( Glycosaminoglycan = Amino sugar + Polysaccharide )
NORMAL BLOOD VESSEL
The basic constituents of the walls of blood
Endothelial cells (ECs)
Smooth muscle cells
Extracellular matrix: elastin, collagen, &
The three concentric layers, intima, media
and adventitia are most clearly defined in
larger vessels particularly arteries.
Coronary Artery Structure
Arteries are divided into three types based on their size and
Large (or elastic) Arteries: Aorta and its major branches (innominate,
subclavian, common carotid & iliac) & Pulmonary arteries.
Medium (or Muscular) Arteries (Coronary & renal)
Small Arteries (less than 2 mm)
Arterioles (20 to 100 µm in diameter)
Capillaries (7 to 8 µm)
Elastic arteries have rich component of elastic fibers in addition to
smooth muscle allow them to expand during systole and propel
blood onwards with elastic recoil during diastole.
Muscular Arteries have no elastic fibers in the media and only
have elastica interna and externa. The muscle fibers have circular &
spiral arrangement in the media. These regulate blood flow by
contraction and dilation of lumina; and are controlled by autonomic
nervous system and/or local control by cellular secretions).
The Vascular Wall
containing a portion of
an artery and adjacent
Elastic membranes are
Because it is exposed
to higher blood
pressures, the artery
has a thicker wall that
maintains an open,
round lumen, even
when blood is absent.
Moreover, the elastin of
an artery is more
organized than in the
The vein has a larger,
but collapsed, lumen,
and the elastin in the
wall is diffusely
A clinicopathologic process characterized by inflammation of and
damage to blood vessels, often resulting in complete or partial
occlusion of the involved vessels, with resulting ischemic damage to
the supplied organ/tissue.
Fairly rare diseases
Presentation: highly variable making delays in diagnosis common
High morbidity and mortality
Therapeutic challenge often requiring prolonged & intensive
Primary vasculitis – occurs in absence of recognized precipitating
secondary to established disease
secondary to infection
secondary to malignancy
secondary to drugs
Caused by the direct invasion of infectious agents, usually bacteria
or fungi, and in particular Aspergillus and Mucor species.
Vascular invasion can be
part of a localized tissue infection (e.g., bacterial pneumonia or adjacent
to abscesses) OR
from hematogenous seeding of bacteria during septicemia or
embolization from sepsis of infective endocarditis. (less common)
Vascular infections can weaken arterial walls and culminate in
mycotic aneurysms, or can induce thrombosis and infarction.
The main immunological mechanisms that initiate
noninfectious vasculitis are
Immune complex deposition
Antineutrophil cytoplasmic antibodies (ANCA)
Anti–endothelial cell antibodies.
Immune Complex Deposition
Antibody and complement are typically detected in vasculitic lesions
or/and in circulation.
Systemic immunological diseases, such as systemic lupus
erythematosus (SLE) and polyarteritis nodosa.
Drug hypersensitivity: In some cases (e.g., penicillin) the drugs bind
to serum proteins; other agents, like streptokinase, are themselves
Secondary to viral infections: Antibody to viral proteins forms
immune complexes that can be found in the serum and the vascular
Anti-Neutrophil Cytoplasmic Antibodies
Ab directed against proteins in the cytoplasmic granules of
PMN’s and monocytes
Wegener’s Granulomatosis (PR3)
Microscopic Polyangiitis (MPO)
Serum from patients bind to cytoplasmic granules and show a
granular appearance on immunofluorescence
Proteinase-3 (PR-3) is the major antigen.
present in azurophilic granules
Localized, peri-nuclear staining pattern on PMN’s
Myeloperoxidase (MPO) is the major target.
normally involved in generating oxygen free radicals
present in lysozomes
A plausible mechanism for ANCA vasculitis is the following:
Drugs or cross-reactive microbial antigens induce ANCAs.
Neutrophil surface expression or release of PR3 and MPO (e.g., in the
setting of infections) incites ANCA formation in a susceptible host.
Subsequent infection, endotoxin exposure, or other inflammatory stimuli
elicit cytokines such as TNF that cause surface expression of PR3 and
MPO on neutrophils and other cell types.
ANCAs react with these cytokine-activated cells and either cause direct
injury (e.g., to endothelial cells) or induce further activation (e.g., in
ANCA-activated neutrophils degranulate and also cause injury by
releasing reactive oxygen species, engendering endothelial cell toxicity
and other indirect tissue injury.
leucocytosis consistent with infection & primary vasculitis
leucopaenia associated with CTDs
eosinophils - elevated in CSS and drug reaction
Assessing Organ Damage
LFTs – May suggest viral
24hr protein excretion
Assessing Immune Mechanisms
Anti-neutrophil cytoplasmic antibodies
ANA nuclear antibodies
Levels are low in SLE and infection but high in primary
Imaging of sinuses
Biopsy of affected organs e.g. skin/kidney/temporal
artery– necessary to confirm diagnosis