[OS 206] E03-T08-Integration_ Regulation of Volume Osmolarity and Body Water_compressed

• The lecture discusses the integration and regulation of volume, osmolarity, and body water.
• The outline includes water compartments, measuring water compartments, relationships of water exchange, effects of IV solutions, edema formation, and a quiz.

Water Compartments

• Water functions in temperature regulation, moistening oxygen for breathing, and constitutes 75% of muscles.
• Water-hydration assists with cancer prevention and complements workouts.
• The human body is approximately 70% water.
• The planet is covered by 75% water, with only 0.08% being used domestically.
• Organs with the:
  • Highest water content: brain, blood, and kidneys
  • High water content: lungs, heart, liver, and muscles

Daily Intake and Output of Water

• Water intake and output should be equal.
• On average, humans ingest about 2.3 liters of water daily.
• Water is excreted through sensible (measurable) and insensible (non-measurable) means.
• Daily intake:
  • Fluids ingested = approximately 2100 mL
  • Formed during metabolism = approximately 200 mL
• Daily output:
  • Via insensible losses through skin and exhalation = approximately 350 mL each
  • Via sweat = approximately 100 mL
  • Via feces = approximately 100 mL
  • Via urine = approximately 1400 mL
• Daily input is ~1500 mL/m².
• Sensible losses ~1000 mL/m²/day
• Insensible losses (lungs, skin) ~500 mL/m²/day.

Body Water Compartments

• Include plasma volume, interstitial fluid, intracellular water, and transcellular water.
• Transcellular water: fluid in the eyes, brain, synovial fluid, and joints.
• Physiologic extracellular water: plasma volume + interstitial fluid.
• Anatomic extracellular water: plasma volume + interstitial fluid + transcellular fluid.

ECF & ICF Compartment Barriers

• Barriers exist between intracellular, interstitial, and intravascular body spaces.
• The cell membrane separates the intracellular and interstitial spaces and is only passively permeable to water.
• Passive water permeability follows osmotic pressure gradients.
• Cell membranes are not leaky.
• Intracellular and interstitial components differ in composition.
  • High intracellular K+ (140 mOsm/L).
  • Low extracellular K+ (4 mOsm/L).
  • Low intracellular Na+ (14 mOsm/L).
  • High extracellular Na+ (139 mOsm/L).
• The capillary membrane separates the interstitial and intravascular spaces.
• Capillary membranes are passively permeable to all except cells and protein.
• Passively permeable to all except cells and protein, follows pressure gradients, and is very leaky.
• Interstitial and intravascular components are similar in solute concentration and osmolarity.
• Osmolality is the same in all three compartments because water can move freely.
• Total mOsm/L = 299.8 (plasma/intravascular),300.8 (interstitial), and 301.2 (intracellular).

Gibbs-Donnan Equilibrium

• The Gibbs-Donnan effect describes the unequal distribution of permeant charged ions across a semipermeable membrane.
• This distribution occurs in the presence of impermeant charged ions.
• Albumin creates a differential component of the difference between sodium and potassium inside and outside of cells.
• Capillary fluid [Na+] = 142, [K+] = 4.2, [Cl-] = 106, [HCO3-] = 24, and [protein] = 1.2.
• Interstitial Fluid [Na+] = 139; [K+] = 4.0; [Cl-] = 108; [HCO3] = 28.3 and [protein] = 102.

Measuring Water Compartments

• Key measurements: total body weight, intracellular fluid, extracellular fluid, plasma volume.
• Total Body Water (TBW) = ICF + ECF.
• Non-Water mass (nWM) = 40%
• Total Body Water (TBW) = ICF + ECF = 60%
• Intracellular Fluid = 40%
• TBW = Total Body Water - Extracellular Fluid and cannot be measured
• Extracellular Fluid = 20%
• ECF = Plasma Fluid + Interstitial Fluid*
• Interstitial Volume = 15%
• Plasma Volume = 5%
• Plasma is part of the Intravascular Volume (IV)
• Intravascular Volume (IV) = Plasma + Blood Cell Volume ≈ 6 L
• Blood Cell Volume = 2.5 L.
• Interstitial Space (IS) cannot be directly measured.
  • Amount: IS = ECF - Plasma Volume ~ 10 L
  • Located in ECF, between cells and blood vessels, and between nephron structures containing interstitial fluid.
• Interstitial space function: facilitates nutrient, oxygen, and waste exchange, maintains osmotic gradients, supports urine concentration/dilution, and contains renin- and erythropoietin-producing cells.
• In the 60-40-20-5 rule: Total body water is 60%, intracellular fluid is 40%, extracellular fluid is 20%, and plasma volume is 5%.
• This equates to 42L, 28L, 14L, and 3.5L respectively for a 70 kilogram individual.
• Clinical significance: Excreting >3.5 liters of blood, feces, or urine may indicate circulatory compromise, such as tachycardia and hypotension.
• Measured via the indicator-dilution principle:

Volume of Distribution (L) = (Marker Amount Given - Lost) / (Marker Concentration).

• Substances used:
  • Indicators in Measuring TBW: Antipyrine, Deuterium, Tritium
  • Indicators in Measuring ECF: Inulin, Sucrose, Mannitol, Thiocyanate
  • Indicators in Measuring Plasma: I-131 serum albumin, Evans blue, Cr-51 erythrocytes.
• Fat competes with water, lowering TBW.
• Females have more fat, thus TBW is 50%
• Babies have less fat, thus TBW is 70%
• TBW is affected by gender and age

Relationships of Water Exchange

• Volume refers to the amount of water in a specific body compartment and is influenced by total body sodium and RAAS regulation.
• Osmolarity indicates solute concentration per liter, influencing water movement, and is determined by serum Na, glucose, and urea, with ADH regulation playing a role.
• Clinical manifestations of problems in volume or osmolarity include dehydration and cholera.
• In healthy conditions, total body sodium and water are in equilibrium.

Iso-osmolar Volume Imbalances

• Clinical correlates:
  • Blood loss leads to iso-osmolar plasma volume loss.
  • Both total body sodium and water decrease
  • Adding 0.9% NaCl solution will result in iso-osmotic plasma volume gain, increasing both total body sodium and water
• Hypernatremia (water loss) causes increased serum Na+
• Osmolar problem is related to a volume condition that can be:
  • Hypovolemic: loss of total Na+ is followed by water loss.
    • Clinical correlation: Diarrhea often involves loss of Na+ but treated with water replacement, should be treated with Na+ replacement
  • Euvolemic : retained Na+ but lost water
  • Hypervolemic: Gain of total Na+, then water follows (e.g. eating too much sodium (potato chips, bagoong, patis)).
• Hyponatremia * (water gain) is decreased serum Na+ due to water gain
  • This is a consequence of mistreating hypernatremia, as introduced earlier
  • Clinically, assess amount of water replacement

Darrow-Yannet Diagrams

• Illustrate the relationship between osmolality and volume compared to normal hydration, showing six disturbances to the extracellular fluid space.
• There are 6 unique equilibration states:
  • Volume contraction- loss of isotonic fluid loss of pure water loss of Nacl only
  • Volume expansion- Gain of isotonic fluid Gain of pure water Gain of Nacl only
• Approach fluid-shift problems with a three-step method:
  • Step 1: construct normal Darrow-Yannet diagram
  • Step 2: Disturb the extracellular compartment only in terms of volume increase/decrease OR osmolarity increase/decrease
  • Step 3: If an osmotic gradient exists, shift the water accordingly to obliterate the gradient

Effects of IV Solutions on Osmolarity & Tonicity

• Osmolarity is the total number of solutes in a solution = 2Na + BUN + Glucose.
• Tonicity = Effective Osmolarity =2Na.
• An isotonic fluid, around 275-295 mOsm/L, maintains cell size.
  • Isotonic fluid: 140 mEq/L of Na.
  • Less is hypotonic and cells will burst.
  • More is hypertonic and cells will shrivel.
• Dextrose as an inital osmotic buffer prevents swelling - maintains tonicity

IV Solution Examples

• Isotonic:
  • 0.9% NaCl, Acetated Ringer's, Sterofundin, Lactated Ringer's
• Hypotonic:
  • D5 0.45% NaCl, Water, Sports drink, ORS, "Am"
• Hypertonic
  • :3.0% NaCl, 8.4% NaCl, Salt binge

Edema Formation

• Defined as excess fluid in body tissue.
• Balancing Act:
  • Excess: Leakage through cappilaries/lymphatic drainage failure
• Starling Equation:
  • Filtration= Kf [(Pc-πί)-(Pi+πc)] Kf *Coefficient

Safeguards Against Edema

• Decrease Filtration
• In negative pressure , increase fluid volume to increase pressure
• Increase in lymph flow
• Decrease washdown of insterstitial proteins

Clinical Manifestations of Edema

• Cardiac:
  • Ascending Edema
• Hepatic:
  • Ascites
• Nutritional:
  • Generalized Edema
• Renal:
  • Periorbital Edema

Proximal Tubule

• Reabsorbs solutes via secondary active transport (e.g., HCO3).
• HCO3 is absorbed by first being converted into H₂O and CO2, with the help of carbonic anhydrase inside the cell.
• Absorbed substances: Amino acids, fats, proteins, sodium, glucose
• Site of glomerulotubular balance is in this tubule.
• With excessive solute, there is increased reabsorption of the solute and 2nd line of defense.

Loop of Henle

• 3 anatomical parts:
  • Thick descending limb: Increasing concentration/osmolarity through water reabsorption; impermeable to ions.
  • Thin ascending limb: Impermeable to water, permeable to salt (NaCl), leading to passive Na and Cl absorption and decreased urine osmolarity.
  • Thick ascending limb: Impermeable to water; salts actively transported through the NK2CC cotransporter.
• Cortical diluting segment
  • K+ passively diffuses into the lumen, creating a positively-charged lumen that repels divalent ions (e.g., Ca2+, Mg2+).
  • Overall urine osmolarity decreases from urine that comes out.
• Urine remains hypoosmolar even with ADH - distal convoluted tubule (DCT)/collecting duct (CD) effects are not yet in effect.

Distal Nephron

• Refining area of the nephron that is selective
• Major functions
  • NaCl pump
  • Magnesium and calcium (actively by PTH) reabsorption

Collecting Duct

• ADH function - acts on it.
• Function :urea management.
• 2 important cells:
  • Intercalated for acid/base secretion.
  • Principal for Aldosterone/sodium.Potassium regulation.