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Local regulation of arterial blood flow Flow = pressure gradient/resistance Remember Poiseuille’s Law: radius is major factor affecting resistance Resistance = 8 x length x viscosity π x radius4 Distribution of blood flow (Cardiac Output) at rest The % of CO each organ receives is not constant Blood delivered to all organs at same MAP: driving force for blood flow is identical for all organs. Blood flow distribution to each organ is controlled by: 1) Vascularisation (ie. the number of blood vessels) 2) Degree of vasoconstriction or vasodilation of arterioles supplying that organ (most important in short term) Local (tissue) blood flow: why does it vary? Tissue blood flow is proportional to metabolic need Tissues need: Oxygen Removal of H+ ions (pH regulation) Nutrients (eg glucose, amino acids) Regulation of other ions (eg. Na+, K+) Removal of carbon dioxide Transport of hormones to tissues Some specific tissues have special requirements eg. Blood flow to the skin: thermoregulation Blood flow to the kidneys: excretion of waste products in urine Acute control of blood flow (short term – seconds to minutes) eg in exercising muscle is achieved by vasoconstriction and vasodilation Long-term control of blood flow (days/weeks/months) eg. scar tissue, cancerous tissue, increased muscle mass. Angiogenesis: growth of new blood vessels. 1 Arterioles The major resistance vessels. Very little elastic tissue Thick layer of smooth muscle (innervated by sympathetic nerves). Vasoconstriction: Contraction of smooth muscle Decrease in radius of arteriole Increased resistance to blood flow Vasodilation: Relaxation of smooth muscle Increase in radius of arteriole Decreased resistance to blood flow Arteriolar smooth muscle has vascular tone. Intrinsic factors influence contractile activity of arteriolar smooth muscle, therefore influencing blood flow. Local control of blood flow: Intrinsic control Changes within tissues that alter radius of arterioles (ie. that affect the smooth muscle of the arterioles supplying the tissue) Important in matching blood flow with the metabolic needs of tissues Local controls are most important in: 1) Skeletal and cardiac muscle. Why? Their metabolic activity varies most 2) Brain Why? Its blood supply must be kept constant Local influences are chemical or physical 2 Local chemical changes Occur during increased metabolic activity in tissues eg oxygen concentration decreases Local vasodilation of arterioles via relaxation of smooth muscle Process is called active hyperaemia (or functional hyperaemia) Active hyperemia can result in up to a 50-fold increase in muscle blood flow with maximal exercise. Increased blood flow meets increased metabolism. When metabolic needs decrease, chemical changes result in vasoconstriction. Local chemical changes Decreased oxygen (hypoxia) Increased CO2: More is produced as a result of increased metabolism. Increased acid: Carbonic acid is generated from CO2; lactic acid is produced from anaerobic metabolism of ATP production. Increased potassium ions Eg. in exercising muscle: Repeated action potentials (K+ out, Na+ in) may outpace the ability of the Na+/K+ pump to restore resting concentration gradients, causing accumulation of K+ in tissue fluid. Adenosine Formed from cellular AMP, especially in cardiac muscle. Released in response to increased metabolism or decreased oxygen. Prostaglandin release Local chemical messengers. 3 Endothelial cells Single layer of specialised epithelial cells lining the lumen of every blood vessel. Release chemicals important in regulation of the radius of arterioles. Chemicals are released in response to chemical (eg. decrease in oxygen) or physical (eg. stretching) changes. Act on the underlying smooth muscle to alter its state of contraction. These chemicals are vasoactive ie. “act on vessels” EDRF Endothelial-derived relaxing factor. Causes vasodilation by stimulating relaxation of smooth muscle. Identified as NO (nitric oxide). Local physical changes Temperature Heat increases blood flow to an area by causing localised vasodilation. Cold causes vasoconstriction and therefore decreased blood flow. Myogenic responses to stretch Nerve-independent contractile activity initiated by the muscle itself. Arteriolar smooth muscle responds to being stretched by myogenically increasing its tone (contracting), therefore resisting the stretch. Conversely, a decrease in stretch results in decreased myogenic tone. Vasoactive substances may also contribute to these responses. Remember: Arterioles do not contain much elastic tissue – not very stretchy, so will respond strongly to this mechanical stretch. Myogenic and metabolic responses are important in reactive hyperaemia. 4 Reactive hyperaemia If blood supply to a region is reduced, arterioles in the region dilate due to 1) myogenic relaxation (less stretch because of reduced blood flow) 2)Changes in local chemical composition: eg. Oxygen concentration decreases Concentrations of carbon dioxide and other metabolites increase – they accumulate in the tissue When blood flow restored, much higher than normal: hyperaemia. Arterioles are vasodilated as a result of chemical changes and myogenic relaxation Pressure autoregulation When mean arterial blood pressure falls (eg. in heart failure), blood flow decreases because driving force decreases. Chemical changes in tissues and reduced stretch cause vasodilation. This causes a further decrease in blood pressure, worsening the problem (other mechanisms try to compensate). Example: Cerebral autoregulation (ie blood flow to brain) In increased blood pressure, vasoconstriction occurs in order to reduce blood flow towards normal. Pressure autoregulation aims to keep tissue blood flow constant despite varying mean arterial pressure. This can be important in hypertension and hypotension 5 Arterioles - extrinsic control Factors outside the organ that influence blood flow Sympathetic nerve influence on smooth muscle (constriction: via action of noradrenaline on α1 receptors) Hormonal influence on smooth muscle (adrenaline constricts via α1 receptors) During exercise, extrinsic factors cause an initial vasoconstriction in muscle Local changes over-ride this and cause dilation - competition between vasoactive factors Effect of exercise on Effect of exercise on blood flow TPR Note large change in muscle blood flow Remember that Total peripheral resistance (TPR) is the sum of the resistance of all peripheral vasculature in the systemic circulation. Because of widespread vasodilation during exercise, TPR decreases This facilitates during exercise blood flow 6