Mechanisms of Vascular Disease: Thrombosis, Embolism & Infarction Flashcards
Describe blood clotting
Haemostatic defence mechanism to minimise blood loss (haemmorhage), forming a solid mass of blood constituents EXTERNAL to the blood vessel
Important mechanism in trauma and surgery/anaetheticss
Describe a thrombus
Solid mass of blood constituents formed WITHIN the BLOOD VESSEL (forms when blood vessel wall is intact but abnormal)
Thrombus formation is dependent on?
Virchow’s triad - at least 1 of the 3 must be present or no thrombus can form:
Vessel wall
Blood flow
Blood constituents
How can the vessel result in thrombus formation?
Loss of endothelial surface - blood is exposed to underlying collagen & extracellular matrix, activating thrombus formation via the coagulation cascade
Inflammation
How can blood flow result in thrombus formation?
Stasis - no flow
Turbulence - esp. present around bifurcations, where as thrombus is more likely to develop
How can blood constituents result in thrombus formation?
Increasing any of the following will make thrombus formation more likely:
Platelets
Coagulation proteins
Viscosity - can increase via polycythaemia (increase in rbcs)
What does thrombus formation involve?
Activation and increase in platelets
Coasulation cascade
Fibrinolytic cascade
Thrombus formation depends on the balance of the two cascades
What are platelets?
Anucleated cell fragments that have adherent (can adhere to themselves and endothelial cell surfaces) and procoagulant properties (activate cascade)
Are storage vehicles of growth factors
Activated in inflammation and endothelial damage
Production of platelets?
Formed in bone marrow by megakaryocytes (multi-nucleated)
Describe the coagulation cascade
Most constituents are in blood are in their inactivated forms
Activated by triggering events at top of the cascade (activate first component leading to AMPLIFIED response)
Two pathways of coagulation cascade?
Intrinsic pathway - (to vascular supply) thrombus formation
Extrinsic pathway - blood clots following haemorrhage
Intrinsic and extrinsic pathways come together to activate Factor X
Describe the end of the coagulation cascade
Forms a CROSS-LINKED FIBRIN POLYMER that is INSOLUBLE and is a constituent of a thrombus & blood clot, along with platelets and other cell types
Reason for thrombus?
ATHEROMA is the most common reason for arterial thrombus via coagulation cascade
Consequences of arterial thrombus?
Leads to VESSEL OCCLUSION or EMBOLISM
Can lead to myocardial infarction (geography of infarction depends on which vessel was occluded) and stroke
Causes of venous thrombus?
Most common reason is BLOOD STASIS (immobilsed) - return of blood to heart against gravity is dependent on contraction of calf muscles, so if patient is immobilised (long travel or post-operative), they are at risk of venous thrombosis
Abnormal constituents of venous thrombosis?
Hypercoagulability (decreased coagulation threshold or more coagulation proteins) - can be inherited, due to drugs or trauma (patients with trauma are put on bed-rest, so risk of thrombus)
Dehydration - on long-haul flights, this increases the risk of thrombus
What is an embolism?
Mass of material in the vascular system, moving from its site of origin, to lodge in the vessels in a distant site
Types of embolism?
Thromboembolism:
DVT and pulmonary thromboembolism
Arterial thrombosis and embolism
Fat embolism
Atheroembolism
Tumour embolism - problem in lung & kidney cancers
Infective - e.g: clumps of bacteria on heart valves
Amniotic fluid - pushed into maternal circulation; life-threatening
Air embolism - MUST TAP TO REMOVE AIR BUBBLE, from iv/injections, etc; IATROGENIC
What is deep vein thrombosis?
DVT
Thrombus in deep veins of, usually, legs
Risks with DVT?
Risk is dislodging and PULMONARY thromboembolism (pulmonary capillaries are smaller)
DVT does not embolise to heart or brain
DVT symptoms?
Unilateral leg swelling
Oedema - increased fluid in tissues
Pain - post-operatives may be on analgesics and so feel no pain; danger that no symptoms present
DVT can occur with no symptoms
Characteristics and potential consequences of pulmonary thromboembolism (PTE)?
SUDDEN ONSET (not gradual) Potentially life-threatening Haemoptysis (coughing up blood) Breathlessness Cardiovascular collapse & shock - perhaps, no return of blood to left atrium Cardiac arrest
Describe atrial thrombosis
Often in people with atrial fibrillation, due to stasis of flow
Thrombus travels through aortic valve and, in a straight line, to the right internal carotid artery and to a brain vessel, which will be occluded
Risks of atrial fibrillation?
Atrial thrombosis and stroke
How can myocardial infarcation cause thrombus formation?
Infarction causes inflammation - may trigger thrombus formation on the wall of a blood vessel which can embolise to cause stroke - MURAL THROMBOSIS (in contact with the endocardial lining of a cardiac chamber, or a large blood vessel, if not occlusive)
Most common organs to suffer infarcation?
Heart, kidneys, brain and gut
Pathological changes due to infarction?
ZONAL NECROSIS due to sudden occlusion of blood supply and, thus, lack of O2 and nutrients (consider anatomy of the blood supply)
Tissues affected by infarction?
Different tissues have different susceptibilities
E.g: brain is highly susceptible to ischaemia (can only survive 3 minutes without O2 - can only carry out aerobic respiration)
Problems after infarction?
Re-perfusion injury - tissue damage caused when blood supply returns to a tissue after ischaemia/lack of O2 (hypoxia)
O2-dependent killing of cells occurs due to ichaemic cell leakage and chemical scavenging
Leads to inflammation and free radical generation
Role of free radicals in re-perfusion injury?
Particularly O2 - superoxide
Chain reaction leads to lipid peroxidation (lipid becomes less soluble/0
Free radical scavengers are up-regulated by bronchioles, etc but can inactivated by dismutase
When does free radical generation occur?
Free radicals cause cell damage and are seen in:
O2 toxicity
Re-perfusion injury
Inflammation
Intracellular killing of bacteria
Drugs, e.g: paracetamol-induced injury (narrow therapeutic ratio and is metabolised in liver to form free radicals so hepatic necrosis occurs)
Describe vaculitis
Inflammation of blood vessel walls that can potentially lead to thromboembolism
