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Homeostasis.

Homeostasis. Definition : Processes by which bodily equilibrium is maintained constant. Examples of Bodily homeostasis: temperature blood pressure heart rate blood glucose level, etc. body fluid composition. BODY FLUID COMPARTMENTS.

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Homeostasis.

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  1. Homeostasis. • Definition: Processes by which bodily equilibrium is maintained constant. • Examples of Bodily homeostasis: • temperature • blood pressure • heart rate • blood glucose level, etc. • body fluid composition

  2. BODY FLUID COMPARTMENTS • General Goal:To describe the major body fluid compartments, and the general processes involved in movement of water between extracellular and intracellular compartments.

  3. The Body as an Open System • “Open System”. The body exchanges material and energy with its surroundings.

  4. Water Steady State. • Amount Ingested = Amount Eliminated

  5. Water Ingestion • Drinking (1.4 L/day). • Water contained in Food (0.85L/day). • Metabolism ----> CO2 and H2O (0.35 L/day).

  6. Water Elimination • Urinary loss (1.5 L/day). • Fecal loss (0.2 L/day). • Insensible H2O loss (0.9 L/day) • Sweat Losses. • Pathological losses. • vascular bleeding (H20, Na+) • vomiting (H20, H+) • diarrhea (H20, HCO3-).

  7. Electrolyte (Na+, K+, Ca++) Steady State. • Amount Ingested = Amount Excreted. • Normal entry: Mainly ingestion in food. • Clinical entry: Can include parenteral administration.

  8. Electrolyte losses • Renal excretion. • Stool losses. • Sweating. • Abnormal routes: e.g.. vomit and diarrhea.

  9. Metabolized Substances. • Chemically altered substances must also be in balance • Balance sheet: conservation between substrates and end products.

  10. Compartment. • DEFINITION. A non-specific term to refer to a region in the body with a unique chemical composition or a unique behavior. • Distribution of substances within the body is NOTHOMOGENEOUS.

  11. Compartment Properties. • Can be spatially dispersed. • Separated by membranes • Epithelial (or endothelial) barriers (cells joined by tight junctions)

  12. II. EXPRESSING FLUID COMPOSITION

  13. Gram Molecular Weight (GMW). • Mole (mol) (6.02x1023 molecules). • Atomic weight in grams • Molecules: sum atomic weight individual atoms.

  14. Physiological Molecular Weights

  15. Expressing Fluid Composition • Percentage • Molality • Molarity • Equivalence

  16. Percent Concentrations: (Solute / Solvent) x 100 • Body solvent is H2O • 1 ml weighs 1 g. • (weight/volume) percentages (w/v). • (weight/weight) percentages (w/w). • Clinical chemistries: mg % or mg / dl.

  17. Molality. • Concentration expressed as:moles per kilogram of solvent. • Rarely used

  18. Molarity (M). • Concentration expressed as:moles per liter of solution. • Symbol “M” means moles/liter not moles. • Physiological concentrations are low. • millimolar (mM) = 10-3 M • micromolar (mM) = 10-6 M • nanomolar (nM) = 10-9 M • picomolar (pM) = 10-12 M

  19. Electrochemical Equivalence (Eq). • Equivalent -- weight of an ionic substance in grams that replaces or combines with one gram (mole) of monovalent H+ ions. • Physiological Concentration: milliequivalent.

  20. Electrochemical Equivalence (Eq). • Monovalent Ions (Na+, K+, Cl-): • One equivalent is equal to one GMW. • 1 milliequivalent = 1 millimole • Divalent Ions (Ca++, Mg++, and HPO42-) • One equivalent is equal to one-half a GMW. • 1 milliequivalent = 0.5 millimole

  21. Complications in Determining Plasma Concentrations. • Incomplete dissociation (e.g. NaCl). • Protein binding (e.g. Ca++) • Plasma volume is only 93% water. • The other 7% is protein and lipid. • Hyperlipidemia • Hyperproteinemia.

  22. III. Distribution and Composition of Body Fluid Compartments

  23. Input PLASMA WATER RBC 3 L BONE 4.5% 3% 2 L INTERSTITIAL FLUID COMPARTMENT ECF CELL WATER 36% 25 L 24% 17 L DENSE CONNECTIVE 11.5% 8 L 4.5% 3 L TRANSCELLULAR WATER 1.5% 1 L Fig 2: Body Water Distribution

  24. Total Body Water • Individual variability = f(lean body mass) • 55 - 60% of body weight in adult males • 50 - 55% of body weight in adult female • ~42 L For a 70 Kg man.

  25. Extracellular Water vs. Intracellular Water • Intracellular fluid • ~36% of body weight • 25 L in a 70 Kg man. • Extracellular fluid • ~24% of body weight • 17 L in a 70 Kg man.

  26. Major Extracellular Fluid Compartments (11L of ECF) • Plasma (blood minus the red and white cells) • ~3 L in a 70 Kg man • ~4.5% of body weight. • Interstitial space (between organ cells) • ~8 L in a 70 Kg man • ~11.5% of body weight.

  27. Minor Extracellular Compartments (6 L of ECF) • Bone and dense connective tissue • Transcellular water (secretions) • digestive secretions • intraocular fluid • cerebrospinal fluid • sweat • synovial fluid.

  28. Blood is Composed of Cells and Plasma. • Hematocrit (Hct). • Fraction of blood that is cells. • Often expressed as percentage. • Plasma volume = Blood volume x (1-Hct).

  29. Ingress and Egress • Plasma water • Ingested nutrients pass through plasma on way to cells • Cellular waste products pass through plasma before elimination • Interstitial space. • Direct access point for almost all cells of the body • Exception -- red and white blood cells

  30. Solute Overview: Intracellular vs. Extracellular • Ionic composition very different • Total ionic concentration very similar • Total osmotic concentrations virtually identical

  31. Plasma Interstitial Cell H2O H2O H2O Figure 3: Summary of Ionic composition

  32. IV. PROTEINS, OSMOTIC CONCEPTS, DONNAN MEMBRANE EQUILIBRIUM

  33. Net Osmotic Force Development • Semipermeable membrane. • Movement some solute obstructed. • H2O (solvent) crosses freely. • End point: • Water moves until solute concentration on both sides of the membrane is equal. • OR, an opposing force prevents further movement.

  34. p = p S S S S S S S S S S S S S Osmotic Pressure (p). • The force/area tending to cause water movement.

  35. Initial Gl Gl Gl Gl 10 L 10 L Final Gl Gl Gl Gl 15 L 5 L Glucose Example

  36. Osmotic Concentration. • Proportional to the number of osmotic particles formed. • Assuming complete dissociation: • 1.0 mole of NaCl forms a 2.0 osmolar solution in 1L. • 1.0 mole of CaCl2 forms a 3.0 osmolar solution in 1L.

  37. Osmotic Concentration • Physiological concentrations: • milliOsmolar units most appropriate. • 1 mOSM = 10-3 osmoles/L

  38. Biological membranes are not impermeable to all solutes. • Endothelial Cell Barriers • All ions can freely cross the capillary wall. • Only proteins exert important net osmotic forces. • Cell Membrane Barriers • Membrane pumps effectively keep Na+ from entering cells, thus forming a virtual barrier. • Proteins can’t escape the cell interior.

  39. Gibbs-Donnan Membrane Equilibrium. • Proteins are not only large, osmotically active, particles, but they are also negatively charged anions. • Proteins influence the distribution of other ions so that electrochemical equilibrium is maintained.

  40. Total Volume 100 ml 50 K+ 50 K+ Initial 50 Cl- 50 Pr - 100 Osmoles 100 Osmoles 67 K+ Ions Move 33 K+ Step 2 17 Cl- 33 Cl- 50 Pr - 66 Osmoles 134 Osmoles 67 K+ H2O moves 33 K+ Final 17 Cl- 33 Cl- 50 Pr - 33 ml 67 ml Figure 5: Donnan’s Law • The product of Diffusible Ions is the same on the two sides of a membrane.

  41. Amount Injected Concentration = Volume of Distribution Measurement of Body Fluid Compartments • Based on concentration in a well-mixed compartment:

  42. Amount Injected - Amount Excreted Vd = Concentration after Equilibrium Measurement of Body Fluid Compartments • Requires substance that distributes itself only in the compartment of interest.

  43. Total Body Water (TBW) • Deuterated water (D2O) • Tritiated water (THO) • Antipyrine

  44. Extracellular Fluid Volume (ECFV) • Labeled inulin • Sucrose • Mannitol • Sulfate

  45. Plasma Volume (PV) • Radiolabeled albumin • Evans Blue Dye (which binds to albumin)

  46. Compartments with no Compartment-Specific Substance • Determine by subtraction: • Intracellular Fluid Volume (ICFV). ICFV = TBW - ECFV • Interstitial Fluid Volume (ISFV). ISFV = ECFV - PV

  47. VI. PRINCIPLES OF H2O MOVEMENT BETWEEN BODY COMPARTMENTS Intracellular vs. Extracellular

  48. Principles of Body Water Distribution. • Body control systems regulate ingestion and excretion: • constant total body water • constant total body osmolarity • Osmolarity is identical in all body fluid compartments (steady state conditions) • Body water will redistribute itself as necessary to accomplish this.

  49. Intra-ECF Water RedistributionPlasma vs. Interstitium • Balance of Starling Forces acting across the capillary membrane. • osmotic forces • hydrostatic forces • Discussed in more detail later in course

  50. Intracellular Fluid Volume • ICFV altered by: changes in extracellular fluid osmolarity. • ICFV NOT altered by:iso-osmotic changes in extracellular fluid volume. • ECF undergoes proportional changes in: • Interstitial water volume • Plasma water volume

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