - Reactive vascular proliferation Intermediate grade

Hemangioendothelioma Kaposi sarcoma

Malignant Neoplasms
Angiosarcoma Hemangiopericytoma

Hemangiomas
Capillary hemangioma Cavernous hemangioma Pyogenic granuloma (lobular capillary hemangioma)

Capillary Hemangiomas
The largest single type Most common in skin, subcutaneous tissues, mucous membranes of oral cavities and lips. Can also occur in liver, spleen, kidneys Juvenile Hemangioma strawberry type of the skin of new borns extremely common.

Morphology Size : few several centimeter Bright red to blue, surface of the skin or slightly elevated with intact covering epithelium. Occasionally pedunculated. Histologically Usually lobulated Unencapsulated agregrates of closely packed, thin-walled capillaries Usually blood-filled and lined by flattened endothelium separated by scant connective tissue stroma The luminal may be thrombosed and organized Ruptur vessels , hemosiderin pigment

Cavernous Hemangioma
Less common Usually larger Less well circumscribed Involve deep structures than capillary hemangiomas Locally destructive, no tendency to regress

Grossly red-blue, soft, spongy mass 1 -2 cm Giant form in subcutaneous areas of face, extremitas or other region rarely Histologically Unencapsulated Large cavernous vascular spaces Partly/completely filled with blood separated by a scant connective tissue stroma Intravascular thrombosis associated dystrophic calcification is common

A, Hemangioma of the tongue. B, Histology of juvenile capillary hemangioma C, Histology of cavernous hemangioma. D granuloma of the lip.

Pyogenic Granuloma

Exophytic red nodule attached by stalk to the skin and ginggival and oral mucosa Bleed easily, often ulcerated 1/3 developped after trauma Maximun size 1-2 cm within few weeks Extensive edema, acute and chronic inflammatory . Histologic examination exuberant granulation tissue

Hemangioendothelioma
A wide spectrum of vascular neoplasm showing histologic features and clinical behavior intermediate beetwen the benign, well differentiated hemangiomas, frankly malignant angiosarcomas Epithelioid hemangioendothelioma , unique vascular tumor occurring around medium-sized and large veins in the soft tissue of adults The tumor cells are plump often cuboidal resembling epithelial cells.

Angiosarcoma

A malignant endothelial neoplasms with structure varying from highly differentiated tumors that resemble hemangiomas Occur in both sexes, older adults Anywhere in the body, commonly in skin, soft tissue, breast and liver. Hepatic angiosarcoma associated with arsenic Can be induced by radiation and associated with foreign material introduced into the body.

Morphology
small, sharply demarcated,asymptomaic, often multiple red nodules, fleshy masses, pale, gray-white soft tissue, necrosis and hemorrhagic areas. ,largelly vascular with plump, anaplastic recognizable endothelial cells to quite undifferentiated blood vessels, atypical, solid spindle cells appearence

Grossly,

Microscopically

. A, Gross photograph of angiosarcoma of the heart right ventr B, Photomicrograph of moderated well differentiated with dense clumps of irregular, moderate anaplastic cells and distinct vascular lumens. C, Positive immunohistochemical staining of angiosarcoma for the EC marker C031

Hemangiopericytoma

A heterogeneous group of neoplasm with a grossly fleshy or spongy consistency and a thinwalled branching (staghorn) vascular pattern Derived from pericytes. Slowly growing masses in the pelvic retroperitoneum or the lower extremities, 5-15 cm in diameters Middle age women. 1/3 are malignant presence of necrosis, high mitotic rate, nuclear pleomorphism.

Kaposi Sarcoma
Kaposi Sarcoma has come to the forefront because of its frequent occurrence in patients with AIDS Four forms are recognized : Chronic Lymphadenopathic Immunosuppression-associated Most common AIDS associated cancer

Morphology Patch, plaque and nodule Patch : pink-red to purple solitary or multiple macules distal lower extremitas or feet. Microscopically irregular, angulated blood vessels lined by endothelial cells with infiltrate of lymphocytes, plasma cells, macrophages, hemosiderin Difficult distinguishing with granulation tissue Mitotic figures may be present Later stage nodular, more distinctly neoplastic may be composed of sheets of plump, proliferating spindle cells. The nodular stage is often accompanied by involvement of lymph nodes and viscera, particularly in the African and AIDS-associated diseases

Kaposi sarcoma. A, Gross photograph, coalescent red-purple macules and plaques of the skin. B, Histologic view ofthe normal form demonstrating sheets of plump, proliferating spindle celJs and vascular spaces