Lecture 1: Blood and vessels Flashcards
What are the different layers of a vessel?
- Tunica adventitia
- Tunica media
- Tunica intima
- Endothelium
What are physiological processes which lead to blood vessel formation?
- Ovulation
- Menstruation
- Placenta formation
- Wound healing
- Retinal development
What are the different types of blood vessel growth?
- Vasculogenesis = de novo formation of blood vessels from progenitor cells
- Angiogenesis = sprouting of new capillaries from existing capillaries
- Arteriogenesis = enlargement of pre-existing arterial connections to completely developed and functional arteries
What triggers angiogenesis?
Hypoxia
Gradient of growth is established by VEGF
Name three promotors of vessel growth
VEGF
FGFs
Angiopoietins
Name an inhibitor of vessel growth
Angiopoietins
How would you induce angiogenesis or arteriogenesis?
Cell therapy → introducing cells in host environment to induce blood vessel formation to decreases chances of blockage
Works better than only introducing growth factors
What are the causes of leg oedema?
- Immobility
- Pregnancy
- Heart failure
- Low plasma protein
- Chronic venous insufficiency
- DVT
- Lymphatic insufficiency
- Chronic renal failure
What factors influence haematological homeostasis?
- Vascular hydrostatic pressure pushing fluid out
2. Plasma colloid pressure drawing fluid in
What are the primary causes of lymphoedema?
- Syndromic primary lymphoedema (Turner’s, Noonans, Prader Willi)
- Lymphoedema with overgrowth, vascular, or cutaneous manifestations
- Congenital onset lymphoedema (<1 year of age) (Milroys: VEGFR3 mutation)
- Late onset lymphoedema (> 1 year age) (FOXC2 mutation)
What are secondary causes of lymphoedema?
- Radiotherapy
- Surgery
- Cellulitis
- Filariasis (parasite)
How would you manage lymphoedema?
- Treatment of underlying cause
- Elevation
- Compression
- Massage
- Good skincare
- Surgery (specifically in lymphoedema)
How do platelets get activated in tissue damage?
- Damage to blood vessel
- Exposure of platelets to collagen and vWF in extracellular matrix and (later) exposure to thrombin
- Platelets adhere and activate
- Release of mediators
- Vasoconstriction + aggregation of platelets
- Formation of soft platelet plug
What does the initiation phase of clotting lead to?
Activated by tissue factor (TF), eventually thrombin activates platelets
What does the amplification phase of clotting lead to?
Initiated by thrombin and takes place on activated platelets, ultimately leads to a significant increase in thrombin accumulation which causes:
- Fibrinogen will be cleaved into fibrin and cross-linking promotes stable clot
- Crosslinking is stimulated by factor XIIIa, which is under the influence of calcium
What are the fibrinolytics?
Alteplase (Activates plasminogen, but only when it is bound to fibrin)
Streptokinase (Binds and activates plasminogen)
What does prothrombin time indicate?
measures the integrity of the extrinsic system as well as factors common to both systems
What does partial thromboplastin time indicate?
measures the integrity of the intrinsic system and the common components
What does thrombin time indicate?
measures the time it takes for a clot to form in anticoagulated blood plasma, after an excess of thrombin is added
What does D-dimer indicate?
are fibrin degradation products. Measured In patients to test suspected thrombotic disorders
What does international normalised ratio indicate?
used to normalise PT, since this will be affected by manufacturer’s TF
Main use is to exclude thromboembolic disease.
What is the mechanism of action of Abciximab, Eptifibatide and Tirofiban?
Glycoprotein IIb/IIIa Inhibitor
What is the mechanism of action of aspirin?
Irreversible inhibition of COX enzyme
What is the mechanism of action of warfarin?
Vitamin K antagonist
What is the mechanism of action of Clopidogrel, Prasugrel and Ticagrelor?
P2Y12 inhibitor
What is the mechanism of action of Argatroban and Dabigatran?
Direct thrombin inhibitor
What is the mechanism of action of Rivaroxaban, Apixaban and Edoxaban?
Factor Xa inhibitors
What are the main antiplatelets used?
Aspirin and clopidogrel
What drugs can clopidogrel not be given with?
Often not given with drugs that activate CYP-enzymes (e.g. omaprazol)
After ACS, what antiplatelets would you give?
- 300mg aspirin in ACS, 75 mg once daily maintenance
- 300-600mg clopidogrel in ACS, 75 mg daily maintenance
When are antiplatelets contraindicated?
Antiplatelets are contraindicated in active bleeding and should be cautious if there was a previous GI bleeds
Aspirin higher chance of causing GI bleeds than clopidogrel
When is GI protection used?
In dual antiplatelet therapy.
Achieved with:
- H2-antagonists (ranitidine)
- PPI (omeprazole)
What do anticoagulants do?
Anticoagulants slow down clot formation
Antiplatelets prevent clotting
What are the main types of anticoagulants?
- Warfarin
2. DOAC
What is warfarin used for?
Prophylaxis of embolisation in rheumatic heart disease and AF
After prosthetic heart valve
Treatment of VTE
For TIA and anti-phospholipid syndrome
What factors does vitamin K produce?
Mainly factor X, II, VII
What are the downsides of warfarin?
Takes longer to work, has longlasting effects
Monitor closely
Administer same time every day, doses can vary
Affected by weight, food etc
What happens when INR is too high (over 1)?
Risk of bleeding
What happens when INR is too low (under 1)?
Risk of blood clot
When are DOACs used?
Prevention of stroke in non-valvular AF
Acute VTE
Longterm VTE prophylaxis
ACS (low dose rivaroxaban)
What tests do you need before you prescribe a DOAC?
Patients will still require regular blood test monitoring: kidney function and liver function (contra-indicated in Child-Pugh level C – severe impairment)
Dose will be dependent on indication, renal function, age
What are the downsides of DOACs?
No antidote!
Take with food
Short half life
Use dependent on renal function
What valves are tricuspid?
Pulmonary
Aortic
Tricuspid
When would you do a CTCA?
Chest pain
How useful is CTCA in detecting atherosclerosis?
Invasive CT coronary angiography are incredible for obstructive disease, but provide little information for minor or early atherosclerotic lesions
During what phase of the cardiac cycle would you do a CTCA?
Image often obtained during diastole, as heart moves the least at this point
Provides information about lumen AND wall
How would you classify stenosis?
Stenosis classification:
- Minimal <24%
- Mild 25-49%
- Moderate 50-69%
- Severe 70-99%
Plaque morphology: non-calcified, partially calcified, calcified plaque
What arteries branch of the abdominal aorta?
- Coeliac trunk (left gastric and left hepatic) (T12)
- Superior mesenteric (L1)
- Left and right renal (L1-L2)
- Inferior mesenteric (L2-4)
What are the disadvantages of invasive angiography?
Invasive
Labour intensive, skill requirements
Long procedure
2D technique
What are the advantages of invasive angiography?
Golden standard
Allows diagnosis and treatment of NSTEMI, STEMI and angina
High resolution
