Vasculature Flashcards
3 Tunics
- Tunica Intima - innermost (closest to lumen); simple squamous epithelium (endothelium) w/ underlying connective tissue (sub-endothelium)
- Longitudinal along lumen
- Tunica Media- smooth muscle cells that make collagen and elastin (instead of fibroblasts)
- Circumferential around lumen
- Tunica Adventitia - more loose; some smooth muscle, fibroblasts; sometimes small nerves (nervi vasorum) and small blood vessels (vast vasorum) and lymphatic caps
- Also longitudinal
BP, Thickness and Lumen of Diff Vessels
- Aorta (thickest wall/smallest lumen) —> artery —> arterioles —> caps —> venules —> veins —> vena cava (thinnest wall/largest lumen)
- Arteries experience highest pressure —> veins experience lowest pressure and arterioles provide transition in pressure
3 Types of Arteries
Elastic - conducting
Muscular - distributing
Arterioles - resistance/ control local capillary flow
3 Types of Veins
Venules - WBC extravasation
Muscular - Capacitance
Elastic (vena cava)
3 Types of Capillaries
Continuous - tight seal
Fenestrated - allows regulated ions and fluid through
Discontinuous/Sinusoids - allow large molecules through
Metarterioles
Arteriovenous Anastomoses
Caps only perfused when needed; so mechanisms to bypass all or most of caps
- Metarterioles - thoroughfare channel that skips most of the true cap
- Arteriovenous Anastomoses - large route to totally bypass caps
Resistance
force against which heart pumps
ARTERIOLES adjust resistance so that there us perfusion w/o capillary damage
Capacitance
how much a container can stretch in response to force
VEINS
Lymphatic System and Vessel Structure
- Lymph = one way system to collect excess interstitial fluid —> thoracic duct —> R atria
- Structure (MOST BARE)
- Endothelium but incomplete basal lamina
- No tight junctions
- Only tunica intima and wisp of adventitia
- Only see WBCs in lumen (NO RBCs)
- Also have one-way valves like veins
Vasculogenesis v Angiogenesis
- Vasculogenesis (de novo) - from progenitor cells from bone marrow or blood islands
- Embryos and in adults
- Angiogensis (elongation/remodeling of existing vasculature) - local endothelial cell proliferation
6 Steps of Vascularization
- 1- Initiating signal (hypoxia, growth factors, stretch, shear stress, etc)
- Hypoxia sensed by parenchymal cells —> HIF-1alpha —> transcription of VEGF
- 2- ECM proteolysis
- Need to degrade basement membrane so vessels have somewhere to grow (so endothelial cells can invade this area)
- ECM being degraded also releases growth factors itself
- 3- Migration of endothelium; Can now migrate through broken down ECM
- 4- Proliferation of endothelial cells
- 5- Formation of blood vessel lumen, maturation of vessels
- 6- Inc permeability
VEGF and ANG 1/2
- VEGF - vascular endothelial growth factor
- 6 diff isoforms (alt splicing)
- 2 diff signaling receptors (both tyrosine kinases)
- Non-signaling receptors (neuropilin 1 and heparin sulfate proteoglycans)
- Function = entice surrounding epithelia to proliferate. move and form tubes to vascularize
- Angiopoietins - (Ang 1 2 3 and 4)
- Function = remodeling anf maturation
- Dual roles…
- Ang 1 is positive regulator of maturation by recruiting ancillary cells
- Ang 2 inc angiogenesis if VEGF present (angiogenic phenotype, breakdown ECM, endothelial motility) OR inc apoptosis (regression of vessels) if VEGF not present
How and why to enhance angiogenesis
**In Diabetes or hypertension
- Bone marrow injections - inc # endothelial cell precursors
- Inc VEGF locally via gene therapy or injecting active protein in area (downside= VEGF also inc permeability so could lead to long term edema/worse wound healing
How and why to inhibit angiogenesis
**dec tumor blood supply
- Block VEGF signaling …
- w/ neutralizing antibody (Avastin)
- VEGF receptor trap
- short strands of RNA that interact w/ VEGF to prevent binding receptor
- tyrosine kinase inhibitor to stop signaling (Tarceva, Nexavar and Sutent)
- antibody to block VEGF binding to tyrosin kinase receptor - Breakdown products of ECM that interact w/ endothelium
- MMP inhibitors (Neovastat) - cannot breakdown ECM
Mechanisms of Vasoconstriction (2)
1- Inc Ca++ (G alpha q & IP3)
- NE, endothelin-1, angotensin II, vasopressin
- myogenic stress response
2- Activate myosin light chain kinase (G alpha i leads to dec in cAMP - remove inhibition of cAMP)
-NE
