• Water makes up a large part of the human body weight.
• The total amount of water in the body is called total body water (TBW).
• Total body water is about 50%–70% of body weight.
• Example:
  • Body weight = 70 kg
  • Total body water = 65% of body weight
  • TBW = 45.5 kg ≈ 45.5 L of water
• Calculation:
  • 70 × 65/100 = 45.5 kg (≈45.5 L) ✔
• In general, more body fat = lower total body water.
• Less body fat = higher total body water.
• Females usually have less body water than males because they normally have a higher percentage of body fat.
• Total body water is divided into two main fluid compartments:
  • Intracellular fluid (ICF) – fluid inside the cells.
  • Extracellular fluid (ECF) – fluid outside the cells.
• ICF forms about two-thirds (2/3) of the total body water.
• ECF forms about one-third (1/3) of the total body water.
• Cell membranes separate ICF from ECF.
• The ECF is further divided into two parts:
  • Plasma – the fluid present inside the blood vessels.
  • Interstitial fluid – the fluid surrounding the body cells.
• Plasma is the smaller of the two extracellular fluid compartments.

KEY CONCEPT

• Total body water = 50–70% of body weight.
• Higher body fat → Lower body water.
• ICF = 2/3 of total body water (inside cells).
• ECF = 1/3 of total body water (outside cells).
• ECF is divided into plasma and interstitial fluid, with plasma being the smaller compartment.

VOLUME AND COMPOSITION OF BODY FLUIDS

• Interstitial fluid is the fluid that directly surrounds and bathes the body cells.
• Interstitial fluid is the larger of the two extracellular fluid (ECF) compartments.
• Plasma and interstitial fluid are separated by capillary walls.
• Interstitial fluid is formed from plasma by the process of filtration across the capillary wall.
• Capillary walls do not allow large molecules, such as plasma proteins, to pass easily.
• Therefore, interstitial fluid contains very little or no protein.
• The method for measuring the volume of body fluid compartments is discussed in Chapter 6.

KEY CONCEPT

• Interstitial fluid directly bathes the cells.
• It is the larger ECF compartment.
• Capillary walls separate plasma from interstitial fluid.
• Interstitial fluid is formed by filtration of plasma.
• Because plasma proteins cannot easily cross capillary walls, interstitial fluid contains very little protein.

Composition of Body Fluid Compartments

• Body fluid compartments do not have the same composition.
• ICF (intracellular fluid) and ECF (extracellular fluid) contain very different concentrations of many solutes.
• Plasma and interstitial fluid also have predictable differences in solute concentrations.
• These differences occur because proteins are mostly prevented from entering the interstitial fluid.
• As a result, plasma contains more protein than interstitial fluid.

KEY CONCEPT

• Body fluid composition is not uniform.
• ICF and ECF have different solute concentrations.
• Plasma and interstitial fluid also differ in composition.
• The main reason is that proteins remain mainly in plasma and are largely excluded from interstitial fluid.

Units for Measuring Solute Concentrations

• The amount of a solute is commonly measured in moles, equivalents, or osmoles.
• Solute concentration is usually expressed as:
  • Moles per liter (mol/L)
  • Equivalents per liter (Eq/L)
  • Osmoles per liter (Osm/L)
• Because body fluids contain low concentrations of solutes, the following smaller units are commonly used:
  • Millimoles per liter (mmol/L)
  • Milliequivalents per liter (mEq/L)
  • Milliosmoles per liter (mOsm/L)
• One mole contains 6 × 10²³ molecules of a substance.
• One millimole (mmol) is 1/1000 of a mole (10⁻³ mole).
• Example:
  • Glucose = 1 mmol/L
  • This means 1 × 10⁻³ mole of glucose is present in 1 liter of solution.
• An equivalent (Eq) measures the amount of a charged (ionized) substance.
• It is calculated by:
  • Equivalent = Number of moles × Valence (charge)
• Example: Potassium chloride (KCl)
  • One mole of KCl separates into:
    • 1 K⁺
    • 1 Cl⁻
  • Therefore:
    • 1 mmol/L K⁺ = 1 mEq/L
• Example: Calcium chloride (CaCl₂)
  • One mole of CaCl₂ separates into:
    • 1 Ca²⁺
    • 2 Cl⁻
  • Calcium has a valence of 2.
  • Therefore:
    • 1 mmol/L Ca²⁺ = 2 mEq/L
• One osmole represents the total number of particles a solute forms after dissolving in solution.
• Osmolarity is the concentration of these particles and is expressed as osmoles per liter (Osm/L).
• If a solute does not break apart in solution (such as glucose):
  • Osmolarity = Molarity
• If a solute breaks into more than one particle (such as NaCl):
  • Osmolarity = Molarity × Number of particles formed
• Example: Sodium chloride (NaCl)
  • NaCl separates into:
    • Na⁺
    • Cl⁻
  • Total particles = 2
  • Therefore:
    • 1 mmol/L NaCl = 2 mOsm/L
• pH is a logarithmic value used to express hydrogen ion (H⁺) concentration.
• Because the H⁺ concentration in body fluids is very low, pH is a more convenient way to express it.
• As H⁺ concentration increases, pH decreases.
• As H⁺ concentration decreases, pH increases.
• Formula:
  • pH = −log₁₀ [H⁺]
• Sample Problem
  • Subject A: Arterial H⁺ = 65 × 10⁻⁹ Eq/L
  • Subject B: Arterial pH = 7.3
• Calculation for Subject A
  • pH = −log₁₀ (65 × 10⁻⁹)
  • pH ≈ 7.19
• Comparison
  • Subject A: pH = 7.19
  • Subject B: pH = 7.30
  • Since 7.19 is lower than 7.30, Subject A has the higher H⁺ concentration.
  • Therefore, Subject A has more acidic blood.

KEY CONCEPT

• Mole measures the amount of a substance.
• Equivalent (Eq) measures the amount of charged particles and depends on valence.
• Osmole measures the total number of dissolved particles.
• Non-ionizing solutes: Osmolarity = Molarity.
• Ionizing solutes: Osmolarity = Molarity × Number of particles formed.
• pH and H⁺ are inversely related: Higher H⁺ → Lower pH; Lower H⁺ → Higher pH.
• In the sample problem, Subject A has the higher H⁺ concentration because its pH (7.19) is lower than Subject B’s pH (7.30).

Solving the pH Formula (Easiest Conceptual Method)

Given

• Hydrogen ion concentration (H⁺) = 65 × 10⁻⁹ Eq/L

Formula

$$\boxed{\text{pH}=-\log_{10}[H^+]}$$pH=−log10​[H+]​Step 1: Write the given value

$$\text{pH}=-\log_{10}(65\times10^{-9})$$pH=−log10​(65×10−9)

Step 2: Make the number easy to calculate

We know:$$65=6.5\times10$$65=6.5×10

So,$$65\times10^{-9}=6.5\times10^{-8}$$65×10−9=6.5×10−8

Now the formula becomes$$\text{pH}=-\log_{10}(6.5\times10^{-8})$$pH=−log10​(6.5×10−8)

Step 3: Split the logarithm

Use this logarithm rule:$$\boxed{\log(ab)=\log a+\log b}$$log(ab)=loga+logb​

Therefore,$$\log(6.5\times10^{-8}) = \log6.5+\log10^{-8}$$log(6.5×10−8)=log6.5+log10−8

Step 4: Find each value

From the logarithm table (or calculator):$$\log6.5=0.81$$log6.5=0.81

Also,$$\log10^{-8}=-8$$log10−8=−8

Step 5: Add the values

$$0.81+(-8) = -7.19$$0.81+(−8)=−7.19

So,$$\log(6.5\times10^{-8}) = -7.19$$log(6.5×10−8)=−7.19

Step 6: Apply the negative sign

Remember the formula:$$\text{pH}=-\log[H^+]$$pH=−log[H+]

Therefore,$$\text{pH} = -(-7.19) = \boxed{7.19}$$pH=−(−7.19)=7.19​

Final Answer

$$\boxed{\textbf{pH = 7.19}}$$pH = 7.19​

Easy Concept to Remember

Think of the calculation in three simple steps:

H⁺ → Take Log → Change the Sign

Example:

• H⁺ = 65 × 10⁻⁹
• Log = −7.19
• Change the sign → +7.19

✅ Final pH = 7.19

Why Did We Change 65 × 10⁻⁹ to 6.5 × 10⁻⁸?

This makes the logarithm easy.

Because$$65=6.5\times10$$65=6.5×10

So,$$65\times10^{-9} = 6.5\times10\times10^{-9} = 6.5\times10^{-8}$$65×10−9=6.5×10×10−9=6.5×10−8

The value does not change—it is only rewritten in standard scientific notation.

Clinical Concept

• Higher H⁺ concentration → Lower pH → More acidic
• Lower H⁺ concentration → Higher pH → Less acidic

Here,

• pH = 7.19, which is lower than the normal arterial pH (7.35–7.45).
• Therefore, this blood is more acidic (acidosis) because it contains more H⁺ ions.

KEY CONCEPT

• pH = −log₁₀(H⁺ concentration)
• Rewrite the number into standard scientific notation first.
• Use:
  • log(ab) = log a + log b
  • log10ⁿ = n
• After finding the logarithm, change its sign because of the negative sign in the pH formula.
• Higher H⁺ = Lower pH = More acidic blood.

Electroneutrality of Body Fluid Compartments

• Every body fluid compartment follows the law of electroneutrality.
• This means that the total positive charges (cations) must always equal the total negative charges (anions).
• The concentrations of cations and anions are equal when measured in mEq/L.
• There cannot be more positive charges than negative charges, and there cannot be more negative charges than positive charges.
• This balance is maintained in every body fluid compartment.
• A small electrical potential difference may exist across the cell membrane.
• Even with this potential difference, the overall fluid on each side of the membrane remains electrically neutral.
• This is because only a very small number of charges are separated near the cell membrane.
• The separated charges are too few to change the overall (bulk) concentrations of cations and anions in the fluid.

KEY CONCEPT

• Every body fluid compartment is electrically neutral.
• Total cations (positive charges) = Total anions (negative charges).
• Charge balance is maintained in mEq/L.
• A small membrane potential does not disturb overall electroneutrality because only a few charges are separated near the cell membrane.

Electroneutrality of Body Fluid Compartments

Sample Problem

A biologic fluid has the following ion concentrations:

Cations (Positive Ions)	mEq/L
Na⁺	140
K⁺	4
Ca²⁺	2
Total Cations	146 mEq/L

Anions (Negative Ions)	mEq/L
Cl⁻	110
HPO₄²⁻	6
Protein⁻	0
HCO₃⁻	?

Question:
What should the HCO₃⁻ concentration be to satisfy the law of electroneutrality?

Step 1: Remember the Main Rule

The law of electroneutrality says:

Total Positive Charges (Cations) = Total Negative Charges (Anions)

So,$$\boxed{\text{Total Cations}=\text{Total Anions}}$$Total Cations=Total Anions​

Step 2: Calculate Total Cations

Add all positive ions:$$Na^+ + K^+ + Ca^{2+}$$Na++K++Ca2+ $$140+4+2=146\ \text{mEq/L}$$140+4+2=146 mEq/L

✅ Total Cations = 146 mEq/L

Step 3: Calculate the Known Anions

Add the measured negative ions:$$Cl^- + HPO_4^{2-} + Protein^-$$Cl−+HPO42−​+Protein− $$110+6+0=116\ \text{mEq/L}$$110+6+0=116 mEq/L

✅ Known Anions = 116 mEq/L

Step 4: Find the Missing HCO₃⁻

Since$$\text{Total Cations}=\text{Total Anions}$$Total Cations=Total Anions $$146=116+\text{HCO}_3^-$$146=116+HCO3−​

Subtract 116 from both sides:$$146-116=30$$146−116=30

Therefore,$$\boxed{\text{HCO}_3^- = 30\ \text{mEq/L}}$$HCO3−​=30 mEq/L​

Final Answer

$$\boxed{\textbf{HCO}_3^- = 30\ \textbf{mEq/L}}$$HCO3−​=30 mEq/L​

Easy Concept

Imagine a balance scale.

⚖️ Left Side (Positive Charges)

• Na⁺ = 140
• K⁺ = 4
• Ca²⁺ = 2

Total = 146

⚖️ Right Side (Negative Charges)

• Cl⁻ = 110
• HPO₄²⁻ = 6
• Protein⁻ = 0

Current Total = 116

The right side is 30 mEq/L short.

So bicarbonate (HCO₃⁻) must provide the missing 30 mEq/L to make both sides equal.

Positive charges = 146 mEq/L

⬇️ Must equal

Negative charges = 110 + 6 + 0 + 30 = 146 mEq/L

Now the solution is electrically neutral.

Memory Trick

Think of electroneutrality as a see-saw.

• More positive than negative? ❌ Impossible
• More negative than positive? ❌ Impossible
• Both equal? ✅ Correct

Always use:$$\boxed{\text{Missing ion}=\text{Total Cations}-\text{Known Anions}}$$Missing ion=Total Cations−Known Anions​

KEY CONCEPT

• Every body fluid must remain electrically neutral.
• Total cations = Total anions (in mEq/L).
• First, calculate the total positive charges.
• Next, calculate the known negative charges.
• The missing anion equals the difference between total cations and known anions.
• In this example:
  • Total cations = 146 mEq/L
  • Known anions = 116 mEq/L
  • HCO₃⁻ = 30 mEq/L to maintain electroneutrality.

Composition of Intracellular Fluid and Extracellular Fluid

• ICF (intracellular fluid) and ECF (extracellular fluid) have very different chemical compositions.
• The main positive ion (cation) in ECF is sodium (Na⁺).
• The main negative ions (anions) in ECF are:
  • Chloride (Cl⁻)
  • Bicarbonate (HCO₃⁻)
• The main positive ions (cations) in ICF are:
  • Potassium (K⁺)
  • Magnesium (Mg²⁺)
• The main negative ions (anions) in ICF are:
  • Proteins
  • Organic phosphates
• Calcium (Ca²⁺) concentration is very different in the two compartments.
• ICF contains an extremely low concentration of ionized Ca²⁺ (≈10⁻⁷ mol/L).
• ECF contains a Ca²⁺ concentration that is about 10,000 times (four orders of magnitude) higher than ICF.
• ICF is more acidic than ECF, so ICF has a lower pH.
• In general:
  • Substances present in high concentration in ECF are present in low concentration in ICF.
  • Substances present in high concentration in ICF are present in low concentration in ECF.
• Although the concentrations of individual solutes are very different, the total solute concentration (osmolarity) is the same in ICF and ECF.
• This happens because water moves freely across the cell membrane.
• If a temporary difference in osmolarity develops, water quickly moves into or out of the cells.
• This water movement restores equal osmolarity between ICF and ECF.

KEY CONCEPT

• ECF: Main cation = Na⁺; Main anions = Cl⁻ and HCO₃⁻.
• ICF: Main cations = K⁺ and Mg²⁺; Main anions = Proteins and organic phosphates.
• ICF has very low Ca²⁺ and a lower pH than ECF.
• ICF and ECF have different solute compositions but the same osmolarity.
• Free movement of water across cell membranes maintains equal osmolarity in both compartments.

Creation of Concentration Differences Across Cell Membranes

• Differences in solute concentrations across cell membranes are created and maintained by energy-dependent transport mechanisms.
• These transport mechanisms use energy to move substances across the cell membrane.
• The best-known transporter is the Na⁺-K⁺ ATPase (Na⁺-K⁺ pump).
• The Na⁺-K⁺ pump moves:
  • Na⁺ from ICF to ECF
  • K⁺ from ECF to ICF
• Both Na⁺ and K⁺ are transported against their electrochemical gradients.
• Because they move against their gradients, the pump requires ATP (adenosine triphosphate) as an energy source.
• The Na⁺-K⁺ ATPase creates and maintains:
  • Low Na⁺ concentration inside the cell.
  • High K⁺ concentration inside the cell.
• Intracellular Ca²⁺ concentration is also kept much lower than extracellular Ca²⁺ concentration.
• This difference is maintained partly by the Ca²⁺ ATPase pump.
• The Ca²⁺ ATPase pumps Ca²⁺ out of the cell against its electrochemical gradient.
• Like the Na⁺-K⁺ pump, the Ca²⁺ ATPase also uses ATP directly.
• Some membrane transporters do not use ATP directly.
• Instead, they use the Na⁺ concentration gradient created by the Na⁺-K⁺ ATPase as their energy source.
• These transporters help create concentration gradients for:
  • Glucose
  • Amino acids
  • Ca²⁺
  • H⁺
• Cell membranes can create large concentration differences for many solutes.
• If the membrane were freely permeable to all solutes, these concentration differences would quickly disappear.
• Therefore, cell membranes are selectively permeable.
• Selective permeability helps maintain the concentration gradients produced by energy-dependent transport.
• The differences between ICF and ECF compositions are essential for normal body functions.
• Examples include:
  • Resting membrane potential of nerves and muscles depends on the difference in K⁺ concentration across the cell membrane.
  • Action potential upstroke depends on the difference in Na⁺ concentration across the cell membrane.
  • Excitation-contraction coupling in muscles depends on the difference in Ca²⁺ concentration across the cell membrane and the sarcoplasmic reticulum (SR).
  • Absorption and reabsorption of glucose depend on the Na⁺ concentration gradient, such as:
    • Glucose absorption in the small intestine.
    • Glucose reabsorption in the renal proximal tubule.

KEY CONCEPT

• Energy-dependent transporters create concentration differences across cell membranes.
• Na⁺-K⁺ ATPase uses ATP to pump Na⁺ out and K⁺ into cells.
• Ca²⁺ ATPase uses ATP to keep intracellular Ca²⁺ very low.
• Some transporters use the Na⁺ gradient instead of ATP directly.
• Selective permeability of the cell membrane prevents concentration gradients from disappearing.
• These concentration differences are essential for nerve impulses, muscle contraction, and nutrient transport.

Concentration Differences Between Plasma and Interstitial Fluids

• ECF (extracellular fluid) is divided into two compartments:
  • Plasma
  • Interstitial fluid
• The main difference between plasma and interstitial fluid is the presence of proteins in plasma.
• Plasma contains proteins such as albumin.
• Interstitial fluid contains very little or no protein.
• Plasma proteins cannot easily cross capillary walls because they are large molecules.
• Therefore, plasma proteins remain mainly inside the blood vessels (plasma).
• The presence of plasma proteins produces secondary effects on ion distribution.
• Plasma proteins carry a negative charge.
• Their negative charge causes a slight redistribution of small ions across the capillary wall.
• This redistribution is called the Gibbs-Donnan equilibrium.
• Because plasma contains negatively charged proteins, it must still remain electrically neutral.
• Therefore:
  • Plasma has a slightly lower concentration of small anions (such as Cl⁻).
  • Plasma has a slightly higher concentration of small cations (such as Na⁺ and K⁺) than interstitial fluid.
• These small concentration differences are expressed by the Gibbs-Donnan ratio.
• Example: Chloride (Cl⁻)
  • Plasma contains slightly less Cl⁻ than interstitial fluid.
  • Gibbs-Donnan ratio = 0.95
  • [Cl⁻]plasma / [Cl⁻]interstitial fluid = 0.95
• Example: Sodium (Na⁺)
  • Plasma contains slightly more Na⁺ than interstitial fluid.
  • Gibbs-Donnan ratio = 0.95
  • [Na⁺]interstitial fluid / [Na⁺]plasma = 0.95
• These differences in the concentrations of small ions between plasma and interstitial fluid are very small.
• In most situations, these minor differences are ignored.

KEY CONCEPT

• Plasma contains proteins; interstitial fluid contains little or no protein.
• Large plasma proteins cannot cross capillary walls.
• Negatively charged plasma proteins create the Gibbs-Donnan equilibrium.
• Plasma has slightly fewer anions (Cl⁻) and slightly more cations (Na⁺, K⁺) than interstitial fluid.
• These ion differences are very small and are usually ignored.