PHGY209 BODY FLUIDS Lectures #1 & #2 2025

Milieu Interieur and Homeostasis

• Fundamental principle: At all levels of organization, functional activities are directed at maintaining HOMEOSTASIS, the relative constancy of the “Milieu Interieur” (internal environment).
• Origin: Claude Bernard (1813–1878).
• The Milieu Interieur comprises the body fluids that bathe and surround cells, providing a stable environment for cellular processes.

Water in the Body: Importance and Variability

• Water (H₂O) is the most abundant single constituent of the body: approximately $45\%\text{ to }75\%$ of body mass.

• Roles of body water:

  • Medium in which solutes are dissolved
  • Site of metabolic reactions
  • Regulates body temperature
  • Moistens and protects mucosal surfaces (mouth, eyes, nose)
  • Lubricates joints; helps prevent constipation
  • Facilitates removal of waste products via kidneys and liver
  • Dissolves minerals and nutrients to make them accessible
  • Transports nutrients and oxygen to cells

• Major question: Why does body water content vary so much among individuals?

  • Variation with age, sex, and body composition (lean body mass vs fat mass)
  • When water is expressed as a fraction of lean body mass, differences among individuals become smaller

• Standard values and references:

  • A physiological reference individual (21-year-old, white male, ~70 kg) has body water ≈ $0.60\times\text{body mass} = 0.60\times 70\text{ kg} = 42\text{ L}$ which is 60% of body mass.
  • Water content declines with age and differs by sex due to body fat content; males typically have higher TBW than females for a given weight.
  • Values vary with body habitus (e.g., very thin vs obese). For example, a very lean 70-kg male may have TBW ≈ 52.5 L in some scenarios, while a typical 70-kg male ~42 L; a 70-kg female may have TBW ≈ 30–35 L, depending on fat proportion.

• Summary: TBW ~60% of body mass in a standard reference young adult male; variability arises from age, sex, and body fat/fat-free mass composition.

Body Water Content by Tissue (% TBW or % Body Mass)

• Tissue water content varies markedly by tissue type:
  • Skin: ~70% water
  • Muscle: ~75% water
  • Heart, liver, brain, kidney: ~70–80% water
  • Bone: ~25% water
  • Adipose (fat): ~10% water
• If expressed as a percentage of Lean Body Mass (LBM), differences between individuals diminish, because fat mass (which has low water) no longer biases the percentage as strongly.

Physiological Reference Values and Variations with Age/Sex

• The body water percentage changes with age and sex:
  • Infants: high % TBW (roughly in the mid-60s to mid-70s percent of body mass)
  • Adults: around 50–65% depending on sex and body composition; males often higher than females
  • Elderly: lower TBW percentage (often around ~50–45% of body mass)
• Key takeaway: TBW declines with age and tends to be higher in males due to greater lean mass and lower fat fraction.

Body Water Compartments (Total Body Water, TBW = 60% of Body Mass)

• Total Body Water (TBW) ≈ 60% of body mass.

• Major division:

  • Intracellular Fluid (ICF): ~40% of body mass (≈ 2/3 of TBW)
  • Extracellular Fluid (ECF): ~20% of body mass (≈ 1/3 of TBW)

• Major subcompartments:

  • ECF subdivides into Plasma, Interstitial Fluid (ISF), Lymph, and Transcellular Fluid.
  • ICF and ECF are dynamic and exchange water continually.

• Numerical example for a 70-kg man (typical values):

  • TBW ≈ $0.60\times 70 = 42\,\text{L}$
  • ICF ≈ $0.40\times 42 = 16.8\,\text{L}$ (often rounded to about 28 L in other common breakdowns; keep consistent with the 60/40/20 split approach below)
  • ECF ≈ $0.20\times 42 = 8.4\,\text{L}$
  • Within ECF: Plasma (~5% TBW), ISF (~15% TBW), Lymph (~1–2% of ECF), Transcellular Fluid (<1% of ECF)
  • Plasma ≈ 0.05\times 42 = 2.1\,\L
  • ISF ≈ 0.15\times 42 = 6.3\,\L
  • Lymph ≈ (1–2% of ECF) ≈ 0.084–0.168 L (roughly a few hundred milliliters total)
  • Transcellular Fluid ≈ <1% of ECF ≈ ~0.084 L
  • Total ISF + Plasma + Lymph + Transcellular Fluid should approximate the ECF total (~8.4 L), with minor rounding differences.

• Interstitial Fluid (ISF) is the true “Milieu Interieur” for most cells, i.e., the fluid that percolates between cells and capillaries.

• Lymphatic drainage contributes to ISF turnover and returns to the circulation.

• Transcellular Fluid includes specialized fluids secreted by epithelial cells; examples include cerebrospinal fluid, synovial fluid, aqueous and vitreous humors, bile, and GI secretions. These fluids are small in volume (usually <1–2% of ECF) and function locally rather than in whole-body water balance.

Practical Measurements: Determining Compartment Volumes

• Total Body Water (TBW) measurement uses indicators that distribute across all body water:

  • Common indicators: Antipyrine, deuterated water (D₂O), tritiated water (T₂O)
  • Indicator dilution formula: $V = \frac{Q}{c}$ where Q is the injected quantity and c is the equilibrium concentration in a measured compartment (often plasma).
  • Example: If you inject 50 mL of D₂O and measure plasma concentration c = 0.001 mL⁻¹, then $V = \frac{50}{0.001} = 50{,}000\text{ mL} = 50\text{ L}$. This approximates TBW.
  • Normal TBW for a typical 70-kg man is around 42 L (≈ 60% of body mass).

• Extracellular Fluid (ECF) measurement:

  • Indicators: Inulin, sucrose, or mannitol (distribute in plasma and ISF but not intracellularly).
  • Normal ECF value for a 70-kg adult is roughly ~14 L (varies with body size and measurement method).

• Plasma Volume measurement:

  • Indicators: Evans’ blue dye or I-131 albumin.
  • Formula: $V_{plasma} = \frac{Q}{c}$ where Q is the injected dose and c is plasma concentration after equilibration.
  • Example: If Q = 200 mg Evans’ Blue and c = 0.055 mg/mL, then $V_{plasma} = \frac{200}{0.055} \approx 3.6\text{ L}$
  • Typical plasma volume is about 3.0–3.5 L in a 70-kg adult.

• Key point: Determining TBW, ECF, and plasma volumes often requires two or more indicators to compute smaller compartments (e.g., ICF vs. ISF).

Hematology and Blood Components Relevant to Fluid Compartments

• Blood is a suspension of cells in plasma.

• Hematocrit (Ht): the fraction of blood volume occupied by red blood cells (RBCs).

  • Normal value: ~45% (Ht ≈ 0.45).
  • Relationship: If Plasma Volume (PV) is known, total Blood Volume (BV) can be calculated as:
  • $BV = \frac{PV}{1 - Ht}$
  • Example: If PV = 3.0 L and Ht = 0.40, then $BV = \frac{3.0}{1 - 0.40} = \frac{3.0}{0.60} = 5.0\text{ L}$; RBC volume ≈ BV − PV ≈ 2.0 L.

• Pt. note: RBC mass contributes to oxygen transport; hematocrit informs total blood volume when plasma volume is measured.

• Ionic composition differences between compartments:

  • Extracellular Fluid (ECF): high Na⁺ and Cl⁻; low K⁺ and Mg²⁺ relatively.
  • Intracellular Fluid (ICF): high K⁺ and Mg²⁺; low Na⁺ and Cl⁻.
  • These disparities drive many osmoregulatory processes and membrane potentials.

Water Balance: Intake vs. Output; Obligatory vs. Facultative Losses

• Water balance goal: intake ≈ output to maintain stable body water.
• Daily typical balance (illustrative values):
  • Intake: Oxidative water from metabolism ≈ $0.4\,\text{L}$; Oral fluid ≈ $1.2\,\text{L}$; Water from food ≈ $0.5\,\text{L}$; Total intake ≈ $2.7\,\text{L}$.
  • Output: Lungs (insensible) ≈ $0.5\,\text{L}$; Skin (insensible yet can be increased with heat) ≈ variable but included in insensible losses; Kidneys (urine) ≈ $0.1\,\text{L}$; Stool (feces) ≈ $0.4\,\text{L}$; Total output ≈ $2.7\,\text{L}$.
• Obilgatory vs. Facultative losses:
  • Obligatory losses: ~1.5 L/day insensible (lungs and skin) + ~0.5 L/day sensible (urine + stool) ≈ total obligatory losses ~2.0 L–2.5