Thrombosis, Embolism, and Tissue Infarction Flashcards
What are the types of ways in which blood clotting occurs?
Clotting can be physiological (response to injury) or pathological (cause of tissue damage/death)
What is the cause of most vascular disease?
Narrowing or blockage of the lumen of blood vessels resulting in tissues being deprived of oxygen and nutrients and causing a buildup of toxic metabolites that cause damage and cell death.
What is ischaemia the result of?
Reduced blood flow (May have normal oxygen content)
What causes ischaemia?
Usually due to obstruction of blood vessel (thrombosis, embolus, microvascular disease, etc)
What causes tissue damage as a result of ischaemia?
Drop in ATP generation anf then failure of Na pump causes a cascade of events such as cell swelling, calcium influx, repture of lysosomes and membrane rupture, production of toxic metabolites and free radicals
What are the external symptoms of ischaemia?
Pale
Painful
Perishing
Cold
What is hypoxia?
Deficiency of oxygen in the blood available to tissues.
Reduced oxidative respiration in cells
What causes hypoxia?
Reduced oxygenation due to cardiorespiratory failure / asphyxia.
Decreased carrying capacity due to anaemia or CO poisoning
Drop in blood volume
What is the end result of ischaemia?
Necrosis
What happens to a cell during necrosis?
Cell swells -> Cell blebs -> Contents begin leaking out
What is an infarct?
An area of ischaemic necrosis caused by occlusion of vascular supply to the affected tissue.
Infarction is the process that leads to an infarct.
Arterial occlusion cause infarctions
What causes arterial occlusions?
Thrombus
Embolus
Vasospasm
Expansion of atherosclerotic plaque
Torsion or compression of vessels
Trauma
Vasculitis
At what point is ischaemia of the heart irreversible?
At the point of infarction
What are the most common and important causes of ischaemia and infarction?
Thrombosis and embolus
What is virchow’s triad?
Endothelial injury
Abnormal blood flow
Hypercoagulability
What causes clot formation?
Virchow’s triad
What causes endothelial injury?
Direct physical injury
Chemical/metabolic abnormality (drugs or hypercholesterolaemia)
Atherosclerosis
Infection
What does endothelial injury lead to?
Activation of endothelial cells, they change gene expression to a pro-coagulant state.
Downregulation in thrombomodulin and subsequent overactivity of thrombin.
Inflammation of endothelium downregulated protein C and other anticoagulant proteins
Antifibrinolytic effects - plasminogen inhibitors decreased production of t-PA
Activation of platelets
Major contributor to thrombosis in high flow / high pressure environment
What type of flow is normal?
Laminar blood flow (straight line flow)
What is abnormal blood flow?
Turbulent flow in which there are counter currents which puts lots of shearing force on blood vessel walls and creates pockets of stasis.
What is stasis?
Pockets of areas where blood is relatively not moving.
How does stasis contribute to clotting?
Allows activation of clotting cascade, platelet aggregation and activation, fibrin aggregation.
Keeps platelets and clotting factors in contact with the vessel wall.
Prevents washout and dilution of activated clotting factors by fresh flowing blood and the inflow of clotting factor inhibitors
What causes hypercoagulability?
Any disorder of the blood that predisposes to thrombosis. Can be primary (genetic) or secondary (acquired)
What are the causes of primary thrombophilia?
Primary:
Factor V abnormalities [2% to 15% of caucasians carry a single-nucleotide variation in factor V called factor V leiden causing a loss of antithrombotic counterregulatory pathway, heterozygotes have a 5x increased risk of venous thrombosis and homozygotes have a 50x increase.
Prothrombin abnormalities:
1 - 2% of the population carry a single nucleotide variation in the prothrombin gene causing elevated prothrombin levels and 3x increased risk of venous thrombosis
What are the causes of secondary thrombophilia?
Immobilisation
Major trauma
Malignancy
DIC: breakdown of cell membrane in some bacteria such as neisseria meningitidis in septicaemia leads to consumption of clotting factors
Consumptive coagulopathy
Many others
What are the characteristics of thrombi?
They are attached to vessel surface and tend to propagate towards the heart and may detatch
Thrombi can have laminations called the lines of Zahn.
Large thrombi attached to wall of heart or aorta are called mural thrombi
What do the lines of Zahn look like?
platelet and fibrin layers alternating with darker red cell-rich layers.
Only seen in flowing blood making them distinguishable from clots formed in postmortem state.
Higher flow = more prominent laminations
What are large thrombi attached to the wall of the heart or aorta called?
Mural thrombi
Where do arterial or cardiac thrombi more likely to arise?
At sites of endothelial injury or turbulence.
What do arterial and cardiac clots look like?
They tend to be platelet rich and often occlusive and more likely to have lines of Zahn.
Where do venous thrombi occur?
Typically at sites of stasis.
They can form a long cast within the lumen.
How do venous thrombi differ from arterial thrombi?
Can form long cast within lumen
tend to have more enmeshed RBCs, fewer platelets, and less often have lines of zahn (due to more time for aggregation)
Deep vens of lower extremities most often affected.
Can occur in upper extremities, periprostatic plexus, or ovarian and periuterine veins.
Arterial thrombus = turbulent flow and stasis causing thrombus
Vein thrombus = Stationary for long time causing thrombus
What are possible sequelae of Clots?
Propagation (extension of clot longitudinally or build up of additional layers
Dissolution (activation of fibrinolysis; after several hours fibrin polymerisation makes thrombus resistant to plasmin-induced proteolysis.
Occlusion (Thrombus blocks lumen)
Organization and recanalisation (Organisation: ingrowth of endothelial cells, smooth muscle cells, and fibroblasts. Recanalisation: Capillary channels form within the fibrotic clot partially reestablishing lumen)
What are emboli?
Embolus is a detatched intravascular solid, liquid, or gaseous mass that is carried by the blood from point of origin to a distant site where it causes tissue dysfunction or infarction.
What are the types of embolic material?
Thromboemboli (pulmonary vs systemic)
Air/Gas emboli
Fat emboli
Amniotic fluid emboli
Septic emboli
Foreign body emboli
What are the types of thromboemboli?
Pulmonary
Systemic (infarcts of heart, lung, bowel, spleen)
What are the effects of PE?
Blood stops reaching involved lung
Leads to VQ mismatch
Increased right ventricular pressure
What does large embolus in the lung do?
Can lead to acute right heart failure (cor pulmonale) and sudden death.
(this is sometimes caused by saddle embolus at bifurcation of pulmonary arteries)
What do smaller emboli in the lung do?
Pulmonary haemorrhage +/- infarct and hypoxia depending on size and other factors.
What happens if there are multiple small emboli in the lung?
Can lead to chronic pulmonary hypertension and chronic right heart failure
What are possible sequelae of pulmonary emboli?
Lysis of the embolus
Superimposed thrombus (another thrombus forms behind the embolus due to static blood)
Organisation and recanalisation
Where do systemic thromboemboli typically occur?
Often arterial/cardiac origin
Lodge in vessels at bifircations or narrowing sites.
Lead to localised infarcts in area of vascular supply (bowel, brain, kidney, spleen, lung)
What cause air or gas emboli?
Air -surgical or trauma
Gas - often nitrogen (at high pressure more nitrogen dissolves into blood and when divers return to low pressure this results in bubbles forming within the microvasculature. (Can damage brain, lungs, joints, and heart)
What causes fat emboli?
Trauma caused by fracture of long bone.
Causes mechanical obstruction and biochemical irritant.
Can trigger intravascular coagulation
What are amniotic fluid emboli?
Rare but critical complication of labour
Tear in placental membrane or uterine veins allow amniotic fluid (including hair, foetal skin, and fat) into maternal circulation.
Can trigger disseminated intravascular coagulation (DIC)
What causes septic and foreign body emboli?
Colonies of bacteria/fungi can detach and lodge elsewhere.
Summary:
Meaning of ischaemia/infarction
Meaning of thrombosis, pathophysiology of thrombosis and possible consequences
Meaning of embolism
Thromboemboli and other forms of emboli
