Download - 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