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Physiology II
Cardiovascular Physiology
Control Of Peripheral Circulation

Key Words

metabolic regulation of blood flow:  The ability of each tissue to control its own local blood flow in proportion to its metabolic needs.  As need increases, flow increases.  Flow follows need.  Guyton pg. 199
There is a quantitative acute effect on local blood flow if you increase the metabolic rate in a local tissue, such as muscle.

metabolic vasodilator theory:  This theory says that the greater the rate of metabolism or the less the availability of oxygen or some other nutrients to a tissue, the greater becomes the rate of formation of a vasodilator substance. This substance then is believed to diffuse back to the precapillary sphincters, metarterioles, and arterioles to cause vasodilation. From class it was discussed that the increase in shear forces on the endothelium would stretch and pull the ends of the endo cells causing a shear deformation that stimulates the release of nitric oxide (NO) which is a potent vasodilator. The velocity in a larger cross-sectional area will decrease thus overall velocity decreases, thus the negative feedback to adjust the changes in diameter in response to changes in velocity. These velocity changes which increase the metab. flow through tissue leads to vasodilation of the SMA so there is decrease in resistance, which will increase flow to tissues. If you increase the flow through the tissues the vessel will have an increase shear and NO will be released further up the line so it allows for a retrograde signal passed back up the cardiovascular system allowing dilation of larger vessels thus an increase in flow. If flow demand is constant and prolonged then there will be a remodeling due to the chronic increased velocity and NO will remodel to increase the radius.

oxygen demand theory:  Also called the nutrient demand theory since other nutrients besides O2 may be involved. This theory states that O2 is required to maintain vascular muscle contraction. Therefore, in the absence of an adequate supply of O2 and other nutrients, it is reasonable to believe that the blood vessels would naturally dilate. Also, increased utilization of O2 in the tissues as a result of increased metabolism would theoretically decrease the availability of O2 to the local blood vessels, and this too, would cause local vasodilation. The strength of contraction of the sphincters would increase with an increase in O2 concentrations. Consequently when the [O2] in the tissues rises above a certain level, the precapillary sphincter and metarteriole sphincter would close and remain closed until the tissue cells consume the excess O2.

vasomotion:  When precapillary sphincters and metarterioles often open and close cyclically several times per minute with duration of open phases proportional to the metabolic needs of the tissues.  Guyton pg. 201

reactive hyperemia:  When the blood supply to a tissue is blocked for a few seconds to several hours and then is unblocked, the flow through the tissue usually increases to four to seven times normal; and the increased flow will continue for an equal amt of time that is was blocked. This is another manifestation of the local control of metabolic blood flow regulation.

active hyperemia:  The increase in local metabolism causes the cells to devour the tissue fluid nutrients extremely rapidly and also to release large quantities of vasodilator substances. The result is to dilate the local blood vessels and, therefore, to increase local blood flow. This pertains to exercising muscle for example.

autoregulation:  In any tissue of the body, an acute increase in arterial pressure will cause an immediate rise in blood flow. Within less than a minute, the blood flow in most tissues returns most of the way back toward the normal level. This return of flow back toward normal is autoregulation.  Regulation of blood flow by the tissue itself.  Whenever excess blood flows through a tissue, local vasculature constricts, decreasing blood flow back toward normal.  Guyton pg. 224

metabolic theory of autoregulation:  States that when the arterial pressure becomes too great, the excess flow provides too much O2 and too many other nutrients to the tissues, and these nutrients then cause the blood vessels to constrict and the flow to return nearly to normal despite the increased pressure.

myogenic theory of autoregulation:  This theory is based on the observation that sudden stretch of small blood vessels will cause the smooth muscle of the vessel wall to contract. Therefore, it is believed that when high arterial pressure stretches the vessel, this in turn causes vascular constriction and reduces the blood flow nearly back to normal. Conversely, at low pressures, the degree of stretch of the vessel is less, so that the smooth muscle relaxes and allows increased flow.

endothelium:  Inner lining of blood and lymph vessels.  Made up of endothelial cells.  Capillaries are only endothelial cells.

endothelial-derived relaxing factor (NO):  Found in the endothelial cells lining the arterioles and small arteries, this substance is a potent vasodilator. It is what is responsible for the shear forces to cause vasodilation. Acetylcholine also causes release of NO from the endothelium, which will then cause vasodilation.

tissue vascularity:  This is a long-term local blood flow regulation mechanism. If arterial pressure falls and remains low for several weeks, the physical structural sizes of the vessels in the tissue increase, and under some conditions, even the number of vessels increases; on the other hand, if the pressure rises to a very high level, the number and sizes of vessels decrease. If the metabolism in a given tissue is increased for a prolonged period, vascularity increases; if the metabolism is decreased, vascularity decreases.   The physical structure and size of blood vessels in the tissue.  (# & size).  Guyton pg. 204

angiogenesis:  This term means growth of new blood vessels. It occurs mainly in response to the presence of angiogenic factors released from ischemic tissues, tissues that are growing rapidly, or tissues that have excessively high metabolic rates. Presumably, it is the deficiency of tissue O2, other nutrients, or both that leads to the formation of the angiogenic factors.

vascular remodeling:  The restructuring and rebuilding of blood vessels in response to chronic changes in pressure or flow. It involves increasing collagen and elastin and building up of vessel wall to either increase or decrease radius of the blood vessel.  (Collateral circulation).  Development of a new vascular channel around a blockage to at least partially resupply blood to the affected tissue.  

vasoconstrictor:  A substance that narrows the diameter of a blood vessel.

norepinephrine:  A hormone released partly from the adrenal medulla (only 20% is secreted from here) and from the nerve endings from the sympathetic nervous system post-ganglionic adrenergic fibers. It is a potent vasoconstrictor and hits mainly the alpha1 receptors. Circulating norepi only lasts about 6 minutes or so, so it is generally secreted directly at the source by the SNS as a neurotransmitter.  Especially powerful vasoconstrictor.  Hormone.  SNS stimulant (adrenal medulla).  Excitatory effect on circulation.

epinephrine:  This is also a hormone released solely by the adrenal medulla and lasts much longer in the blood. It is the child chemically to norepi. It also has an affinity for the alpha1 receptors so if it is in supply in a larger concentration than norepi, it will vasoconstrict. Epi has a stronger affinity for the beta receptors, both 1 and 2. Beta1 stimulation will increase heart rate and contractility while beta2 stimulation will bronchodilate and relax.  Less powerful vasoconstrictor hormone.  Dilates (mildly) heart arteries.  SNS stimulant (adrenal medulla).  Excitatory effect.

angiotensin:  This is a very powerful vasoconstrictor. It normally acts simultaneously to vasoconstrict all the arterioles of the body to increase the total peripheral resistance, thereby increasing arterial pressure. This hormone also has renal and adrenocortical effects of stimulating renin and aldosterone secretion.  One of the most powerful constrictors.  Takes very little to cause marked increase in blood pressure.  Increased effect on small muscular arterioles.  If at isolated tissue area then powerful decrease flow.  If in blood and body then increased TPR, increased arterial BP.  Adrenal cortical and renal stimulating effects.

vasopressin:  Also known as antidiuretic hormone or ADH – this hormone is even more powerful than angiotensin as a vasocontrictor. It is formed in the hypothalamus and stored and secreted from the posterior pituitary. Vasopressin also controls water reabsorption in the renal tubules and therefore, controls body fluid volume.   Antidiuretic hormone.  More powerful than angiotensin as constrictor.  Formed in hypothalamus, posterior pituitary.  Normally released in minute quantities.  Can increase BP by 60 mmHg during hemorrhage.  Controls H2O reabsorption in kidneys.

endothelin:  Large peptide (21 amino acids).  Present in endothelial cells of most blood vessels.  Usually released upon damage to vessel walls.  Constricts umbilical artery in newborn.  Prevents bleeding after vessel injury.  Prolonged vasoconstriction causes remodeling(+ vascular smooth muscle, + collagen, + elastin, + hypertrophy, - radius).  Part of humoral autoregulatory response.  Keeps tissue flow appropriate with changes in peripheral pressure.  

vasodilator:  Substances that can widen the diameter of a blood vessel.

bradykinin:  This is formed in the blood and tissue fluid of some organs. Kallikrein is activated by maceration of the blood, tissue inflammation, and other similar chemical and physical effects on the blood or tissues. Kallikrein is eventually converted to bradykinin, which doesn’t last long before it is inactivated. Once activated it causes powerful arteriolar dilatation and increased capillary permeability. There is reason to believe that kinins play special roles in regulating blood flow and capillary leakage of fluids in inflamed tissues. It is also believed that bradykinin plays a role in regulating blood flow in the skin as well as in the salivary and gastrointestinal glands.  Small polypeptides split away by proteolytic enzymes in plasma or tissue fluids.  Persists for only few minutes.  Causes powerful arteriolar dilation and increased capillary permeability to fluid (causing edema).

serotonin:  This is present in large [] in the intestine and other abdominal structures as well as in the platelets. Serotonin can have either a vasodilator or a vasoconstrictor effect, depending on the condition or the area of the circulation. Serotonin is not known for any widespread role in circulatory regulation.  Present in large concentrations in chromaffin tissue of the intestine and other abdominal structures and in platelets.  Can vasodilate or vasoconstrict depending on condition or area of circulation (doesnt play widespread role in circulatory regulation).  

histamine:  This is released by every tissue in the body when it becomes damaged or inflamed or is the subject of an allergic reaction. Most of the histamine is derived from mast cells in the damaged tissues and from basophils in the blood. Histamine has a powerful vasodilator effect on the arterioles and like bradykinin, has the ability to greatly increase capillary porosity, allowing leakage of both fluid and plasma protein into the tissues. The local vasodilatory and edema-producing effects of histamine are especially prominent in allergic reactions.  Released in every tissue of body when they become damaged or inflamed or subject to allergic reaction.  Derived from mast cells of damaged tissue or from basophils in blood.  Powerful vasodilator on arterioles.  Increase capillary porosity, allowing leakage of fluid and plasma protein into tissues (edema)

prostaglandins:  Almost every tissue of the body contains small to moderate amounts of several chemically related substances called prostaglandins. They have important intracellular effects, but in addition, some of them are released into the local tissue fluids and the circulating blood under both physiological and pathological conditions. Some cause vasoconstriction but the more important ones seem to be mainly vasodilator agents.  Found in almost all body tissues.  Intracellular effects.  Myriad of effects on circulation; some dilate, some constrict.  

learning objectives

compare and contrast the relative significance of the LOCAL REGULATION OF BLOOD FLOW through various individual peripheral vascular beds and the CENTRAL REGULATION OF MEAN SYSTEMIC ARTERIAL PRESSURE in normal cardiovascular homeostasis:  The significance of regulation of blood flow is that flow needs will meet specific metabolic needs of each organ or tissue. This can be accomplished either locally at the site of tissue or it can be controlled centrally. Both act on a negative feedback system. Both can act on a specific blood vessel to give it an overall tone, which is the extent of contractile force generated by vascular smooth muscle. It is the pressure gradient that will drive the blood flow through each organ and the pressure gradient is set up as the difference in MSAP and CVP. The vascular smooth muscle receives signals from local tissue by direct messages of different receptors. Some act generally impairing the VSM to contract and some are subject to the tissue cells themselves. There are also local controls from the endothelium that can generate substances that diffuse into the endothelium and cause vasoconstriction or vasodilation. Central control has signals that come from a long way off either via nerve impulses with the release of neurotransmitters like the SNS and the release of norepi or from plasma and the release of hormones like epi or angiotensin II. The VSM must integrate all the signals and the net result of all the vasoconstrictors and vasodilators is the vessel tone.

describe HUMORAL FACTORS and neurotransmitters that might influence the contractile force of vascular smooth muscle for the purpose of CENTRAL REGULATION OF MEAN SYSTEMIC ARTERIAL BLOOD PRESSURE:  Humoral regulation of the circulation means regulation by substances secreted or absorbed into the body fluids, such as hormones and ions. Centrally regulated humoral factors will be secreted and transmitted through the blood to the site of control or they can be signaled to be secreted at the site but the signal came from central control. Central or systemic constrictors include epinephrine, norepi (but in a lessor amt since norepi doesn’t last long in the circulation so most likely won’t make it to its target. Norepi can be secreted as a neurotransmitter right at the site and then is a very powerful vasoconstrictor when it binds with the alpha1 receptors.) Epi is the child of norepi and lasts longer in the blood and does have some affinity for those alpha-receptors and can then cause vasoconstriction. Epi has a higher affinity for Beta1 and 2 receptors where beta 1 causes increase heart rate and increase contractility in the heart and beta2 cause vasodilation in the lungs. Dopamine is another vasoconstrictor; it is dose dependent and at lower doses spares the kidney. Vasopressin and angiotensin II are also vasoconstrictors. Systemic vasodilators are the epi and ACh which acts on the muscarinic3 receptors which cause release of NO which then causes vasodilation.

compare and contrast the PROPERTIES OF VASCULAR BEDS whose control is either predominantly NEURAL, predominantly LOCAL, or a COMBINATION of both, and give examples of each:  Tissues whose primary functions must stay carefully regulated and can’t be subject to SNS stimulation to constrict or dilate are governed by local control. These tissues include the brain and the heart. They would not survive if they were allowed to vasoconstrict and shut down blood flow to these areas. The kidneys or gut for instance can have their flow rates dropped way down to just barely meet metabolic needs during times of acute stress from a hemorrhaging accident or when skeletal muscles are exercising. Blood can be shunted away from these areas to allow increased blood flow to others. This is a function of neural or central control. Skeletal muscles on the other hand, have a combination of control so that they can have that local vasodilation during exercise or the central vasoconstriction just after a meal.

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describe LOCALLY PRODUCED factors arising from the tissues or from the endothelium which might influence the force of contraction of vascular smooth muscle for the purpose of MATCHING TISSUE BLOOD FLOW WITH TISSUE METABOLISM:  Endothelin is a locally produced substance that will vasoconstrict as a result of an increase in pressure within the blood vessel in an attempt to keep the flow constant in the face of changes in pressure. The body will try to minimize an excess blood flow, which would put an eventual strain on the heart by always pumping to such high demands. This autoregulatory mechanism will vasoconstrict the vessel to decrease the blood flow to match the needs of the tissues. If there is a chronic increase in pressure, then endothelin will lead to a remodeling of the vessel – a structural change that involves wall hypertrophy and a decrease in radius. Nitric oxide on the other hand causes vasodilation as a response to shear forces causing a stretching on the endothelial cells. This stretching is due to an increase in flow velocity. When the endothelium is stretched, it will release NO which will cause vasodilation, which will cause a decrease in flow velocity. The velocity decrease can be felt backstream and you can get a retrograde signal of vasodilation and will get a resultant increase in flow. If this flow demand is constant and prolonged, NO will remodel to increase the radius.

compare and contrast the PHYSICAL and FUNCTIONAL PROPERTIES of the arterial and venous systems, and describe factors controlling VASCULAR REMODELING in response to changes in transmural pressure and the velocity of flow:  The arterial system runs under a higher pressure than the venous system. If for instance you were to take a vein and use it for a graft in an artery, the vein would remodel itself to have the thicker walls of the artery. NO and endothelin counteract each other as the vein remodels in the face of higher pressures and an increase in flow velocity. The surgeon must make sure there are no tortuosities or turbulent areas in order to balance the affects of NO and endothelin or else endothelin will win out and you will have vasoconstriction and restenosis of the graft.


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