CVS-atherosclerosis, circulation and clotting Flashcards
what is an embolus?
material that causes blockage
what is an embolism?
when the embolus gets lodged in a blood vessel (e.g. pulmonary embolism)
name some types of embolism
- blood clot (thrombus)
- fat embolism (fat globule)
- gas embolism (bubble of air)
- amniotic fluid embolism (amniotic fluid)
- foreign material
what is atherosclerosis?
development of an atherosclerotic plaque in tunica intima of large/ medium sized arteries (e.g. coronary arteries)
where do atherosclerotic plaques build up?
tunica intima of medium/ large arteries
what is plaque made up of?
- fat
- cholesterol
- calcium
what happens to plaque over time and what does this cause?
plaque hardens and narrow arteries-decreasing blood flow to tissues
when does the formation of a lesion start (beginning of plaque build-up)?
in young children
what risk factor increasing the formation of lesions?
high fat diet
what is the earliest significant lesion called?
fatty streak
what do fatty streaks consist of?
lipid-containing foam cells in the artery just deep to the endothelium
what do fatty streaks evolve into?
evolve into atherosclerotic plaques; which remain stable or regress
outline the steps of fatty streaks formation and development into atherosclerotic plaques
- injury to endothelium of artery caused monocyte adhesion and loosening of endothelial cell junctions
- monocytes migrate deep to endothelium and differentiate into macrophages
- macrophages phagocytose LDLs (enter initima via permeable endothelium) –>now foam cells
- progressive accumulation of lipid/ smooth muscle in intima forms (via cytokines released by T cells)
- growing lesion begins to raise endothelium and encroach on lumen of artery–>atherosclerotic plaque
what are the two types of atherosclerotic plaques?
- stable
- unstable
how are stable atherosclerotic plaques formed?
- they are slow growing plaques which expand gradually due to the accumulation of lipid in foam cells and migration and proliferation of smooth muscle cells
- fibrin cap on lesion matures
what does atherosclerotic narrowing of coronary artery lead to?
stable angina
what is stable angina characterised with?
chest pain that comes on during exertion
how do unstable plaques form?
- grow more rapidly as a result of more rapid lipid deposition
- have a thin fibrin cap-prone to rupture-can trigger acute thrombosis (by activating platelets and clotting cascade)
what happens when an unstable plaque ruptures?
-mural thrombosis forms on top of ruptured plaque
–>causes variable obstruction of coronary artery–>unstable angina
(can also cause death of cardiac muscle just under endocardium->subendocardial infarction)
how is an acute transmural myocardial infarction caused?
-a thrombus forms on top of a ruptured plaque and occludes the lumen of the coronary artery -> leads to death of the full thickness of cardiac muscle supplied by that artery (myocardial infarction)
what is peripheral arterial disease (PAD)?
disease presentation that results when atherosclerosis of arteries of lower leg causes symptoms of ischaemia and/or infarction to occur
what is the most common presenting symptom of peripheral arterial disease?
intermittent claudication (pain/ cramping in legs relieved by rest)
what does fluid balance involve?
maintaining the amount of water as as a result the concentrations of ions in solution within healthy ranges
on average how many L of water is in the human body?
42L (in 70kg male)
what is hydrostatic pressure?
pressure of blood against the wall–>pushes substances out
what is oncotic pressure?
a form of osmotic pressure exerted by proteins in a blood vessel’s plasma -> holds substances in
which protein does oncotic pressure notably involve?
albumin
what is osmotic pressure?
related to total number of particles of solute
which force is the opposing force to HP?
oncotic pressure
describe the structure pf capillaries in the circulatory system-what does this enable?
semi-permeable
- ->enables fluids to pass across
- ->larger proteins cannot
when HP and OP are in balance is there a net gain or loss of fluid from the cirulatory system?
no neither
what does movement of fluid across capillaries depend on?
the balance between:
- capillary HP and interstitial fluid HP
- plasma oncotic pressure and interstitial fluid oncotic pressure
what is oedema?
an increased volume of interstitial fluid in a tissue or organ
what are the 4 potential causes of oedema?
- Raised hydrostatic pressure (e.g. cardiac failure after myocardial infarction)
- Low oncotic pressure (e.g. liver disease → not enough albumin produced)
- Impaired lymphatic drainage (e.g. tumours, lymph node removal → no lymphatic drainage of excess interstitial fluid); lymphoedema
- Endothelial damage (e.g. inflammation → increased capillary permeability so more fluid leaks out)
how can cardiac failure following a heart attack result in oedema?
- infarction causes damage impairing cardiac function
- blood not pumped effectively->blood backlogs in veins
- pressure in veins increases->pressure at capillary bed increases
- higher capillary HP at venous end->more fluid forced out–>oedema
what is haemostasis?
the cessation of bleeding
opposite to haemorrhage-blood loss
what does haemostatis do?
- prevents loss of blood through walls of damaged vessels
- establishes a framework for tissue repair
what are the 3 phases of haemostasis?
- vascular
- platelet
- coagulation
what triggers the vascular phase of haemostasis?
when a blood vessel is cut it triggers smooth muscle fibres of vessel wall–>vascular spasms
what do vascular spasms cause?
a decrease in blood vessle diameter at the injury site and prevent flow of blood through vessel wall
how long do vascular spasms last?
30 minuutes
what do endothelial cells in the vascular phase release to stimulate smooth muscle contractions?
endothelins–>cause vasoconstriction of vessel
what happens to endothelial cells at the end of the vascular phase ready for the platelet phase?
cells become sticky-ready for platelets to adhere to it in platelet phase
what is Von Willebrand’s factor?
-A blood glycoprotein involved in haemostasis (specifically platelet adhesion)
what is VWF produced by?
endothelial cells
where does inactive VWF circulate?
in the plasma complexed with Factor VIII
outline the steps in the platelet phase of haemostasis
- Platelets adhere to sticky endothelial surfaces, basement membranes & exposed collagen fibres beneath the endothelium (via the collagen receptor called glycoprotein la/lla)
- Adhesion occurs via bridging with von Willebrand’s factor (VWF)
- When the collagen and VWF interact, a complex is formed that binds fibrinogen from plasma → platelet is activated
which chemicals do activated platelets release in the platelet phase of haemostasis?
- ADP
- Thromboxane A2 & serotonin (vasoconstrictors)
- Clotting factors, PDGF (platelet-derived growth factor) and calcium ions
- > promote vasoconstriction and further platelet activation
what does the release of ADP from activated platelets cause?
- makes other platelets sticky → helps them aggregate and stick to the originally activated platelets → forms a platelet plug, which closes small breaks in the vessel
what does the surface of activated platelets serve as a site for?
coagulation-formation of thrombus–>in coagulation phase
how soon after injury does the coagulation phase begin?
30+ seconds after injury
which 3 pathways does the coagulation phase involve?
- intrinsic
- extrinsic
- —>both lead to common pathway
where are most clotting factors synthesised?
in the liver
which pathway in the coagulation phase is faster intrinsic or extrinsic?
extrinsic
where does the extrinsic pathway of the coagulation phase begin?
in vessel wall outside bloodstream
in the extrinsic pathway what does the damaged endothelium release and what does it cause?
-Damaged endothelium releases tissue factor (TF)/Factor III
-TF + other compounds form an enzyme complex
→ activates Factor X
where does the intrinsic pathway of the coagulation phase begin?
Begins with circulating proenzymes WITHIN bloodstream
what happens in the intrinsic pathway of coagulation phase?
-Activation of Factor XII exposed to collagen
-Platelets release factors (e.g. PF-3)
→ series of reactions activates Factor X
outline the steps of the common pathway
- Activated Factor X combines with Factor V in presence of Ca2+ to form active prothrombinase
- Prothrombinase converts prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
what is fibrin?
insoluble protein that covers the platelet plug
what causes the conversion of prothrombin—->thrombin?
prothrombinase
what causes the conversion of fibrinogen—>fibrin?
thrombin
give an example of positive feedback in clotting
Positive feedback -
generation of thrombin amplifies clotting cascade
Stimulates further formation of tissue factor & further release of PF-3 → accelerates clotting
give examples of negative feedback in clotting
Negative feedback; factors that restrict blood clotting:
- Anticoagulants (plasma proteins) e.g. antithrombin-III
- Heparin; released by basophils and mast cells
- Aspirin, protein C; activated by thrombomodulin
- Prostacyclin (inhibits platelet aggregation)
what is fibrinolysis?
-the dissolving of the fibrin strands
- Plasminogen is activated to produce plasmin (which digests fibrin strands)
- > restores normal blood flow through repaired vessel
which ion and vitamin are essential to the clotting process?
Ca2+
vitamin K
what type of vitamin is Vitamin K?
fat soluble
where can vitamin K be obtained?
via green vegetables and bacteria in the gut
what is vitamin K essential for?
- Required for liver to synthesise prothrombin, Factor VII, Factor IX, and Factor X
- Deficiency in Vit K affects coagulation
- Antagonist of Vit K = warfarin
what is Virchow’s triad?
three broad categories of factors that influence the occurrence of thrombosis (formation of a blood clot):
what are the 3 categories of Virchow’s triad?
hypercoagulability, vascular damage & circulatory stasis
In an average 70kg male, how much water is present in the blood plasma?
A-10.5 litres B-28 litres C-14 litres D-7 litres E-3.5 litres
E
What stimulates the migration of smooth muscle from the tunica media into the tunica intima during atherosclerosis?
A-Foam cells B-LDLs C-Cytokines D-Monocytes E-Calcium ions
C
Which of the following is a circulating plasma protease inhibitor that inhibits thrombin?
A-Intrinsic factor B-Tissue factor C-Factor X D-Factor XII E-Factor V F-Heparin G-Warfarin H-Thrombin I-Antithrombin
I-Antithrombin
Which clotting factor is involved in the intrinsic pathway?
A-Intrinsic factor B-Tissue factor C-Factor X D-Factor XII E-Factor V F-Heparin G-Warfarin H-Thrombin I-Antithrombin
D-Factor XII
Which of the following cleaves fibrinogen to form insoluble fibrin?
A-Intrinsic factor B-Tissue factor C-Factor X D-Factor XII E-Factor V F-Heparin G-Warfarin H-Thrombin I-Antithrombin
H-thrombin
Which of the following is a mixture of mucopolysaccharides derived from mast cells & activates antithrombin?
A-Intrinsic factor B-Tissue factor C-Factor X D-Factor XII E-Factor V F-Heparin G-Warfarin H-Thrombin I-Antithrombin
F-Heparin
Which of the following is a vitamin K antagonist ?
A-Intrinsic factor B-Tissue factor C-Factor X D-Factor XII E-Factor V F-Heparin G-Warfarin H-Thrombin I-Antithrombin
G-Warfarin
