Vascular Pathology

• A thrombus is a solid mass of blood constituents formed within the vascular system during life.
• Embolism is the passive transport of a substance within the vascular system.
• Ischaemia is an appropriate reduction in blood supply to an organ or tissue - generally occurs when an artery is blocked.
• Infarction is death of tissue due to ischaemia - ischaemia doesn't always lead to infarction though, may just lead to fibrosis and scarring.
• An aneurysm is a localised permanent abnormal dilation of a blood vessel due to weakening of the blood vessel wall.
• Thrombosis:

  • A thrombus is a solid mass of blood constituents formed within the vascular system during life
  • Virchow's triad - three things that might result in thrombosis
• Virchow's Triad - three things that might result in thrombosis:

  • Changes in intimal surface of the vessel - e.g. changes associated with atherosclerosis (intimal surface may be ulcerated/damaged by atheroma & lead to thrombus formation on arterial wall)
  • Changes in pattern of blood flow
  • Venous stasis - blood flow is stagnant, platelets drop out and clot
  • Injury/compression to the vessel where the turbulence results in adherence of platelets to endothelium and thrombus formation
  • Changes in blood constituents - anything that makes the blood hypercoagulable may predispose to thrombus formation
• Arterial thrombosis:

  • We get thrombosis when platelets land on top of and stick to the atheromatous plaque
  • In health there's a v fine layer of liquid serum between the endothelium and the cells in the blood which are circulating, but when there's a projection into the lumen then platelets can adhere to the surface, aggregate and release locally active clotting factors - that clotting cascade results in the generation of fibrin
• Arterial thrombosis:

  • Red blood cells become trapped in that fibrin meshwork - leads to a cycle of further platelet aggregation, further activation of the clotting cascade and further trapping of red blood cells
  • This way the thromus can propagate across and obstruct the lumen or even extend for a distance down the vessel
• Venous thrombosis:

  • Stasis - mostly occurs at valves
  • Can be secondary to:
  • Burns and trauma
  • Surgery - why pts are encouraged to get out of bed and walk around as soon as possible after surgery
  • Cardiac failure
  • Pregnancy
  • Immobility
  • Long haul flights
• Venous thrombosis - deep vein thrombosis (DVT):

  • Thrombophlebitis - occurs when there is inflammation (-itis) of the deep vein
  • Phlebothrombosis - stasis of the vein, no inflammation - platelets drop out of circulation and form a thrombus in the vein
• Cardiac thrombosis - atrial:

  • Atrial fibrillation
  • Mitral stenosis
  • The blood flow is altered, the platelets are contacting a normal endothelium in a way which they wouldn't normally contact due to turbulence - thrombus can sometimes fill entire atrium then break off and form a ball within the atrial chamber

  
• Cardiac thrombosis - valvular:

  • Rheumatic fever
  • Endocarditis
  • Thrombosis may occur on top of vegetations

  
• Cardiac thrombosis - ventricular:

  • Normally follows myocardial infarction (death of heart wall) - usually due to coronary thrombosis - underlying dead heart muscle causes abnormality in the overlying endothelium lining the heart chamber - thrombi predisposed to breaking off and entering the systemic circulation

  
• Fate of thrombi:

  • Lysis and resolution
  • Retraction and re-canalisation
  • Organisation and scarring
  • Embolism
• Fate of thrombi - lysis and resolution:

  • Best outcome
  • Lysis = complete dissolution of the thrombus
  • Resolution = complete return to normal tissue architecture
  • Many therapies (e.g. Fibrinolysin therapies) can be given to hopefully cause this but can also occur as a totally natural process
• Fate of thrombi - retraction and re-canalisation:

  • Thrombus and blood clot can retract (shrink away) - creates space within the vessel
  • Blood can then find its way past the thrombus, leading to re-canalisation and the re-establishment of a blood flow
  • Endothelium can then grow from the wall and can line the thrombus - heal vessel with some scarring - near return to normal
• Fate of thrombi - organisation and scarring:

  • Blood flow will be reduced through scarred vessels
• Fate of thrombi - embolism:

  • Thrombus breaks off and is passively transported into circulation
• An embolus is a mass of material in the vascular system able to become lodged within a vessel and block its lumen. The majority are fragments of thrombus.
• The majority of emboli are fragments of thrombus, however, other embolic events can result from:

  • Atheromatous debris that break off
  • Vegetations on heart valves that break off - particularly those in infective endocarditis, where there are masses of bacteria/fungi forming on the heart valve tip - they can break off can cause infection more so than blockage (known as septic emboli)
  • Fat can circulate in the bloodstream - fracture of a long bone means fatty marrow enters the circulation and becomes an embolus
• The majority of emboli are fragments of thrombus, however, other embolic events can result from:

  • Gas (Caisson's disease = the Bends, from diving) - gas can embolise around the body - occurs when the body is subjected to increased pressure - gas then dissolves in the bloodstream and when there's decompression the gas comes out of solution and forms bubbles, which can spread around the body - can also happen if air is inadvertently injected into a blood vessel; it can circulate around the bloodstream and damage the heart
  • Amniotic fluid can embolise at the time of birth
• The majority of emboli are fragments of thrombus, however, other embolic events can result from:

  • Tumour - can grow into veins (sarcomas do this lots) - bits of the sarcoma can break off in a vessel and block it further down, or can cause the establishment of a secondary tumour
  • Foreign material can embolise around the circulatory system - e.g. When a cosmetic material (like a filler) is injected into soft tissue it may inadvertently be injected into a vein - the material can then set and travel through the circulation causing trouble, even death if the bit of material is big enough
• Pulmonary embolism:

  • Occurs on venous side
  • Come from legs (Deep Vein Thrombosis) - as a result of thrombophlebitis or phlebothrombosis
  • Can also occur in pelvic veins
  • Consequences dependent on size of the embolus
• • Thrombus has formed in deep vein in leg - breaks off & travels through venous system & heart to block pulmonary artery
  • If it's large it can spiral up & block entire pulmonary artery - shock effect can lead to sudden death
  • If the embolism is smaller and only blocks a branch of the pulmonary artery -> classic symptoms of chest pain & breathlessness
  • Where the artery is blocked, you get a wedge-shaped area of damage beyond that tissue - an area of ischaemia/infarction
  • Can have pulmonary emboli that aren't clinically detected - block small arteries & can lead to pulmonary hypertension

  
• Systemic embolism:

  • Arterial side
  • Left side of the heart
  • Typically caused by thrombi formed on atheromatous plaques
  • Consequences dependent on size of embolus and the site it lodges
• Systemic embolism - can get emboli to:

  • Heart
  • Brain
  • Spleen
  • Kidney
  • Intestine
  • Limbs & digits
• Systemic embolism: when a piece of thrombus is travelling through the arterial system, the system is branching into smaller and smaller vessels, so eventually it will travel to a vessel and likely block it. Often those vessels are in the extremities of the body, for example in a limb, and if you have one there the effects would be seen in the fingers and toes, where the vessels are at their narrowest.
• Infarction:

  • Ischaemia is an inappropriate reduction in blood supply to an organ or tissue
  • Chronic ischaemia can lead to fibrosis and organisation of tissue - doesn't always result in death
  • Infarction is death of tissue due to ischaemia
• Causes of infarction:

  • Atheroma - can cause infarction by blocking a vessel
  • Thrombosis
  • Embolism
  • Vasculitis
  • Inflammation of the vessel wall can cause infarction
  • Compression (either by tumour or injury)
  • Spasm - vascular spasm rarely causes infarction, but can
  • Hyperviscosity - hyperviscosity syndromes affecting the blood content can produce infarcts
• Myocardial infarction:

  • <6 hours - no visible changes pathologically (biological and ECG changes will be present)
  • 24-48 hours - pallor with red rim
  • Several days - pallow with red rim -> soft (haemopericardium) haemorrhage into the pericardial sac)
  • Several weeks - heart muscle becomes organised (grey and fibrotic)
• Determinants of infarction:

  • Vascular anatomy
  • Duration of occlusion
  • If the thrombus is there for a short amount of time you might not get infarction
  • More lengthy duration = more likely to have an infarct
  • Metabolic requirements of tissue
  • eg brain tissue has high metabolic requirements for glucose and oxygen - so even just a few minutes of blockage will result in death of brain tissue
  • General circulatory factors - reduction in availability of nutrients
  • Heart failure
  • Anaemia
  • Reperfusion injury
• Aneurysms - a localised permanent abnormal dilation of a blood vessel due to weakening of blood vessel wall:

  • Atherosclerotic aneurysm
  • Mycotic aneurysm - related to infection
  • Syphilitic aneurysm (not seen really nowadays - part of secondary syphilis)
  • Berry aneurysm - occur at base of brain around Circle of Willis
  • Micro-aneurysms - can occur in the small vessels within the brain and in the retina
• False aneurysm is a blood filled space due to following vascular rupture (haematoma) - when a vessel is damaged, the blood escapes and we have a mass of blood on the edge of the side of the vessel.
• Dissecting aneurysm - damage to the intima of the vessel - blood then ruptures into the vessel wall, effectively dissecting the layers apart.
• Type of aneurysm:

  • Atherosclerotic

  Where it occurs:

  • Thoracic aorta
  • Abdominal aorta

  Associated with:

  • Pulsatile abdominal mass
  • Lower limb ischaemia
  • Retroperitoneal haemorrhage
• Type of aneurysm:

  • Mycotic (infective) aneurysm

  Where it occurs:

  • Root of aorta (aortic valve endocarditis)
  • Cerebral arteries

  Associated with:

  • Thrombosis
  • Haemorrhage
  • Cerebral infarction
• Type of aneurysm:

  • Syphilitic aneurysm

  Where it occurs:

  • Arch of aorta

  Associated with:

  • Aortic incompetence
• Type of aneurysm:

  • Berry aneurysm

  Where it occurs:

  • Circle of Willis

  Associated with:

  • Subarachnoid haemorrhage
• Type of aneurysm:

  • Micro-aneurysms (Charcot-Bouchard)

  Where it occurs:

  • Intracerebral capillaries
  • Retinal capillaries
  • Hypertension, diabetes

  Associated with:

  • Cerebral haemorrhage
  • Retinal haemorrhage