THE CELL MEMBRANE AND IT'S STRUCTURE.
The body fluids could be divided into two kinds, one which occupies the space inside the cell, called the intra cellular fluid and the extra-cellular fluid constituted by the interstitial fluid and the blood. There are wide differences in the constitution of these fluids . Some constituents are found in massive quantities within the cell whereas some are found in large quantities in the extra-cellular fluid.

Components Extra-cellular       Intra-cellular
Sodium ions 142mcg /L           10mcg/l
Potassium ions 4                     140
Calcium ions 5                         < 1
Magnesium ions 3                    58
Chloride ions 103                     4
Bicarbonate ions 28                10
Phosphate ions 4                     75
Sulphate ions 1                        2
glucose 90&sp;                  0 -  20
Amino acids 30                        200
Cholest/ph.lipids/neutral fat 0.5  2 - 95
P O2 35mm of hg                   20 mm of hg
P CO2 46mm of hg                50mm of hg
PH 7.4                                   7.0
Proteins 2 gm%                    16 gm%

This difference between intra-cellular and extra-cellular fluid is brought about by transport through the cell membrane.
The cell membrane completely envelops the cell and is composed of
1. PROTEINS : 55%
2. PHOSPHOLIPIDS: 25%
3. CHOLESTEROL : 13%
4. OTHER LIPIDS :4%
5. CARBOHYDRATES :3%

Roughly the cell membrane is constituted by a lipid bilayer in which protein molecules are interspersed, which is covered by a calyx of carbohydrate molecules.
The lipid bilayer forms a barrier against free movement of water and water soluble substances. This layer is composed entirely by phospho-lipids and cholesterol. The phosphate radical in phospho-lipids and hydroxyl radical in cholesterol are hydrophilic and the remaining part of both molecules are hydrophobic. As the hydrophobic part is repelled by water and attract one another mutually, these line up . The hydrophobic part occupies the center and hydrophilic part occupies the periphery .The latter projects to the surface in contact with the surrounding water.
The protein molecules penetrate through the lipid bilayer, disrupting the continuity of the lipid layer and provide pathways for the passage of specific substances through the plasma membrane. The protein molecules are of two types.

1. INTEGRAL PROTEINS
2. PERIPHERAL PROTEINS.

The integral proteins protrude all the way along the lipid bilayer and provide structural channels or pores through which water soluble substances enter the cell from the extra cellular fluid (channel proteins) . They sometimes act as carrier proteins for transporting large molecules and are highly selective. Some other type of integral proteins act as enzymes.The peripheral proteins are attached to the integral proteins and normally act as enzymes.
The carbohydrate coat is formed by glycolipids and glycoproteins. The 'glyco' part protrudes outside the cell and forms a loose carbohydrate covering called the glycocalyx. These carbohydrate molecules are negatively charged , and gives the cell an overall negative charge. This helps to repel the negatively charged particles. Some carbohydrates act as receptors for binding hormones like insulin. Some enter into immune reactions.
Because of the fluid lipid layer, portions of lipid soluble proteins tend to diffuse to all areas of the membrane.

Transport through the cell membrane occurs by two processes :-

1. PASSIVE TRANSPORT BY DIFFUSION.
2. ACTIVE TRANSPORT.

In active transport , there is movement of ions or other substances across the membrane against an energy gradient, such as from low concentration to high concentration, a process that requires chemical energy to cause the movement.

PASSIVE TRANSPORT or DIFFUSION
Molecules of a substance are constantly in motion. This motion is minimum in solids, more in liquids and most in gases. When two substances are mixed together, the molecules of the two substances will move from one place to the other until a uniform mixture is obtained. This is called diffusion. Motion of these particles , is what physicists call heat. More heat more the motion. This motion is found until the temperature is absolute zero.
Diffusion through the cell membrane is divided into two different kinds,
1. SIMPLE DIFFUSION
2. FACILITATED DIFFUSION.

SIMPLE DIFFUSION
Simple diffusion means movement of molecules through the cell membrane without binding with a carrier protein. The rate of diffusion is determined by,
1. The amount of substance available.
2. Velocity of kinetic motion.
3. Number of openings in the cell membrane.

Simple diffusion takes place by two pathways ,
1. Interstices in lipid bilayer
2. Water channels in transport proteins.

1.THROUGH INTERSTICES.
Lipid soluble substances diffuse directly through the plasma membrane. Here the rate of diffusion is directly proportional to the lipid solubility of the substance. Substances like oxygen, nitrogen and alcohol are lipid soluble and are hence transported by this method.
Water and other lipid insoluble substances pass either directly through the plasma membrane or sometimes through the water channels in integral proteins. In this type of transport, the rapidity of transport is dependant upon.
a. size of the molecule, inversely.
b. Kinetic energy of the molecule ,directly .
Glucose which has a larger molecular size penetrates the lipid layer 100,000 times less rapidly than water. Thus lipid insoluble substances which penetrate the lipid layer are usually very small ones.
Ions are transported less readily through the lipid layer, because the lipid layer is charged negatively in the outside and positively inside, ions of any charge are repelled. Charged ions combine with water molecules to form hydrated ions which are much larger in size.

2.THROUGH WATER CHANNELS IN CARRIER PROTEINS.
The transport through water channels is distinguished by two important characteristics.
a. protein channels are selectively permeable.
b. Many channels are opened or closed by gates.

Selective permeability is provided as a result of several characters of the channel which includes
1. size of the channel
2. shape of the channel
3. nature of electrical charges in the interior surfaces of the channel.
Thus sodium channels are different from potassium channels.
Gates are actually, gate like extensions of the transport protein molecules, which can close over the opening of the channel or can be lifted away from the opening by a conformational change in the shape of the protein molecule itself. The opening and closing of gates are controlled by at least two principal ways.

VOLTAGE GATING: Molecular conformation of the gate responds to the electrical potential across the cell membrane . Eg , When there is strong negative charge inside the cell, the gates remain closed. Once this internal negative charge is lost, the gates open and Na ions rush in. This type of gating is found in initiating nerve action potential. Potassium channels also open when the cell becomes positive inside, but this channel is too slow.
LIGNAND GATING: Some protein channel gates are opened by the binding of another molecule within the protein, thus causing a conformational change in the protein molecule that opens or closes a gate. This type of gating is found in acetyl choline channels.

FACILITATED DIFFUSION.
Facilitated diffusion is otherwise called carrier mediated diffusion, because of the necessity of a specific carrier protein. Facilitated diffusion always reaches a probable maximum limit, because for obvious reasons the rate at which the molecules can be transported by this mechanism can not be more than the rate at which the carrier protein molecule can undergo the conformational change.

MECHANISM OF FACILITATED DIFFUSION.
There are carrier proteins among the lipid layer with specific binding sites. Once the molecule enters the channel, it binds with the carrier binding site. Within a fraction of a second a conformational change is produced and the channel opens to the opposite side. Because the binding force of the molecule is weak, the thermal motion of the attached molecule causes it to break off and move in the opposite direction. This mechanism allows transport in either directions. Among the most important substances that cross cell membranes by facilitation are glucose and aminoacids. Insulin can increase the rate of facilitated diffusion of glucose a much as 10 - 20 folds. This is how insulin controls glucose utilization of the body.
To conclude, net diffusion through the protein channels are influenced by
1. permeability of the membrane
2. difference in concentration of the diffusing substance across the membrance.
3. pressure difference across the membrane.
4. electrical potential across the membrane.

PHYSIOLOGICAL IMPORTANCE OF DIFFUSION.
Diffusion is employed in
a. Absorption from the intestine.
b. Exchange between plasma and red cells.
c. Exchange in capillary bed.
d. Exchange in lung capillaries.
e. Admixture of gases in lungs.

OSMOSIS

NET DIFFUSION OF WATER ACROSS SEMI PERMEABLE MEMBRANE
The diffusion of water through a semi- permeable membrane is called osmosis. If two solutions of different solute concentrations are separated by a semi-permeable membrane, water moves from an area of lesser solute concentration to an area of greater solute concentration. Soon a stage will come, when movement of water will be in the opposite direction, due to increased hydrostatic pressure of the solution. Next, the movement of water to both sides will be the same, so that no alteration in volume is observed.
The amount of pressure which can prevent the movement of water molecules is the osmotic pressure. In other words, the force under which, a solvent moves from a solution of lower solute concentration to a solution of higher solute concentration, when separated by a selectively permeable membrane is the osmotic pressure. If a pressure greater than the osmotic pressure is applied at the stronger solution, water flows against the concentration gradient. This process is called Ultra-filtration.
When solution with different osmotic pressures are considered, one with lesser osmotic pressure is called hypotonic and one with greater osmotic pressure is called hypertonic. If both have same osmotic pressure, they are called isotonic solutions. Sodium chloride isotonic with plasma is called normal/ physiological saline. A 5% glucose solution also has the same osmotic pressure. Saline purgatives and saline diuretics work on the same principle.

Osmosis is applied in various physiological processes like
1. Absorption from intestine.
2. Exchange in capillary bed.
3. Re-absorption from C.S.F.