Control of Tssue Blood Flow

# Sheet 15 Subject Physiology Done by Corrected by … Doctor Control of tissue blood flow Each tissue regulates its own blood flow just proportional to its needs, as this needs could be decreases or increases depends on the metabolic rate of these tissues. This regulation mechanism is called( autoregulation.) the tissue itself controls its blood flow local regulation -High blood need  causing vasodilation of arterioles -Less blood need causing vasoconstriction of arterioles *Why do tissues need oxygen? 1) Delivery of oxygen to tissues 2) Delivery of nutrients such as glucose, amino acids, etc. 3) Removal of carbon dioxide ,hydrogen and other metabolites from the tissues 4) Transport various hormones and other substances to different tissues *Previously, we talked about the positive relationship between the cardiac output and the O2 consumption, and this relationship is 1|Page due to the fact that during exercise there will be increase in the metabolic rate of the tissues, which cause increase in the O2 consumption, so in order to compensate that increasing demand, we will have more blood flow to the tissues, and this meaning more cardiac output. Athletes have high O2 consumption compared to lazy people. Also, we talked about this figure that represents cardiac output during rest and during exercise Cardiac output during rest is around 5L, but during exercise it might reach 12L. During exercise, Most of blood (64%) is going to the skeletal muscles. Also, the skin blood flow will increase (not for the sake of O2), but to control the body temperature. Remember that the heart has the highest blood perfusion per 100g of tissue ((For the sake of O2 consumption)) 2|Page ◊Acute control of local blood flow (minute to minute),(hour to hour) We mean by control of local blood flow, that the control happening at the level of the tissue only (locally) not systemically. Remember that Flow= P/R, but P is almost constant so we can play with the resistance, by causing vasoconstriction or vasodilation in order to control the blood flow  Some of tissues are controlled through neural control  by stimulation or inhibition of sympathetic system  causing vasoconstriction or vasodilation, respectively.  So the blood flow will change if we have: 1- Changed the tissue metabolism 2- Changed the O2 availability in the tissues  Increases in tissue metabolism lead to increase in blood flow.  More metabolism  needs more oxygen  more blood flowincrease the CO, why does the CO increase ? because the CO is the sum of all blood flow in the tissues 3|Page  Decreases in oxygen availability to tissues increases tissue blood flow.( decrease in the oxygen saturation will increase the blood flow)  when the rate of metabolism increases this causes decreased PO2 and increased PCO2.  Look at the PO2 in this curve (important curve); when the arterial oxygen saturation is lower, the blood flow is higher -Please Notice that the numbers in the x-axis are flipped.(from 100-25), BUT , if the x-axis is (from 25-100) the curve will be flipped.  There are variations in the blood flow between the different tissues , we said that the heart has the highest blood flow Actually, we can explain this control by two theories: ①Vasodilator theory ②Oxygen demand theory These theories can explain why increasing in the metabolic rate will increase the blood flow. ①The vasodilator theory When there is increase in the metabolism of the tissues (there is breakdown of some cells and release of certain substances); it will produce local vasodilators, these will cause vasodilatation, and as a result we will have a decrease in the Resistance, and this will cause increase in the blood flow. At first the scientists thought that only one of these local vasodilators can cause the dilation but then the found that these local vasodilators work together. 4|Page These local vasodilators work together to cause the vasodilatation effect and explain the whole theory. Any one alone will do nothing and doesn’t give any explanation for this theory. These local vasodilators are Adenosine,CO2, Lactic acid, ADP compounds, Histamine, K+ ions, H+ ions, Prostacyclin, Bradykinin (most potent local vasodilation), and Nitrous oxide (NO) it was called endothelial cell releasing factor  it released from endocardium and endothelial cells.  Endothelium cells release nitric oxide and endothelin ( local vasoconstriction) that has opposite action to NO so when do endothelium cells release NO and enothelin?  That will depend on the tissues need of oxygen  Sources of local vasodilatations: -H+ ions could be produced directly or indirectly (there is increase in the CO2,CO2 will binds water in the presence of 5|Page Carbonic anhydrase, this reaction will produce carbonic acid, which will dissociate into H+ and HCO3-) -Adenosine could be produced during the utilization of ATP, once you utilize ATP ,it will converted to ADP, and so on until Adenosine Note: adenosine is an important vasodilator in skeletal muscles. ②Oxygen demand theory When there is increase in the tissue metabolism, there will be decrease in the O2 delivery to tissuesthat means the tissues needs more oxygen. (main factor according to this theory), and this will cause vasodilatation, then decrease the resistance which will increase the blood flow. This increase in blood flow, due to the decrease in the O2 delivery is associated with the vasomotion tone; once there is decrease in the O2 delivery the vasomotor tone (the rate of the opening and closing of the blood vessels) increases, because of increased blood flow.  Vasomotor activity of arterioles  depends on the oxygen contents in the tissues , which mean when there is low oxygen ,the vasomotor activity will increase 6|Page ◊Autoregulation during the change of Arterial pressure Autoregulation during the change of Arterial pressure: ability of a tissue to maintain blood flow relatively constant over a wide range of arterial pressures. The blood flow to the tissue is almost (not 100%) constant along with varying blood pressure Theories that can explain this Autoregulation: ①Metabolic theory  we talked about this theory , whenever we have increased in metabolic activity there will be released of local vasodilators in order to dilate the blood vessels then increase the blood flow and the oxygen ②Myogenic theory  When the pressure decreases, the stretch at the blood vessels decreases that will cause decrease in the permeability of smooth 7|Page muscles to Ca+2, and this will cause vasodilatation as well as more blood flow.  When the pressure increases, the stretch of the blood vessels increases that will cause increase of the permeability of smooth muscles to Ca+2, and this will cause vasoconstriction as well as less blood flow. 8|Page We can explain this theory by Laplace’s law: T= distending Pressure × Radius Once we have increase in the pressure, arterial wall tension will increase, but in order to restore the tension to normal, the radius decreases by vasoconstriction. SO, if we have high pressure, we have high tension, and to return this tension to its normal value we reduce the radius by vasoconstriction, and this vasoconstriction is done by the above mentioned mechanism. But this theory is not exactly 100%, because at the long term, it will cause some problems, for example: -When the pressure increases in the vessel, we induce vasoconstriction. But this response will also cause increase in the pressure, as a positive feedback; after a while, by the vasoconstriction-pressure increasing cycle, we can end up with ischemia. -On the other hand, if we have decrease in the pressure, we induce vasodilatation. But this response will induce further decrease in the pressure and so on until we have shock. -So, we can say that this theory works to a certain extent only. ◊Long term regulation of blood flow If we want to talk about long term regulation, we have to talk about permanent change, but what are those changes? 1-Change in tissue vascularity in hyperthyroidism ( over activation of the thyroid gland )  the gland will need more oxygen in order to function  means more blood flow  more capillaries are formed this is called angiogenesis 9|Page This can be done by changing the size and number of vessels. Oxygen is an important stimulus for regulating tissue vascularity main stimulus for angiogenesis is ischemia (decrease in oxygen supply) The development of new blood vessels is called angiogenesis, and this process occurs due to angiogenic factors that could be released from 1) ischemic tissues 2) Rapidly growing tissues(in tumors) 3) Tissue with high metabolic rates Most angiogenic factors are small peptides such as vascular endothelial cell growth factors (VEGF), fibroblast growth factor (FGF), and angiogen these are released by ischemic tissues * example: -The blood vessels of the eye will be fully developed after delivery, but some babies are birthed pre-term, and they put in neonatal incubator. In this incubator, the O2 concentration is 100%, so the normal O2 concentration for these babies is 100%. After 2-3 weeks the baby will get out from the incubator and go home, but after a short time, the parents of baby will come to you, and told you that the baby cannot see, but what happened to that baby?! When this baby was in the incubator, he/she adapt to 100% O2 concentration, as this baby got out from the incubator, and face 20% O2 concentration (Atmospheric O2 conc.), his system will consider this (20% O2 conc.) as if there is ischemia, and that will cause the stimulation of blood vessels formation in the front of the retina, and we will end up with blind. This process is called retro-lental hyperplasia. -We can prevent this case from happening by Weaning; and this means that before the baby got out of the incubator, we reduce the 10 | P a g e O2 from 100% to 90% and so on until 20%, that make his body adapt to that O2 concentration ②Development of collateral circulation sometimes there is block in a specific blood vessels that supply certain tissue  leading to decrease the blood supply to this tissue collateral circulation developed. -These collateral circulation increases as he/she gets older due to certain blocks in the major coronary arteries throughout life, and that can explain why MI is less fatal in old person than younger one. ◊Humoral control of the circulation - Vasoconstrictor agents: o Norepinephrine and epinephrine → systemic oAngiotensin → systemic oVasopressin → systemic oEndothelin → local - Vasodilator agents: o Bradykinin o Nitric oxide In the heart local vasodilators oSerotonin o Histamine oProstaglandins o Adenosine>>>>The most important in the skeletal muscles o CO2>>>>The most important in the brain 11 | P a g e ◊Blood flow to the muscles The blood flow to the skeletal muscles is controlled mainly locally The flow depends on the exercise, but we have two types of exercise: 1) Isotonic: contraction with change in the length, contraction → decrease in flow. Relaxation → Increase in flow. The final effect is increase in flow. That is what is called→ active hyperemia: Increase in the flow of the tissue due to hyperactivity.--> during exercise Eg: measuring blood pressure, and MI → after the blockage, bulk of vasodilators will rush through the vessels, grossly it will become red as a result. 2) Isometric: contraction without change in the length, this type of exercise will press on the vessels, that will cause increase in the resistance as well as decrease in the flow, but at the same moment the vessels accumulate local vasodilators, then after you release the pressure, these vasodilators will be released making increase in the flow, and this process is called reactive hyperemia. -Actually this process is similar to what happened in the MI; Block in the vessels(due to thrombus), then vasodilators will accumulate, after that, if the thrombus resolved, we will have very large vasodilatation as well as very large flow to heart, that could be toxic to the heart. Also, the muscles during exercise can meet its demand of O2 without increase the blood flow, by regulation the so-called Extraction ratio -Normally, what comes of oxygen to the relaxed skeletal muscle is 20mL per 100mL of blood. And what goes out through the veins is 15mL of oxygen per 100mL of blood. that means that the extraction 12 | P a g e ratio of the skeletal muscles in the normal state is 25%, but during exercise, we can increase this ratio up to 75% without increase the blood flow. ◊Blood flow of the heart The extraction ratio of the cardiac muscle at rest is 75% (the maximum), and it cannot increase above that. So the only solution for the cardiac muscle if it needed more oxygen the only way is to increase its blood flow. You can’t increase it up to 100%, because the blood is flowing, and you can’t stop the blood to take all the O2 carry 13 | P a g e