Atheroma, thrombosis and embolism Flashcards
is ischaemia reversible?
yes depending on multiple factors including speed of onset, local demand and duration
is infarction reversible
no, you get repair by scarring .
In the liver though you may get regeneration
what are the 2 functions of haemostasis?
1 – maintain blood in a fluid, clot free state in normal vessels;
2 – induce rapid, localised haemostatic plug at site of vascular injury.
what is thrombosis ?
pathological corruption of haemostasis. The formation of a solid or semi-solid mass from the constituents of blood, within the vascular system, during life.
what is the role of platelets?
to close small breaches in vessel walls
what are the haemostatic contents of platelet alpha granules
adhesion components e.g. fibrinogen, fibronecton, PGDF, anti-heparin. Also vWF and factor V
what are the haemostatic contents of platelet dense granules
they are important for aggregation and contain ADP and 5HT
what are the 8 main functions of endothelial cells
- maintain a permeability barrier
- elaborates anticoagulant, antithrombotis, fibrinolytic regulators
- elaborates prothrombotic molecules
- produces EC matrix
- modulates blood flow and vascular reactivity
- regulates inflammation and immunity
- regulates cell growth
- role in LDL oxidation
give some examples of the anticoagulant, antithrombotic, fibrinolytic regulators produced by endothelial cells?
Prostacylcin, Thrombomodulin, Heparin-like molecules, Plasminogen activator
give some examples of the prothrombotic molecules produced by endothelial cells?
VWF, Tissue Factor, Plasminogen activator inhibitor
how do endothelial cells modulate blood flow and vascular reactivity?
by secreting:
- Vasoconstrictors – endothelin, ACE
- Vasodilators – NO, prostacylcin
how do endothelial cells Regulates inflammation and immunity?
by
IL-1, IL-6, chemokines
Adhesion molecules – VCAM-1, ICAM-1, E-selectin, P-selectin
how do endothelial cells Regulates cell growth?
Growth stimulators
Growth inhibitors
name examples of growth stimulators?
PDGF, CSF, FGF
name examples of growth inhibitors?
heparin, TGF-beta
what are some causes of endothelial injury ?
Hyperlipidaemia Hypertension Smoking Toxins Vasculitis Viruses - cytomegalo virus e.g. Immune reactions- coagulation cascade, antibody complexes
what effects does stasis and turbulence have? 4 things
- platelets come into contact with the endothelium
- activated clotting factors are not dilutes by the normal rapid flow of blood
- inflow of anticoagulant factors is slowed, allowing thrombi to persist
- activation of endothelial cells in promoted
what are some examples of situations in which turbulence and stasis are important factors in thrombosis ?? name 4
- DVT
- non -contractile areas of myocardium following an MI
- aneurysm
- AF
what is hypercoagulability?
any alteration in the coagulation pathway which predisposes to thrombosis.
hypercoagulable states can be acquired or genetic. what are the high risk acquired states?
Myocardial infarction Immobilisation Tissue damage Cancer Prosthetic heart valves DIC Heparin induced thrombocytopenia Antiphospholipid syndrome
what is disseminated Intravascular coagulation (DIC) ?
is a serious disorder in which the proteins that control blood clotting become over active. Causes.
what is Heparin-induced thrombocytopenia (HIT) ?
development of thrombocytopenia (a low platelet count), due to the administration of heparin.
HIT is caused by the formation of abnormal antibodies that activate platelets.
hypercoagulable states can be acquired or genetic. what are the lower risk acquired states?
Atrial fibrillation Cardiomyopathy Nephrotic syndrome Hyperoestrogenic states Oral contraceptive use Late pregnancy Sickle cell anaemia Smoking
hypercoagulable states can be acquired or genetic. What are the genetic states?
- Factor V mutations (2-15% of Caucasians)
- Defects in anticoagulant pathways – antithrombin III deficiency, protein C or S deficiency
- Defects in fibrinolysis
- prothrombin 20210 mutation and others
there is a synergy in these
where are the common site of arterial thrombus?
coronary, cerebral and femoral
what are arterial thrombi associated with?
atheroma
Arterial thrombi
- they often ____ the lumen
- they show ____ attachment to the wall
- They also show lines of_____
- they often occlude the lumen
- they show firm attachment to the wall
- They also show lines of Zahn
what are the main causes of mural thrombi in the ventricles?
MI, arrhythmias
what are the main causes of mural thrombi in the aorta?
atheroma
what causes mural thrombi to show lines of zahn?
Laminated due to alternating pale (platelet & fibrin) and dark (RBC/WBC) bands
what component of virchow’s triad is most often implicated in venous thrombosis?
- venous stasis
what does venous thrombi often evoke?
inflammation - phlebothrombitis
where are the common places for venous thrombi?
popliteal, femoral, iliac, pelvic
what are Large vessel thrombi prone to do?
embolise
what colour are venous thrombi?
reddish blue and are adherent to the wall
what are the fates of thrombi? name 4
Propagation proximally (small to large vessel)
Embolisation
Resolution (fibrinolysis)
Organisation (granulation tissue, recanalisation)
[DIC]
what are the types of embolism/
Thromboembolism Fat embolism Marrow embolism Air embolism Septic embolism Amniotic fluid embolism Tumour embolism
where do most PEs arise from?
large leg veins (popliteal, femoral, iliac)
what shape of infarction do PE normaly cause?
wedge shape
what colour are PE infarctions and why?
haemorrhagic so they are red - this is because lung has two circulations - pulmonary and also oxygenated circulation from bronchial arteries
do venous emboli cause infarcts in peripheral arterial circulation?
no unless you have a Atrial/Ventricular Septal Defect
why would someone get a fat embolism ?
over time long bones become more fatty and if the bones have been fractured e.g. during major soft tissue trauma, then the fat can embolise
where do most fatty marrow emboli go?
to the lungs but some reach the peripheral circulation leading to skin rashes and CNS confusion
what may cause gas/air embolism?
- barotrauma
- Occurs during delivery or abortion
- Iatrogenic
- Many anecdotal cases
how much gas is required to enter venous circulation?
100ml
where do the air bubbles occlude?
the major vessels
what causes amniotic fluid embolism . It is rare
Amniotic fluid and debris enters torn veins and embolises to lungs.
what does an amniotic embolism cause?
marked oedema, often DIC (leading to haemorrhage)
where do most systemic emboli come from?
heart chambers or on valves
give examples of causes of systemic emboli?
Arrhythmias - AF
Mural thrombus post MI
Aneurysm
what do systemic emboli cause?
gangrene, CVA, visceral - very painful
what is Monckeberg Medial Calcific Sclerosis
Calcification of medium sized arteries in those >50yrs.
what is arteriolosclerosis?
Small arteries and arterioles
Hyaline and hyperplastic types
Associated with diabetes mellitus and hypertension
what are some outcomes of atherosclerosis?
MI PVD - gangrene Mesenteric artery occlusion Ischaemic encephalopathy (dementia) Aortic aneurysm
what are the risk factors for atherosclerosis
Age Sex “Genetics” Hypertension BP 160/95 → 5 x increased risk of IHD Smoking Increases IHD by 70-200% Diabetes Increases risk of MI by 2x Increases risk of gangrene by 8x – 150x Hyperlipidaemia Positive association with LDL Negative association with HDL
other risk factors for atherosclerosis?
Lack of Exercise Obesity Induces H-T, DM, hypertriglyceridaemia, reduced HDL High Carbohydrate Diet Saturated Fats/Trans(unsaturated)Fats Oestrogenic status Post-menopausal Oral Contraceptive Pill Stress [Protective role of Alcohol]
where is atherosclerosis distributed commonly?
Thoracic aorta Mainly arch branch points Carotid artery bifurcations Especially internal carotid Circle of Willis Coronary arteries Particularly ostia Left anterior descending Arms and associated vessels normally clear
what happens next in atherosclerosis?
can get resolution, repair (stabalisation by fibrosis and eventually calcification) or complication
what complications can you get?
1.Ulceration of atheromatous plaque and thrombosis
2- also can get Haemorrhage into plaque with plaque rupture and embolism of plaque contents
Ongoing narrowing → critical stenosis
Aneurysm formation
