MAINTENANCE OF A NORMAL INTRA- & EXTRACELLULAR

ENVIRONMENT IS FUNDAMENTAL TO LIFE

Life originated in an aqueous environment; enzyme reactions, cellular and subcellular processes, and so forth
have therefore evolved to work in this milieu. Since mammals live in a gaseous environment, how is the aqueous
state maintained? Membranes accomplish this by internalizing and compartmentalizing body water.
The Body’s Internal Water Is Compartmentalized
Water makes up about 60% of the lean body mass of the human body and is distributed in two large
compartments.
Intracellular Fluid (ICF)
This compartment constitutes two-thirds of total body water and provides a specialized environment for the cell
(1) to make, store, and utilize energy; (2) to repair itself; (3) to replicate; and (4) to perform special functions.
Extracellular Fluid (ECF)
This compartment contains about one-third of total body water and is distributed between the plasma and
interstitial compartments. The extracellular fluid is a delivery system. It brings to the cells nutrients (eg, glucose,
fatty acids, amino acids), oxygen, various ions and trace minerals, and a variety of regulatory molecules
(hormones) that coordinate the functions of widely separated cells. Extracellular fluid removes CO2 , waste
products, and toxic or detoxified materials from the immediate cellular environment.
The Ionic Compositions of Intracellular & Extracellular Fluids Differ Greatly
As illustrated in Table 40–1, the internal environment is rich in K+ and Mg2+, and phosphate is its major anion.
Extracellular fluid is characterized by high Na+ and Ca2+ content, and Cl_ is the major anion. Note also that the
concentration of glucose is higher in extracellular fluid than in the cell, whereas the opposite is true for proteins.
Why are there such differences? It is thought that the primordial sea in which life originated was rich in K+ and
Mg2+. It therefore follows that enzyme reactions and other biologic processes evolved to function best in that
environment—hence the high concentration of these ions within cells. Cells were faced with strong selection
pressure as the sea gradually changed to a composition rich in Na+ and Ca2+. Vast changes would have been
required for evolution of a completely new set of biochemical and physiologic machinery; instead, as it happened,
cells developed barriers—membranes with associated “pumps” such as the Na+-K+ -ATPase (see below)—to
maintain the internal microenvironment

Water and Solutes
All biological cells contain essentially the same building blocks and types of macromolecules. The general classes 
of substances in cells are presented in Table 1.1. 
There are significant variations in concentration of specific components in different cell types and in organelles of 
eukaryotic cells. Microenvironments are also 
created by macromolecules and membranes in which the composition differs from that of the surrounding milieu. 
Cells depend on the external environment for nutrients 
required for replacement of components, growth, and energy needs. They have a variety of mechanisms to cope w
ith variations in composition of the external 
environment. Water is the one common component of all environments. It is the solvent in which the substances r
equired for the cell's existence are dissolved or 
suspended. The unique physicochemical properties of water make life on earth possible.
Hydrogen Bonds Form between Water Molecules
Two hydrogen atoms share their electrons with an unshared pair of electrons of an oxygen atom to form a water m
olecule. The oxygen nucleus has a stronger 
attraction for shared electrons than hydrogen, and positively charged hydrogen nuclei are left with an unequal shar
e of electrons, creating a partial positive charge on 
each hydrogen and a partial negative charge on oxygen. The bond angle between hydrogens and oxygen is 104.5°, 
making the molecule electrically asymmetric and 
producing an electric dipole (Figure 1.2). Water molecules interact because positively charged hydrogen atoms on 
one molecule are attracted to the negatively charged 
oxygen atom on another, with formation of a weak bond between two water molecules (Figure 1.3a). This bond, i
ndicated by a dashed line, is a hydrogen bond. A 
detailed discussion of noncovalent interactions between molecules, including electrostatic, van der Waals, and hy
drophobic, is presented on page 64. Five molecules of 
water form a tetrahedral structure (Figure 1.3b), because each oxygen shares its electrons with four hydrogen ato
ms and each hydrogen with another oxygen. A 
tetrahedral lattice structure is formed in ice and gives ice its crystalline structure. Some hydrogen bonds are broke
n as ice is transformed to liquid water. Each bond is  relatively
weak compared to a covalent bond but the large number of hydrogen bonds between molecules in liquid water i
s the reason for the stability of water. Liquid water 
actually has a definite structure due to hydrogen bonding that is in a dynamic state as these bonds break and ref
orm. Hydrogen bonds in water have a halflife of less  than 1 × 10–
10 s. Liquid water contains a significant number of hydrogen bonds even at 100°C, which accounts for its high he
at of vaporization; in the transformation  from liquid to vapor state, hydrogen bonds are disrupted.
Water molecules hydrogen bond to different chemical structures. Hydrogen bonding also occurs between other 
molecules and within a molecule wherever 
electronegative oxygen or nitrogen comes in close proximity to hydrogen covalently bonded to another electron
egative atom. Representative hydrogen bonds are 
presented in Figure 1.4. Intramolecular hydrogen bonding occurs extensively in large macromolecules such as pr
oteins and nucleic acids and is partially responsible for  their structural stability.
Many models for the structure of liquid water have been proposed, but none adequately explains all its properti
es.
Water Has Unique Solvent Properties
The polar nature and ability to form hydrogen bonds are the basis for the unique solvent 
properties of water. Polar molecules are readily dispersed in water. Salts in 
which a crystal lattice is held together by attraction of positive and negative groups disso
lve in water because electrostatic forces in the crystal can be overcome by 
attraction of charges to the dipole of water. NaCl is an example where electrostatic attra
ction of individual Na+  and Cl– atoms is overcome by interaction of Na+  with 
the negative charge on oxygen atoms, and Cl–
with positive charges on the hydrogen atoms. Thus a shell of water surrounds the indivi
dual ions. The number of weak  charge–charge interactions between water and Na+
and Cl– ions is sufficient to separate the two charged ions.
Many organic molecules that contain nonionic but weakly polar groups are soluble in wa
ter because of attraction of these groups to molecules of water. Sugars and 
alcohols are readily soluble in water for this reason. Amphipathic molecules, compounds 
that contain both polar and nonpolar groups, disperse in water if attraction of 
the polar group for water can overcome hydrophobic interactions of nonpolar portions 
of the molecules. Very hydrophobic molecules, such as compounds that contain 
long hydrocarbon chains, however, do not readily disperse as single molecules in water 
but interact with one another to exclude the polar water molecules.
Properties Of Water
• Cohesion : water attracting to itself
• Adhesion : water attracting to other surfaces
• Lower density of ice : Ice is less dense than liquid water
• Surface tension : Creates strong force on surface of water because of hydrogen bond
of water molecule with neighboring molecule
• Versatile solvent : Water easily dissolve ions and other polar molecules
• High specific heat : Water can absorb a lot of heat before its temperature changes
• High heat of vaporization
• Viscosity is a measure of a fluid's resistance to flow. It describes the internal friction
of a moving fluid.
pH
The importance of hydrogen ions in biological systems will become apparent in subsequent chapters. For conve
nience [H+ ] is usually expressed in terms of pH, calculated as follows:

In pure water [H+ ] and [OH–] are both 1 × 10–7
M, and pH = 7.0. [OH–] is expressed as the pOH. For the equation describing dissociation of water, 1 × 10–14 = 
[H+ ]
[OH–]; taking negative logarithms of both sides, the equation becomes 14 = pH + pOH. Table 1.2 presents the rel
ationship between pH and [H+ ].
The pH values of different biological fluids are presented in Table 1.3. In blood plasma, [H+ ] is 0.00000004 M or 
a pH of 7.4. Other cations are between 0.001 and  0.10 M, well over 10,000 times higher than [H+ ]
An increase in hydrogen ion to 0.0000001 M (pH 7.0) leads to serious medical consequences and is life threateni
ng;  a detailed discussion of mechanisms by which the body maintains intra
and extracellular pH is presented in Chapter 25.

Many Biologically Important Molecules Are Acids or Bases
The definitions of an acid and a base proposed by Lowry and Brønsted are most convenient in considering biolog
ical systems. An acid is a proton donor and a base is a proton acceptor.
Hydrochloric acid (HCl) and sulfuric acid (H2SO4) are strong acids because they dissociate totally, and OH–
ion is a base because it accepts a  proton, shifting the equilibrium

When a strong acid and OH– are combined, H+  from the acid and OH–

interact and are in equilibrium with H2O. Neutralization of H+  and OH– occurs because the ion 
product for water is so small. Anions produced when strong acids dissociate totally, such as Cl–
from HCl, are not bases because they do not associate with protons in solution. When an organic 
acid, such as lactic acid, is dissolved in water it dissociates only partially, establishing an equilibrium between an 
acid (proton donor), an anion of the acid, and a proton  as follows:

Lactic acid is a weak acid. The anion is a base because it accepts a proton and reforms the acid. The weak acid an
d the base formed on dissociation are referred to 
as a conjugate pair; other examples are presented in Table 1.4. Ammonium ion (NH4
+ ) is an acid because it dissociates to yield H+  and ammonia (NH3), an 
uncharged species, which is a conjugate base. Phosphoric acid (H3PO4) is an acid and PO4 3–
is a base, but H2PO4 – and HPO4 2– are either a base or acid depending 
on whether the phosphate group is accepting or donating a proton.
The tendency of a conjugate acid to dissociate H+  can be evaluated from the   of 1 × 10–14 at 25°C.
A convenient method of stating the   is in the form of pK¢ , as

Buffer
A buffer solution is one which resists changes in pH when small quantities of an acid or an alkali are added to
it.
(Acidic Buffer)
A buffer can be created by mixing a weak acid (HA) with its conjugate base(A-)
An acidic buffer solution is simply one which has a pH less than 7
(Basic Buffer)
A buffer can be created by mixing a weak base with its conjugate Acid
An basic buffer solution is simply one which has a pH more than 7.
Buffer Mechanism of Action
 Colloids
A homogeneous non-crystalline substance consisting of large molecules or ultramicroscopic particles of one
substance dispersed through a second substance.
Every colloid consists of two parts: Colloidal particles and the dispersing medium.
The particles do not settle, and cannot be separated out by ordinary filtering or centrifuging like those in a
suspension.
A common method of classifying colloids is based on the phase of the dispersed substance and what phase it is
dispersed in.
The types of colloids includes sol, emulsion, foam, aerosol and gel.
 Sol is a colloidal suspension with solid particles in a liquid. 
 Aerosol  contains small particles of liquid or solid dispersed in a gas. 
 Emulsion is between two liquids.
 Foam is formed when many gas particles are trapped in a liquid or solid. 
 Gel Liquid in Solid

Examples Of Colloids