Week 9 Pathology

Endothelial cell functions

  • Maintain nonthrombotic interface – prostacyclin, thrombomodulin, heparin like, pasminogen ativator
  • Store and release vWF, plasminogen activator inhibitor, tissue factor
  • Maintain permeability – Controls trasfer of small and medium size molecules from blood stream to tissues.
  • Modulate blood flow via vascular resistance
  • Metabolism of hormones
  • Regulation of immune and inflammatory reactions
  • Growth regulation of smooth muscle cells.
  • ECM production
  • Oxidation of LDL

 

Arteriosclerosis:

  • Definition – thickening or loss of elasticity in arterial walls
  • Associated with diabetes and HTN

 

Atherosclerosis:

  • Definition- intimal lesions called atheromas which protrude in vascular lumen.
  • Risk factors.
    • Non modifiable – age, male, family Hx, genetic abnormalities
    • Modifiable – hyperlipidaemia, hypertension, diabetes, smoking
  • Pathogenesis.
    • Chronic endothelial injury –> accumulation of LDL in vessel wall–> modification of LDL by oxidation –> ahdesion and migration of monocytes–> adhesion of platelets–> release of factors from macrophages and platelets –> migration of SMCs from media to intima–> proliferation of SMCs–> elaboration of ECM–> accumulation of intracellular and extracellular lipids in the plaque.
  • Clinically silent and from 1st decade: Isolated Foam cells –> fatty streaks–>
  • From 3rd decade: Atheromas(now has core of extracellular fat)–>
  • Lipid core + fibrotic layer or multiple, mainly calcific or fibrotic(accelerated smooth muscle and collagen increase): fibroatheromas–>
  • Surface defect, haematoma, haemorrhage, thrombus: complicated lesions
  • Mostly affects large elastic and large/medium muscular arteries.
  • Stable plaque – has a dense collagenous and thick fibrous capsule with minimal inflammation and a small underlying atheromatous core
  • Vulnerable plaque – thin fibrous cap, large lipid core and increased inflammation so it is prone to rupture.
  • Pathological changes
    • Rupture/fissuring – leads to exposure to highly thrombophilic lipid core
    • Erosion/ulceration – exposing subendothelial basement membrane – also thrombophilic
    • Haemorrhage into atheroma – expanding volume
  • Clinical significance / complications.
    • Consequences
      • Small vessel occlusion- compromising distal perfusion
      • Ruptured plaque–> can embolise or cause acute thrombus
      • Destruction of vessel wall leading to aneurysm–> secondary rupture/thrombus

 

Hypertension:

  • Causes / Pathogenesis.
    • Genetic
      • Familial multi gene foci interactions- vascular smooth muscle, Na metabolism,
    • Environmental
      • Stress
      • Obesity
      • Smoking
      • High salt intake
      • Physical inactivity
    • Vasoconstrictive influences
      • Primary HTN
  • Consequences
    • Atherosclerosis
    • CAD, CVD, aortic dissection, renal failure, cardiac hypertrophy, CCF, retinal changes
  • Malignant HTN – clinical syndrome of SBP>200, DBP>120, renal failure, encephalopathy, CVS abnormalities, rapidly rising BP, <5% of HTN patients, undtreated can cause death in 1-2yrs,

 

Aneurysms:

  • Sites.
    • Berry aneurysm in intersections of cerebral arteries.
    • Abdominal
  • Causes / Pathogenesis. – structure or function of the vascular wall connective tissue is compromised
    • Poor intrinsic quality of the vascular wall connective tissue eg Marfans, Ehlers Danlos
    • Collagen degradation vs synthesis by local inflammation inbalance – atherosclerosis, vasculitis
    • Loss of vscular smooth muscle cells or inappropriate synthesis of noncollagenous or non elastic ECM(cystic medial degeneration) Grow at 0.2cm/yr
    • Operative mortality 5% vs 50% if already ruptured.
  • Complications.
    • Rupture into peritoneum or retriperitoneum –> potentially lethal
    • Obstruction of branching vessel–> ischaemic injury
    • Embolisation – atheroma or mural thrombus
    • Impingement of adjacent structures eg ureter
    • Nothing esp if <4cm
  • Risk of rupture
    • 4cm or less = nil
    • 4-5cm – low risk 1%
    • 5cm-6cm 11%
    • >6cm high risk 25% rupture per year

 

Aortic dissection.

  • Defect in endothelial wall between intima and media and blood begins tracking down between the laminar planes of the media between middle and outer third.
  • RFs – HYPERTENSION, collagen defects eg Elher’s Dhanlos, Marfans; iatrogenic during angiogram; age, pregnancy
  • Pathogenesis – medial weakness due to underlying cause, medial hypertrophy of vaso varum, cystic medial degeneration.
  • Cx – hypovolaemic shock, tamponade, MI, loss of end  organ perfusion –> kidney failure etc, rupture and death.
  • Split into Stanford
    • type A (ascending aorta or both) and
    • type B (descending aorta)
  • De Bakey
    • 1 – 60% involves ascending and descending
    • II – 10-15% involves only ascending
    • III – 25-30% involves only descending

 

Vasculitides:

  • Direct infection – Neisseria, Rocky mountain spotted fever, aspergillosis
  • Immunologic
    • immune complex mediated
      • Henoch Schonlein purpura, SLE, RA, cryoglobulinaemia, serum sickness
    • ANCA mediated
      • Wegners, microscopic polyangiitis, Churg-strauss
    • Direct antibody mediated
      • Good pasture(antiGBM), Kawasaki(antiendothelial Abs)
    • Cell mediated
      • Organ rejection
    • Inflammatory bowel disease
    • Paraneoplastic
  • Giant cell arteritis – large vessel
  • Takayasu arteritis – large vessel
  • Polyarteritis nodosa – medium vessel

 

Varicose veins:

  • Abnormally dilated and tortuous veins produced by prolonged, increased intraluminal pressures and loss of vessel wall support
  • Pathogenesis.
    • Intraluminal thrombosis(DVT) or other valvular deformities –> venous pooling in superficial veins.
  • Complications.
    • Congestion, oedema, pain, thrombosis. Dermatitis, ulceration, prone to injury, poor healing

 

Vascular tumours

  • Benign
    • Haemangioma – present at births, grows but usually regresses by puberty.
    • Lymphangioma
    • Glomus tumour
    • Vascular ectasis
  • Intermediate neoplasm
    • Karposi sarcoma – HHV 8
    • Haemangioendothelioma
  • Malignant
    • Angiosarcoma
    • Haemangiopericytoma