Body Fluid Compartments & Physiological Solutions

1. Body Fluid Compartments & Physiological Solutions By Halil DÜZOVA, M.D. Physiology, University of Inonu Faculty of Medicine

2. Body Water Content • Infants have low body fat, low bone mass, and are 73% or more water • Total water content declines throughout life • Healthy males are about 60% water; healthy females are around 50% • This difference reflects females’: • Higher body fat • Smaller amount of skeletal muscle • In old age, only about 45% of body weight is water

3. Water Balance and ECF Osmolality • To remain properly hydrated, water intake must equal water output • Water intake sources • Ingested fluid (60%) and solid food (30%) • Metabolic water or water of oxidation (10%)

4. Water Balance and ECF Osmolality • Water output • Urine (60%) and feces (4%) • Insensible losses (28%), sweat (8%) • Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH)

5. Water Intake and Output Figure 26.4

6. Fluid Compartments • Water occupies two main fluid compartments • Intracellular fluid (ICF) – about two thirds by volume, contained in cells • Extracellular fluid (ECF) – consists of two major subdivisions • Plasma – the fluid portion of the blood • Interstitial fluid (IF) – fluid in spaces between cells • Other ECF – lymph, cerebrospinal fluid, eye humors, synovial fluid, serous fluid, and gastrointestinal secretions

7. Fluid Compartments Figure 26.1

8. PERCENTAGE OF WATER IN TISSUES

9. Composition of Body Fluids • Water is the universal solvent • Solutes are broadly classified into: • Electrolytes – inorganic salts, all acids and bases, and some proteins • Nonelectrolytes – examples include glucose, lipids, creatinine, and urea • Electrolytes have greater osmotic power than nonelectrolytes • Water moves according to osmotic gradients

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

11. 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.

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

13. Osmolality • Osmolality is the number of dissolved particles per kg of solution. • As osmolality increases, the relative number of water molecules in the solution decreases. • Osmolality is an inverse measure of water concentration. Low osmolality High osmolality

14. 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

15. 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.

16. 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

17. Electrolyte Concentration • Expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical charges in one liter of solution • mEq/L = (concentration of ion in [mg/L]/the atomic weight of ion)  number of electrical charges on one ion • For single charged ions, 1 mEq = 1 mOsm • For bivalent ions, 1 mEq = 1/2 mOsm

18. Molar and Equivalent Concentrations

19. Osmolality Osmolality: millimoles of solute/Kg of H2O; Osmolarity: millimoles of solute/L of H2O Activity of H2O decreases as Osmolality increases. Colligative Properties of Solutions: Depend on number of molecules and not on their nature. • Boiling Point • Freezing Point • Vapor Pressure • Osmotic Pressure A B

20. APPROXIMATE IONIC COMPOSITION OF THE BODY WATER COMPARTMENTS

21. Extracellular and Intracellular Fluids • Each fluid compartment of the body has a distinctive pattern of electrolytes • Extracellular fluids are similar (except for the high protein content of plasma) • Sodium is the chief cation • Chloride is the major anion • Intracellular fluids have low sodium and chloride • Potassium is the chief cation • Phosphate is the chief anion

22. Extracellular and Intracellular Fluids • Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposites • This reflects the activity of cellular ATP-dependent sodium-potassium pumps • Electrolytes determine the chemical and physical reactions of fluids

23. Extracellular and Intracellular Fluids • Proteins, phospholipids, cholesterol, and neutral fats account for: • 90% of the mass of solutes in plasma • 60% of the mass of solutes in interstitial fluid • 97% of the mass of solutes in the intracellular compartment

24. Comparison of the Three Major Compartments Capillary Interstitium Intracellular Permeable to most solutes but imperm- eable to large proteins Impermeable to most solutes Na+ 140 mM Na+ 142 mM Na+ 10 mM K+ 4.5 mM K+ 4.5 mM K+ 140 mM Proteins 1.5 mM Proteins 0.1 mM Proteins 3 mM Pc = 25 mmHg P = 0 mmHg = 28 mmHg = 3 mmHg Osm. = 286.5 mOsm/L 285 mOsm/L 285 mOsm/L Colloid Osmotic Pressure, Protein Osmotic Pressure, Oncotic Pressure

25. Electrolyte Composition of Body Fluids Figure 26.2

26. Fluid Movement Among Compartments • Compartmental exchange is regulated by osmotic and hydrostatic pressures • Net leakage of fluid from the blood is picked up by lymphatic vessels and returned to the bloodstream • Exchanges between interstitial and intracellular fluids are complex due to the selective permeability of the cellular membranes • Two-way water flow is substantial

27. Extracellular and Intracellular Fluids • Ion fluxes are restricted and move selectively by active transport • Nutrients, respiratory gases, and wastes move unidirectionally • Plasma is the only fluid that circulates throughout the body and links external and internal environments • Osmolalities of all body fluids are equal; changes in solute concentrations are quickly followed by osmotic changes PLAY

28. Continuous Mixing of Body Fluids Figure 26.3

29. Compartment Amount of Tracer Added (A) Amount of Tracer Lost From Compartment (E) Measuring Compartment Size(Law of Mass Conservation) Volume (V) Tracer Concentration (C) Amount of Tracer Remained in Compartment = A - E Compartment Volume = (A – E)/C

30. DILUTION PRINCIPLE • Inject x gm of marker into compartment • measure concentration at equilibrium (y gm/L) • Since concentration = mass/ volumeVolume = mass / concentration = x/y L

31. BODY FLUID MARKER • Non-toxic • Even mixing • No physiological activity • Not metabolised • Easy to measure

32. MEASUREMENT OF BODY FLUID VOLUMES • TBW : labelled water (3H2O or 2D2O) or sometimes ethanol • Plasma volume: dye which associates with plasma proteins (eg Evans Blue) or 131I-labelled albumin • Red cell volume: sample of erythrocytes pre-labelled with 51Cr

33. MEASUREMENT OF BODY FLUID VOLUMES • ECF volume - difficult to measure precisely. Any of the following may be used-inulin, sucrose, 22 Na+, thiocyanate …. • Interstitial fluid volume is calculated by difference ECF – PV • ICF volume : also calculated by difference TBW - ECF

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

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

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

37. MEASURING THE SIZE OF COMPARTMENTS

38. Plasma Osmolarity Measures ECF Osmolarity • Plasma is clinically accessible. • Dominated by [Na+] and the associated anions • Under normal conditions, ECF osmolarity can be roughly estimated as: POSM = 2 [Na+]p 270-290 mOSM

39. transient osmotic pressures (DPs) are produced by concentration differences of diffusible solutes across the capillary walls (DCs). • By van't Hoff's Law for non-dissociating molecules:  DPs = RTDCs, where R is the kinetic gas constant, T the absolute temperature.  Thus DCs = DPs/RT.

40. Osmotic pressure ; the pressure required to prevent the osmosis • π = CRT (van't Hoff's law) • C; concentration of solutes in osmoles per liter • T; absolute temp. (273° + 37° = 310° kelvin) • R; ideal gas constant • ∵1 osm/L = 19,300 mm Hg, 1 mOsm/L = 19.3 mm Hg

41. Relation between osmotic pressure and osmolarity • • One molecule of albumin with molecular weight of 70,000 has the same effect as one molecule of glucose with a molecular weight of 180. • • One molecule of NaCl has two osmotically active particles, and therefore has the twice the osmotic effect of either an albumin molecule or a glucose molecule.

42. Calculation of the osmolarity and osmotic pressure of a solution          ex) 0.9% NaCl solution          0.9 g/dl = 9g/L          Molecular weight of NaCl = 58.5g/mol          NaCl osmotic coefficient = 0.93           (osmotic coefficient; ionic attraction, binding protein etc) 58.5g/mol  ≒ 286 (308 × 0.93) mOsm/L  = 308 mOsm/L  = 0.308 (0.154 × 2 )/L  = 0.154 mol/L      9g/L 

43. Osmolarity of the body fluids •          Corrected osmolar activity of the body fluids •          ;because of interionic or intermolecular attraction or repulsion   •          Total osmotic pressure exerted by the body fluids

44. Clinical Laboratory Measurement.

45. Plasma osmolality is maintained within narrow range around 290m mOsm /kg Day to day fluctuations : < 0.2% Changes in osmolality could be caused by body fluid gain/loss, and changes in ion concentrations Significant changes -> clinical problems Control of body fluid osmolality We can estimate plasma osmolality with formulas

46. Effective Osmolarity. • Urea (BUN) crosses cell membranes just as easily as water. • [BUN]E = [BUN]i • No effect on water movement

47. Effective Osmolarity.

48. Osmolar Gap. • Posm (measured) - Posm (calculated) • Suggests the presence of an unmeasured substance in blood. • e.g. following ingestion of a foreign substance (methanol, ethylene glycol, etc.)

49. 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.

50. 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).