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74 Cards in this Set
- Front
- Back
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What cells is the intima composed of?
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endothelial cells
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What cells is the media composed of?
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Vascular smooth muscle cells and ECM
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What separates the media from the other two layers?
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Boundaries of elastin
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What cells does the adventitial layer contain?
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Nerves, lymphatics, blood vessels (vasa vasorum) that nourish the blood vessel wall
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What affect does blood pressure have on the vessel wall? Which direction does the vector point?
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Represents the dilating force of blood pressure on the vessel
Points perpendicular to the wall and represents blood pressure |
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What affect does shear stress have on the vessel wall? what direction does the vector point?
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Represents the frictional force that blood flow exerts on the endothelial surface of the vessel wall
Force is parallel to the vessel wall |
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What disrupts steady laminar flow of blood? how does this affect shear stress?
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Curvatures at the arterial wall such as the aortic arch and at bifurcations and near branches
Decreases shear stress |
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How are endothelial cells arranged in areas of high shear stress? low shear stress?
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high shear stress: endothelial cells are aligned in the direction of flow w/ the formation of very long, well-organized, parallel actin stress fibers
low shear stress: Configured w/o preferred orientation |
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What does a reduction in mean shear stress in a vessel promote?
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Formation of atherogenesis and inflammation
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What is sustained laminar blood flow and high shear stress associated with?
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downregulation of atherogenic genes and upregulation of antioxidant and growth-arrest genes in endothelial cells
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What would downregulation of monocyte chemotactic proteins 1 (MCP-1) be associated with? what mediates this pathway?
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Sustained laminar flow in vessels and high shear stress
Mediated by the MAPK pathway |
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What would upregulation of antioxidant and growth-arrest genes in endothelial cells be associated with?
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sustanined laminar flow and high shear stress
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What would disturbed flow and the associated low shear stress induce genetically in endothelial cells?
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Activation of a number of atherogenic genes in endothelial cells that enhance monocyte adhesion and infiltration into the arterial wall
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What can cause enhanced monocyte-endhothelial cell adhesion?
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1. altered expression of ICAM-1 and E-selectin on endothelial cell surfaces
2. enhanced collision and prolonged contacts b/e circulating monocytes and ECs as a result of higher near-wall concentration 3. longer resident time 4. smaller tangential velocity along the wall in disturbed areas |
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Where does atherosclerosis preferentially develop?
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At arterial branches and curvatures
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What is flow dependent vasodilation?
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An acute increase in blood flow increases shear stress which induces nitric-oxide induced vasodilation
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What molecule principally performs biosynthesis of nitric oxide?
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NO is principally performed by the calcium-dependent endothelial isoform of endothelial nitric oxide synthase (eNOS)
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How does NO induce vasodilation?
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1. shear stress or binding of agonist
2. eNOS catalyzed conversion of the L-arginine into NO, w/ L-citrulline as a byproduct 3. diffusion of NO into adjacent smooth muscle cells where it activates its effector enzyme, guanylate cyclase (GC) 4. GC converts GTP into cGMP which activates PKG 5. Activation of PKG leads to modulation of myosin light-chain kinase and smooth muscle relaxation 6. PKG also modulates the activity of potassium channels (Ik;6) increasing cell membrane hyperpolarization and causing relaxation |
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What cofactors facilitate shear stress/binding of agonists to initiate vasodilation?
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heat shock protein 90
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What are the vasoconstricting molecules?
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1. endothelin
2. thromboxane A2 3. endothelium-derived contracting factor (EDCF) |
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What pathological conditions can promote the release of endothelin, and therefore vasoconstriction?
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hypoxia
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What does binding of endothelin to its receptor cause?
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Promotes an increase in [Ca] intracellularly via the PLC/IP3 pathway
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How do endothelial cells and platelets metabolize arachidonic acid?
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Through the COX pathway to produce TXA2,
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What does binding of TXA2 to its receptor cause?
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Opens L-type Ca channels => increases the intracellular [Ca]
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What is EDCF?
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A superoxide anion that antagonizes the effect of NO
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What enzymatic actions do endothelial cells have on plasma? what do these enzymes specifically do?
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luminal surface of endothelium has ACE and carbonic anhydrase.
ACE converts angiotensin to angiotensin II which is an important vasoconstrictor Carbonic anhydrase is important in acid-base regulation |
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What are the antihemostatic and hemostatic roles of the endothelium of vessels?
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NO and prostacyclin not only affect vascular tone, but also inhibit platelet aggregation and thus blood clotting
Von Willebrand factor is a vital component of the clotting cascade |
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How does the endothelium participate in defense against pathogens?
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Endothelium plays an active role in the inflammatory response to pathogens by producing adhesion molecules which induce circulating WBCs to emigrate into the affected tissue
ALSO endothelial permeability to immunoglobulins is dramatically increased by the active formation of endothelial cell gaps |
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What is the angiogenic role of the vessel endothelium?
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Angiogenesis begins at the endothelial level which occurs in wound repair and tissue growth, also occurs in tumor growth
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What is autoregulation?
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The ability of an organ to maintain normal blood flow in the faces of arterial pressure
A local phenomenon that is INDEPENDENT OF ANY NERVE ACTIVITY |
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what mechanisms is autoregulation related to?
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metabolic and myogenic control mechanisms as well as to an increased release of NO
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When is blood flow pressure-passive?
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At pressures outside the autoregulatory range:
i.e. pressures above 160mmHg vascular resistance decreases b/c the pressure forces the vessel to dilate Pressures below 60mmHg the vessels are fully dilated and resistance cannot drop any further |
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What is the metabolic control of blood flow?
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A period of flow restriction (like ischemia) to a local tissue bed can decrease O2 and lead to an accumulation of metabolites such as:
*lactate, adenosine, CO2, H+, K+ and inc. osmolarity which all result in vasodilation ALSO increased ATP utilization (exercise) leads to accumulation of the above metabolites, as well as NO-mediated vasodilation (from inc. shear stress) and opening of Katp channels |
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What is the myogenic mechanism of autoregulation?
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dec. blood flow/ dec ATP / opening of Katp channels / inc. N.O. => vasodilation
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How does decreased blood flow and dec ATP lead to vasodilation?
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Through accumulation of metabolites such as adenosine, CO2, H+, K+, lactic acid and inc. osmolarity
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What does removal of flow restriction lead to? what is it?
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reactive hyperemia; a period of higher than normal blood flow that occurs transiently
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What is the myogenic mechanism of autoregulation?
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increased blood flow/perfusion pressure => vascular smooth muscle stretched => inc. stretch opens cation channels => membrane depolarizes => Cav channels open => Ca influx triggers contraction => vasoconstriction => dec. blood flow/perfusion
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What receptors are on veins and arterioles? what is the action of this receptor?
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alpha-1 adrenergic vasoconstrictor receptors
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What metabolites act on veins?
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B/c veins have such little basal tone and are usually in a dilated state metabolites that accumulate have no effect on veins
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What do veins have that prevent reverse flow?
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Valves
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What effect on blood flow does lying have? standing? prolonged standing? walking?
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lying makes all venous valves open and allows venous blood to flow to the heart continuously
standing causes venous pressure in the foot to rise as blood pools in the veins of the lower extremity due to gravity prolonged standing causes edema walking causes a pumping action of leg muscles on leg veins and facilitates venous return, causing venous pressure to decrease |
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What is vasomotion? what causes it?
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Blood does not flow continuously but flows intermittently turning on/off every few seconds
due to intermittent contraction of arterioles and pre-capillary sphincters |
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What is the most important factor that regulates opening and closing of arterioles?
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The concentration of oxygen in the tissues. When oxygen usage is great and [O2] decreases below normal, the intermittent periods of blood flow occur more often and duration of flow lasts longer allowing capillary blood to carry increased quantities of oxygen to the tissues
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What is the formula to calculate extraction ratio of oxygen from tissue?
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EO2 = ([O2]a - [O2]v)/[O2]a
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How do lipid soluble substances cross the capillary endothelium? water soluble substances?
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lipid soluble substance (including O2 and CO2) diffuse directly through the cell membranes of the capillary endothelium
water soluble substances (Na, Cl-) diffuse through intercellular pores/fenestra/gaps in the endothelium |
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What is the equation to calculate the quantity of substance moved per unit time?
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J = P x S (Co-Ci)
J= flux P=permeability S=surface area Co=concentration of substance outside the capillary Ci=concentration of substance inside the capillary |
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What is the relationship b/e quantity of substance that diffuses across the capillary membrane per unit time (J) and surface area? concentration gradient?
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J is directly proportional to surface area and concentration gradient
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What is flow limited exchange?
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exchange of solutes is limited by the rate at which plasma delivers the solute b/c the rate of diffusion is much faster that blood flow out of the vessel.
Like if you were delivering a herd of cheetahs to the zoo they would run through the gate super fast, the only way to speed up putting the cheetahs in the zoo is to speed up the trucks delivering the cheetahs |
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What molecules are flow limited?
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small lipid-soluble substances like O2 and CO2, and lipid insoluble substances like glucose and urea
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What is diffusion limited exchange?
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Exchange through the capillary wall that is limited by the rate at which the capillary wall allows solutes across
LIke if you were delivering a herd of elephants to a zoo but the trucks only slowed down during delivery and didn't stop, so the number of elephants that got through the gates into the zoo would be limited by the speed you could throw them out of the truck |
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What molecules are limited by diffusion?
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Large molecules and when distance b/e capillaries and cells are great like in tissue edema or very low capillary density
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What factors control the permeability coefficient?
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1. fraction of capillaries open to blood flow
2. signaling molecules 3. molecular radius of the solute 4. electrical charge of the solute |
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What is the permeability coefficient?
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The factors that control solute diffusion through a capillary wall
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what signaling molecules increase leakiness of endothelial cells?
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Histamine
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What affect on permeability does increased molecular radius of the solute have?
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Permeability falls as radius increases
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What effect does the electrical charge of the solute have on permeability?
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positively charged > neutral > negatively charged
Fixed negative charges in diffusion path exclude negative charged solutes and favor transmission of positively charged solutes |
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What is filtration? what is reabsorption?
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filtration: Net movement of solutes out of capillaries
reabsorption: net movement of fluid into capillaries |
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What is the equation to calculate net filtration rate? what does a positive value mean? negative value?
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Qf = k[(Pc - Pi) - (πc - πi)]
Positive value: means net filtration Negative value: means net reabsorption |
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What is the hydrostatic pressure? what factors contribute to it?
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Capillary blood pressure
1. arteriolar dilation / venous constriction 2. arteriolar constriciton / venous dilation 3. location (higher Pc in renal glomerular capillaries 4. gravity |
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What effect on hydrostatic pressure does arteriolar dilation / venous constriction have?
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increases capillary hydrostatic pressure leading to filtration
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What do high net filtration rates lead to?
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edema (excess fluid) in the interstitial space
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What effect does arteriolar constriction / venular dilation have? how does this help in bleeding?
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Decreases capillary hydrostatic pressure leading to reabsorption
In the face of severe loss of blood volume (hypovolemia) it can help restore the volume of circulating blood |
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What opposes capillary filtration?
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hydrostatic or blood pressure in the interstitial space (or tissue pressure)
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What is the colloid osmotic pressure (oncotic pressure)? what factors control it?
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Osmotic pressure from plasma proteins in the capillaries
Controlled by the reflection coefficient, composition and concentration of plasma proteins, negative charges carried by plasma proteins |
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What factor prevents excessive fluid loss from the capillaries?
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Capillary colloid osmotic pressure
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What does a reflection coefficient = 1 mean? =0?
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=1: no particle can pass through a membrane
=0: every particle can pass through a membrane |
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What organ has the lowest reflection coefficient? highest?
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Liver has the lowest, brain has the highest
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How do negative charges carried by plasma proteins affect the capillary colloid osmotic pressure?
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Negative charges carried by plasma proteins increase the concentration of cations inside the capillary; increasing osmotic pressure
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What is the interstitial osmotic pressure? what alters it?
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The small amount of albumin that escapes capillaries causes a small osmotic pressure
altered by location along the capillary (the farther along the capillary the higher the interstitial osmotic pressure) |
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What is responsible for movement of large lipid insoluble molecules b/e the blood and interstitial fluid?
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Pinocytosis
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How do plasma proteins in the interstitial space reenter circulating blood?
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Lymphatic system
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What tissues do not have lymphatics? what tissue has the most lymphatics?
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Brain and myocardium have no lymphatics
GI, skin, GU and respiratory system have the most lymphatics |
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What restricts the movement of lymph?
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One-way valves
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What pumps lymph through lymph vessels?
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passive processes such as extravascular pressure changes elicited by skeletal muscle contraction, respiratory movements and intestinal contractions
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