Exam1Lec4ControlofBloodFlowandTheMicrocirculation Flashcards
What are blood vessels for?
Delivery of nutrients, removal of wastes, and gas exchange
How do blood vessels nutrients to the tissues?
Microvascular exchange a consequence of vessel permeability
Are all blood vessels perfused all the time?
NO, so your body must prioritize blod flow to the metabolically active organs.
What constitutes the highest surface area?
Capillary beds
with high surfce areas you can get as much o2 into your blood quickly
Where do we see the lowest/slowest blood velocity?
Capillaries
they are known as the exchange vessels to allow tfor maxiumum exchanfe
Most of the blood volume in what?
Veins
Label capillaries, veins, and arterioles as
exchange vessels
capitance vessels
resistance vesses
capillaries-exchange vessels
veins-capitance vessels
arterioles-resistance vesses
What are the 3 types of capillaries?
- Continuous (very controlled-BBB)
- Fenestrated (most normal)
- Sinusoidal (discontinous- spleen or liver)
What do arterioles respond to?
- Tissue demand (metabolite)
- Flow and pressure inside the vessel
- neurogenic stimuli
- hormones, drugs, other chemical stimuli
arteriorles simultaneouslt control SVR (Systemic vascular resistance) and blood flow to tissues
When looking at a cross section of an arteriole, what is the order of layers from innermost to outermost?
- Endothelial cells
- SM cells ( these constrict or dilate to regulate vessel diameter)
- Nerve bundles
- CT
Give a general explanation of electrochemical coupling
There’s a membrane dep, and there is an influx of ca2+ causing muscle contraction/constriction
main thing is that calcium comes inside smooth muscle cell and causes contraction/constriction
Give a general explanation of pharmacomechanical coupling
a vasoconstrictor agonist drug binds to gpcr causing different signaling cascades and specifically IP3 open Ip3 receptors on sarcoplasmic reticulum and releases ca2+ into smooth muscle cells causing constriction
main thing is that calcium comes inside smooth muscle cell and causes contraction/constriction
Sympathetic stimulation results in what?
Vasoconstriction (arterioels can constict and shunt blood flow to the body)
for ex, in an experiment they shunted epineph and the smc consticted all the way so that rbc can’t go through
neurogenic control of arteriolar tone
Sympatheitc NS
releases____ which binds to ____ causing ____
It can also have ____ released inside the cell which then triggers the release of ____ from the SR.
NE, alpha receptors on vmsc, constriction, ip3 Ca2+
What is innervated by sympathetic ns by SNS fibers:?
arteries, arterioles, veins, and lymphatics
neurogenic control of arteriolar tone
Parasympathetics NS releases____ which binds to ____. A signaling cascade occurs and can lead to an activation of an enzyme called ____
Ach, muscarinic receptors on endothelial cells, eNOS
eNOS enzyme is going to produce ____ which then diffuses to ____ and these activate____, which then produces ____ which leads to ____.
NO, VSMC, sGC, cGMP, dilation
small fracion of vessels are innervated with parasymp fibers
In the experiment that has to do with endothelial regulation of arteriolar tone, what are the main points.
When adding CCh and ACh they both causes relaxation bc of decr tension and dilation occuring with endothelium present. If you take a helical strip, the endothelium was removed, killing endothelial cells. So when you add a higher dose of CCh it is unable to produces NO and eNOS causing constriction.
cannot dilate vessel w/o endothelial cells
Explain endothelial regulation of arterioriolar tone.
We have a ligand such as ACh, serotonin, thrombin, or bradykinin binding to a muscrinic receptor releasing Ca2+ into the endothelial cell. This release activates eNOS which needs a co-factor of eitherr Calmodulin, NADPH, FAD, BH4 to catylze a rxn of turning L-Arginine to both L-Citrulline and NO( eNOS turning to NO). NO freely diffuses into vascular smooth muscle cell activating GC with is an enzyme that converts GTP into cGMP causing relaxation.
slide 18 of lecture
cGMP activates myosin light chain phosphotase> muscle relaxation
Calcium in endothelial cell causes relaxation
Calcium in in smooth muscle cell causes constriction
What is Sidenafil?
It is a cGMP phosphodiesterase inhibitor (PDE5). It breaks down cGMP deactivating the pathway of relaxation .
turns cGMP to GTP leading to contraction remaining
Explain how arterioles contribute to myogenic response of autoregulation of blood flow
Arterioles protect capillary beds bc with an incr of pressure, the arteriole dilate transiently and then constricts to limit the amount of pressure reaching capillary beds to prevent rupturing and bledding from capillaries bc they don’t have a layer of smooth muslcle cells to expand.
For myogenic response for autoregulation, is endothelium involved?
How can this response eliminated? what is required?
- Endotheloum is not involved (kill endothelial cells and smc still does the job)
- Treatment with NO will cause smc to completely dilate, so no constric occurs
- VSMC alone is required ( no nerves )
What is the myogenic hypotheis of autoregulation?
Vascular SMC themselves contracts/constricts in response to an incr in pressure. Conversely, VSMC relaxes in response to a decr in pressure.
With incr transmural pressure, incr stretch, incr constriction
transmural pressure= (pressure inside-pressue outside)
What is active hyperemia?
Incr metabolic activity that creates byprodycrs that induce vasodilation and a subsequent incr in blood flow (hyperemia)
ex: working out; lots of reps, little weigjt, incr bf to muscles
eating a meal, decr in vaso resistnace, incr bf into gut to meet tissue needs
What is reactive hyperemia?
Ischemia also creates a buildup of metabolic waste products that induce reactive hypermia once blood flow is reestablished (reperfusion injury)
certain amount of blood flow and it stops
This happends durign heart attacks
Iscemia, see a decr in pressure of O2, incr lactate production, CO2, and adenosine which are all potent vasodilators. Hyperemia when blood flow is restored (this isnt good bc the dilators let blood flood into the body at once)
Explain the metabolic hypothesis of autoregulation
Blood flow in a given tissue is controlled by the metabolic activity of the tissue. Any intervention thatg results in an inadequate O2 supply prompts the formation of metabolic byproducts that vasodialte arteries.
lack of O2–> metabolic products–> vasodilation
Explain flow-induced vasodialation
Pressure is incr on one side and lowered on the other equally. You see increases flow w/o changing pressure and you see more dilation.
Endothelium explains this and confirms that NO plays a part
endothelial regulation of blood flow
The endothelium is a ____ and stimulates ____ in repsonse to an incr in flow by producing an ____
mechanosensor, vasodilation, endothelial-derived relaxing factor (NO)
smooth muscle cells can respond to
metabolism with?
pressure with?
blood flow with?
neural stimuli with?
- metabolic autoregulation
- myogenic autoregulation
- endothelial-dependent control of arteriolar tone
- autonomic ns (primarily sympathetic)
What is the main site for exchange?
Capillaries
What are 4 features of capillaries?
- Single layer of endothelial cells
- Huge surface area
- Low flow velocity
- Cannot dilate (no smc)
What are three different pathways that make capillaries permeable?
how do we get stuff from inside bloodstream to outside bloodstream
- Cell to cell junctions: gaps b/w epithelial cells and can let things leak out ( CONT CAP)
- Fenestrae: allows lots of fluid to pass though w/o proteins coming through
- Caveolae: vesicles within cells can transport things from inside cell to outside (SINUSOIDAL/DISCONT)
- fluid and protein
- only fluid
- pits that move nutrients across capillary beds
What are 4 ways that vascular permeability is medically crucial?
- Bathing tissues in nutrients and removal of wastes
- Maintianing basal permeability to prevent edema
- Inflammatory responses: incr vascular perm is 1st step in inflammation
- Regulating the transmigration of immune cells to fight infection or resolve inflammation
Explain what happens with a mosquito bite
- Mast cells in tissue are activated
- Histamine is released
- You then see
-tumor: swelling (incr perm)
-rubor: redness (vasodilation, bf)
-calor: hot (vasodilation, bf)
-dolor: pain (swelling, histamine)
4 r’s of inflammation
How does stuff get out the capillaries? (name the types of ways)
- Convection (filtration): high hydrostatic pressure in the capillaries forces water across the endothelium, which can drag solutes with it. (solutes follow water)
- Diffusion (osmosis): solutes across the semi-perm endothelium according to their concentration gradients ( water follows solutes)
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What side is filtration and do you see high or low hydrostatic pressure? and do you see high or low oncotic pressure?
- Arterial side
- High hydrostatic pressure
- Low oncotic pressure
What side is reabsorption and do you see high or low hydrostatic pressure? and do you see high or low oncotic pressure?
- Venous side
- Low hydrostatic pressure
- Similar low oncotic pressure
What is starling’s law of filtration?
Fluid is filteres from the arterial side of the capillary bed and ~90% is reabsorped on the venous side
What is the starling’s law of filtration equation?
Describes fluid flux (volume flux/fluid movement)
for the revised law of filtration is that the effectice osmotic gradient is 0
What is fick’s first law?
Describes solute flux
Does fluid and solute flux go hand in hand or are they independent of one another?
They go hand in hand, (co-dependent of one another) if you have a lot of fluid coming out or in, its going to take the solute with it. There is an equation that puts both of them together, but it wont be on the test.
What regulates endothelial permeability?
Glycoocalyx: keeps albumin inside bloodstream so it doesnt leak out. It can use vesicles if it wants to transport albumin
Juction proteins
Caveolae
How do we maintain fluid homeostasis?
Lymphatic vessels (capillaries) absorb tissue fluids that your blood vessels leak out and yout smc and collecting lymphatic vessels does action potentials and pumps it towards lymph nodes to initiate an immune response.
If we don’t do this, bc will leak out everything.
What is the general flow for how lymphatic vessels act as immune cells?
Blood Vessel filtration–>interstitial space & immuhne cellls–> lymphatic absorption
How can lymphatic vessels prevent edema?
Incr tissue pressre (Pt) drives lymph flow, which clears excess fluid
Why are lymphatic vessels permeable?
Collecting lymphatic vessels actively pump (like cardiomyoctes in the heart) and they lose small amounts of fluid and solutes ( albumin, lipids)
How does lymph flow initiate immune respones?
Lymph is carried to lymph nodes along with immune cells to initate immune responses.
What is the largest lymphatic in the body and what does it do?
Thoracic duct, and it empties all lymph into the left subclavian vein
How does lymphatic vessel play a role in diet and cholesterol?
It is requires to the absorption of dietary lipids from the intestinal lumen and for the removal of cholesterol from peripheral tissues (rev chol transport) to take it to the liver to be excreted
What is the macromolecule responsible for 85% if osmotic pressure gradieny in plasma?
Albumin and it is remived from the tissues by lymphatic vasculature
When lymphatic vessels fail to remove fluid, what occurs?
Interstitial fluid builds up causing lymphedema.
What are two ways a person can get lymphedema?
Inherited because of genetic mutations (Foxc2) or it can be acquired later in life ( axillary dissection for breast cancer)
Incr lymphatic vessel permeability can lead to what?
Adipose deposition and obesity
Cholesterol removal from artersclerotic plaques may be dependent on what?
Lymphatic vessels
What are the 3 types of capillaries?
- Continuous (very controlled-BBB)
- Fenestrated (most normal)
- Sinusoidal (discontinous- spleen or liver)
