blood vessel diseases level ii

8/8/2019 Blood Vessel Diseases LEVEL II

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diseases of blood vessels-Vaculitides

and degenerative

27th may 2009


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Objectives

Understand the classification of BV dx

List the causes Be able to describe the pathogenesis and

possible complications


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Broad classification 1. Inflammatory- vasculitides, vasculitis

2. Degenerative- hypertension andatherosclerosis


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Causes of athero and arteriosclerosis

Arteriosclerosis

Atherosclerosis

Modifiable causes- diet high in salt, cholesterol,

cigarette smoking, diabetes, hyperlipidemia,

hypertension, C-reactive protein

Non-modifiable-genes, environment, familialhistory, gender, increasing age


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atherosclerosis Coronary atherosclerotic heart disease-more

pathologically correct. IHD-non-specific

This accounts for 80-90% of cardiac mortalities inthe west

The commonest cause of myocardial ischaemia isatherosclerotic coronary arteriole disease

Cardiac ischaemia may also be observed in

hypertensive heart dx, anaemia, chronicobstructive airway disease, and cyanoticcongenital heart disease


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atheroma Athero-porridge

The factors leading to coronary

insufficiency are:

a) -the plaque size- 75% causesymptoms when stressed, 90% at

rest-the plaque integrity-ulceration,thrombosed or haemorrhage


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atheroma These events lead to gradual increase on the

luminal occlusion and sudden acute

symptomatology

66% MI due to plaque rupture and

thrombosis had < 50% narrowing while

80% had


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Pathogenesis of atheroma

Plaque formation- LDL, VLDL, TGS- endothelial damage,absorption by macrophages

Depostion in the tunica media

Smooth muscle proliferation and inflammation anddegeneration


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atheroma

Plaque rupture occurs due to intrinsic and extrinsic

factors, extrinsic=adrenergic stimulation in stress andhypertension, hence increase in deaths after stressand uncontrolled hypertension-e.g.homo case

Intrinsic= position of the plaque in relation to

1.turbulence, 2.the thinnest part of the shoulder, thejunction between the plaque and normal endothelium,3. amount of inflammatory cell aggregates andinflammatory process,

4. number of smooth muscles.


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atheroma coronary thrombus- following a plaque rupture a

thrombus forms due to platelet aggregation; may

be mural thrombus or complete occlusivethrombus; formed as a result of exposure of sub-endothelial collagen, stimulating plateletaggregation and de-granulation releasingthromboxane A2, Serotonin and platelet factor 3and 4. (intrinsic coagulation pathway)

Extrinsic coagulation pathway also activated

The thrombus may dislodge and cause a embolus


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atheroma Inflammatory processes-the plaque formation is an

inflammatory process. The endothelial cells

release chemotactic factors and adhesins-ICAM-1, VCAM-1 E-selectin and P-selectin.

The chemokines attract macrophages and T-

lymphocytes. The T-lymphocytes release-TNF,

IFN-gamma, and IL-6 which stimulate endothelialcells and macrophages to engulf oxidized LDL

C-reactive proteins also increase


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atheroma Rupture

Aneurysm

Arrthymias due to scar formation

Mural thrombus

Arteriole thrombo-embolism

Cerebral infarcts Renal infarcts

death


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Systemic arteriole hypertension Small and medium sized BV

The kidneys

Eyes

brain


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hypertensionPrimary and secondary

The pathology similar

Effects on the media

Diffuse hyalinization

Or medial proliferation- hyperlastic medialdegeneration,


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PATHOLOGY IN VARIOUS

ORGANS

Retinal copper wire and cotton woolchanges

Kidneys- onion skin appearance of thearterioles

Glomerulosclerosis, flee beaten appearance,

granular scars, shrinkage Complications- brain, eyes, heart- LVH,

KIDNEYS


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vasculitides Introduction:

Vasculitides=Inflammation of blood vessel wall.This

may affect any of the blood vessels , from large to thelarge arteries to arterioles.

They are as a result of direct effects of infections and

indirect effects as a result of immune complexes and

immune response there after.

Generally these diseases present with local and

constitutional symptoms ( fever, myalgia, arthritis and

malaise)


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Classification

Direct infection

Bacterial-N.gonorrhoea

Rickettsiae-rocky mt. spotted

fever

Fungal-aspergillosis Viral-herpes zooster

Spirochaets-Syphillis

Immune complexmediated-hep B/C, SLE,

RA, Henoch-Schonlen

purpura, Drugs,

cryoglobulinaemia, serumsickness

Anti-nutrophil cytoplasmic antibody

(ANCA-c or p)

Wegeners granulomatosis Microscopic polyangitis/arteritis

Churg-Straus syndome

Antibody-mediated Good Pastures syndrome

Kawasakis disease

Cell mediated

Organ allograft rejection


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classificationImmune-

Paraneoplastic syndrome

Inflammatory bowel disease-eg ulcerative

colitis

Unknown-giant cell temporal arteritis,

Takayasus disease, polyarteritis nodosa


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Pathogenesis

Imuune mediated vasculitis

1. IMMUNE COMPLEX

AB+AG

2. ANCA-Cytoplasmic or

perinuclear3. Antiendothelial cell antibodies


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Immune complex mediatedFormation of antibody-antigen complex- TYPE III Hypersensititvy

Following introduction of a foreign protein or endogenousprotein,immune competent cells recognise them and change intoplasma cells and start AB production to mop out the antigens.

Large complexes are easily mopped out by macrophages

The small and intermediate complexes deposit easily onto theendothelium.

The avidity and the affinity of the AB to the AG, the affinity of the AGto tissues, the shape of the complexes and the haemodynamic factorsinfluence the binding to the endothelium


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Immune complex mediated

vasculitis Some of the complexes bind to NEUTROPHILS

through the FC portion of the AB orC3b receptors

This triggers release of vaso-active factors such asserotonin,C3a and C5a(anaphylatoxins)

This leads to an increase in permeability- withchemotaxis of macrophages and more neutrophils

SLE-DNA and nucleoproteins; PAN-hep B

Surface AG; Arthus Disease and serum sickness various foreign proteins eg anti thymocyteglobulin


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Mediators of Inflammatory damage

of the BV wall Prostaglandins

Proteases

Lysosomes

Vasodilators Chemotactic factors

Release of free radicals-superoxides from neutrophils

Lead to digestion of collagen, elastin, and basement

membranePlatelet aggregation and release of Hageman factor-leads to

thrombosis, necrosis and more vasculitis

Chronic exposure to AG eg in SLE leads to chronicimmunecomplex vasculitis


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Morphology mainly microscopic

Fibrinoid necrosis-deposits of eosinophilic

protein

Immunoflourescent granular lumpy deposits

on the basement membrane(BM)

EM-electron dense deposit on the BM


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Antineutrophil cytoplasmic

antibodies (ANC

A) mediatedvasculitis The exact mechanism is unknown

Its postulated that the presence of an antigen leads to cytokine release-eg TNF and GCSF and MCSF

These lead to neutrophil expression ofProteinase (PR3)-CYTOPLASMICAG in the neutrophil granules and (MPO)-Myeloperoxidase.

These lead to production of c-ANCA and p-ANCA respectively(c=cytoplasmic; p=perinuclear)

The ANCAS react with circulating neutrophils leading todegranulation leading to endothelial damage

Seen in sclerosing cholangitis, RA, Autoimmune liver disease andinflammatory bowel disease

The level of Serum ANCAS can give an indication of the activity ofthe disease


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Anti-endothelial cell antibodies Thought to cause damage in SLE and

Kawasakis disease


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Temporal (giant cell arteritis) Common in the Nordic countries

Affects the aorta, temporal and ophthalmic

arteries. May be a medical emergency-

blindness or aneurysm

Associated with HLA-DR and responds

well to steroids therefore thought to beimmune-related


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Polyarteritis nodosa (

PAN)

DX of young adults but also seen in

children and elderly

Presents with fever, weight loss,

hypertension and meleana

30% show hep Bs AG


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PAN

Medium and small vessel disease

Transmural necrotising arteritis, fibrinoid

necrosis,

Segmental affecting mainly the bifurcations

Complicated by aneurysms, renal failure

and haemorrhage


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Takayasus arteritis (pulseless Dx) Young females dx., weak pulse, hypotension,

numbness and visual impairment

Japanese show HLA-a24, B52, DR-52 Aorta and the brances mainly affected leading to

pulseless in the upper limbs

Transmural necrotising granulomatous arteritis,

not easy to distinguish from giant cell arteritisbefore the age of 40 years. Narrowing of thelumen


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Wegener granulomatosis Middle aged males, with pneumonitis, pulmonary nodules, cavitation,

sinusitis and nasopharyngeal ulcers

Acute necrotising ganulomatous arterits, in the ENT/Sinuses,

Focal crescenteric glomerulonephritis

Pulmonary Dx

Morphology-granulomas, necrotising, giant cells, plasma cell ,lymphocytes, numerous eosinophils, may cavitate and alveolarcongestion and haemorrhage,

To exclude TB and fungi-special stains-ZN and Grocots methenaminesilver respectively

C-ANCA positive, used for follow up

Necrotising glomerulonephritis-haematuria and proteinuria


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Bacillary angiomatosis Bartonela spp

HIV patients- presents as a nodular skin

lesion, numerous neutrophil infiltrate with

capillary proliferation, has granular particles

of bacteria


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refer Thromboangitis obliterans

thrombophlebitis,

tumors- haemangiomas,

arteriovenous malformations,

Kaposis sarcoma, haemangiopericytoma,

lymphangiomas


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Giant cell arteritis

blood vessel diseases level ii

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