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BIOC33/34 Lec 8.docx

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Biological Sciences
Stephen Reid

BIOC34 Lec 8. Jan 29/14  Midterm o Mon. March 3 @ 5pm  Blood flow (slide 32 lec 7) o Change in P/ resistance to blood flow o Flow = ∆P/R  CO = blood pumped per minute  All CO flows through systemic circuit  CO - Flow (ml/min)  MAP - Venous pressure = MAP  MAP drives blood flow in systemic circulation  MAP = ∆P  R = TPR o Major factors affecting:  Vessel radius o 2 things to keep in mind when talking about blood flow/BP regulation  BP regulation = overall body phenomena  Blood flow can be regulated  Blood flow within the systemic and pulmonary circuits is in parallel o Blood does not go from one organ to the next  Each organ receives fully oxygenated blood  Independent regulation of blood flow to each organ o Distribution of blood flow to various organs under different conditions of rest and exercise o Within both systemic and pulmonary circuit, blood flow is parallel - each organ is receiving oxygenated blood from an artery coming from left hand side of heart o Going from rest to exercise  blood flow distribution changes o Most notably, skeletal muscle and skin which received low blood flow at rest, blood flow increases during exercise  Skeletal muscle is involved in powering exercise and skin is site of thermal regulation o When exercising, metabolic rate increases and heat increases blood flow to skin is enhanced and heat can dissipate to environment o Organs such as liver, gut, kidneys which receive high volumes of blood during rest receive less during exercise o Brain and heart are protected; blood flow is kept constant or higher o With heart, proportion of blood flow is constant but because blood flow is 5x higher during exercise, it is receiving more blood than when under rest o Though the proportion drops in the brain, amount of blood flow is enhanced because lower proportions are going into brain but absolute values are higher  Resistance within a parallel circuit o Total resistance of a network of parallel vessels is less than the resistance of the vessel having the lowest resistance  Parallel arrangement of vessels greatly reduces resistance to blood flow  With many parallel vessels, changing the resistance of a small number of these vessels will have little effect on total resistance for the segment  Local (intrinsic) control of blood flow o Independent regulation flow to organs by vasoconstriction or vasodilation of blood vessels (small arteries, arterioles) that are leading to the various organs o Have a small arteriole and venule on the other side  Rings of smooth muscle on arterioles - not much smooth muscle on capillaries o Possible to contract smooth muscle, causing it to squeeze in on blood vessel, increasing resistance and reducing flow o If smooth muscle is relaxed, blood vessel diameter increases, resistance decreases and flow increases o Vascular smooth muscle is control of local blood flow - acted on by hormones  Ad, NAd from sympathetic nervous system or adrenal glands o Can have local factors exerting effects - low oxygen, high CO2 causes vasodilation o Myogenic smooth muscle - high pressures cause smooth muscle to stretch and in response to stretch, it contracts o Happens in brain and kidneys o Regulation of oxygen and CO2 is simple - if oxygen goes down in EC fluid, blood flow goes up and if CO2 goes up, blood flow also goes up  Local Changes in Metabolism (O2) o 1. Steady state O2 delivery to tissues  Rate of O2 consumption = rate of O2 delivery o Increasing metabolic rate, tissues use more oxygen; as they use oxygen, gradient for oxygen movement into EC fluid is enhanced, tissue oxygen decreases and oxygen will diffuse into tissues where it is used in the mitochondria  Get reductions of oxygen in EC fluid as oxygen consumption increases  Mismatch of use and delivery from cardiovascular system  Local changes in Metabolism (O2) o 2. Increase in metabolic rate o 3. O2 consumption by the tissues increases o Direct effect on vascular smooth muscle, decrease in oxygen levels in EC fluid causes rings of smooth muscle to relax; no longer constricting; vessel dilates, diameter increases and enhancement in blood flow o Before we get an enhancement in blood flow  ischemia: insufficient blood flow is being met for metabolic demands o Vascular smooth muscle dilates, oxygen delivery has increased o Keep in mind: change in oxygen in EC fluid; not changes within blood itself oxygen levels in blood remain constant o Cardiovascular/respiratory system want to maintain oxygen uptake and CO2 secretion in the lungs; blood remains constant o See a similar thing in metabolically active tissues in CO2 production; CO2 produced in excess is removed o (s42) Increase in metabolic rate - CO2 levels are greater on production side than removal side - see direct effect of CO2 on blood vessels o High levels of CO2 work on smooth muscles and cause vessels to dilate o See direct effect of pH on vascular smooth muscle  Relationship between CO2 and pH  in aqueous solution, CO2 reacts with water and forms carbonic acid to produce H + bicarbonate ion o In aqueous solution, if CO2 goes up, pH goes down o Important to remember: if CO2 is going up and making bicarbonate; pH is a measure of H not bicarbonate concentration  When CO2 goes up, see a decrease in pH because H ion levels go up o When looking at acid-base balance, relationship between pH and bicarbonate levels change based on source of acid-base disturbance;  If have direct effect of CO2, as CO2 goes up, pH goes down because H+ ions are produced  If we have metabolic causes, disturbance is different o High levels of CO2 with decreases in pH cause vasodilation.Also, metabolically active muscles tend to release K and lactic acid - these directly work on smooth muscle to cause vasodilation o Vasodilation - increased blood flow to match CO2 reduction  Reactive hyperaemia: compensatory changes in blood flow resulting from a previous reduction in blood flow o Reactive hyperaemia: It is the enhanced blood flow caused by previous reduction in flow o Graph on left  Get excess of flow after reduction of flow to supply oxygen and get rid of CO2 build-up and other metabolic waste products  This sequence of events is same in oxygen and CO2  No flow - CO2 goes up, works on smooth muscles causing vasodilation - get an increase in radius and increase in blood flow  Smooth muscle stretching regulates local blood flow o Can have local control of blood flow by myogenic muscle o Unique situation o Some vascular smooth muscle is stretch-sensitive  See this type of muscle in the brain and around the capillaries in the initial regions of nephrons - first site of blood filtration o Myogenic response: a direct response of vascular smooth muscle to changes in pressure  This is a situation where change in blood pressure and constriction/dilation of vessel is opposite to conditions seen in normal regulation of BP  This response was created to protect small vessels in the brain o If there is an increase in blood pressure, smooth muscle around small vessels will contract causing vessel to constrict - vessel constriction usually increases peripheral resistance BUT in this case, the goal is not to regulate BP but to prevent exposing delicate arteries to high levels of blood pressure  If they were exposed to these high levels, could get ruptures, aneurysm  Local blood flow regulation by nitric oxide (NO) o Regulation of local blood flow by nitric oxide - produced in nerves, epithelial cells by nitric oxide synthase - its effect related to blood flow is to activate guanylate cyclase to produce cGMP which has effects on smooth muscle to cause vasodilation and increased blood flow  Nitric oxide synthase - non-cholinergic, non-adrenergic because these use NTs different from catecholamines and NAd  cGMP acts on smooth muscle to vasodilate - it is decreased by PDE  13 PDES in the body. PDE5 is a site of action of Viagra - it has only been found in the penis. Inhibiting it will increase blood flow  PDE5 small amounts have been found in coronary arteries - Viagra might work for increasing blood flow in coronary arteries  Local blood flow regulation by various vasoactive substances o Final factor - lipopolysaccharide produced by invading bacteria - endotoxins  Activate nitric oxide synthase in cells from the immune system (macrophages) in response to endotoxin  Produces NO  This can cause vasodilation - reduction in TPR and decreases in BP  Septic shock: BP that is too low to keep a person alive  This endotoxin can lead to large reductions in BP and can be very dangerous - high mortality rates if not treated  Fetal heart o Similar to adults o Difference in fetal heart - receiving most of its oxygenated blood from the maternal circulation coming from umbilical vein  Umbilical vein because it is draining INTO the fetal heart - not artery flowing away from maternal heart o 2 major differences -2 holes  Foramen ovale - connects left and right atria  Ductus Arteriosus - connects aorta to systemic circulation with pulmonary arteries going to the lungs  These holes are important - keep blood flow away from lungs • Developing fetus is in utero and its lungs are not exposed to air so lungs are not involved in gas exchange - no reason to send blood to lungs  Fetal Heart o Foramen ovale - Separates left and right atria o As blood flows up from placenta, enters
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