Squamous endothelium
thin cell layer that covers the blood and lymphatic vessels (very heterogenic according to organ/tissue)
Polarity of endothelium
luminal = blood vessels
aluminal = tissue
polarity is guaranteed tough tight junctions
polarity is required for lumen formation
Zona occulens
formed by tight junctions → “occluding junctions”
Zona adherence
formed by adhesion junctions/belt, desmosomes, hemidesmosomes → “anchoring junctions”
Structure and function of tight junctions
- built by occludin and claudia (+ JAM) protein complex which connect directly to the plasma
- impermeable occlusion → no transport between cells → keeps polarity
Structure and function of gap junctions
- build by connexins which form a connexone which forms a hemichannel → connecting channel between cells
- allows <1,2 nm molecules to pass through (Ca2+, cAMP, Metabolites)
- high amounts of extracellular calcium (injury) can close GJ to seal of neighbouring cells
- functions: 1. metabolite transfer 2. intercellular communication via 2.messenger 3. modulate opening and closing
Structure of the adhesion belt
- located under tight junctions
- cells form a band of cadherin to stabilise their interaction
- supporting function and mechanical coherence
Structure of the basal membrane
- Network of collagen type IV cross linked via laminin, entactin and proteoglycan perlecan
- Laminin connects to integrins through collagen IV and sulphated lipids
- Integrins connect ECM and cell
Types of capillary endothelia
- Continuous endothelia: muscle, heart, lung, brain
- Fenestrated endothelia: kidney, intestinal villus
- Discontinuous/ Sinusoid endothelium: liver, spleen, bone marrow
Structure of the blood brain barrier
Is a system of BMVEC (brain microvascular endothelial cells) that together with astrocytes, pericytes, neutrons and basement membranes for the neuromuscular unit.
Endothelia of the kidney
- glomeruli endothelial cells
- fenestrae
- glomerular filtration of water and small solutes through fenestrae
Endothelia of the liver
- liver sinusoidal endothelial cells (LSEC)
- sinusoids: capillaries with pores and fenestrae lacking a diaphragm
What causes dilation/ contraction of fenestrae?
Dilation: Acetylcholin, Ethanol
Contraction: Nicotine, Ethanol abuse, Adrenalin
Diameter of fenestrae is regulated by actin, myosin and calmodulin (Ca2+ dependant)
What regulated the vascular tonus?
- contraction state of smooth muscle cells
- circulating factors (acetylcholine, bradykinin, angiotensin II)
- heamodynamic forces (stress)
Endothelial vasodilators
- NO (Nitric oxide)
- PGI2 (Prostacyclin)
- EDHF (Endothelial hyperpolarising factor)
Vasodilating effect of NO
Acetylcholin or bradykinin bind to beta-receptor on endothelial cell → Ca2+ released and signals NO-Synthetase III to release of NO from L-Arginine → NO activates guanylcyclase in smooth muscle cells to form cGMP from GTP → cGMP activates protein kinase G-type (PKG) → smooth muscle cells relax
Prostacyclin
- Synthesised by arachidonic acid
- enhances NO release (vasodilating)
- Thromboxan A2 antagonist
Mechanism of Endothelial derived hyper polarising facto
Haemodynamic forces → EDHF release in endothelial cells → K+ storms out of smooth muscle cell → causes hyper polarisation → relaxation of smooth muscle cell
Endothelial vasoconstrictors
- Endothelia-1
2. Angiotensin II
Adhesion of leukocytes to the endothelium
- Rolling/Chemotaxis: Leukocytes interact with Selectins expressed by endothelial cells
- Adhesion: Leukocytes bind to ICAMs through interns → firm adhesion
- Diapedesis: leukocytes form pseudopods that dissolve cell contacts to facilitate extravasation of leukocytes
- Migration: extravasation of leukocytes towards the site of inflammation
Arteriosclerosis
stiffening or hardening of the artery wall
Atherosclerosis
narrowing of the artery due to plaque formation
Fibroatheroma
Formation of fibrous plaque
Sepsis/SIRS
= systemic inflammatory responce syndrome
exaggerated defence response to a noxious stressor
Aneurysm
abnormal localised dilation of a blood vessel → weakens blood vessel