Atheroma, Thrombosis, Embolism and Infarction Flashcards
What is ischaemia?
Result of impaired vascular perfusion depriving the affected tissue of nutrients, inc. oxygen
Can be REVERSIBLE depending on speed of onset, local demand and duration - amongst other factors
What is infarction?
ISCHAEMIC NECROSIS of a tissue/organ secondary to occlusion/reduction of arterial supply/venous drainage
Recovery depends on tissue’s regenerative ability, e.g: scarring or, in liver, regeneration may occur
Haemostasis regulates?
Maintain blood in a fluid, clot free state in normal vessels
Induce rapid, localised haemostatic plug at site of vascular injury
What is thrombosis?
Pathological corruption of haemostasis - forms a solid/semi-solid mass from blood constituents, WITHIN the VASCULAR system, during LIFE
Virchow’s Triad?
Changes in VESSEL WALLS (endothelial injury)
Changes in BLOOD CONSTITUENTS (hypercoagulability)
Changes in BLOOD FLOW
Functions of platelets?
Close small breaches in vessel walls
Haemostatic contents of platelets?
α-granules: adhesion components (promote clotting), e.g: fibrinogen, fibronectin, Platelet-Derived Growth Factor - PDGF, anti-heparin, etc)
Dense granules: contents cause platelet aggregation, e.g: ADP
Functions of endothelial cells?
Maintains a permeability barrier
Elaborates anti-coagulant, anti-thrombotic, fibrinolytic regulators, e.g: heparin-like molecules, plasminogen activator
Elaborates pro-thombotic molecules, e.g: vWF, tissue factor (TF), plasminogen activator inhibitor
Produces EC matrix
Modulates blood flow and vascular activity, using vasoconstrictors and dilators
Regulates inflammation and immunity by altering, e.g: IL-1, IL-6, chemokines and adhesion molecule expression
Regulates cell growth, using growth stimulators, e.g: PDGF, and growth inhibitors, e.g: heparin
Role in LDL oxidation
Causes of endothelial injury?
Hyperlipidaemia Hypertension Smoking Toxins Vasculitis Viruses Immune reactions
Effects of stasis and turbulence on platelets?
Disrupt laminar blood flow so:
Platelets come into contact with endothelium
Activated clotting factors are not diluted by normal, rapid flow
Inflow of anti-coagulant factors is slowed, allowing thrombi to persist
Activation of endothelial cells is promoted
Situations where turbulence and stasis commonly cause thrombosis?
Impairing venous drainage of the lower limbs, predisposing to DVT
Non-contractile areas of myocardium following MI
Aneurysms
AF
Mitral valve stenosis and left atrial dilation (poor flow)
What is hypercoagulability?
Any alteration in the coagulation pathway that predisposes to thrombosis
Two categories of diseases causing hypercoagulability?
Acquired genetic
Acquired hypercoagulable states that are high risk?
MI Immobilisation Tissue damage Cancer Prosthetic heart valves DIC (disseminated intravasculat coagulation - proteins controlling blood clotting become overly active) Heparin-induced thrombocytopaenia
Acquired hypercoagulable states that are lower risk?
AF Oral contraceptive use Late pregnancy and post-partum Sickle cell anaemia Smoking
Genetic hypercoagulable states?
Factor V mutations
Defects in anti-coagulant pathways -antithrombin III deficienct
Defects in fibrinolysis
Morphology of arterial thrombi?
Often occlude LUMEN, in common sites like coronary, cerebral and femoral arteries
Associated with ATHEROMA and have a firm attachment to the wall
Appearance of arterial thrombi?
Show LINES OF ZAHN - laminated due to alternating pale (platelet and fibrin) and dark (rbc/wbc) bands
Morphology of venous thrombi?
Most occlude VEIN LUMEN, often STASIS related
Evokes inflammation - thrombophlebitis
Most important and common venous thrombi?
DVT of calf - most important
Less common are popliteal, femoral, iliac and pelvic thrombi
Large vessel thrombi are prone to embolise
Fates of thrombi?
Propagation proximally, small to large vessel
Embolisation
Resolution (fibrinolysis)
Organisation (granulation tissue, recanalisation)
DIC
Most common emboli?
Thromboemboli
Types of embolism?
Thromboembolism
Fat embolism
Marrow embolism
Air embolism
Septic embolism
Amniotic fluid embolism
Tumour embolism
Difference between red and white infarct?
White infarct (lack of rbs accumulation) - usually in organs with only one circulation
Red infarct - cause by haemorrhage, usually in organs with 2 circulations, e.g: lungs
Rare occasions where venous emboli cause infarcts in peripheral arterial circulation?
Venous emboli do NOT cause infarcts in peripheral arterial circulation unless:
Atrial/ventricular septal defect
Paradoxical embolus
…rare
Causes of fat embolism?
Major soft tissue trauma
Major bone fractures:
Fatty marrow enters venules, most globules arrest in lungs to cause dyspnoea
Some reach peripheral circulation to cause skin rashes, CNS confusion
Potentially fatal
Causes of gas/air embolism?
Barotrauma - in divers
During delivery or abortion
Iatrogenic
Frothy bubbles occlude major vessels - at least 100ml gas required to enter venous circulation
Describe amniotic fluid embolism
Post-partum (high mortality)
Amniotic fluid (prostaglandin-rish) and debris enters torn veins and embolises to lungs - causes marked oedema, often DIC (leads to heamorrhage)
Origins of systemic emboli?
Most from thrombi within heart chambers/on valves, e.g:
In AF
Mural thrombus, post-MI (formation of a thrombus in contact with the endocardial lining of a cardiac chamber, or a large blood vessel)
Aneurysm
Destinations of systemic emboli?
Legs - gangrene
Brain - infarct/CVA
Visceral - GI, kidney, spleen
Arms - gangrene
What does arteriosclerosis mean?
Hardening of the arteries
Three disease patterns under arteriosclerosis?
Atherosclerosis - disease of intima
Monckeberg Medial Calcific Sclerosis - calcification of medium-sized arteries, in those > 50 years of age
Arteriolosclerosis - disease of small arteries and arterioles (hyaline and hyperplastic types); assoc. with diabetes mellitus and hypertension
Main targets of atherosclerosis?
Aorta - aneurysm
Coronary arteries - MI, chronic myocardial ischaemia (anginal pain/cardiac failure)
Cerebral arteries
Genetic polymorphisms associated with atherosclerosis?
Lipoprotein Lp(a) (apo-B100+apo-A) Inflammatory Markers (CRP) Fibrinolytic Markers (PAI-1)
Which infections can contribute atherosclerosis?
Inflammation arises from:
Chlamydia
Constituents of atherosclerotic plaque?
Raised focal lesion of intima
Lipid core of cholesterol, esters and lipoproteins
Fibrous cap
How is the artery wall structure medial to the plaque degraded?
Weakening of arterial wall
Aneurysm development
Key stages in atherosclerosis?
Chronic endothelial injury Endothelial dysfunction Macrophages activation Lipoprotein oxidation Foam cell formation, fatty streak Plaqure formation and growth
What does endothelial dysfunction involve?
Increased permeability
Monocyte adhesion
Monocyte emigration
Platelet adhesion
Roles of activated macrophages in atherosclerosis?
Generation of reactive oxygen species leading to oxidation of lipoproteins
Production of cytokines which promote chemotaxis and adhesion of further leucocytes
Production of growth factors contributing to smooth muscle proliferation
Why are lipoproteins oxidised in atherosclerosis (functions)?
More easily ingested by macrophages
Act as chemotactic factors for monocytes
Increase monocyte adhesion
Inhibit macrophage motility, Trapping macrophages within the plaque
Stimulate cytokine and growth factor release
Directly damage endothelial and smooth muscle cells
Induce an antibody response
What does foam cells and fatty streak formation involves?
Macrophages and smooth muscle cells engulf lipid to become foam cells
How can fatty streak be reversed?
At this stage, which is visible as a fatty streak on the wall of the artery, the process may still be reversible if the level of blood cholesterol is reduced.
What does plaque formation and growth involve?
When hypercholesterolaemia persists, smooth muscle proliferation and collagen deposition convert the fatty streak into a mature fibrofatty atheroma
Common areas of atherosclerosis?
Thoracic aorta - mainly arch branch points
Carotid artery bifurcations - esp. internal carotic
Circle of Willis
Coronary arteries - part. ostia and LAD
What happens after atherosclerosis?
Resolution: reabsorb lipid at fatty streak stage (pre-extracellular lipid) - maybe using high-dose statins
Repair: stabilisation by fibrosis (scarring), thick cap or total fibrosis; omega-3 fish oils promote this. Also, calcification
Complications of atherosclerosis?
Ulceration of atheromatous plaque and THROMBOSIS
Haemorrhage into plaque, causing rupture and embolism of plaque contents; leads to critical stenosis or aneurysm formation
