The Cardiovascular System Flashcards
vascular system mission
maintain quality & volume of ECF
- this occurs in the microvascular (i.e. capillary) bed - all cells must be <200 micrometers of a capillary (or else the cells will die)!
at what level of the vascular system does metabolism, gas and nutrient exchange take place?
at the microscopic capillary level
BVs have 3 “tunics”. what are the 3 tunics and what comprises each layer?
from the outside in: Tunica Adventitia: outer – CT (connective tissue) Tunica Media: most variable – SMCs (especially on the arterial side, less on the venous side) & CT Tunica Intima: inner – endothelium, of endothelial cells (ECs) • simple squamous with basal lamina
what is the turnover rate of endothelial cells?
1%/day
what are the layers of the heart?
from inside out:
Tunica Intima = endocardium – simple squamous endothelium/basal lamina Tunica Media = myocardium – myocytes &fibroblasts – attaches to dense CT ‘skeleton’ Tunica Adventitia = epicardium – simple squamous – niche of adult resident cardiac stem cells? (NEW idea!)
how do epicardial cells grow during development?
during development, epicardial cells grow over the surface of the heart as a mono-cellular layer.
what do epicardial cells give rise to?
• “cardiac” fibroblasts (we are not sure if these are the same or different from fibroblasts we find elsewhere)
• coronary arteries
– endothelial cells
– SMCs
* cardiac myocytes?composition and characteristics of large arteries
Large “Elastic” Arteries: thick wall
1. Adventitia: external elastic membrane
2. Media: thickest
• circular SMCs with 40-70 elastic lamellae
3. Intima: endothelial cells
• tight junctions (so things cannot get into the extracellular space) & pinocytotic vesicles (nutrients exchange occurs through this mechanism)
function and clinical applications related to large arteries
Function: elastic recoil to maintain BP during diastole
Clinical: aneurysm
composition and characteristics of large veins
Large Veins: thin wall
The adventitia is the thickest tunic in large veins.
composition and characteristics of medium arteries
Medium Vessels Muscular Arteries: 1. Adventitia: 2. Media: prominent ~ 40 layers SMC, less elastin 3. Intima: internal elastic lamina
function of medium arteries
Function: SMCs regulate BP.
clinical relevance related to medium arteries/vessels
Atherosclerosis = intimal plaques from ‘foam cells’
1.macrophagesingestLDL(badcholesterol)
2. SMCs –> intima, ingest LDL
=macrophages and SMCs form foam cells
Plaques calcify, platelets attach–>thrombus–> MI/stroke
composition and characteristics of small arteries and arterioles
Small Arteries & Arterioles:
t. media: ~8 layers SMC in small artery, down to ~2 layers SMC in arteriole
functional and clinical relevance related to small arteries and arterioles
Function: SMC (in the tunica media) regulates bloodflow to capillary bed (where metabolic action occurs).
Clinical: lipid uptake by SMCs narrows lumen –> hypertension
composition and characteristics of capillaries
• diameter of lumen accepts ~1 RBC ~ 7.5 micrometers
• 1 endothelial cell can make up a tube
• simple squamous endothelium with basal lamina
- no media, no adventitia
3 types of capillaries
- Type I: continuous
- Type II: fenestrated
- Type III: sinusoidal
characteristics of Type I capillaries
– tight junctions: admit proteins only smaller than 10 kDa
– pinocytotic vesicles: permit passage of proteins >10 kDa
– Pinocytotic vesicles are not present in the CNS.
characteristics of Type II capillaries
– 100 nm windows = permanent pinocytotic vesicles (holes in the cells…things can get through easily)
characteristics of Type III capillaries
- discontinuities (spaces between cells)
- larger than capillaries type I & II; ~30 μm diam. (about 4 RBCs can pass through a Type III capillary at the same time)
Locations of Type I capillaries and the items transported
locations: CNS heart skeletal muscle lung item transported: oxygen/gases
Locations of Type II capillaries and the items transported
locations: endocrine glands GI tract kidneys items transported: hormones, nutrients, ions
Locations of Type III capillaries and the items transported
locations: bone marrow spleen liver item transported: whole cells
function of endothelial cells
- exchange gases & nutrients
– gases: thru cell membrane
– nutrients: thru pinocytotic vesicles, fenestrations, discontinuities
2. secrete regulatory molecules – vasoactive factors
• endothelin:vasoconstrictor
• NO (nitric oxide): vasorelaxant
– growth factors
• FGF: fibroblast growth factor
• PDGF: platelet-derived growth factor
• VEGF: vascular endothelial growth factor
=>PDGF, VEGF (and maybe FGF too) are growth factors for active angiogenesis!!
angiogenesis
new blood vessels growing out perpendicular from existing BVs -7 steps first and last step: 1. Activation... • of endothelial cell receptors 7. Inhibition... • of angiogenic growth
angiogenesis; targets, receptors, inhibitors
Angiogenesis: new vessels from existing BVs (adult)
• Vasculogenesis is embryonic BV development.
• target –> endothelial cells
– receptors: VEGFR, FGFR, TIE-2
– ligands:VEGF, FGFs, angiopoietin-1
– inhibitors: angiostatin, endostatin
clinical therapies that target angiogenesis
Clinical Therapies
• Pro-Angiogenic: for ischemia in heart & extremities
– VEGF & FGF-induced BV growth
• Anti-Angiogenic: combat tumors
– 1 endothelial cell can support 50 tumor cells!
– angiostatin & endostatin inhibit new BV growth
examples in which angiogenesis has been used for treatments
- Pro-Angiogenic gene therapy for lower limb ischemia, using VEGF cDNA (at this point, this is not clinically useful, however. Dr. Lough things FGF injection may be more promising!)
- Anti-Angiogenic Therapy in Mice using Endostatin (translating this into a human context has been much more difficult!)
Bevacizumab (Avastin)
anti-VEGF monoclonal antibody
- ->this attacks and neutralizes VEGF
- ->shrinks the vascular supply of tumors
