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Body Fluids Bruce M Faculty version with model answers Body Fluids Bruce M. Koeppen, M.D., Ph.D. University of Connecticut Health Center Introduction By weight, water comprises approximately 60% of the adult human body (this percentage varies with the amount of adipose tissue (as the amount of adipose tissue increases the percentage of body weight attributed to water decreases). This total body water (TBW) is contained within two major compartments; the intracellular fluid (ICF – 40% of body weight) and the extracellular fluid (ECF – 20% of body weight). Fluid within the ECF is further subdivided into plasma and the fluid surrounding cells (interstitial fluid). Water readily moves between these various fluid compartments. Water movement between the ICF and ECF is driven by differences in osmotic pressure, whereas movement between the vascular compartment (i.e., plasma) and the interstitial fluid compartment is driven by Starling forces across the wall of the capillaries. In this conference we will examine the volumes and composition of the various body fluid compartments, and how fluid shifts occur under a number of conditions. Recommended Reading: Pg. 1 - 15: Renal Physiology, 3rd ed., Koeppen & Stanton, C.V. Mosby, 2001. ___________________________ Capillary Fluid Movement Fluid movement across the wall of a capillary is driven by the sum of the Starling forces; two of which favor (Pc and Πis) and two of which oppose (Pis and Πc) fluid movement out of the capillaries. • Pc: hydrostatic pressure in the capillary • Pis: hydrostatic pressure in the interstitium • Πc: oncotic pressure of proteins in the capillary • Πis: oncotic pressure of proteins in the interstitium Fluid movement across the capillary can be quantitated as: Fluid Flow = Kf [(Pc - Pis) - σ(Πc-Πis)] Where: Kf is the filtration coefficient and takes into consideration the intrinsic permeability of the capillary wall to fluid movement (also called the hydraulic conductivity), as well as the surface area available for fluid flow; and σ is the reflection coefficient for proteins, which varies from 0 (i.e., the capillary wall is freely permeable to proteins) to 1 (i.e., the capillary wall is impermeable to proteins). Fluid Movement Between the ICF and ECF Water can move between the ICF and ECF under a number of important clinical situations. The effects of these shifts on the volumes of the body fluid compartment can be approximated using the following principles: ©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -1- • The volumes of the various body fluid compartments can be estimated in the normal adult as: Total Body Water (TBW) = 0.6 x body weight Extracellular Fluid Volume (ECF) = 0.2 x body weight Intracellular Fluid Volume (ICF) = 0.4 x body weight Plasma Volume (P) = 0.25 x ECF volume Interstitial Fluid Volume (IF) = 0.75 x ECF volume • All exchange of water and solutes with the external environment occur through the ECF (e.g., intravenous infusion and intake or loss via the gastrointestinal tract). Changes in the ICF are secondary to fluid shifts between the ECF and ICF. Fluid shifts only occur if the perturbation of the ECF alters its osmolality. Note: the osmolality of the ECF can be quickly estimated by doubling the plasma [Na+], because Na+ and its attendant anions are the major osmoles of the ECF. • Except for brief periods of seconds to minutes, the ICF and ECF are in osmotic equilibrium. A measurement of plasma osmolality will provide a measure of both ECF and ICF osmolality. • For the sake of simplification, it can be assumed that equilibration between the ICF and ECF occurs only by movement of water, and not by movement of osmotically active solutes. • Conservation of mass must be maintained, especially when considering either addition of water and/or solutes to the body or their excretion from the body. ____________________________ 1. Use the following Starling forces for questions 1A and 1B. Arterial End Venous End Pc 35 mmHg 10 mmHg Pis - 3 mmHg -3 mmHg Πc 26 mmHg 26 mmHg Πis 5 mmHg 5 mmHg A. On the following graph, plot: (Pc - Pis) and σ(Πc - Πis). Assume that plasma proteins cannot cross the capillary wall (i.e., that σ = 1). 50 40 30 Pc-Pis mmHg 20 σ(Πc-Πis) 10 ©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -2- 0 Arterial Venous End End Note that proteins cannot exert an oncotic pressure if they freely cross the capillary wall. Accordingly, the reflection coefficient (σ) takes into account the permeability of the capillary to proteins. A capillary that is essentially impermeable to proteins (e.g., glomerular capillary of the kidney) will have σ = 1 as in this example. If the capillary is freely permeable to protein (e.g., liver sinusoid) σ = 0. What can you conclude from this graph about the movement of fluid into and/or out of the capillary? The Starling forces are such that there will be net movement of fluid out of the lumen of the capillary at the arterial end, and net movement into the capillary lumen at the venous end. B. Replot (Pc - Pis) and σ(Πc - Πis) on the following graph assuming that the capillary wall has a significant permeability to plasma proteins (i.e., σ = 0.4). 50 40 30 Pc-Pis mmHg 20 10 σ(Πc-Πis) 0 Arterial Venous End End This clearly emphasizes the importance of considering the permeability of the capillary to proteins. With a significant permeability (i.e., σ = 0.4) there is a much reduced effect of protein on the movement of fluid across the capillary. In the extreme where σ = 0, as in the liver sinusoids, the only driving forces for movement of fluid across the capillary wall would be the capillary and interstitial hydrostatic pressures. What can you conclude from this graph about the movement of fluid into and/or out of the capillary under this condition? As noted above, because σ is less than 1, the protein within the capillary lumen and interstitium will not exert the full oncotic pressure (in this example it is reduced by 60%). As a result of this, fluid leaves ©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -3- the capillary lumen along its entire length. This overall net movement of fluid into the interstitium will result in formation of lymph. Recent studies indicate that σ in muscle capillaries is in the range of 0.8 - 0.9, and given the estimated Starling forces, fluid is probably filtered along the entire length of the capillary. In liver sinusoids, σ is near 0, and fluid is filtered through out the sinusoid driven by hydrostatic pressure only. 2. Edema is the abnormal accumulation of fluid in the interstitial fluid compartment. Edema can be localized or generalized. The formation of edema requires an alteration in the Starling forces across the capillary wall, or a change in the permeability of the capillary wall such that there is increased movement of fluid out of the capillary into the interstitium. As the terms imply, localized edema is confined to a particular portion of the body or vascular bed, whereas generalized edema results from increased movement of fluid out of the capillaries into the interstitum in vascular beds through out the body. Give an example of localized edema, and an example of generalized edema. Explain the pathogenesis of each in terms of the Starling forces across the capillary wall. Localized edema: A bee sting is an example of localized edema. In the case of the bee string, inflammatory and vasoactive mediators (e.g., histamine, cytokines, etc.) at the sting site increase both capillary permeability and cause local vasodilation. This increases permeability of the capillary wall to protein (i.e., reduces σ), and increases capillary hydrostatic pressure. The net effect of these two changes is illustrated below (compare to graph shown in 1A). These changes in capillary permeability and capillary hydrostatic pressure will result in more fluid moving out of the capillary with localized edema formation. 50 40 Pc-Pis 30 mmHg 20 10 Πc-Πis 0 Arterial Venous End End Generalized edema: The classic example of generalized edema is that seen with congestive heart failure. Hydrostatic pressure within the capillary lumen is an important driving force for the movement of fluid out of the capillary; this pressure is determined by precapillary and postcapillary resistances. Most capillary beds have a well developed precapillary sphincter that helps maintain a relatively constant capillary hydrostatic pressure in the face of changes in arterial pressure. In most capillary beds there is not an effective postcapillary sphincter (the exception is the glomerulus of the kidney). Therefore changes in venous pressure can have important effects on capillary hydrostatic pressure. With congestive heart failure there is an increase in venous volume and pressure. The increased venous pressure is transmitted down to the level of the capillary resulting in an increase in capillary hydrostatic pressure. This increased pressure will in turn cause excess accumulation of fluid in the interstitial ©Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center -4- space (i.e., edema). Because the change in venous pressure effects the Starling forces in capillaries throughout the body the formation of edema is generalized. Edema is most easily detected in the lower extremities, this occurs because gravity acting on the column of blood in the veins further increases the hydrostatic pressure in the capillaries. The following graph depicts the changes in Starling forces that would be seen in this situation. In this example σ = 1(compare to graph shown in 1A). 50 40 30 Pc-Pis mmHg 20 Πc-Πis 10 0 Arterial Venous 3. Patients with generalized edema are frequently treated with low salt diets, or diuretics.
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