Module 10 - Circulatory System: The Circulation PDF

MODULE 10 - CIRCULATORY SYSTEM: THE CIRCULATION PHYSICAL CHARACTERISTICS OF THE PRESSURES IN THE VARIOUS PORTIONS OF THE CIRCULATION CIR...

MODULE 10 - CIRCULATORY SYSTEM: THE CIRCULATION PHYSICAL CHARACTERISTICS OF THE PRESSURES IN THE VARIOUS PORTIONS OF THE CIRCULATION CIRCULATION FUNCTIONAL PARTS OF THE CIRCULATION  Mean pressure in the aorta is high averaging about 100  Arteries – transport blood under high pressure to the mmHg tissues  Because the pumping action of the heart is pulsatile, the o Strong vascular walls and blood flows at a high velocity aortic arterial pressure rises to its highest point, the systolic  Arterioles – last small branches of the arterial system that pressure, during systole and falls to its lowest point, the act as conduits through which blood is released into the diastolic pressure, at the end of diastole capillaries  Pulse pressure – difference between systolic and diastolic o Strong muscular walls that can be constricted or pressure dilated, giving them the capability of markedly altering  As blood flows through the systemic circulation, its pressure blood flow to the capillaries in response to changing falls progressively to approximately 0 mmHg by the time it tissue needs reaches the termination of the vena cavae in the right atrium  Capillaries – exchange fluids, nutrients, and other  Pulmonary capillary pressure averages only 8 mmHg, yet substances between the blood and the interstitial fluid the total blood flow through the lungs is the same as that in o Thin walls and are highly permeable to small molecules the systemic circulation because of the lower vascular  Venules – collect blood from the capillaries and gradually resistance of the pulmonary blood vessels coalesce into progressively larger veins  Low pressures of pulmonary system is because all that is  Veins – function as conduits to transport blood from the required of it is to expose the blood in the pulmonary tissues back to the heart and also serve as reservoirs for capillaries to oxygen and other gases in pulmonary alveoli blood o Thin walls, low pressure, and rapid blood flow Systemic circulation Pressure Average systolic pressure VOLUMES OF BLOOD IN THE DIFFERENT PARTS 120 mmHg (resting condition) OF THE CIRCULATION Average diastolic pressure 80 mmHg Percentage of total (resting condition) blood volume Systemic circulation 84% Average “functional” 17 mmHg  Veins 64% capillary pressure  Arteries 13% * As high as 35 mmHg in  Arterioles & capillaries 7% arteriolar ends Heart 7% * As low as 10 mmHg in Pulmonary circulation 9% venous ends Pulmonary circulation Pressure Average pulmonary artery 25 mmHg systolic pressure Average diastolic pressure 8 mmHg Mean pulmonary arterial 16 mmHg pressure Mean capillary pressure 7 mmHg average GROUP 2 & GROUP 7 1  TRANS: Module 10 BASIC PRINCIPLES OF CIRCULATORY FUNCTION  The blood flow to most tissues is controlled according to the tissue need o Tissues need more blood flow when active than at rest – occasionally as much as 20 to 30 times more o The microvessels of each tissue continuously monitor the tissue needs and control the blood flow at the level required for the tissue activity o Nervous and hormonal mechanisms provide additional control of tissue blood flow o It is not possible to simply increase blood flow everywhere since the heart normally cannot increase its cardiac output more than 4-7 times  Cardiac output is the sum of all the local tissue flows BLOOD FLOW o After blood flow through a tissue, it immediately returns  Blood flow – quantity of blood that passes a given point in by way of the veins to the heart the circulation in a given period of time o The heart responds automatically to the inflow of blood  Expressed in milliliters per minute (mL/min) by pumping almost all of it immediately back into the  The overall blood flow in the total circulation of an adult arteries person at rest is about 5000 mL/min o The heart responds to the demands of the tissues,  Laminar flow – when blood flows at a steady rate through although it often needs help in the form of nervous stimulation to make it pump the required amount of along, smooth blood vessel, it flows in streamlines, with blood flow each layer of blood remaining the same distance from the vessel wall  Arterial pressure regulation is generally independent of either local blood flow control or cardiac output control  Turbulent flow – blood flowing in all directions in the vessel o If arterial pressure falls below normal, a barrage of and continually mixing within the vessel nervous reflexes elicits a series of circulatory changes  When laminar flow occurs, the velocity of flow in the center that elevate the pressure back toward normal, of the vessel is far greater than that toward the outer edges including:  Parabolic profile for velocity of blood flow – when the  increased force of heart pumping portion of fluid adjacent to the vessel wall has hardly moved,  contraction of large venous reservoirs to provide the portion slightly away from the wall has moved a small more blood to the heart distance, and the portion in the center of the vessel has  constriction of most of the arterioles moved a long distance o Over more prolonged periods, kidneys play additional o Cause: fluid molecules touching the wall move slowly roles by secreting pressure-controlling hormones and because of adherence to the vessel wall by regulating blood volume  Turbulent flow means that the blood flows crosswise in the vessel and along the vessel, usually forming whorls in the INTERRELATIONSHIPS OF PRESSURE, FLOW, AND blood called eddy currents RESISTANCE  Eddy currents – similar to whirlpools seen in a rapidly flowing river at a point of obstruction  Blood flow through a vessel is determined by the pressure o When eddy currents are present, blood flows with difference and vascular resistance much greater resistance than when the flow is  Pressure difference – also called pressure gradient along streamlined, because eddies add tremendously to the the vessel, which pushes the blood through the vessel overall friction of flow in the vessel  Vascular resistance – impediment to blood flow through  Tendency for turbulent flow increases in direct proportion to the vessel the velocity of blood flow, the diameter of the blood vessel,  Resistance occurs as a result of friction between the flowing and the density of the blood and inversely proportional to blood and the intravascular endothelium inside the vessel the viscosity of the blood  The flow through the vessel can be calculated by Ohm’s law: Re = Reynold’s number ∆𝑷 v = mean velocity of blood flow 𝑭= 𝒗.𝒅.𝝆 (cm/sec) 𝑹 F = blood flow 𝑹𝒆 = d = vessel diameter (cm) 𝒏 ΔP = pressure difference between two p = density ∆𝑷 = 𝑭 𝒙 𝑹 ends of the vessel (P1 – P2) n = viscosity (poise) ∆𝑷 R = resistance 𝑹= 𝑭  Reynold’s number = measure of the tendency for turbulence to occur  It is the difference in pressure between the two ends of the o Reynold’s number rises above 200 to 400 → turbulent vessel that provides the driving force for flow, not the flow will occur at some branches of vessels but will die absolute pressure in the vessel out along the smooth portions of the vessels o Reynold’s number rises above ~2000 → turbulence will usually occur even in a straight, smooth vessel o Re can rise to several thousand during the rapid phase of ejection by the ventricles, which causes considerable turbulence in the proximal aorta and GROUP 2 & GROUP 7 2  TRANS: Module 10 pulmonary artery where conditions are appropriate for  Mean pulmonary arterial pressure = 16 mmHg and mean turbulence: left atrial pressure = 2 mmHg, having net difference of 14  High velocity of blood flow mm  Pulsatile nature of the flow o When the cardiac output is normal at about 100 ml/sec,  Sudden change in vessel diameter the total pulmonary vascular resistance calculates  Large vessel diameter to be about 0.14 PRU CONDUCTANCE  Conductance – measure of the blood flow through a vessel for a given pressure difference  Expressed in terms of milliliters per second per millimeter of mercury pressure, or in any other units of blood flow and pressure  Conductance is exact reciprocal of resistance 𝟏 𝑪𝒐𝒏𝒅𝒖𝒄𝒕𝒂𝒏𝒄𝒆 = 𝑹𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆  Small changes in vessel diameter markedly change its conductance  The conductance of the vessel increases in proportion to the fourth power of the diameter BLOOD PRESSURE  Blood pressure – the force exerted by the blood against any unit area of the vessel wall Conductance ∝ Diameter4  Expressed in millimeters of mercury (mm Hg)  Occasionally measured in centimeters of water (cm H20)  1 mL of mercury pressure = 1.36 cm of water pressure RESISTANCE  Resistance – impediment to blood flow in a vessel, but it cannot be measured by any direct means  If the pressure difference between two points is 1 mmHg and the flow is 1 mL/sec, the resistance is said to be 1 peripheral resistance unit (PRU)  A basic physical unit called the CGS (centimeters, grams, seconds) unit is used to express resistance  Unit is dyne sec/cm5 𝒅𝒚𝒏𝒆 𝒔𝒆𝒄 𝟏𝟑𝟑𝟑 × 𝒎𝒎 𝑯𝒈 𝑹 (𝒊𝒏 )= 𝒄𝒎𝟓 𝒎𝒍/𝒔𝒆𝒄  Rate of blood flow through the entire circulatory system = rate of blood pumping by the heart (cardiac output)  In adult human being, rate of blood flow through the entire circulatory system is approximately 100 mL/sec  Pressure difference from the systemic arteries to the systemic veins is about 100 mmHg  In the small vessel, essentially all the blood is near the wall, so the extremely rapidly flowing central stream of blood TOTAL PERIPHERAL VASCULAR RESISTANCE & simply does not exist TOTAL PULMONARY VASCULAR RESISTANCE  Total peripheral resistance – resistance of the entire F = rate of the blood flow systemic circulation ΔP = pressure difference between o 100/100 or 1 PRU 𝝅∆𝑷𝒓𝟒 the ends of the vessel o Blood vessels throughout the body are constricted → 𝑭 → r = radius of the vessel 𝟖𝒏𝑰 total PRU rises to as high as 4 PRU l = length of the vessel Blood vessels become dilated → resistance can fall to n = viscosity of the blood as little as 0.2 PRU GROUP 2 & GROUP 7 3  TRANS: Module 10  The diameter of a blood vessel plays the greatest role of all  The viscosity of blood increases drastically as the factors in determining the rate of blood flow through a hematocrit increases vessel  The viscosity of whole blood at normal hematocrit is 3-4  2/3 of total systemic resistance to blood flow is arteriolar  Polycythemia – hematocrit rises to 60 or 70 and the blood resistance in the small arterioles viscosity can become as great as 10 time that of water, its  Arterioles internal diameters = 4 -25 micrometers flow through blood vessels is greatly retarded  The fourth power law makes it possible for the arterioles  Other factors that affect blood viscosity are plasma protein either to turn off almost completely the blood flow to the concentration and types of proteins in the plasma tissue or at the other extreme to cause a vast increase in  The viscosity of blood plasma is about 1.5 times that of flow water RESISTANCE TO BLOOD FLOW IN SERIES AND EFFECTS OF PRESSURE ON VASCULAR PARALLEL VASCULAR CIRCUITS RESISANCE & TISSUE BLOOD FLOW  The arteries, arterioles, capillaries, venules, and veins are  An increase in arterial pressure not only increases the force collectively arranged in series that pushes blood through the vessels but also initiates  Flow through each blood vessel is the same and the total compensatory increases in vascular resistance within a few resistance to blood flow (Rtotal) is equal to the sum of seconds through activation of local control mechanisms resistances of each vessel  With reductions in arterial pressure, vascular resistance is reduced in most tissues and blood flow is maintained at a constant rate  Blood flow autoregulation – the ability of each tissue to 𝑹𝒕𝒐𝒕𝒂𝒍 = 𝑹𝟏 + 𝑹𝟐 + 𝑹𝟑 + 𝑹𝟒 … adjust its vascular resistance and to maintain normal blood flow during changes in arterial pressure between 70 and 175 mmHg  Blood vessels branch extensively to form a parallel circuit  Changes in blood flow can be caused by strong that permits each tissue to regulate its own blood flow sympathetic stimulation, which constricts the blood vessels independent of other tissues  Hormonal vasoconstrictors (norepinephrine, angiotensin II, vasopressin, or endothelin) can reduce blood flow transiently 𝟏 𝟏 𝟏 𝟏 𝟏  The reason for the relative constancy of blood flow is that = + + + … each tissue’s local autoregulatory mechanisms eventually 𝑹𝒕𝒐𝒕𝒂𝒍 𝑹𝟏 𝑹𝟐 𝑹𝟑 𝑹𝟒 override most of the effects of the vasoconstrictors to provide a blood flow that is appropriate for the needs of the tissue  The total resistance is far less than the resistance of any  Increased arterial pressure not only increases the force that single blood vessel pushes blood through the vessels but also distends the  Flow through each of the parallel vessel is determined by elastic vessels, actually decreasing vascular resistance the pressure gradient and its own resistance, not the  Decreased arterial pressure in passive blood vessels resistance of other parallel blood vessels increases resistance as the elastic vessels gradually  Increase resistance → increase total vascular resistance collapse due to reduced distending pressure  Many parallel blood vessels make it easier for blood to flow  Critical closing pressure – pressure falls below a critical through the circuit because each parallel vessel provides level and flow ceases as the blood vessels are completely another pathway, or conductance, for blood flow collapsed  Total conductance for blood flow is the sum of the  Inhibition of sympathetic → dilates the vessels and can conductance of each parallel pathway increase the blood flow twice or more  Very strong sympathetic stimulation → constrict vessels 𝑪𝒕𝒐𝒕𝒂𝒍 = 𝑪𝟏 + 𝑪𝟐 + 𝑪𝟑 + 𝑪𝟒 … CLINICAL METHODS FOR MEASURING SYSTOLIC & DIASTOLIC PRESSURES  Direct measurement - most direct approach for measurement of pressure in a blood vessel is to introduce EFFECT OF BLOOD HEMATOCRIT & BLOOD a needle or catheter into a vessel and position the open tip VISCOSITY ON VASCULAR RESISTANCE at a particular site. The open tip is then connected to a  The greater the viscosity, the lower the flow in a vessel if all manometer which will then record the pressure. This type other factors are constant of blood pressure measurement measures end pressure.  The viscosity of normal blood is about three times as great  Indirect measurement - Unlike direct measurement which as the viscosity of water actually measures end pressure, indirect measurements tend to measure lateral pressure, and therefore values  The large number of suspended red cells in the blood, each obtained via indirect measurements are not the same as of which exerts frictional drag against adjacent cells and that obtained by direct measurement. There are several against the wall of the blood vessel, is what makes the ways of measuring blood pressure indirectly: blood so viscous o Palpatory method - This measures only systolic  Hematocrit – the proportion of blood that is red blood cells pressure, and is used to estimate systolic pressure in  Hematocrit in men averages about 42, whereas that of a noisy environment women averages about 38 GROUP 2 & GROUP 7 4  TRANS: Module 10 o Auscultatory method (Korotkoff method) - This  The progressive increase in pressure with age results from measures both systolic and diastolic pressures, and is the effects of aging on the blood pressure control based on development of Korotkoff sounds. mechanisms. o Oscillatory method - The cuff is placed around the  Kidneys are primarily responsible for this long-term arm (or leg) 1-2 inches above the antecubital fossa. regulation of arterial pressure; it is well known that the The cuff in turn, is attached to a mercury manometer kidneys exhibit definitive changes with age, especially after (sphygmomanometer). Pressure is then estimated by the age of 50 years. raising the pressure in the cuff higher than the pressure  A slight extra increase in systolic pressure usually occurs in the brachial artery, then lowering it slightly and beyond the age of 60 years. This increase results from feeling for the radial pulse, or by listening over the decreasing distensibility, or hardening, of the arteries, brachial artery for the Korotkoff sounds (Korotkoff which is often a result of atherosclerosis. The final effect is method). a higher systolic pressure with considerable increase in  Raising the pressure in the cuff to a pressure higher than pulse pressure. the brachial artery narrows the lumen of the brachial artery  Mean arterial pressure - average of the arterial pressures and causes development of turbulent flow within the artery. measured millisecond by millisecond over a period of time  Turbulent flow produces the Korotkoff sounds  The arterial pressure remains closer to diastolic pressure than to systolic pressure during the greater part of the cardiac cycle. The mean arterial pressure is therefore determined about 60% by the diastolic pressure and 40% by the systolic pressure. MECHANISM OF INCREASED FLUID VOLUME IN ELEVATING ARTERIAL BLOOD PRESSURE  The overall mechanism whereby increased extracellular fluid volume may elevate arterial pressure, if vascular capacity is not simultaneously increased Korotkoff sounds A sharp tapping sound heard as a small amount of blood starts entering the previously compressed Phase 1 brachial artery. This becomes louder as pressure is lowered. This sound represents systolic pressure. There is a shift to a softer, more hissing (murmuring) sound as more Phase 2 blood passes through the brachial artery. The sound becomes more thudding Phase 3 in nature as pressure is lowered further. The thudding sound becomes Phase 4 muffled.  Increased extracellular fluid volume → increases blood Phase 5 Disappearance of the sound. volume → increases mean circulatory filling pressure → increases venous return to the heart → increases cardiac output → increases arterial pressure GROUP 2 & GROUP 7 5  TRANS: Module 10  The increased arterial pressure, in turn, increases the renal accumulation leads to an increase in blood volume and if excretion of salt and water and may return extracellular fluid vascular capacity is not simultaneously increased. volume to nearly normal if kidney function is normal and  Increasing salt intake in the absence of impaired kidney vascular capacity is unaltered. function or excessive formation of antinatriuretic hormones  2 ways in which an increase in cardiac output can increase usually does not increase arterial pressure much because the arterial pressure: the kidneys rapidly eliminate the excess salt, and blood o Direct effect of increased cardiac output to increase the volume is hardly altered pressure o Indirect effect to raise total peripheral vascular resistance through autoregulation of blood flow  Autoregulation simply means regulation of blood flow by the tissue itself. When excess amount of blood flows through a tissue, the local tissue vasculature constricts and decreases the blood flow back toward normal  Increased blood volume raises the cardiac output → blood flow tends to increase in all tissues of the body  Increased blood flow exceeds the metabolic needs of the tissues → autoregulation mechanisms constrict blood vessels all over the body → increases the total peripheral resistance  Arterial pressure = cardiac output x total peripheral resistance  The secondary increase in total peripheral resistance that results from the autoregulation mechanism helps increase the arterial pressure.  For example, only a 5% to 10% increase in cardiac output can increase the arterial pressure from the normal mean arterial pressure of 100 mm Hg up to 150 mm Hg when accompanied by an increase in total peripheral resistance due to tissue blood flow autoregulation or other factors that cause vasoconstriction. The slight increase in cardiac output is often not measurable. EFFECT OF SALT IN RENAL-BODY FLUID SCHEMA  Increase in salt intake → elevate arterial pressure, especially in people who are salt-sensitive ROLE OF RENIN-ANGIOTENSIN IN BLOOD  Pure water is normally excreted by the kidneys almost as PRESSURE CONTROL rapidly as it is ingested, but salt is not excreted so easily.  As salt accumulates in the body, it also indirectly increases the extracellular fluid volume  2 reasons for increase extracellular fluid volume: o Some additional sodium may be stored in the tissues when salt accumulates in the body, excess salt in the extracellular fluid increases the fluid osmolality  The increased osmolarity stimulates the thirst center in the brain, making the person drink extra amounts of water to return the extracellular salt concentration to normal and increasing the extracellular fluid volume. o The increase in osmolality caused by the excess salt in the extracellular fluid also stimulates the hypothalamic–posterior pituitary gland secretory mechanism to secrete increased quantities of antidiuretic hormone  The antidiuretic hormone then causes the kidneys to reabsorb greatly increased quantities of water  Renin – protein enzyme released by the kidneys when the from the renal tubular fluid, thereby diminishing the arterial pressure decreases. It is synthesized and stored in excreted volume of urine but increasing the an inactive form called prorenin in the juxtaglomerular cells extracellular fluid volume. (JG cells) of the kidneys. JG cells are modified smooth  Increase ADH → Increase blood pressure → decreases muscle cells located in the wall of afferent arterioles, urine output → increases ECF proximal to the glomeruli.  The amount of salt that accumulates in the body is an  RAS is only activated when the blood pressure decreases. important determinant of the extracellular fluid volume  Angiotensinogen - a renin substrate, made from liver  Relatively small increases in extracellular fluid and blood where renin acts on it to release angiotensin 1 a 10 amino volume can often increase the arterial pressure acid peptide substantially. This is true, however, only if the excess salt  Two additional amino acid peptides are split to form angiotensin 2. This conversion occurs to a great extent in GROUP 2 & GROUP 7 6  TRANS: Module 10 the lungs while the blood flows through the small vessels of THE INTEGRATED, MULTIFACETED SYSTEM FOR the lungs, catalyzed by an enzyme called angiotensin ARTERIAL PRESSURE REGULATION converting enzyme (ACE).  Nervous control system – first line of defense against  Angiotensin 2 - an extremely powerful vasoconstrictor, acute changes in arterial pressure persisting in the blood for only 1 or 2 minutes. It is rapidly  Kidney mechanisms – second line of defense for the long- inactivated by multiple blood and tissue enzymes called term control of arterial pressure angiotensinases.  Angiotensin 2 has two principal effects: o Vasoconstriction in many areas of the body  occurs intensely in the arterioles and much less so in the veins  Constriction of the arterioles → increases the total peripheral resistance → raising the arterial pressure o Decrease excretion of both salt and water by the kidneys  Increases the extracellular fluid volume → increases the arterial pressure during subsequent hours and days  Angiotensin 2 causes the kidneys to retain both salt and water in two major ways: o Angiotensin 2 acts directly on the kidneys to cause salt and water retention  constricts the renal arterioles → diminishing blood flow through the kidneys.  Has important direct actions on the tubular cells to increase tubular reabsorption of sodium and water.  The combined effects of a tensin II can sometimes decrease urine output to less than one fifth of normal. o Angiotensin 2 causes the adrenal glands to secrete  Arterial pressure control mechanism that act within seconds aldosterone, and the aldosterone in turn increases salt or minutes: and water reabsorption by the kidney tubules o Baroreceptor feedback  Increased sodium → water retention → increasing o CNS ischemic mechanism the extracellular fluid volume → long-term o Chemoreceptor mechanism elevation of the arterial pressure.  Arterial pressure control mechanisms that act after minutes- hours: o Renin-angiotensin vasoconstrictor mechanism o Stress relaxation of vasculature – pressure in blood vessels become too high → vessels stretch → continue to stretch for minutes or hours → pressure goes back to normal o Shift of through the tissues capillary wall – low capillary pressure → absorb fluid from tissue to capillaries → increase blood volume → blood pressure back to normal  Long term mechanisms for arterial pressure regulation o Renin-blood volume pressure control o Renin-angiotensin aldosterone system STRUCTURE OF MICROCIRCULATION & THE CAPILLARY SYSTEM  Blood enters the capillaries through an arteriole and leaves through a venule  Each nutrient artery entering an organ branches six to eight times before the arteries become small enough to be called arterioles  Arterioles – internal diameter of 10 to 15 micrometers  Arterioles branch two to five times, reaching diameters of 5 to 9 micrometers at the ends where they supply blood to the capillaries o Highly muscular and diameters can change many times GROUP 2 & GROUP 7 7  TRANS: Module 10 o Metarterioles (terminal arterioles) – do not have a  Plasmalemmal vesicles or caveolae (small caves) – from muscular coat, but smooth muscle fibers encircle the from oligomers of proteins called caveolins that are vessel at intermittent points associated with molecules of cholesterol and sphingolipids.  Precapillary sphincter – smooth muscle fiber that usually o Believed to play a role in endocytosis and transcytosis encircles the capillary at the point where each true capillary of macromolecules across the interior of the originates from a metarteriole. It can open and close the endothelial cells entrance to the capillary. o The caveolae at the surface appear to imbibe small  Venules – larger than the arterioles and have a much packets of plasma or extracellular fluid that contain weaker muscular coat. plasma proteins o Pressure in the venules is much less than that in the o Vesicles may coalesce to form vesicular channels all arterioles so the venules can still contract considerably the way through the endothelial cell despite the weak muscle  The metarterioles and precapillary sphincters are in close contact with the tissues they serve. Thus, local conditions of the tissues can cause direct effects on the vessels to control local blood flow  Special types of pores: o In the brain – tight junctions that allow only extremely  The thin capillary wall consists of a single layer of small molecules such as water, oxygen, and carbon endothelial cells dioxide to pass into or out of the brain tissues  Capillaries are also very porous, with several million slits or o In the liver – the clefts between the capillary pores, between the cells that make up their walls to each endothelial cells are wide open so that almost all square centimeter of capillary surface dissolved substances of the plasma, including plasma  Intercellular cleft – thin-slit, curving channel that lies at the proteins, can pass from the blood into the liver tissues top of the figure between adjacent endothelial cells o In the gastrointestinal capillary membrane – o Each cleft is interrupted periodically by short ridges of midway in size between those of the muscles and thos protein attachments that hold the endothelial cells of the liver together, but between these ridges, fluid can percolate o In the glomerular capillaries of kidney – numerous freely through the cleft small oval windows called fenestrae penetrate all the o The cleft normally has a uniform spacing with a width way through the middle of the endothelial cells so that of about 6-7 nanometers (60 to 70 angstroms) tremendous amounts of small molecular and ionic o The rate of thermal motion of water molecules, as well substances can filter through the glomeruli without as most water-soluble ions and small solutes, is so having to pass through the clefts between the rapid that all of these substances diffuse with ease endothelial cells between the interior and exterior of the capillaries through the intercellular clefts GROUP 2 & GROUP 7 8  TRANS: Module 10 VASOMOTION of the muscle capillaries but this is not true for the plasma  Vasomotion – intermittent contraction of the metarterioles proteins. and precapillary sphincters  The most important factor affecting the regulation of vasomotion is the concentration of oxygen in the tissues  High rate of oxygen usage → oxygen concentration decreases → more intermittent periods of capillary blood flow → longer duration of each period of flow → allow capillary blood to carry increased quantities of oxygen  There is an average rate of blood flow through each tissue capillary bed, an average capillary pressure within the capillaries, and an average rate of transfer of substances between the blood of the capillaries and the surrounding interstitial fluid. EXCHANGE OF WATER, NUTRIENTS, AND OTHER NUTRIENTS  Diffusion – results from thermal motion of the water molecules and dissolved substances in the fluid  The blood flows along the lumen of the capillary, the numbers of water molecules and dissolved, particles diffuse back and forth through the capillary wall, providing continual mixing between the interstitial fluid and the plasma.  Proteins are the only dissolved constituents in the plasma EFFECT OF CONCENTRATION DIFFERENCE ON and interstitial fluids that do not readily pass through the NET RATE OF DIFFUSION capillary membrane.  The greater the difference between the concentrations of a  Lipid-soluble substances diffuse directly through the cell substance on the two sides of the capillary membrane, the membranes of the capillary endothelium greater the rate of diffusion in one direction through the  O2 & CO2 are permeable substances - It can diffuse directly membrane through cell membranes without going through pores. Their  Slight difference causes enough oxygen to move from the rates of transport are faster than lipid-insoluble substances blood into the interstitial spaces to provide all the oxygen such as H20 molecules, Na+, Cl- ions and glucose required for tissue metabolism often as much as several liters of oxygen per minute during very active states of the WATER-SOLUBLE, NON–LIPID-SOLUBLE body SUBSTANCES DIFFUSE THROUGH  The rates of diffusion through the capillary membranes of most nutritionally important substances are so great that INTERCELLULAR PORES IN THE CAPILLARY only slight concentration differences cause more than MEMBRANE adequate transport between the plasma and interstitial fluid.  Substances that are water-soluble but cannot pass through  The concentration of oxygen in capillary blood is normally lipid membranes of endothelial cells: greater than in the interstitial fluid. Therefore, large o H2O molecules quantities of oxygen normally move from the blood toward o Na+ ions the tissues o Cl- ions  Conversely, the concentration of carbon dioxide is greater o Glucose in the tissues than in the blood, which causes excess  The pores of some capillary membranes, such as the liver carbon dioxide to move into the blood and to be carried capillary sinusoids, are much larger and are therefore much away from the tissues. more highly permeable to substances dissolved in plasma  Thermal molecular motion in clefts are greater despite THE INTERSTITIUM & INTERSTITIAL FLUID 1/1000 surface area  Interstitium – spaces between cells. It is 1/6 of the total volume of the body EFFECT OF MOLECULAR SIZE ON PASSAGE  Interstitial fluid – fluid present in the interstitium THROUGH THE PORES  Two major types of solid structures:  The permeability of the capillary pores for different o Collagen fiber bundles - strong and provide most of substances varies according to their molecular diameters the tensional strength of the tissues, it also extends  Water and most electrolytes have a molecular size that is long distances in the interstitium smaller than the pore size, allowing rapid diffusion across o Proteoglycan filaments - a thin, coiled or twisted the capillary wall. However, plasma proteins have a molecules composed of about 98% hyaluronic acid and molecular size that is slightly greater than the width of the 2% protein. They form a mat of very fine reticular pores, restricting their diffusion. filaments aptly described as a brush pile.  The capillaries in various tissues have extreme differences  The fluid in the interstitium is derived by filtration and in their permeabilities. diffusion from the capillaries  The membranes of the liver capillary sinusoids are so  It contains almost the same constituents as plasma except permeable that even plasma proteins pass through these for much lower concentrations of proteins walls, almost as easily as water and other substances.  The interstitial fluid is entrapped mainly in the minute  The permeability of the renal glomerular membrane for spaces among the proteoglycan filaments water and electrolytes is about 500 times the permeability GROUP 2 & GROUP 7 9  TRANS: Module 10  Tissue gel - combination of proteoglycan filaments and is positive, but outward when Pif is negative. The Pif is interstitial fluid entrapped mainly in the minute spaces very low because the fluid is trapped in the gel. among the proteoglycan filaments has the characteristics of o Plasma colloid osmotic pressure (IIp) – is from a gel plasma proteins. By osmosis, it will pull fluid inward  Because of the large number of proteoglycan filaments, it is through the capillary membrane difficult for fluid to flow easily through the tissue gel. It o Interstitial fluid colloid osmotic pressure (IIif) – is moves molecule by molecule from one place to another by from proteins in the interstitium and causes osmosis of kinetic thermal motion rather than by large numbers of fluid outward through the capillary. molecules moving together.  There are 2 hydrostatic pressures which would be the  Diffusion through the gel occurs about 95% to 99% as pressure exerted by the fluid itself on either side. rapidly as it does through free fluid. o In the capillary, it is the capillary hydrostatic pressure  For the short distances between the capillaries and tissue (Pc) and for the interstitial fluid, It is the interstitial fluid cells this diffusion allows for rapid transport through the hydrostatic pressure (Pif) interstitium, not only of water molecules but also of  There are 2 colloid osmotic or oncotic pressure, which are substances such as electrolytes, low-molecular-weight controlled by proteins. nutrients, cellular excreta, oxygen, and carbon dioxide. o For the capillary, it is the plasma colloid osmotic  Free fluid – small rivulets of free fluid and small free fluid pressure (IIp) and interstitial fluid colloid hydrostatic vesicles usually less than 1% pressure (IIif) for the interstitial fluid. o Free of the proteoglycan molecules and therefore can  Net filtration pressure is positive → there will be net fluid flow freely filtration across capillaries  Net filtration pressure is negative → there will be net fluid absorption  Net filtration pressure is calculated by: 𝑵𝑭𝑷 = 𝑷𝒄 − 𝑷𝒊𝒇 − 𝑰𝑰𝒑 − 𝑰𝑰𝒊𝒇  Capillary filtration coefficient (Kf) – a measure of the capacity of the capillary membranes to filter water for a given NFP and is usually expressed as ml/min per mmHg NFP 𝑭𝒊𝒍𝒕𝒓𝒂𝒕𝒊𝒐𝒏 = 𝑲𝒇 × 𝑵𝑭𝑷  Various methods have been used to estimate the capillary EFFECTS OF HYDROSTATIC & COLLOID OSMOTIC hydrostatic pressure. PRESSURES, AND THE CAPILLARY FILTRATION  First off, direct micropipette cannulation of the capillaries - COEFFICIENT ON FLUID FILTRATION which gives an average capillary pressure of 25 mmHg in  The rate at which ultrafiltration occurs across the capillary some tissues, such as the skeletal muscle and gut depends on the difference in hydrostatic and colloid osmotic  Second, the indirect functional measurement of the pressures of the capillary and interstitial fluid. These forces capillary pressure – which gives a capillary pressure are often called Starling forces. averaging about 17 mmHg in these tissues.  The capillary is surrounded by interstitium, so the 2 are  The micropipette method had given pressures of 30-40 separated by the capillary membrane. mmHg in the arterial ends of the capillaries, 10-15mmHg in  The interstitium is like a gel with collagen and the venous ends, and 25 mmHg in the middle. proteoglycans. There's a fluid trap in between and that’s the  In some capillaries, such as the glomerulus of the kidneys, interstitial fluid. averaging about 60mmHg, while the peritubular capillaries  Since protein can’t fit through the capillary membrane, the average only about 13mmHg. interstitium has lesser protein and the protein that’s present  There are 3 ways to measure interstitial fluid hydrostatic comes from the leakage of the capillaries. pressure:  There are 4 forces that determine which way fluids can o Micropipette inserted into the tissues: which gives a move. These are called starling forces: range −2 to +2 mm Hg in loose tissues. o Capillary hydrostatic pressure (Pc) - the pressure o Implanted perforated capsules: −6 mm Hg in loose exerted by fluid outward through the capillary subcutaneous tissue membrane thus encouraging filtration. This can be o Cotton wick inserted into the tissue. affected by the changes in the arterial and venous  In most of these tissues, regardless of the method used for pressures and resistance which get transmitted to the measurement, the interstitial fluid pressures are positive. capillary. An increase in pressure increases the Pc.  However, these interstitial fluid pressures almost invariably o Interstitial fluid hydrostatic pressure (Pif) - pushes are still less than the pressures exerted on the outsides of fluid inward through the capillary membrane when Pif the tissues by their encasements. GROUP 2 & GROUP 7 10  TRANS: Module 10  In most natural cavities of the body, where there is free fluid in dynamic equilibrium with the surrounding interstitial fluids, the pressures that have been measured have beennegative. Some of these cavities and pressure measurements are as follows: o Intrapleural space: -8 mmHg o Joint synovial spaces: -4 to -6 mmHg o Epidural space: -4 to -6 mmHg PLASMA COLLOID OSMOTIC PRESSURE  Only the molecules or ions that fail to pass through the pores of a semipermeable membrane exert osmotic pressure.  Since proteins are the only dissolved constituents in the plasma and interstitial fluids that do not readily pass through the capillary pores, it is the proteins of the plasma and interstitial fluids that are responsible for the osmotic pressures on the two sides of the capillary membrane.  To distinguish this osmotic pressure from that which occurs at the cell membrane, it is called colloid osmotic pressure or oncotic pressure.  The colloid osmotic pressure of normal human plasma averages about 28 mm Hg; 19 mm of this pressure is caused by molecular effects of the dissolved protein, and 9 mm is caused by the Donnan effect.  The summation of forces at the arterial end of the capillary  The plasma proteins are a mixture that contains albumin, shows a net filtration pressure of 13 mm Hg, tending to globulins, and fibrinogen. move fluid outward through the capillary pores.  About 80% of the total colloid osmotic pressure of the  This 13 mm Hg filtration pressure causes, on average, plasma results from the albumin, 20% from the globulins, about 1/200 of the plasma in the flowing blood to filter out and almost none from fibrinogen. of the arterial ends of the capillaries into the interstitial  Therefore, from the point of view of capillary and tissue fluid spaces each time the blood passes through the capillaries. dynamics, it is mainly albumin that is important.  Donnan effect – extra osmotic pressure caused by sodium, VENOUS END OF CAPILLARY potassium, and the other cations held in the plasma by the  There is a net reabsorption pressure of 7 mm Hg at the proteins venous ends of the capillaries.  This reabsorption pressure is considerably less than the INTERSTITIAL FLUID COLLOID OSMOTIC filtration pressure at the capillary arterial ends PRESSURE  But the venous capillaries are more numerous and more  Small amounts of plasma proteins do leak into the interstitial permeable than the arterial capillaries. Thus, less spaces through pores and by transcytosis in small vesicles. reabsorption pressure is required to cause inward  The total quantity of protein in the entire 12 liters of movement of fluid. interstitial fluid of the body is slightly greater than the total quantity of protein in the plasma but, because this volume is four times the volume of plasma, the average protein concentration of the interstitial fluid of most tissues is usually only 40% of that in plasma, or about 3 g/dl  Quantitatively, the average interstitial fluid colloid osmotic pressure for this concentration of proteins is about 8 mm Hg. CAPILLARY FILTRATION COEFFICIENT  The filtration coefficient can also be expressed for separate parts of the body in terms of the rate of filtration per minute per mm Hg per 100 grams of tissue  On this basis, the capillary filtration coefficient of the average tissue is about 0.01 ml/min per mm Hg per 100 g of tissue  The concentration of protein in the interstitial fluid of muscles is about 1.5 g/dl in subcutaneous tissue, it is 2 g/dl in the intestine, it is 4 g/dl And, in the liver, it is 6 g/dl. ARTERIAL END OF CAPILLARY  The approximate average forces operative at the arterial end of the capillary that cause movement through the capillary membrane are shown as follows: GROUP 2 & GROUP 7 11  TRANS: Module 10 STARLING EQUILIBRIUM FOR CAPILLARY o Transport of various hormones and other substances EXCHANGE to the different tissues.  Large blood flow through the kidneys—1100 ml/min. This  A state of near equilibrium exists in most capillaries. That extreme amount of flow is required for the kidneys to is, the amount of fluid filtering outward from the arterial ends perform their function of cleansing the blood of waste of capillaries equals almost exactly the fluid returned to the products and precisely regulating composition of the body circulation by absorption fluids.  The slight disequilibrium that does occur accounts for the  LOW BLOOD FLOW OF INACTIVE MUSCLES: 750 ml/ fluid that is eventually returned to the circulation by way of min lymphatics  METABOLIC ACTIVITY OF MUSCLES (RESTING  Mean functional capillary pressure calculates to be 17.3 STATE): 4 ml/min/100 g mmHg  DURING HEAVY EXERCISE: 16,000 ml/min in the body’s total muscle vascular bed  The slight imbalance of forces, 0.3 mmHg, causes slightly more filtration than reabsorption of fluid into the interstitial spaces.  An abnormal imbalance of pressures in the capillary can  We shall see that these factors exert extreme degrees of cause edema local blood flow control and that different tissues place o If the mean capillary pressure rises significantly above different levels of importance on these factors in controlling the average value of 17 mm Hg, the net force tending blood flow. to cause filtration of fluid into the tissue spaces rises. o If capillary pressure falls very low, net reabsorption of IMPORTANCE OF BLOOD FLOW CONTROL BY THE fluid into the capillaries will occur instead of net filtration, and the blood volume will increase at the LOCAL TISSUES expense of the interstitial fluid volume.  Very large blood flow through every tissue of the body would require many times more blood flow than the heart LOCAL & HUMORAL CONTROL OF TISSUE BLOOD can pump FLOW  Blood flow to each tissue usually is regulated at the minimal level that will supply the tissue’s requirements—no more,  A fundamental principle of circulatory function is that most no less tissues have the ability to control their own local blood flow  Control by substances secreted or absorbed into the body in proportion to their specific metabolic needs. fluids, such as hormones and locally produced factors  Some of the specific needs of the tissues for blood flow  By controlling local blood flow in such an exact way, the include the following: tissues almost never experience oxygen nutritional o Delivery of oxygen to the tissues deficiency and the workload on the heart is kept at a o Delivery of other nutrients such as glucose, amino minimum. acids, and fatty acids o Removal of carbon dioxide from the tissues o Removal of hydrogen ions from the tissues MECHANISMS OF BLOOD FLOW CONTROL o Maintenance of proper concentrations of ions in the  There are mechanisms that are used by the tissues to tissues control their blood flow. Like how the muscles, the kidneys, the liver, the skin, how they control their own blood flow and GROUP 2 & GROUP 7 12  TRANS: Module 10 how sometimes the blood flow to these organs is less or o Experiments have shown that decreased oxygen high. availability can cause adenosine and lactic acid  Vasodilation - causes blood vessels in your body to widen, (containing hydrogen ions) to be released into the allowing more blood to flow through them and lowering your spaces between the tissue cells; these substances blood pressure. Mostly beneficial, as it helps deliver oxygen then cause intense acute vasodilation and therefore and nutrients throughout your body. are responsible, or partially responsible, for the local  Vasoconstriction - When you're out in the cold, blood flow regulation. vasoconstriction helps keep you warm. But there are times o They help increase tissue blood flow and returning the when vasoconstriction — especially too much of it — is tissue concentration of the metabolites toward normal. harmful.  Oxygen demand theory / Nutrient demand theory - The  2 basic mechanisms that are used by tissue or 2 precapillary sphincters are normally completely open or phases of local blood flow control: Acute control & completely closed. The number of precapillary sphincters long-term control that are open at any given time is roughly proportional to the requirements of the tissue for nutrition. PHASES OF LOCAL BLOOD FLOW CONTROL o Vasomotion - Cyclical opening and closing of  Acute control - Acute control is achieved by rapid changes precapillary sphincters and metarterioles. in local vasodilation or vasoconstriction of the arterioles, o Inadequate O2 = Vasodilation metarterioles, and precapillary sphincters o Increased O2 concentration → increased strength of o All within seconds to minutes to provide rapid contraction of sphincter = closure of sphincter maintenance of appropriate local tissue blood flow. o Decreased O2 concentration = sphincter opens o Acute control is due to increase in size (vasoconstriction) and decrease in size (vasodilation). Increasing or decreasing blood supply.  Long-term control - slow, controlled changes in flow over a period of days, weeks, or even months. o These long-term changes provide even better control of the flow in proportion to the needs of the tissues. o These changes come about as a result of an increase or decrease in the physical sizes and numbers of blood vessels supplying the tissues.  Increase in tissue metabolism → increase tissue blood flow o Increase metabolism on skeletal muscle by 8 times the normal increases tissue blood flow acutely by 4 times.  Reduced O2 availability → increase tissue blood flow o 25% decrease in arterial O2 saturation increases blood flow by 3 times o Instances when availability of oxygen to the tissues decreases: High altitude at the top of mountain, pneumonia, carbon monoxide poisoning (poisons the ability of hemoglobin to transport oxygen), cyanide poisoning (poisons the ability of the tissue to use oxygen) ACUTE LOCAL BLOOD FLOW REGULATION  Vasodilator Theory (Vasodilation) - Vasodilation is a mechanism to enhance blood flow to areas of the body that are lacking oxygen and/or nutrients. Meaning, Vasodilator substances may be released from the tissue in response to oxygen deficiency. o Greater rate of metabolism / less availability of oxygen  Lack of glucose, amino acids, or fatty acids → vasodilation = greater rate of formation of vasodilator substances  Beriberi - Vitamin B deficiency (thiamine B1, riboflavin B2, o The vasodilator substances are then believed to diffuse niacin B3) through the tissues to the precapillary sphincters, o Increase in peripheral vascular blood flow by 2-3 times metarterioles, and arterioles to cause dilation. o Diminished smooth muscle contractile ability → local o Vasodilators: vasodilation  Adenosine – many believe that adenosine is an important local vasodilator for controlling local blood flow and also others believe that they are ACUTE METABOLIC CONTROL OF LOCAL BLOOD released in cardiac muscles when coronary flow FLOW decreases to cause local vasodilation of heart to  Reactive hyperemia - When the blood supply to a tissue is return coronary flow to normal. blocked for a few seconds to as long as 1 hour or more and  carbon dioxide then is unblocked, blood flow through the tissue usually  adenosine phosphate compounds increases immediately to 4-7 times normal.  histamine o Increases local blood flow toward tissue which have  potassium ions been occluded prior.  hydrogen ions – can be found in lactic acid o Lasts long enough to repay the tissue O2 deficit during period of occlusion (period of diminished blood supply) GROUP 2 & GROUP 7 13  TRANS: Module 10  Active hyperemia - When a tissue becomes highly active, o Role in blood flow regulation is unclear (pressure- the rate of blood flow through the tissue increases sensing mechanism cannot detect changes in blood o Occurs when tissue metabolic rate increases: flow in tissue directly) Exercising muscle, gastrointestinal gland in  During circumstances where metabolic demands of tissue hypersecretory period, and brain during increased are significantly increased (vigorous muscle exercise), mental activity Metabolic Autoregulation overrides (is dominant) Myogenic o Vasodilation → increase in local blood flow Autoregulation. SPECIAL MECHANISMS FOR ACUTE BLOOD FLOW CONTROL IN SPECIFIC TISSUES  Kidneys - Tubuloglomerular feedback o Macula densa found in early distal tubule of Juxtaglomerular nephrons senses the composition of fluid o Too much fluid filters from the blood → macula densa cause constriction → renal blood flow & glomerular filtration reduced back to normal  Brain – CO2 and H+ ions concentration o Increase in either or both ions → dilation of cerebral vessels → rapid washout of excess CO2 or H ions  Skin – body temperature regulation o Skin blood flow is controlled largely by CNS through sympathetic nerves. o Cool weather - 3 ml/min/100g; vasoconstriction; heat preserved o Body heating - 7 to 8 L/min; vasodilation; heat loss o Reduced body temperature → skin blood flow decreases ENDOTHELIAL-DERIVED RELAXING OR CONSTRICTING FACTORS IN ARTERIAL PRESSURE  Endothelium-Derived Relaxing Factor (EDRF) - Released from healthy endothelial cells in response to many physical and chemical stimuli. Acts on larger vessel  Nitric oxide - Most important of the endothelium derived relaxing factors. o Lipophilic gas which is synthesized from Arginine + O2 + reduction of inorganic nitrate AUTOREGULATION OF BLOOD FLOW o After diffusing from endothelial cells, half-life in the  In any tissue of the body, a rapid increase in arterial blood is 6 seconds. pressure causes an immediate rise in blood flow. However, o Activates Soluble Guanylate Cyclases in vascular within less than 1 minute, the blood flow in most tissues smooth muscle cells à conversion of Cyclic returns almost to the normal level, even though the arterial Guanosine Triphosphate (cGTP) to Cyclic Guanosine pressure is kept elevated. This return of flow toward normal Monophosphate((cGMP) and activation of cGMP- is called autoregulation. dependent protein kinase → causes blood vessel to  Metabolic theory - When the arterial pressure becomes relax. too great, the excess flow provides too much oxygen and o Impaired NO synthesis → excessive vasoconstriction too many other nutrients to the tissues and washes out the vasodilators released by the tissues. These nutrients (especially oxygen) and decreased tissue levels of vasodilators then cause the blood vessels to constrict and return flow to nearly normal, despite the increased pressure. o Arterial pressure becomes too great → excess O2 and other nutrients → “washes out” vasodilators → vasoconstriction → normal local blood flow  Myogenic theory - Suggests that another mechanism not related to tissue metabolism explains the phenomenon of autoregulation. Based on Sudden Stretch of small blood vessels which causes smooth muscle of vessel wall to contract o High arterial pressure → Reactive vascular contraction → reduce blood flow to nearly normal o Important in preventing excessive stretching of blood vessels when BP is increased GROUP 2 & GROUP 7 14  TRANS: Module 10  Endothelin - Powerful vasoconstrictor released from COLLATERAL CIRCULATION damaged endothelium  When artery/vein is blocked, new vascular channel o Released by damaged endothelium (Crushing, develops around the blockage allowing partial resupply of Chemical injury) blood to affected tissue o Function: prevention of bleeding (enhance platelet  Dilation of small vascular loops that already connect the aggregation). vessel above the blockage to the vessel below → initial o Present in endothelial cells of all or most blood vessels opening of collateral vessels → further opening → few but greatly increases when the vessels are injured days, blood flow is sufficient o Severe blood vessel damage → endothelin release →  Collateral vessels continue to grow for many months vasoconstriction thereafter LONG-TERM CONTROL OF LOCAL BLOOD FLOW HUMORAL CONTROL OF THE CIRCULATION  We know the rapidity of the acute mechanisms for local  Humoral control - control by substances secreted or blood flow regulation. We should also know that the absorbed into the body fluids, such as hormones and locally regulation is still incomplete. However, over a period of produced factors hours, days, and weeks, a long-term type of local blood flow  Formed by special glands and transported in the blood regulation develops in addition to the acute control. throughout the entire body. Some are formed in local tissue  Gives far more complete control of blood flow. areas and cause only local circulatory effects.  Especially important when the metabolic demands of a tissue change. VASOCONSTRICTOR AGENTS  Chronically overactive tissue → increased need for O2 &  Norepinephrine & epinephrine - released by the adrenal other nutrients → blood vessels increase in both number medulla, act as vasoconstrictors in many tissues by and size stimulating α-adrenergic receptors; however, epinephrine is  Vasculature - it allows exchange of nutrients and waste to much less potent as a vasoconstrictor and may even cause and from every cell. mild vasodilation through stimulation of β-adrenergic  Angiogenesis - the process of new capillaries forming out receptors in some tissues, such as skeletal muscle. of preexisting blood vessels in your body. It's normally a  Angiotensin II - a powerful vasoconstrictor that is usually helpful, important process that supports wound healing and formed in response to volume depletion or decreased blood supplies oxygen-rich blood to your organs and tissues. pressure. o Begins with new vessels sprouting from other vessels  Vasopressin - also called antidiuretic hormone, is one of o Dissolution of basement membrane → rapid the most powerful vasoconstrictors in the body. It is formed reproduction of new endothelial cells that stream in the hypothalamus and transported to the posterior outward in extended cords → cells in each cord pituitary, where it is released in response to decreased continue to divide and fold into a tube → tube connects blood volume, as occurs with hemorrhage, or increased with another tube → forms a capillary loop plasma osmolarity, as occurs with dehydration. o Good flow → smooth muscle cells invade wall → new  Prostaglandins - formed in almost every tissue in the body. arterioles or venules or large vessels These substances have important intracellular effects, but  Neonate - vascularity will adjust to match almost exactly the some of them are released in the circulation, especially needs of the tissue for blood prostacyclin and prostaglandins of the E series, which are  Older tissues - vascularity frequently lags far behind the vasodilators. Some prostaglandins, such as thromboxane needs of the tissues. A2 and prostaglandins of the F series, are vasoconstrictors.  Vascular growth factors - Small peptides that increase growth of new blood vessels VASODILATOR AGENTS o Four factors: vascular endothelial growth factor (VEGF), fibroblast growth factor, platelet-derived  Bradykinin - formed in the blood and in tissue fluids, is a growth factor (PDGF), and angiogenin powerful vasodilator that also increases capillary o Deficiency of tissue oxygen/nutrients → formation of permeability. For this reason, increased levels of bradykinin angiogenic factors may cause marked edema and increased blood flow in some tissues.  Antiangeogenesis – opposite of angiogenesis  Histamine - a powerful vasodilator, is released into the  Steroid hormones - causes dissolution of vascular cells & tissues when they become damaged or inflamed. Most of disappearance of vessels the histamine is released from mast cells in damaged  Peptides - can also block growth of new blood vessels tissues or from basophils in the blood. Histamine, like o Angiostatin - inhibitor of angiogenesis; fragment of the bradykinin, increases capillary permeability and causes protein plasminogen tissue edema, as well as greater blood flow. o Endostatin - antiangiogenic peptide derived from collagen type XVII VASCULAR CONTROL BY IONS & OTHER  Vascularity is determined by maximum blood flow need o Heavy exercise → whole body blood flow increases 6 CHEMICAL FACTORS to 8 times the resting blood flow → muscles form  Many ions and chemical factors can either dilate or constrict angiogenic factors → increase vascularity local blood vessels. o After development of extra vascularity, extra blood  Increased calcium ion concentration → vasoconstriction vessels normally remain mainly vasoconstricted  Increased potassium ion concentration → vasodilation  Increased magnesium ion concentration → vasodilation  Increased sodium ion concentration → vasodilation  Increased osmolarity of the blood, caused by increased quantities of glucose or other nonvasoactive substances → vasodilation GROUP 2 & GROUP 7 15  TRANS: Module 10  Increased hydrogen ion concentration (decreased pH) → SYMPATHETIC VASOCONSTRICTOR SYSTEM vasodilation  Vasoconstrictor area - located bilaterally in the  Increased carbon dioxide concentration → vasodilation in