Lecture 6 - thrombosis, embolism and infarction

define haemostasis

blood stopping

orchestrated process involving platelets, clotting factors. and endothelium that occurs at the site of vascular injury

also maintains blood in a fluid state in normal vessels

thrombus vs clot

thrombus - a solid mass of coagulated blood formed within the CVS

clot - a solid mass of coagulated blood that firms outside the CVS or post-mortem

very similar

thrombosis 

the formation of a thrombus 

embolism 

an obstruction in a blood vessel due to material that gets stuck whilst traveling through the bloodstream 

can be composed of thrombus, air, fat, amniotic fluid but are most commonly thromboelboli  

what are the four stages of haemostasis

vasoconstriction

primary haemostasis

secondary haemostasis

thrombotic and anti-thrombotic events

transient vasoconstriction

neurohormonal vasoconstriction - endothelin from endothelial cells 

temporarily slows bleeding, helps platelets and factors come into contact with each other 

primary haemostasis 

subendothelial ECM epxosed (to blood)

subendothelial components are high thrombogenic (von Willebrand factor) 

platelets adhere, activate and release granules that recruit more platelets to form a platelet plug 

secondary haemostasis

tissue factor released - glycoprotein from endothelial cells, initiates coagulation cascade

throbin is generated (from circulating prothrombin) - recruits and activates more platelets, converts fibrinogen to fibrin

fibrin polymerises - acts like a net, stabilising platelet plug and trapping other cells 

thrombotic and anti-thrombotic events

counter-regulatory mechanisms

limit the plug to the site of injury

what causes of thrombosis are asosciated with arteries

endothelial injury

abnormal blood flow - turbulence 

less associated with hypercoagulability (platelets) 

what causes of thrombosis are asosciated with veins

less endothelial injury

abnormal blood flow - stasis

hypercoagulability - coagulation 

risk factors for arterial thrombosis

dyslipidaemia

diabetes mellitus 

hypertension 

risk factors for venous thrombosis

trauma

surgery

cancer

previous venous thrombosembolism

pregnancy

thrombophilia

common risk factors fro thrombosis

age

obesit

smoking

estrogens

hyperhomocysteinemia

what is an aneurysm

a sac filled with thrombus

very dangerous if burst

can be repaired surgically

what is the blue in this image 

fibrin

lines of zahn 

alternating layers of platelets and blood cells 

only form when the blood is moving quickly - arterial not venous thrombi 

canaliculi 

perpendicular to lines of zahn

allow more porous parts to drain through the thrombus 

important for fibrolytic zone - allows fibrolytic zone to drain down 

fibrinolytic zone 

fibrin turns from a darker blue to a lighter colour

what are the possible fates of the thrombus

resolution

organisation and recanalisation 

propagation 

embolisation 

resolution

fibrinolysis, blood flow re-established, most likely when thrombi are small

organisation and recanalisation

epithelium can grow over the thombosis and incorporate it into the wall (organisation) 

can grow epithelial cells through the middle - create a new lumen to bypass the thrombus (recanulize) 

propagation

the thrombus gets longer

the end that is growing can form a tail which can break off and form an emboli

embolisation

part of the thrombus breaks off and travels through the bloodstream

lodges at distant site 

• systemic veins → lungs (pulmonary thrombi) 

• left heart (mural thrombus) → aorta → renal, mesenteric, femoral and other arteries 

• carotid arteries → brain 

• abdominal aorta → arteries of the leg 

pulmonary embolism

95% arise from DVT in the leg

contributes to ~10% acute adult hospital deaths 

usually in predisposed patients - underlying disorder, immobilised, hypercoaguable 

may result in pulmonary infarction, pulmonary hypertension, right ventricular failure 

other types of embolism 

air

amniotic fluid 

nitrogen

fat 

tumour cells 

infarction 

a form of ischaemic necrosis caused by the occlusion of arterial or venous vessels 

myocardial, cerebral, pulmonary, bowel, skin 

99% due to thrombosis, mostly arterial occlusion 

other causes include vasospasm, external pressure, trauma, twisting of organs, oedema 

infarct development depends on

nature of blood supply - red from dual blood supply or venous occlusion, white from end arterial occlusion

rate of occlusion - gradual from atherosclerosis of coronary arteries, acute from pulmonary embolism from DVT

white infarcts

arterial insufficiency

AND

single blood supply (end artery)

AND not reperfused

red infarcts 

venous occlusion OR dual blood supply OR reperfused