L48 2024 Capillary Fluid Exchange PDF

48 Capillary fluid exchange and response to hemorrhage ILOs By the end of this lecture, students will be able to 1. Identify the forces favoring filtration and reabsorption across the capillary vessel wall in relevance to tissue fluid formation 2. Relate the starling forces to the rate of fluid move...

48 Capillary fluid exchange and response to hemorrhage ILOs By the end of this lecture, students will be able to 1. Identify the forces favoring filtration and reabsorption across the capillary vessel wall in relevance to tissue fluid formation 2. Relate the starling forces to the rate of fluid movement across the capillary wall 3. Analyze the forces at the arterial and venous end of the capillaries 4. Interpret the link between blood loss and arterial blood pressure 5. Summarize the compensatory responses helping to restore ABP triggered by CVS reflexes 6. Discuss the internal transfusion mechanisms for the short term restoration of blood volume 7. Interpret the role of the kidney in the long-term restoration of blood loss 8. Correlate the hormonal response to the long-term restoration of blood loss Introduction Extracellular fluid is transported through the body first by movement of blood in the blood vessels. Secondly, by movement of fluid between the blood capillaries and the intercellular spaces between the tissue cells. The human body contains about 10 billion capillaries with a total surface area estimated to be 500-700 square meters. In general, each artery entering an organ branches six to eight times to give rise to smaller arterioles. The terminal arterioles, metarterioles, branch two to five times and give rise to capillaries. At the point where each true capillary originates from a metarteriole, a smooth muscle fiber usually encircles the capillary. This structure is called the precapillary sphincter. This sphincter can open and close the entrance to the capillary (figure 1). The metarterioles and precapillary sphincters are in close contact with the tissues they serve. Therefore, the local conditions of the Figure 1:Vascular tree arrangement tissues—such as the concentrations of nutrients, end products of metabolism, and hydrogen ions— can cause direct effects on the vessels to control local blood flow. Blood flows through the capillaries intermittently, turning on and off every few seconds or minutes. The cause of this intermittency is the phenomenon called vasomotion, which means intermittent contraction of the metarterioles and precapillary sphincters. The most important factor affecting the degree of opening and closing of the metarterioles and precapillary sphincters is the concentration of oxygen. When the rate of oxygen usage by the tissue is great and oxygen concentration decreases, the intermittent periods of capillary blood flow occur more often allowing more oxygen entry. Page 1 of 6 Capillary tone refers to the percentage of partially and totally closed capillaries at a specific time which is about 90% (~ 80% are completely closed). Functions of capillaries 1- Allow exchange of gases, nutrients, and wastes between blood and tissues. As blood passes through blood capillaries, a continual exchange of extracellular fluid occurs between the plasma portion of the blood and the interstitial fluid that fills the intercellular spaces. The capillary walls are permeable to most molecules in the blood plasma, except for plasma proteins, which are too large to pass. 2- Capillary tone is essential for normal venous return, cardiac output, and arterial blood pressure. Movement of substances across capillary walls Diffusion through the capillary membrane is the most important means of transferring substances between plasma and interstitial fluid. Lipid-soluble substances diffuse directly through the cell membranes of the capillary endothelium. Water-soluble, non–lipid-soluble substances diffuse through intercellular pores in the capillary membrane. Fluid filtration across Capillaries Hydrostatic and colloid osmotic forces determine fluid movement through the capillary membrane. The hydrostatic pressure in the capillaries tends to force fluid and its dissolved substances through the capillary pores into the interstitial spaces. Conversely, colloid osmotic pressure caused by the plasma proteins tends to cause fluid movement by osmosis from the interstitial spaces into the blood. This osmotic pressure exerted by the plasma proteins prevents loss of fluid volume from the blood into the interstitial spaces. The lymphatic system returns to the circulation the small amounts of excess protein and fluid that leak from the blood into the interstitial spaces. Four primary forces determine whether fluid will move out of the blood into the interstitial fluid or in the opposite direction known as Starling Forces. 1. The capillary hydrostatic pressure (Pc), which tends to force fluid outward through the capillary membrane. Usually is 25-35 mm Hg on arteriolar side and 10-15 mmHg on venular side. 2. The interstitial fluid hydrostatic pressure (Pif), which tends to force fluid inward through the capillary membrane when Pif is positive but outward when Pif is negative. 3. The capillary plasma colloid osmotic pressure (Πp), which tends to cause osmosis of fluid inward through the capillary membrane. It is about 28 mm Hg (25-30 mm Hg). 4. The interstitial fluid colloid osmotic pressure (Πif), which tends to cause osmosis of fluid outward through the capillary membrane. It is about 5-6 mm Hg. Þ If the sum of these forces—the net filtration pressure— is positive, there will be a net fluid filtration across the capillaries. Þ If the sum of the Starling forces is negative, there will be a net fluid absorption from the interstitial spaces into the capillaries. Page 2 of 6 Þ The net filtration pressure (NFP) is calculated as follows: Jv= rate of fluid movement across the capillary wall Kf= filtration coefficient Pc= Capillary hydrostatic pressure Pi= Interstitial pressure s= colloid osmotic reflection coefficient P p Capillary Oncotic pressure P i Interstitial Oncotic pressure HEMORRHAGE Blood volume in the human body is 5 L and about 65% of this volume is in the venous compartment of the circulation. A reduction in blood volume may occur in many ways. Þ Loss of whole blood through blood vessel trauma either directly out of the subject or into other tissues such as the lumen of the stomach or a thigh muscle is referred to as hemorrhage. Þ Or through excessive vasodilatation of peripheral blood vessels which will induce similar physiological responses to loss of blood volume. Normal physiological compensatory responses will usually cope with low levels of blood loss (up to 10% blood volume e.g., 500 mL blood during blood donation) without problem. The fundamentals of these physiological responses are: Þ Firstly, short-term arterial blood pressure regulation, so that tissue perfusion is sustained and, Þ Secondly, long-term regulation to replace the lost blood volume. Arterial blood pressure changes in response to hemorrhage Þ Rapid (within minutes) blood volume losses of 5 – 10% of blood volume in someone with normally functioning circulatory reflexes produce little if any change in mean arterial pressure. Þ A rapid 15 – 20% hemorrhage will cause a modest reduction in mean arterial pressure from about 93 mm Hg to about 80– 90 mm Hg. Recovery from such a hemorrhage using normal physiological mechanisms is expected. Þ A 20 – 30% blood volume loss might typically result in a drop in mean arterial blood pressure to 60– 80 mm Hg and generate some indications of shock responses but such a hemorrhage would not normally be fatal. Page 3 of 6 Þ A blood volume loss of 30 – 40% however would lead to a substantial reduction of mean arterial blood pressure to 50 – 70 mm Hg with serious shock responses which may become irreversible. Þ Blood volume loss beyond 50% would normally be fatal. Causes of Arterial blood pressure changes in response to hemorrhage Decreased blood volume leads to decreased right atrial pressure and consequently decreased filling of the right ventricle. This leads to a decrease in stroke volume (Starling’s law) and therefore to a reduction in cardiac output. A 20% reduction in blood volume would typically result in an initial reduction in resting cardiac output from about 5 L/min to about 3 L/min. As mean arterial pressure is the product of cardiac output and peripheral resistance there is a fall in blood pressure as identified above. Short-term regulation: The compensatory responses to restore blood pressure o Carotid sinus baroreceptor reflex Figure 2: Link between hemorrhage and fall in arterial blood pressure. The modified nerve endings that constitute the baroreceptors (mainly in the carotid sinuses) become less stretched as blood pressure falls. Fewer action potentials will therefore pass up the glossopharyngeal nerve and enter the brain at the level of the medulla. Following central processing of the baroreceptor input there will be activation of sympathetic outflow and inhibition of the parasympathetic nerve supply to the heart. The consequences are an increased heart rate (tachycardia) and an increase in cardiac contractility, both of which contribute to a raised cardiac output (figure2). o Sympathetic nervous system activation Sympathetic nervous system activation also leads to α1 -receptor-mediated vasoconstriction. The regions of the circulation that are particularly affected by sympathetic vasoconstriction responses include the skin, gut, kidney, and skeletal muscle. The brain and coronary circulations are relatively preserved, especially during the sequel to a hemorrhage amounting to about 20% or less blood volume loss. Concurrent sympathetically mediated venoconstriction will help to maintain central venous pressure and hence limit the fall in preload on the right side of the heart. When hemorrhage reaches levels of the order of 25 – 35% blood loss the sympathetic activation outlined above is succeeded by inhibition of sympathetic outflow and progression to circulatory shock. Page 4 of 6 Short-term regulation: The compensatory responses to restore blood volume Þ Following hemorrhage, there may be a fall in mean arterial pressure but, in addition, a compensatory peripheral vasoconstrictor response occurs. As the main resistance vessels are the arterioles, vessels that come immediately before the capillaries, there will be a fall in capillary blood pressure following a hemorrhage. This will alter the balance of the Starling forces and, as the colloid osmotic pressure of plasma is initially unchanged, this will result in a net movement of water from the interstitial space into the blood, a process known as internal transfusion (figure 3). A rapid loss of 20% of blood volume (about a 1000 mL hemorrhage will lead to ~ 600 mL of interstitial fluid entering the blood over ~10 minutes. Þ A further factor that helps to maintain the internal transfusion is hormonally driven glycogen breakdown in the liver. Sympathetic activation and release of adrenaline (epinephrine) from the adrenal medulla led to the release of glucose from glycogen stores and, as a consequence, an increase in plasma and interstitial fluid osmolarity. The rise in osmolarity draws fluid into the interstitial space from the intracellular compartment (figure 3). Figure 3: Factors influencing internal transfusion The colloid osmotic pressure of plasma will gradually fall as a result of dilution with interstitial fluid. At the same time, capillary blood pressure will gradually rise back to normal levels as a result of the internal transfusion. Eventually, a new equilibrium will be established between the Starling forces and so the internal transfusion will cease. Long-term responses which help to restore lost blood volume and electrolytes Replacing the overall water loss following a hemorrhage is achieved by a combination of changes in glomerular filtration rate in the kidneys and hormonally mediated changes in kidney tubular function. Þ Sympathetic activation, as a result of the fall in blood pressure and the baroreceptor reflex, leads to intrarenal vasoconstriction. This particularly affects the afferent arterioles but also the efferent arterioles at the glomeruli. This leads to a reduction in glomerular filtration rate which helps to conserve water and electrolytes. However, prolonged intrarenal vasoconstriction leads to ischemia and acute tubular necrosis (ATN). The nephron becomes blocked with swollen and necrotic tubular epithelial cells and the patient becomes oliguric (less than 100 mL urine per day). Page 5 of 6 Þ Renin-angiotensin aldosterone system The JG cells respond directly to a fall in renal artery blood pressure to increase renin secretion. An increase in renin secretion will increase the generation of angiotensin II (Ang II). This has three beneficial roles in the acute response to hemorrhage (figure 4). § The immediate Vasoconstrictor effect of Ang II helps to maintain arterial Blood pressure. § Ang II is also the major stimulus to increased aldosterone synthesis in the zona glomerulosa of the adrenal cortex. Aldosterone has a sodium retaining and potassium excreting action on the distal segments of the nephron. Water is absorbed osmotically along with the sodium retained. § Ang II is also involved, by its action on the subfornical organ of the brain, in promoting thirst responses. Figure 4: Summary of the hormonal control of salt and water retention in the kidney. Page 6 of 6