Endothelium Flashcards
Where are Endothelilal cells found?
They make up the single cell layer lining the inner surface of blood vessels. Found in lymph vessels too
Processes controlled by endothelial cells
Vaso reactivity (tissue perfusion), initiating, stopping and reversing clotting, directing immune cells, gas, waste & nutrient exchange, tissue repair & angiogenesis
4 layers of arteries
Adventitia, elastic lamina, media, intima (endothelial cells)
What happens to the volume and pressure in capillaries compared to arteries?
Volume increases, pressure drops
Embryological origin of endothelium
Mesoderm - primitive vasculoblast forms arteries and veins
Direction of endothelial cells in relation to smooth muscle cells
Perpendicular to increase contact
Function of pericytes
Support and maintain structure of endothelium - can become muscle or endothelium
Function of tight junctions
Stops anything passing between cells and maintains polarity of cell by keep transporters and receptors in the right place
Function of gap junctions
Allow communication between endothelium cells - rapid
Function of adherens junctions
Hold cells together for structure in endothelium and epithelium - connected to actin so involved in movement of the cell and important in angiogenesis
Transport across endothelium - filtration
Moves down a pressure gradient (hydrostatic and oncotic)
Where is active transport found in the endothelium?
The brain
Locations of continuous capillary endothelium
Skin, muscle, lung and cns-allows smooth passage of blood
Locations of fenestrated endothelium
Exocrine glands, renal glomeruli, intestinal mucosa - leaky so parts of blood pass out
Locations of discontinuous endothelium
Liver, spleen, bone marrow -whole cells can pass out eg immune cells
Function of blood brain barrier
Protect brain from circulating toxins and infection etc
Structure of BBB
Endothelial cells with extremely tight tight junctions, high density of pericytes on basal lamina, surrounded by astrocytes (structural cells in brain)
What molecules can cross bbb?
Very small ones and lipid soluble ones(esp if small)
Effect on filtration if efferent renal arteriole constricts
Filtration increases as pressure increases
What are podocytes? Function?
Epithelial cells lining capillaries of Bowman’s capsule - prevent passage of large molecules such as proteins, support membrane and allow small water soluble molecules to pass through such as urea
Function of renal endothelium
Ready passage of small water soluble molecules, prevent passage of proteins and cells, sense change in flow rate and secrete renin accordingly
Structure of liver endothelium
Sinusoidal, no basement membrane - sinusoids contain mix from hepatic artery and portal vein
Function of endothelial cells in angiogenesis
Can divide in situ (clonal expansion) or migrate locally - also have circulating endothelial progenitor cells from BM.
Growth factors that cause migration of endothelial cells in angiogenesis
VEGF and PDGF
Benefits of angiogenesis for malignancy
Promotes primary tumour growth and facilitates malignancy - tumour secrets growth factors to cause angiogenesis - target angiogenesis to treat
Why do CNS primaries rarely metastasise?
Hard for tumour cells to break through BBB tight barriers
How do endothelial cells rapidly auto regulate blood flow?
Direct contact with smooth muscle cells - detect change in pressure and signals accordingly
Does the endothelium secrete mainly vaso constrictive or dilatory factors?
Dilatory
What factors control vascular tone?
Neuronal, hormonal and local factors
How does calcium influx cause dilation?
Activates nitric oxide synthase
Vasodilatory molecules
NO, prostanoids, hyperpolorizing factors
Vasoconstrictive molecules
Endothelin
How does the endothelium regulate platelet aggregation and coagulation?
Releases pro and antithrombotic factors
Under normal conditions, what does the endothelium promote with regards to clotting?
Anti platelet aggregation factors, fibrinolytic proteins, anticoagulant factors
What does chronic endothelial damage do to its control of clotting?
Reduces its anti-clotting effects
What does VWF do in clotting and when is it released? Role in atherosclerosis?
Its released when collagen exposed, binds to platelets and activates fibrinogen cascade forming platelet clump - happens pathological in atherosclerosis
What does VWF protease do?
Cleaves platelet aggregation and turns off clotting
How does the endothelium interact with the immune system?
Expresses selectins and adherins at site of infection to bind immune cells (adhesion) and allow extravasation (follow chemokine gradient after this)
Release pro inflam cytokines to recruit immune cells
Cause local tissue damage by releasing proteases and inducing necrosis
Why do steroids cause a rise in neutrophil level?
Stops immune cell adhesion so less neutrophils stuck to lining and more free in plasma
5 features of inflammation
Pain, erythema, fever, oedema, loss of function
Effects of sepsis on endothelium and smooth muscle
Triggers localised apoptosis and necrosis (cytokines), weakens junctions between endothelial cells, increases expression of adhesion molecules, increase NO & prostacyclin synthesis (vasodilation), Increase VWF and prothrombotic factors (clotting then bleeding when all used up)
Effect of excess NO production (may be from bacterial endotoxin)
Hypotension, oedema with protein loss reducing hydrostatic and oncotic pressure (can breakdown BBB)
What is vasculitis? Severity?
Inflammation of the blood vessels-can occlude or can leak (primarily arteries but can be others). Severity ranges from benign to rapid life threatening
Causes of vasculitis
Infections Autoimmune (immune complex deposition or immune mediated tissue destruction)
Causes of chronic activation of the endothelium
Hyperlipidaemia, hyperglycaemia, smoking, hypertension
How does chronic endothelial activation cause atherosclerosis/diabetic vasculopathy?
Reduces NO production causing unopposed sympathetic constriction
Cells more permeable to lipoprotein which accumulates
Increased production of extra-cellular matrix helping form plaque
Inflam response alters expression of cell surface receptors regulating anticoag and neutrophil/monocyte diapedesis
How does impaired NO production in endothelial dysfunction contribute to angina and PVD?
Can’t increase NO when required e.g. in exercise
How does atherosclerotic plaque rupture lead to thrombus formation?
Exposes collagen causing clotting
