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BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body Fluids, Tonicity P BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 1 Terms you should understand: intracellular compartment, plasma compartment, interstitial compartment, extracellular compartment, dilution technique, concentration, quantity, volume, Evans blue, plasma volume, interstitial fluid, inulin, total body water, intracellular volume, diffusion, osmosis, colligative property, osmotic pressure, iso-osmotic, hypo-osmotic, hyperosmotic, tonicity, isotonic, hypotonic, hypertonic, active transport, symporter, antiporter, facilitated diffusion. I. Body fluids are distributed in a variety of compartments. A. The three major compartments are: 1. Intracellular compartment = total volume inside all body cells. 2. Plasma compartment = fluid volume inside the circulatory system. 3. Interstitial compartment = volume between the plasma and intracellular compartments. 4. Extracellular compartment = plasma + interstitial fluid B. Slowly-exchanging compartments include bones and dense connective tissues, fluids within the eyes and in the joint capsules; in total, they comprise a small volume. C. Cells exchange materials with the environment almost entirely through the plasma. Fig. 15.1. The major fluid compartments of the body and how water, ions, and metabolites pass among them. D. Under normal conditions, the three compartments are in osmotic equilibrium with one another, but they contain different distributions of solutes. 1. There is a lot of organic anion (mostly proteins) inside cells, essentially none in interstitial fluid, and small quantities in the plasma. 2. Na+ and K+ have inverse concentration profiles across the cell membranes. 3. The total millimolar concentration of solutes is equal in each of the three compartments. 4. Materials that exchange between compartments must cross barriers: a. Cell membranes separate the intracellular and interstitial compartments. b. Capillary walls separate the interstitial and plasma compartments. BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 2 II. The dilution technique for measuring fluid volumes. A. Put a known quantity of an appropriate marker molecule into the volume that you want to measure, to mix it thoroughly in the compartment, and then measuring the concentration of the marker. 1. The basic calculation is based on the following equation: concentration (C) = quantity (Q) / volume (V) to measure the volume: V = Q / C (usually measured in liters) 2. There are several possible sources of error in this method: a. Inadequate mixing. b. Loss by metabolism or excretion. c. Leakage into other compartments. 3. The ideal marker substance for these measurements: a. goes only into the compartment that you want to measure. b. is broken down or excreted very slowly compared to its mixing time. c. is lost as a simple exponential function of time, allowing you to extrapolate back to its initial concentration from your data. Fig. 15.2. Using the dilution method to measure the volume of body fluid compartments. BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 3 B. Markers used to measure fluid compartments: 1. Plasma volume is measured using Evans blue, which binds to blood cells and plasma proteins, or radioactive albumin. 2. Interstitial volume is measured using molecules that equilibrate between the plasma (Pl) and the interstitial fluid (ISF), but that won't enter cells. a. These molecules measure the volume of the plasma plus the volume of the interstitial fluid. You get the interstitial volume by subtraction (total extracellular volume – plasma volume). b. Examples of these molecules are large carbohydrates (e.g., inulin, raffinose, or mannitol) or large radioactive ions (e.g., sulfate, thiosulfate, or thiocyanate). 3. Total body water (TBW) is measured by deuterated or tritiated H2O. By subtraction you can get the intracellular volume (ICF). Fig. 15.3. Approximate volumes of the major fluid compartments of the body. Fig. 15.4. Tables showing the volumes of the fluid compartments and the major ionic components in them. BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 4 III. Mechanisms of movement between compartments. A. Several molecules move across cell membranes, into or out of the intracellular compartment. 1. Passive movement of a substance down its concentration gradient is called diffusion. a. The diffusion of water is called osmosis. b. Osmotic movement is driven by inequalities of the concentration of water, but we talk about these inequalities in terms of solute concentration. c. Osmotic pressure: the force generated by osmosis; it can be measured in different ways: Fig. 15.5. Measuring osmotic pressure as height of a water column. (Membrane is permeable only to water.) Fig. 15.6. Osmotic pressure is also the force required to keep water from flowing across a membrane. BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 5 d. Osmotic pressure is a colligative property: it depends only on the number of molecules present, not their size, weight, or charge. (Others: boiling point elevation, freezing point depression, evaporation temperature.) e. Definition: osmotic pressure = π = nCRT where T = temperature (oK) R = gas constant (0.082 atm L / mol oK) C = total solute concentration n = number of dissociable particles per molecule A 1 mOsm solution produces a pressure of 19.3 mmHg. d. When two solutions contain equal amounts of solute (and hence have equal partial molar fractions of water) we say that they are iso-osmolar. NOTE: Osmolarity is a physical chemical property of solutions. e. Isotonic is a term that is often mistakenly used as a synonym for iso-osmolar, but it has a very different meaning. DEFINITIONS: Tonicity is a physiological property in which a solution is compared with particular cells; it depends on the movements of both solutes AND water. Isotonic solution: cells will neither swell nor shrink. Hypotonic solution: water moves into the cells and they swell. Hypertonic solution: water moves out of the cells and they shrink. Fig. 15.7. The tonicity of a solution depends upon the relative concentrations of the non-permeable (N) and permeable (P) solutes BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 6 2. Test your understanding of tonicity: Consider a cell containing 100 mM KCl in a solution of 100 mM NaCl: If the membrane is permeable to: The solution is: H2O only _______________ H2O + Cl- _______________ H2O + Cl- + Na+ _______________ H2O + Cl- + K+ _______________ B. Molecules move across membranes only by way of in which specific membrane proteins translocate them at the expense of ATP. 1. Ions move through channels or on membrane-bound carrier proteins. a. Active transport: e.g., the Na+/K+ ATPase (the “sodium pump") is in all cell membranes. b. Carrier: e.g., H+ exchanges with either for Na+ or K+, on different membrane carriers. c. Channels: e.g., Ca++ moves across cell membranes, as in the control of muscle contraction. 2. Amino acids and sugars are coupled to the movement of ions, primarily Na+. 3. Gases and hydrophobic molecules can move through the lipid bilayer. 4. The relative rates of diffusion are water > gases > ions. Fig. 15.8. Examples of types of transporters that move molecules across membranes. BIPN100 F15 Human Physiology 1 (Kristan) Lecture 15. Body fluids, tonicity p. 7 C. Materials move across capillary walls by diffusion and by filtration (Starling equation). 1. Produces complete mixing of the plasma and interstitial compartments in about 20 minutes. 2. If filtration > reabsorption, edema occurs. D. Dynamics of equilibrium among body fluid compartments: 1. If you add water (with no solute) to the plasma compartment: a. because both capillary walls and cell membranes are relatively permeable to water, water moves fairly rapidly between compartments. b. because water moves between compartments faster than most solutes: i. the osmolarities of the three compartments are reduced equally, and ii. the volumes of all three compartments increase by the same percentage. 2. If you add ions (with little or no water) to the plasma compartment: a. plasma osmolarity increases b. as the hypertonic solution enters the interstitial fluid, water moves out of cells. i. the volume of the extracellular fluid increases at the expense of the intracellular fluid. ii. the osmolarity of the three compartments increases equally: • ECF osmolarity increases because ions were added. • ICF osmolarity increases because water moved out of cells. 3. If you add isotonic solution to the plasma compartment: a. the increased plasma volume equilibrates with the interstitial fluid, so the ECF volume increases by the same percentage. b. because there is no osmotically driven exchange between the ECF and the ICF, the volume of the cells remains the same. .
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