aetiology and pathogenesis of vascular disease Flashcards
what is an aneurysm?
localised abnormal dilation of a blood vessel or the heart; they can be congenital or aquired
what does a true aneurysm involve?
intact attenuated arterial wall or thinned ventricular wall of the heart
causes of true aneurysms (4)
atherosclerosis; syphilis; congenital vascular aneurysms; ventricular aneurysms that follow transmural myocardial infarctions
types of true aneurysms (3)
saccular; fusiform; dissecting
what is an arterial dissection
when blood enters the arterial wall itself as a haematoma dissecting between its layers
what is a false aneurysm (pseudoaneurysm)
defect in the vascular wall leading to an extravascular haematoma; blood flow outside normal layers of arterial wall
characteristics of a false aneurysm (4)
freely communicates w the intravascular space; pulsating haematoma; surrounded by a thin fibrous capsule in communication with the lumen of a ruptured vessel; DOES NOT INVOLVE ALL THREE TUNICA LAYERS (i.e. rupture interna + media but not externa)
difference between a pseudoaneurysm and a dissection
Pseudoaneurysm: all three walls of the vessel have been broken through, and blood collects just outside the vessel, it doesn’t spread through the vessel and blood organises and become firm
Dissection: only the inner portion of the vessel wall is damaged, blood enters into that damaged area and tunnels up or down within the wall of the vessel
how are aneurysms generally classified?
shape and size
what are saccular aneurysms
spherical outpouchings involving only a portion of the vessel wall; between 5-20cm; often contain thrombus
what are fusiform aneurysms
diffuse, circumferential dilation of long vascular segment; up to 20cm in diameter and length; may involve the aortic arch, abdominal aorta, iliac arteries
what is the pathogenesis of aneurysms (4)
the intrinsic quality of the vascular wall connective tissue is poor; the balance of collagen degradation and synthesis is altered; the vascular wall is weakened through loss of smooth muscle; arteries are dynamically remodelling tissues
conditions associated with poor intrinsic vascular connective tissue (3)
Marfan’s syndrome - defective synthesis of fibrillin and progressive weakning of elastic tissue results in progressive dilation of BVs due to remodelling of inelastic media;
EDS - weak vessel walls due to defective type III collagen synthesis;
Vit C deficiency - altered collagen cross linking
pathogenesis of collagen degradation and aneurysms
local inflammatory infiltrates that produce destructive proteolytic enzymes; increased MMP production by macrophages in atherosclerotic plaques/vasculitis - these can degrade all he components of arterial walls
how can the vascular wall be weakened
loss of smooth muscle cells with inappropriate synthesis of non-collagenous/non elastic ECM
how does ischaemia of the inner media occur
atherosclerotic thickening of the intima increases the distance that oxygen and nutrients have to diffuse
how does ischaemia of the outer media occur
systemic hypertension causing narrowing of the arterioles of the vasa vasorum resulting in cystic medial degeneration
what is cystic media degeneration
degenerative changes with smooth muscle cell loss and loss of elastic fibres, inadequate ECM synthesis and production of amorphous ground substances
factors predisposing to weakening of arterial wall (in descending order -6)
- atherosclerosis
- hypertension (usually ascending aortic aneurysms)
- trauma
- vasculitis
- congenital defects (e.g. in the circle of Willis causing berry aneurysms)
- infections (mycotic aneurysms)
where can mycotic aneurysms originate from (3)
embolization of a septic thrombus (usually a complication of endocarditis); an extension of an adjacent suppurative process; circulating organisms directly infecting the arterial wall
how can syphilis cause aneurysms?
obliterative endarteritis is a characteristic of late-stage syphilis which has a predilection for small vessels which can result in ischemic injury of the aortic media and aneurysmal dilations - leads to aortic incompetence
pathological characteristics of AAA (3)
associated w atherosclerosis; atherosclerotic plaque in the intima compresses the underlying media; nutrient and waste diffusion from the vascular lumen to arterial wall is compromised; media undergoes degeneration and necrosis resulting in weakness/thinning
typical AAA patient
50+ male smoker w atherosclerosis
arteries usually involved in AAA
renal; superior/inferior mesenteric
consequences of AAA (5)
- rupture into peritoneal cavity/retroperitoneal tissues may result in fatal haemorrhages;
- obstruction og vessels leads to ischaemic injury of downstream tissues (e.g. leg, kidney);
- embolism from atheroma/mural thrombus
- impingement of adjacent structures
- presentation as an abdominal mass that simulates a tumour
what is an aortic dissection
when blood leaks out and separates the laminar planes of the media to form a blood-filled channel within the aortic wall
when can an aortic dissection be catastrophic?
if the dissection ruptures through the adventitia (externa) and haemorrhages into adjacent spaces
is aortic dissection associated with aortic dilation?
not always, unlike aneurysms
examples of what can cause aortic dissections (4)
being a 40-60yro man with antecedent hypertension; being a younger patient with abnormal connective tissues (e.g. marfan’s); iatrogenic (e.g. complicating during cannulations); during/after pregnancy
why is dissection uncommon in the presence of atherosclerosis/ medial scarring?
medial fibrosis inhibits propagation of the dissecting haematoma
pathogenesis of aortic dissection
a tear occurs in the intima; blood flow under systemic pressure dissects through the media - here aggressive pressure reducing therapy may be effective in limiting a dissection;
when can an intramural haemotoma without an intimal tear occur?
when there is disruption to penetrating vessels of the vasa vasorum
aortic dissection classifications
A - more proximal, involves either the ascending + descending aorta or just the ascending, the most common type; B - distal to the subclavian artery
where is the most serious place to have a dissection
aortic valve to the arch
Classical symptoms of aortic dissection (4)
sudden onset excruciating pain; beginning in the anterior chest and radiating to the back (between scapulae); moving downward as dissection progresses; changes in pulses
most common cause of death (due to dissection)
outward rupture into the pericardia, pleural or peritoneal cavities
what can retrograde dissection (into the aortic root) result in? (4)
disruption of the aortic valvular apparatus leading to: cardiac tamponade; aortic insufficiency; myocardial infarction
what can extension of the dissection into large arteries result in?
vascular obstruction resulting is ischaemia
what is vasculitis
vessel wall inflammation
what are the two most common pathogenic mechanisms of vasculitis?
immune mediated inflammation; direct invasion of vascular walls by pathogens
examples of large vessel vasculitis
granulomatous disease - GCA, takayasu arteritis
examples of medium vessel vasculitis
polyarteritis nodosa (immune complex mediated); Kawasaki disease (anti-endothelia cell antibodies)
examples of small vessel vasculitis (6)
immune complex mediated: SLE (ANA, Anti-dsDSN, Anti-smith), henoch schonlein purpura; cyroglobulin vasculitis;
ANCA associated: microscopic polynagitis (pANCA), Wegener granulomatas (cANCA), Chrug-Strauss syndrome (pANCA)
what are the two main immunological mechanisms that initiate vasculitis
anti-endothelial cell antibodies; antineutrophil cytoplasmic antibodies
what is ANCA
circulating antibodies that react with neutrophil cytoplasmic agents; a heterogenous group of antibodies directed against neutrophil granules, monocyte lysosome etc.
p-ANCA target
anti-myeloperoxidase (MPO) - usually used to generate oxygen free radicals in phagocytosis
c-ANCA target
anti-proteinase 3 (PR3) - a neutrophil azurophilic granules consitituent
how can ANCA lead to damaged blood vessels
ANCA can directly activate and stimulate neutrophils to release ROS and proteolytic enzymes
Buerger’s disease typical patient
under 35s who smoke heavily, usually men
pathophysiology of Buerger’s disease (5)
thrombosis of medium sized arteries and veins with marked inflammatory reaction; thrombus contains microabsesses of neutrophils; tibial and radial arteries usually involved; secondary extension into veins and nerves of extremities can be seen; leads to vascular insufficiency
pathogenesis of Buerger’s disease
direct endothelial cell toxicity by tobacco components; idiosyncratic immune response to tobacco agents; genetic component - increased prevalence in israeli, south asian, japanese ethnicities; association with HLA haplotypes
clinical features of Buerger’s disease
cold sensitivity in hands (similar to raynauds); pain in instep of foot; severe pain even at rest (neural involvement); chronic ulcerations of toes, feet, fingers etc. (often followed by frank gangrene); dramatic relief by smoking assistance (early stages)
what are varicose veins
abnormally dilated, tortuous veins produce by prolonged/increased intraluminal pressure and loss of vessel wall support (valve function loss)
how can venous pressure increase
when legs are depended for prolonged periods (leads to pedal oedema and venous stasis); pregnancy; obesity
how can chronic varicose ulcer occur? (5) pathway
varicose dilation renders venous valves incompetent -> stasis, congestion, oedema, pain and thrombosis occur -> disabling sequelae occur (persistent oedema in extremities, ischaemic skin changes ) -> stasis dermatitis and ulcerations occur -> poor wound healing and superimposed infections leads to chronic varicose uclers
are varicose veins a risk for PE
no, embolism from superficial veins is very rare
how do venous ulcer develop?
persistently high BP in the veins causes damage to skin which eventually breaks down and forms an ulcer
what is thrombophlebitis?
an inflammatory process that causes a blood clot to form and block one or more veins, usually in the legs
where does thrombophlebitis most commonly occur in men
periprostatic venous plexus
where does thrombophlebitis most commonly occur in women
pelvic venous plexus
what increases the risk of DVT (3)
prolonged immobilisation (decreases the blood flow through the veins) e.g. bed rest, airplane travel; being postoperative (esp. ortho); factors that slow venous return (pregnancy, obesity, congestive heart failure etc.)
what increases the risk of DVT
prolonged immobilisation (decreases the blood flow through the veins) e.g. bed rest, airplane travel; being postoperative (esp. ortho); factors that slow venous return (pregnancy, obesity, congestive heart failure etc.)
examples of local signs/symptoms of thrombi
distal oedema, cyanosis, heat, tenderness, redness, swelling, pain may be elicited or may be absent
what is a pulmonary embolism
the fragmentation/detachment of the whole venous thrombus - lets lodged in the pulmonary system; it may be a complication of DVT; it can be the first manifestation of thrombophlebitis
what causes Raynaud’s
exaggerated vasoconstriction of digital arteries/arterioles; temporary spasm of blood vessels in response to cold or emotional stresses
clinical signs of Raynaud’s
paroxysmal pallor/cyanosis f the digits, nose, earlobes, lips etc.
