1 Blood Vessels

Dr. Muhammad Mudassar Majeed

M.B.B.S, FCPS (HISTOPATHOLOGY)

Blood vessels

Before starting the discussion Be ready for questions

from each of you during the session……no body spared…

Don’t fear, just friendly questions………….

What would we cover MAIN TOPICS

Atherosclerosis

Myocardial infarction

Hypertension

Rheumatic heart diseases

Congenital heart diseases

Aneursysms

The vascular wall

Normal structure Endothelial cells

Single cell thick

Continuous lining

Smooth muscle cells

Extracellular matrix Elastin

Collagen

Glycosaminoglycans

Endothelial cell response to enviornmental stimuli

Mechanism of intimal thickening Vascular injury stimulates smooth muscle cell growth.

Reconstitution of the damaged vascular wall is a physiologic healing response that includes the formation of neointima in which SMC’s

Migrate from the media to intima

Multiply as intimal SMC

Synthesize and deposit ECM

Just wait…. What is the difference

between atherosclerosis and arteriosclerosis ?

Mechanism of intimal thickening

Before starting atherosclerosis, lets see a clip

Clip no 1

ARTERIO-SCLEROSIS

GENERIC term for ANYTHING which HARDENS arteries

Atherosclerosis (99%)

Mönckeberg medial calcific sclerosis (1%)

Arteriolosclerosis, involving small

arteries and arterioles, generally regarded as NOT strictly being part of atherosclerosis, but more related to hypertension and/or diabetes

ATHEROSCLEROSIS (classical)

Etiology/Risk Factors

Pathogenesis

Morphology

Clinical Expression

MORPHOLOGIC CONCEPTS Intimal Thickening

Lipid Accumulation

Streak

Atheroma

Smooth Muscle Hyperplasia and Migration

Fibrosis

Calcification

Aneurysm

Thrombosis

PLAQUE

Risk Factors for Atherosclerosis

Major Minor

NON-modifiable Modifiable

Increasing age Obesity

Male gender Physical inactivity

Family history Stress ("type A" personality)

Genetic abnormalities Postmenopausal estrogen deficiency

High carbohydrate intake

Modifiable

Hyperlipidemia Alcohol

Hypertension Lipoprotein Lp(a)

Cigarette smoking Hardened (trans)unsaturated fat intake

Diabetes Chlamydia pneumoniae

MAJOR factors

Hyperlipidemia

Hypertension

Cigarette Smoking

Diabetes Milletus

Who would repeat major factors of atherosclerosis

HYPERLIPIDEMIA Chiefly CHOLESTEROL,

LDL>>>>HDL HDL mobilizes

cholesterol FROM atheromas to liver

LOW CHOLESTEROL diet is GOOD

UNSATURATED fatty acids GOOD

Omega-3 fatty acids GOOD

Exercise GOOD

CHOLESTEROL CLEFTS

CIGARETTES What more

needs to be said?

PATHOGENESIS SAGA Chronic endothelial injury

LDL, Cholesterol in arterial WALL

OXIDATION of lipoproteins

Monocytes migrate endothelium*

Platelet adhesion and activation

Migration of SMOOTH MUSCLE from media to intima to activate macrophages (foam cells)

Proliferation of SMOOTH MUSCLE and ECM

Accumulation of lipids in cells and ECM

Who would repeat steps of pathogenesis ?

Not clear yet ?

Lets have the clip again……. Clip no 4

Classification of atherosclerosis american heart association

Lumen in atherosclerosis

Lumen narrowing in atherosclerosis

Tear in the wall

Lumen of the vessel

Atherosclerosis in aorta

Atheromatous plaque in coronary artery

Morphology and complications of Atherosclerosis

Clinical Scenario Exam question A 65 year old dictator of banana republic, who was an

alcoholic and fond of red meat, suffered a short episode of unexplained chest pain after he was forced to resign and died before he could reach the hospital. At autopsy the pathologist found thickened walls of many arteries including the coronary arteries with luminal narrowing. The lesions consisted of raised plaques having a soft centre with a fibrous cap.

A; what is the process known as and what other arteries it most commonly involves?

B; what are the principal components of these plaques?

Hypertension

What is the definition of hypertension ?

DEFINITION 140/90

SUSTAINED diastolic >90

SUSTAINED systolic >140

BP = CO x PR

ALL Hypertension

Hypertension Elevation of blood pressure is known as hypertension

Hypertension can lead to

Cardiac hypertrophy

Heart failure (hypertensive heart disease)

Aortic dissection

Renal failure

Systolic greater than 140mm and diastolic greater than 90mm is hypertension

Classification of hypertension Essential hypertension Secondary hypertension

Renal Acute glomerulonephritis Chronic renal disease Renal artery stenosis Renal vasculitis Renin producing tumours

Endocrine Adrenocortical hyperfunction Exogenous horomones Phaeochromocytoma

Classification of hypertension Acromegaly

Hyperthyroidism

Hypothyroidism

Pregnancy induced

Cardiovascular Coarctation of aorta

Polyarteritis nodosa

Neurologic Pychogenic

Increased intracranial pressure

Acute stress including surgery.

Hypertension

Regulation of blood pressure and role of Renin Angiotensin system

Mutations altering the blood pressure in humans

Vascular changes in hypertension Hypertension is associated with two forms of

blood vessel disease Hyaline arteriosclerosis

Homogenous pink hyaline thickening of the walls of arterioles with loss of underlying structural detail

Narrowing of the lumen Major characteristic of benign nephrocalcinosis

Hyperplastic arteriosclerosis Characteristic of malignant hypertension Onion skin concentric thickening of walls of arterioles Progressive narrowing of the lumen Deposits of fibrinoid and acute necrosis of vessel wall

(necrotizing arteriolitis)

HISTOPATHOLOGY of ESSENTIAL HYPERTENSION

“HYALINE” = BENIGN HTN. “HYPERPLASTIC” = MALIGNANT HTN.

SYS>200 1) ONION SKIN 2)“FIBRINOID” NECR.

What is an aneurysms ?

Aneurysm

A localized balloon-like enlargement of an artery.

Aneurysms Is a localized abnormal dilation of blood vessel or the

wall of the heart

True aneurysm: aneurysm bounded by arterial wall components or the attenuated wall of the heart is true aneurysm

False aneurysm is a breach in the vascular wall leading to an extravascular haematoma that freely communicates with the intravascular space (pulsating haematoma)

Atherosclerotic Abdominal Aortic Aneurysm

Aneurysm with

thrombus

Kidney Kidney

Aorta

True and false aneurysm

Aneurysms Abdominal aortic aneurysm

Thoracic and abdominal aneurysms

Popliteal and cerebral aneurysm Cerebral aneurysm Popliteal aneurysm

Infarction and aneurysm Infarction and aneurysm Cerebral aneurysm

Aneurysms According to aetiology they are divided into

Atherosclerotic

Cystic medial degeneration

Traumatic aneurysm

Arteriovenous aneurysms

Congenital aneurysms

Mycotic aneurysms

Aneurysms According to shape and size

Saccular

Fusiform

Morphology of aneurysm

Morphology of abdominal aortic aneurysm

Usually below the renal arteries and above bifurcation of aorta

Saccular or fusiform 15 cm in diameter and variable length

Two variants

Inflammatory abdominal aortic aneurysms

Mycotic abdominal aortic aneurysms

Atherosclerotic aneurysm Pathogenesis

Atherosclerosis is the major cause

Genetic susceptibility Altered balance of collagen degradation & synthesis

Matrix metalloproteinases

Syphlitic aneurysms

Obliterative endarteritis (tertiary)

Vasa vasorum (syphlitic aortitis)

Cow’s heart

Abdominal aortic aneurysm

Aortic disseection Is characterized by dissection of blood between and

along the laminar planes of media with the formation of a blood filled channel within the aortic wall which often ruptures outward causing massive haemorrhage.

Age:

Men between 40 and 60years with hypertension

Younger with connective tissue disorder

Iatrogenic (arterial cannulization

Syphilis

Rarely in pregnancy

Morphology of aortic dissection In spontaneous dissection the intima is usually 10 cm

of aortic valve.

Tears are transverse or oblique

1-5 cm in length

Sharp and jagged edges

Dissection can extend along the aorta proximally towards the heart or distally to the iliac or femoral vessels

Haemorrhage or double barrelled aorta with false channel. If channel is endothelized :chronic dissection

Aortic dissection

Aortic dissection (dissecting haematoma)

Dissecting aneurysm

Cystic Medial Necrosis Cystic Medial Necrosis is characterised by

Elastic tissue fragmentation

Separation of elastic and fibromuscular elements of tunica media

Small cleft like spaces

Loss of elastic tissue

Presence of amorphous extracellular matrix

Cysts

Medial degeneration

UHS exam question A 55 year old male presents with left sided facial pain

with palpable left temporal artery. Biopsy of the artery reveals fragmentation of internal elastic lamina with granulomas containing Langhan’s and foreign body giant cells?

A. what is the diagnosis?

B. which other condition should be considered in the d/d of a granulomatous vasculitis involves the aorta?

C. List the 3 pathogenetic mechanisms involved in non infectious vasculitides?

Dr Muhammad Mudassar

Inflammatory vasculitis Inflammation of the vessel wall is called vasculitis

Clinical features include

Fever

Myalgias

Arthralgias

Malaise

Local ischaemia

Common Pathogenetic mechanism of vasculitis Direct infection

Bacterial

Rickettsial

Spirochaetal

Viral

Fungal

Immunological Immune complex mediated

Infection induced

Henoch Schonlein purpura

SLE and rheumatoid arthritis

Common Pathogenetic mechanism of vasculitis Immunological

Antineutrophilic cytoplasmic antibodies

Wegener’s granulomatosis

Microscopic polyangitis

Direct antibody mediated

Good Pasteur’s syndrome

Kawasaki’s disease

Cell mediated

Inflammatory bowel disease

Paraneoplastic vasculitis

Common Pathogenetic mechanism of vasculitis Unknown

Giant cell arteritis

Takayasu’s arteritis


Pathogenesis of vasculitis Infectious vasculits

Non infectious vasculitis

Immune complexes

Antineutrophil cytoplasmic antibodies

Anti endothelial cell antibodies

Vasculitis

Classification of Vasculitis

Classification Large vessel vasculitis; (Aorta and Large Branches to

Extremities, Head, and Neck)

Giant cell ( temporal )arteritis

Takayasu arteritis

Medium vessels vasculitis; (Main visceral arteries and their branches)


Kawasaki disease

Small vessels vasculitis; (Arterioles, venules, capillaries, and occasionally small arteries)

Wegener granulomatosis

Churg-Strauss syndrome

Microscopic polyangiitis

Giant cell or temporal arteritis Most common

Acute and chronic often granulomatous inflammation of arteries of large to small size with multinucleated giant cells

Nodular thickening with reduction of the lumen

May become thrombosed

Fragmentation of the internal elastic lamina

Temporal arteritis

Temporal arteritis

Takayasu’s arteritis Characterized by ocular disturbances and marked

weakening of the pulses in the upper extremities (pulseless disease

Vasculitis with fibrous thickening or obliteration of the lumina.

Classically involves the aortic arch and its branches.

Takayasu’s arteritis Gross

Irregular thickening of the aortic or the branch vessels with intimal wrinkling

When the aortic arch is involved the orifices to the major arteries to the upper portion of the body maybe markedly narrowed or obliterated

Histological findings

Adventitial mononuclear infiltrate

perivascular cuffing of the the vasa vasorum.

In some cases granulomatous inflammation maybe seen

Takayasu’s arteritis

Polyarteritis nodosa PAN Systemic vasculitis of small or medium sized muscular

arteries.

Typically involving the renal and visceral vessels but sparing the pulmonary vessels

Predilection for branching points and bifurcations

Polyarteritis nodosa Segmental transmural inflammation of arteries of

medium to small size with neutrophils monocytes and eosinophils with fibrionoid necrosis

Lumen may become thrombosed

Acute inflammatory cells disappear and be replaced by fibrous tissue.

All stages of activity may co exist in the same vessel or within different vessels

A)Polyarteritis nodosa B) leucocytoclastic vasculitis

Kawasaki’s disease Also known as muco cutaneous lymph node syndrome

Often involves the coronary arteries

Young children and infants less than 4 years of age

Fever

Conjuctival and oral erythema

Erosion

Edema of the hands and feet

Erythema of the palms and soles

Skin rash with desquamation

Kawasaki’s disease Vasculitis is polyarteritis nodosa like

Inflammation of the entire wall

Fibrinoid necrosis is less common

Complications

Aneurysm

Thrombosis

Myocardial infarction

Aetiology

Immune mediated ( T cell and B cell activation)

Kawasaki disease

Kawasaki disease

Leucocytoclastic vasculitis It is necrotizing vasculitis of arterioles, capillaries and

venules (vessels smaller than PAN)

All lesions tend to be at the same age (in contrast to PAN)

Presents as purpura on skin mucous membranes, lungs brain heart gastrointestinal tract kidneys and muscles

Morphology

Similar to PAN but muscular and larger arteries are spared.

Neutrophils are fragmented as they follow the vessels.

Leucocytoclastic vasculitis

Leucocytoclastic vasculitis

Wegener’s granulomatosis Necrotizing vasculitis characterized by

Acute necrotizing granulomas of upper respiratory tract

Necrotizing or granulomatous vasculitis

Renal disease crescenteric glomerulonephritis

Pathogenesis

Immunologic mechansim

Hypersensitivity to inhaled or infectious agents





Thromboangitis obliterans Also known as Burger’s disease

Segmental thrombosing acute or chronic inflammation of medium and small sized arteries

Tobacco sensitivity

Morphology

Sharply segmental acute and chronic vasculitis

Thrombosis

Organization and recanalization

Microabscesses with central focus of neutrophils

Vaculitis associated with other disorders Vasculitis resembling hypersensitivity angitis or classic

PAN may sometimes be associated with some underlying disorder

SLE

Malignancy

Mixed cryoglobulinemias

Henoch Schonlein purpura

Vasculitis with fibrinoid necrosis (SLE)

Raynaud’s phenomenon Refers to paroxysmal pallor of finger tips or digits of

hands or feet and infrequently of tips of nose and ears due to cold induced vasoconstriction of digital arteries.

Structural changes in arterial walls are absentexcept late in the course when intimal thickening appears

Secondary Raynaud’s phenomenon is due to arterial insufficiency of the extremities due to SLE, systemic sclerosis atherosclerosis or Buerger’s disease.

Raynaud’s phenomenon

Raynaud’s phenomenon

Varicose veins Common sites

Superficial veins of upper and lower legs

Predisposing factors

Dependence for prolonged periods of time venous pressures are elevated

Long period of standing

Long automobile and air plane rides

Familial tendency

Varicose veins Morphology

Dilated toruous elongated and scarred

Thinning at points of maximal dilatation

Valvular deformities

Thickening rolling and shortening of cusps

Elastic tissue degeneration

Spotty calcification within the media

Clinical features

Venous congestion edema thrombosis pain,stasis dermatitis ulcerations vulnerability to infections ulcers

Varicose veins

Varicose veins

Dr Muhammad Mudassar

Tumours of blood vessels Benign tumours and tumour like conditions.

Haemangiomas

Capillary hemangioma

Cavernous hemangioma

Lobular capillary haemangioma

Lymphangioma

Capillary Lymphangioma

Glomus tumour (glomangioma)

Tumours of blood vessels Vascular ectasia

Nevus flammeus

Spider telangiectasia

Hereditary haemorrhagic telangiectasias

Bacillary angiomatosis

Intermediate Grade (borderline low grade malignant tumours

Kaposi’s sarcoma

Haemangioendothelioma

Malignant tumours

angiosarcomas

Haemangiomas Capillary haemangiomas

Cavernous haemangiomas

Pyogenic granuloma

Haemangioma

Haemangioma Haemangioma of lip Haemangioma on leg

Haemangioma Haemangioma face Haemangioma face

Haemangiomas

Lymphangiomas Are composed of small lymphatic channels and tend to

occur subcutaneously in the head and neck region and in the axilla

Histology

Cystic hygroma

Lymphangioma/lymphangioma Lymphangioma Lymphangioma

Lymphangioma

Glomus tumour benign

Painful

Arteriovenous junction

Distal portion of digits

Microscopy:

Branching vascular channels separated by connective tissue containing glomus cells

Bacillary angiomatosis Opportunistic infection of immunocompromised

persons by gram negative bacilli of Bartonella family particulary Bartonella henselae.

Red papules or nodules

Proliferation of capillaries that exhibit protuberant epitheliod endothelial cells with nuclear atypia and mitosis.

Bacillary angiomatosis

Intermediate grade or borderline tumours Kaposi sarcoma

Classical or European Kaposi’s sarcoma

Lymphadenopathic African or Endemic Kaposi’s sarcoma

Transplant associated kaposi’s sarcoma

KS associated with AIDS

Kaposi’s sarcoma Morphology

patch

Pink to red purple solitary or multiple macules in the lower limbs

Dilated irregular angulated blood vessels

On the lower limbs

Plaque

Large vilaceous plaques

Spreads proximally

Dialted jagged vascular channels lined by plump spindle cells surrounded by spindle cells

Kaposi’s sarcoma Nodular

The lesions become nodular

Vessels have slit like spaces with rows of red blood cells

Mitosis are present.

This stage is associated with involvement of lymph nodes and viscera.

Pathogenesis

KS associated herpes virus

Kaposi’s sarcoma

Haemangioendothelioma Benign

Borderline

Malignant

Malignant tumours Angiosarcoma

Are malignant endothelial neoplasms varying from highly differentiated to highly anaplastic lesions

Hepatic angiosarcomas are associated with carcinogens

May arise in setting of lymphoedema

Angiosarcoma Angiosarcoma abdomen Angiosarcoma breast

angiosarcoma Angiosarcoma on heel Angiosarcoma abdomen

Microscopic features Angiosarcoma Angioma

Angiosarcoma

Balloon angioplasty stents and restenosis

Hyperplasia in a graft

Coronary artery stent with thickened intima

Documents

1 Blood Vessels