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MEDICAL PHYSIOLOGY

MEDICAL PHYSIOLOGY. CELLULAR PHYSIOLOGY VOLUME AND COMPOSITION OF BODY FLUIDS INSTRUCTOR: GEORGE ANOGIANAKIS MD, PhD Professor of Physiology Faculty of Medicine Thessaloniki, Greece. Instructor Contact Details. Email: anogian@auth.gr anogian1@yahoo.com will answer within 48 hours

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MEDICAL PHYSIOLOGY

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  1. MEDICAL PHYSIOLOGY CELLULAR PHYSIOLOGY VOLUME AND COMPOSITION OF BODY FLUIDS INSTRUCTOR: GEORGE ANOGIANAKIS MD, PhD Professor of Physiology Faculty of Medicine Thessaloniki, Greece

  2. Instructor Contact Details Email: anogian@auth.gr anogian1@yahoo.com will answer within 48 hours FAX: 00302310288156 (no cover page necessary) 00302310999079 (cover page necessary) Phone: 00306976637334 (only if absolutely necessary)

  3. CELLULAR PHYSIOLOGY VOLUME AND COMPOSITION OF BODY FLUIDS

  4. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Lecture objectives I: • The concept ofHomeostasis • What is an“open system”; why is the human body an open system • Water intake/gain and water loss • Expressing solute concentrations:w/v; molarity; equivalents; osmolarity • Intracellular and extracellular water compartments

  5. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Lecture objectives II: • Osmosis • The Gibbs-Donnanmembrane equilibrium • TheNernstequation • Estimating the size of the various body-fluid compartments • Movement of H2O between body-fluid compartments

  6. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Homeostasis: resistance to change The maintenance of the internal equilibrium (read “steady state”) of the body, is the ultimate gauge of its proper functioning.It involves the maintenance of a constant concentration in the blood of certain molecules and ions that are essential to life and the maintenance at specified levels of other physical parameters such as temperature.This is accomplished in spite of modifications of the environment.

  7. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS • In 1865 Claude Bernard noticed, in his Introduction to Experimental Medicine that the "constancy of the internal milieu was the essential condition to a free life" • In 1932, the American physiologist Walter Cannon, impressed by "the wisdom of the body," coined the word homeostasis from two Greek words meaning to remain the same.

  8. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS EXAMPLE: The body of a person facing danger, mobilizes reserves of energy and produces certain hormones which prepare it for conflict or flight. In the presence of emotion, danger, or physical effort the heart beats faster and respiration quickens. The face turns red or pales and the body perspires. The individual may experience shortness of breath, cold sweats, shivering, trembling legs. These physiological manifestations reflect the efforts of the body to maintain its internal equilibrium. Action can be voluntary - to drink when one is thirsty, or to open a window when one is too warm - or involuntary, such as shivering or sweating.

  9. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Homeostasis is the most remarkable and one of most typical properties of highly complex open systems.A homeostatic system is an open system that maintains its structure and functions by means of a multiplicity of dynamic equilibriums rigorously controlled by interdependent mechanisms.Such a system reacts to every change in the environment, or to every random disturbance, through a series of modifications of equal size and opposite direction to those that created the disturbance. The goal of these modifications is to maintain the internal balances.

  10. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS The “rigorous control by interdependent mechanisms” is accomplished by a process callednegative feedback control. Examples include the control of • Temperature • blood sugar concentration and • water concentrations

  11. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS The principle of negative feedback control is illustrated by the diagram to the right

  12. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Control of Temperature: • Temperature is regulated via negative feedback control • It is controlled in a variety of ways • The hypothalamus detects fluctuations in temperature (thermoreceptor). • The skin also possesses thermoreceptors which detect the temperature of the external environment. This information is relayed to the hypothalamus which transmits nerve impulses to actuate corrective mechanisms

  13. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Corrective Mechanisms in Temperature Control: • Increased sweating aims to reduce the temperature of the organism  • The blood vessels close to the skin surface dilate (vasodilation), increasing their surface area so that heat is lost to the external environment. The opposite (vasoconstriction) occurs when the body temperature drops. • When the hairs on the body 'stand on end,' they trap an insulating layer of air between the hair and the skin. • When the temperature increases the metabolic rate drops • When the temperature drops, shivering is initiated

  14. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS • The body requires volumes of glucose in order to create ATP. The demand for ATP fluctuates and, therefore, the body needs to regulate the availability of glucose. • The hormones responsible for controlling the concentration of glucose in the blood are insulin and glucagon.

  15. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS

  16. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Homeostatic control of water • Changes in water concentration are countered by negative feedback control • Osmoreceptors are located in the hypothalamus • Cells in the paraventricular nucleus of the hypothalamus produce the anti-diuretic hormone (ADH) which is transported to the posterior pituitary, through axoplasmic transport, where it is secreted • ADH modulates the permeability of the kidney tubules since high or low concentrations of ADH make the tubules more permeable or less permeable respectively.

  17. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS The homeostatic control of wateris illustrated by the flow chart on the right

  18. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Maintenance of the Water Content Steady State in the Body Water “Sources”: • Drinking • Food • Metabolism to CO2 and H2O Water “Sinks” (losses): • Urinary loss • Fecal loss • Insensible loss (respiration and evaporation from skin) • Sweat loss (normally 25% of heat losses) • Pathological losses (bleeding, vomiting, diarrhea)

  19. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Maintenance of Electrolyte Steady State in the Body We consume and eliminate equal quantities of electrolytes such as sodium (Na+) and potassium (K+)

  20. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Electrolyte Sources: • Normally Na+ and K+ enter the body mainly by ingestion in food. • Clinically, electrolytes also can enter the body parenterally, eg. when a physician administers an intravenous (i.v.) solution Electrolyte losses: • Renal excretion. • Stool losses • Sweating • Abnormal routes: e.g. vomiting and diarrhea

  21. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Maintenance of the Steady State of metabolites in the Body The products of substances which are chemically altered must also balance with the amounts of these substances that enter the body. However, the amounts ingested do not have a simple one-to-one relationship to the amounts eliminated.

  22. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Fact: The global distribution of the various substances within the body is NOT HOMOGENEOUS This necessitates the use of Compartment Theory in order to describe and understand it

  23. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Compartment Theory 3 pillars: • Compartments are physical or virtual regions in the body with a unique chemical composition or a unique behavior • Compartments are spatially dispersed, and all the parts of a compartment need not be in contact with each other • Compartments are usually separated from each other either by membranes or by whole cells forming an epithelial (or endothelial) lining

  24. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS DISTRIBUTION AND COMPOSITION OF BODY FLUID COMPARTMENTS Total body water makes up approximately 55 to 60% of body weight in adult males and somewhat less, perhaps 50 to 55%, in adult females (due to a higher proportion of body fat). Within both sexes there is considerable variability in water content, again presumably related mainly to differences in lean body mass. For a 70 Kg man, body water is around 42 L.

  25. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS

  26. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Composition of the blood compartment • Blood is composed of cells and plasma. • Hematocrit (Hct) is the fraction of Red Blood Cells within the whole blood volume. Sometimes expressed as a percentage. • Plasma volume = Blood volume x (1-Hct).

  27. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Concatenation of the body fluid compartments • Plasma water is the initial body access point for ingested nutrients, and the exit point for the body’s waste products. • Except for the blood cells, access to all cells of the body is via the interstitial space.

  28. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Ionic composition and equilibrium among the different fluid compartments of the body • The principle extracellular cation is Na+. The principle extracellular anions are chloride and bicarbonate. • The principle intracellular cation is K+. The principle intracellular anions are phosphates [both inorganic (HPO42-, H2PO4-) and organic (ATP, etc.)] and proteins. • However, the extracellular and intracellular fluids are in osmotic equilibrium with each other

  29. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Ionic composition and equilibrium among the different fluid compartments of the body

  30. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS EXPRESSING FLUID COMPOSITION I • Gram Molecular Weight (GMW). The number of grams of a substance it takes to provide a mole (mol) of that substance (i.e., 6.02x1023 molecules). The gram molecular weight of a molecule is calculated by summing the atomic weight of its individual atoms. • Percent Solution Concentrations. Water is the most common solvent. Under standard conditions 1 ml of water weighs 1 g. Solutions are commonly expressed as weight/volume (w/v) percentages, that is, solute weight divided by solvent volume (H2O) times 100. Occasionally, solutions are expressed as weight/weight percentages (w/w) • Clinical chemistries generally deal with mg quantities and are reported as mg percentages or mg/dl.

  31. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS EXPRESSING FLUID COMPOSITION II • Molality. Concentration expressed as moles solute per kg of solvent. • Molarity (M). Concentration expressed as moles solute per liter of solution. Note that the symbol “M” means “moles/liter”. Physiological concentrations are low, so they are often expressed in millimoles (mM = 10-3 M), micromoles (mM = 10-6 M), nanomoles (nM = 10-9 M), picomoles (mM = 10-12 M), or femtomoles (mM = 10-15 M),

  32. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS EXPRESSING FLUID COMPOSITION III Electrochemical Equivalence (Eq).Salts such as NaCl and CaCl2 dissociate into positive ions (cations) and negative ions (anions). An “equivalent” is the weight in grams of an ionic substance that replaces or combines with one gram (mole) of monovalent H+ ions. For monovalent ions like sodium and chloride one equivalent is equal to one GMW. For divalent ions like calcium, magnesium, and HPO42-, one equivalent is equal to one‑half a GMW. Physiological concentrations are small and are often measured in mEq/L = 10-3 Eq/L. These units are useful when considering how much of a substance is needed to maintain electroneutrality.

  33. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Complications in determining plasma concentrations • Many substances bind to proteins within the bloodstream or within cellular compartments. Calcium, e.g., is about 50% bound to albumin and citrate in the blood. • Plasma volume is only 93% water. The other 7% is protein and lipid. Thus, ionic concentrations in plasma water are somewhat underestimated when expressed in terms whole plasma (as they are by clinical laboratories). This is not generally a problem, but must be considered when interpreting lab data in the presence of hyperlipidemia or hyperproteinemia.

  34. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS OSMOSIS, PROTEINS AND THE DONNAN MEMBRANE EQUILIBRIUM

  35. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Osmotic Forces If a semipermeable membrane separating two chambers obstructs the movement of solute particles but not the solute water, water will cross the membrane until the solute concentration on both sides of the membrane is equal. The force driving the water movement is the osmotic pressure (p).

  36. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Osmotic Concentration Particles which dissociate to form ions exert an osmotic force in proportion to the number of osmotic particles formed. For example, 1.0 mole of NaCl, if completely dissociated, forms a 2.0 osmolar solution. One mole of CaCl2, if completely dissociated, forms a 3.0 osmolar solution

  37. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Biological membranes are differentially impermeable to solutes Corollary: Not all solutes can exert effective osmotic forces between the various body compartments.

  38. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS From the tissue standpoint: • Except for plasma proteins, all ions can cross the capillary endothelial cell membranes which separate the plasma water from the interstitium. • Therefore, only proteins (which are in higher concentration in the plasma) exert important net osmotic forces across the capillary barrier. An increase in plasma protein concentration causes water to move from the interstitium into the plasma. A decrease in plasma protein concentration causes water to move from the plasma into the interstitium.

  39. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS From the cellular standpoint: The osmotic force generated when there is an increase in extracellular sodium concentration causes water to move out of cells into the extracellular space. The osmotic force generated by a decrease in extracellular [Na+] causes extracellular water to move into cells.

  40. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Gibbs-Donnan Membrane Equilibrium Proteins are not only large, osmotically active, particles, but they are also negatively charged anions. Because the proteins can not move, the distribution of other ions is influenced in an attempt to maintain electroneutrality (equal numbers of positive and negative charges) as well as osmotic equilibrium on the two sides of the membrane.

  41. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Gibbs-Donnan Membrane Equilibrium An explanatory diagram of events leading to its establishment

  42. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS MEASUREMENT OF BODY FLUID COMPARTMENTS

  43. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS For well mixed compartments:

  44. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS If excretion is taken into account: Vd=Volume of distribution

  45. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS Measurement of compartment volume To measure the volume of a compartment, one must have a substance that distributes itself only in the volume of the compartment of interest. Volumes for compartments where no such substance exists may be determined by subtraction.

  46. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS To measure Total Body Water (TBW) Use: • Deuterated water (D2O) • Tritiated water (THO), or • Antipyrine

  47. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS To measure Extracellular Fluid Volume (ECFV) Use: • Inulin • Sucrose • Mannitol, or • Sulfate

  48. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS To measure Plasma Volume (PV) Use: • Radiolabeled albumin or • Evans Blue Dye (which binds to albumin)

  49. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS To measure Intracellular Fluid Volume (ICFV) Use:

  50. CELLULAR PHYSIOLOGY: VOLUME AND COMPOSITION OF BODY FLUIDS To measure Interstitial Fluid Volume (ISFV) Use:

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