Angiogenesis, lymphatics and oedema Flashcards
(32 cards)
List the layers of an artery/vein starting from the endo
- endo
- tunica intima
- tunica media
- tunica adventitia
How is blood distributed in the body?
- 65% venous
- 30% arterial
- 5% cap
What are the PHYSIOLOGICAL causes of neovascularisation?
Ovulation Menstruation Placenta formation Wound healing Retinal development
What PATHOLOGICAL causes decrease neovascularisation?
Pulmonary fibrosis
Emphysema
Delayed ulcer healing
What are the PATHOLOGICAL causes increase neovascularisation?
Tumour development Retinopathies Psoriasis Rheumatoid arthritis Plaque progression? Restenosis Endometriosis Vascular Malformations
What is neovascularisation?
dev of new blood vessels
What is vasculogen?
De novo formation of blood vessels from
progenitor cells
Progenitor cells in bone marrow in tissues –> Cells form blood islands –> endo differentiation –> new cap plexuses
What is Angiogenesis?
Sprouting of new capillaries from existing
capillaries
Hypoxic trigger
What is arteriogenesis?
Enlargement of pre-existing arterial connections to completely developed and functional arteries Fluid shear stress Small vessels have a trigger e.g. fluid stress or blockage in 1 vessel inc demand on smaller vessel which causes it to stretch + get muscularised
Describe angiogen
VEGF induces blood vessel formation – causes cell migration form parent vessels
Zone I cells migrating
Zone II cells dividing
Zone III cells maturing
Gradients established by affinity of binding of VEGF to matrix
Describe the role of cellular chaperones
Monocyte macrophages interact with tip of migrating stalk of endo cells to direct, mature them etc
Macrophages + endo cells have receptors e.g. angiopoietin 1, ag2, VEGFR2 which have ligands that bind and stim the cell to prod angiogen factors etc VEGF
Cells then go through maturation
What regulates angiogen?
PROMOTERS OVERWHELM INHIBITORS –> ANGIOGENIC SWITCH
List promoters of angiogen
VEGFs FGFs Angiopoietins IGF1 TGFb Erythropoietin NO Thrombin Fibrinogen
List inhib of angiogen
Angiopoietins – difference in ratio between AG1:AG2 can be inhib or promote angiogen
Troponin-I
Soluble VEGF receptors
IL12
Which factors regulate vessel growth?
Hypoxia
Metabolic stimuli - hypoglycemia, low pH, endothelial metabolism
Mechanical factors - Flow shear stress, Stretch
Growth and inhibitory factors - VEGF, PlGF, Ang1 , Ang 2
(stress-responsive gene transcription)
How does hypoxia stim new vessel growth?
Centre of tumor becomes hypoxic as O2 can’t reach it
Hypoxic inducible factor triggers hypoxia regulator gene to produce angiogen factors e.g. VEGF to promote new blood vessel formation
What is flow shear stress?
inc flow through small vessel, becomes bigger + thicker
Describe symptoms of PAD
– most is asymptomatic Claudication = pain on walking Rest pain – usually worse at night without skin changes Final stage is skin changes Gangrene can be dry or wet
List the branches of the femoral artery
profunda femoris –> superficial femoral –> popliteal –> ant. Tibial –> peroneal trunk split into peroneal + post. Tibial
How do GF induce angio/arteriogenesis?
Factors that mobilise progenitors e.g. GM-CSF, G-CSF, SCF
Induction of homing e.g. SDF-1
How does cell therapy induce angio/arteriogenesis?
Identification of organ-specific cytokines
• Ability of cells to incorporate and function in hostile environment e.g. ischaemic muscle
List causes of leg oedema
- Dependency/immobility
- Pregnancy
- Heart Failure
- Low plasma proteins
- Chronic venous insufficiency
- Deep vein thrombosis
- Lymphatic insufficiency
- Chronic renal failure
What is chronic venous insufficiency?
Superficial (greater and lesser saphenous vein) and deep (femoral and popliteal) venous circ drain blood up towards heart
DVT blocks deep veins which stops BF back up to heart and damages deep vein valves –> venous hypertension + swelling of the leg
What is Starling’s Law?
The stroke volume of the heart increases in response
to an increase in the volume of blood in the ventricles,
before contraction, when all other factors remain
constant.
