1. Department of Physiology
&
BIOPHYSICS

2. Guided By
Dr.A.K.Dwivedi

3. CONTENTS
Biophysics – Introduction
Units of Concentration of solution
Ions
Electrolytes and Non Electrolytes
Filtration
Ultra filtration
Dialysis
Surface tension

4. 9. Adsorption
10. Diffusion
11. Osmosis
12. Colloid
13. Emulsion and Suspensoid
14. Hydrotrophy
15. Donnan’s Equilibrium
16. Acid Base & pH
17. Acid base Buffer

5. BIOPHYSICS Introduction: 2. Osmosis 3. Emulsion and suspensoid
Biophysics includes all physiochemical process occurring in the living cell and in its surrounding atmosphere that is in Intracellular fluid and extra cellular fluid.
It includes: 1. Diffusion
2. Osmosis
3. Emulsion and suspensoid
4. Filtration, ultra filtration and dialysis
5. Colloids
6. Adsorption
7. Hydrotrophy
8. Donnan’s equilibrium
9. Electrolytes and electrolyte balance
10. Surface tension
11. Acid Base and pH and its balance

6. Units of concentration of solution
Molar Solution: Moles of solute per liter of solution, and molecular weight in grams of solute dissolved in 1000 ml is molar solution.
Ex. Mol wt of H2SO4 is so a molar solution is gms per 1000 ml.
Moles of solute
Molarity (M) = x 1000
Vol. of solution (in ml.)
Unit of molarity – mol L -1 or M

7. Molality: Moles of solute per kilogram of solvent and
Molal solution – Molecular weight in gram of a solute dissolved in 1000 gms of solvent.
Unit of molality – mol kg-1 or m.
Mole of solute
Molality (m) = x 1000
Mass Of solvent (in g)

8. From the discussion of molarity and molality, it is evident that in molarity we consider the volume of the solution while in molality we take the mass of the solvent. Therefore the two are never equal.
Molality is considered better for expressing the concentration as compared to Molarity because the molarity changes with the temperature because of the expansion or contraction of the liquid with temperature. However molality does not change with temperature because mass of the solvent does not change with change in temperature.

9. Normal solution: A normal solution is one which contains per liter, the amount equal to gram molecular weight of the substance divided by equivalent hydrogen atoms.
Gram equiv. of solute
Normality (N) = x 1000
Vol. of solution (in ml)

10. Normality = Molarity x Eq. mass
Molecular mass
Normality = Molarity x Eq. mass
Example: Mol. Wt. of H2SO4 is where
H+ + H+ and SO4-- ions are present. As number of replaceable hydrogen atom is 2, thin normal solution of H2SO4 will contain divided by 2, i.e gms in a liter.

11. Relationship between Normality and Molarity of solution:-
Molar mass
Normality = Molarity x
Equivalent mass
For acids,
Normality = molarity x basicity
Where basicity is the number of H+ ions that a molecule of a acid can give in solution.
For bases,
Normality = Molarity x acidity
Where acidity is the number of OH- ions that a molecule of base can give in a solution.

12. Percentage: Weight in grams of solute per 100 grams of solution is percent by weight and the same amount dissolved in 100 ml is % by volume.
Gram equivalent: Is the molecular weight in grams divided by the number of valency of ions present. One milliequivalent is one thousandth of such gram equivalent.

13. IONS
On an electric current being through solution of a compound in water, some elements migrate at the positive pole or anode and some at the negative pole or cathode. The charged particles are called ions. Negative ions (anions) move towards the anodes and positive ions (cations) to cathode due to attractions of unlike charges.
The most important ions in the cell are K, Mg, PO4, SO4, CO3, and small quantities of Na, Cl and Ca.

14. The ions provide inorganic chemicals for cellular reaction
The ions provide inorganic chemicals for cellular reaction. Also they are necessary for operation of some of the cellular control mechanism. For instance, ions acting at the cellular membrane are required for transmission of electrochemical impulse in nerve and muscle fibers.

15. ELECTROLYTES
Electrolytes are compound which can be dissociated into anions and cataions on an electric current being passed. Example Acid, base, salts etc.
Electrolytic ionic compound, e.g. Sodium chloride dissolved in water is called an electrolyte because it can conduct electricity. Electrolytes are important body constituents because:
1. Some conduct electricity essential for muscle and nerve function.
2. Some exert osmotic pressure, keeping body fluid in their own compartments.
3. Some function in acid base balance, as buffers to resist pH changes in body fluids.

16. A large number of compounds present in the body are not ionic, and therefore have no electrical properties. Electrolytes other than sodium and chloride include potassium, calcium, bicarbonate, and phosphate.
Non- electrolytes
Compounds which cannot be dissociated are called non-electrolytes.

17. FILTRATION
Definition: Filtration is a process by which undissolved particle are separated from a liquid through a membrane as a result of mechanical force (filtering force). It is done through a porous substance such as a piece of linen or filter paper.
This filtering force is either gravity or hydrostatic pressure – positive or negative.

19. Filtration is the bulk movement of fluid as a result of pressure difference on two side of a barrier, containing pores, through which the fluid can pass. The particles which are smaller than the holes can pass through retaining the larger ones. In the capillaries that are non-fenestrated, small molecules like Na+, Cl- come out of the gaps between endothelial cells but the corpuscles and large colloid molecules are retained.

20. The amount of filtrate formed per unit time will depend upon the pressure difference across the membrane, the surface area available, and the permeability of the membrane and inversely to the viscosity of the fluid concerned.
Filtration occurs across capillaries, everywhere but in the kidney the rate of filtration is enormous because of large pressure gradient and increased permeability. In every site of filtration, it is opposed by the osmotic forces due to non-permeable particles called colloid osmotic pressure or oncotic pressure. The net filtration is determined by their counter balancing effect.

21. Whenever there is a difference of hydrostatic pressure between the two sides of a membrane, filtration will occur.
Examples:
- Absorption from the small intestine.
passage of water, salts, food stuffs etc., from the blood stream to the tissue fluid. - Hydrostatic pressure in the capillaries being higher than in the later.

22. ULTRAFILTRATION
Definition: If we try to pass a solution through a filter the solvent and other small molecules pass through while large molecules stay on the filter. Whether a given substance will pass through depends on the relative size of molecules and that of the pores in the filter. The rate of filtration can be increased by applying pressure.
I t is a kind of filtration through a jelly filter on any ultra filter which serves to separate colloid solution from crystalloids and to separate particles of different size in a colloid mixture due to opposite of osmosis.

23. Example: the hydrostatic pressure in renal glomeruli is higher than that in any other capillaries of the body.
Result: Water and small molecules filter through the glomeruli rapidly while proteins and blood cells do not.
Filtration under pressure is called ultra filtration.

25. Physiological importance: The plasma is placed in a vessel of which one end is a colloidian membrane. Now, if a pressure is exerted on the blood plasma an ultra filtration will be separated. This separation will take out from the solution all the constituents of the plasma except the protein which has been contained in the gross plasma. This occurrence result in due to small pores of the colloidian membrane. The extra cellular fluid (ECF) is also on ultrafirtate into the plasma through the porous capillary membrane.
If the counter pressure is not exerted on the plasma the ECF shall pass back into plasma.

26. DIALYSIS
Definition: The process in which more diffusible materials can be separated from non-diffusible materials is called dialysis.
Water solution of egg albumin and sugar has taken in the upper smaller container whose open bottom is covered with a semi permeable membrane has got selective permeability to water and sugar molecules but not to macromolecules – the egg albumin.
This container is suspended (partially) in the water of a large container. Due to selective Permeability, the sugar molecules will ultimately go into the water leaving behind only albumin and little water. As the albumin is impermeable to this membrane, this will rebound from the membrane during the process of dialysis.

27. Example: Dialysis is a procedure in which the principle of diffusion is applied for the treatment of renal failure. In the patient’s blood, nitrogenous waste products accumulate and electrolytes imbalance may occur due to renal failure. A solution is prepared in which the waste products are absent, electrolyte concentration is appropriately adjusted and nutrients are provided. The solution is separated from the patient’s blood by a dialyzing membrane. The process of diffusion tends to normalize the composition of patient’s blood.

28. Physiological importance:
Whenever the bigger particles are held back and only the smaller particles are allow passing through a membrane – depending upon osmotic pressure (i.e. diffusion), dialysis comes into action.
For instance-
- During absorption from the intestine bigger food particles are held back.
- In the capillary area the bigger albumin, globulin etc particles are not ordinarily allowed to pass into tissue fluid.
-It is to be noted that diffusion, osmosis and dialysis are the manifestation of the same principal (inherent molecular movement) and usually go on simultaneously.

29. SURFACE TENSION
Definition: Surface tension is a manifestation of attracting forces in between atoms or molecules. As elsewhere, so also in a liquid, the molecules attract each other. Within the depth of the liquid each molecule is attracted equally from all directions. Hence the molecules can move freely in all directions. But a molecule at the liquid air surface is attracted only by the molecules within the depth of the liquid and there are relatively few molecules in the gas above the water surface to exert any upward force.

30. Consequently it tends to be pulled inward and its freedom of movements is restricted.
Thus at the surface of a liquid layer is formed in which the molecules are arranged more densely. For the same reason the surface of the liquid tries to pull it together and shrinks in order to occupy the least possible area. This energy with which the surface molecules closely adhere together is called surface tension.

31. Example: Solutes alter surface tension.
Inorganic salts generally rise while organic substance reduce surface tension of water. Of the later – bile salts, protein, phospholipids, oils, soaps, etc are important.

32. Physiological importance:
1.The globular shape of an oil drop in water, of the fat precipitate in milk etc, is due to surface tension.
2.Bile salts reduce the surface tension of the fat converting it into an emulsion in the intestine. This helps in digestion and absorption of the fat.
3.The formation of cell membrane is at least partly due to surface tension of cell cytoplasm.

33. ADSORPTION
Definition: Adsorption is a peculiar form of combination in which substance adheres together on their surface.
Introduction:
It is a sort of union by surface contact. It is not true chemical reaction because no definite quantitative relation is found.
The possible mechanism of adsorption as follows:
1.Surface tension: adsorption is probably a manifestation of surface tension developed from the attraction of dissimilar molecules of two substances.

35. 2.Residual valency: the Chemical nature of the particles and their residual valencies may be such as to make such a loose combination possible.
3.Electrical state: The electrical change of the particle may be of opposite nature. So that they attract each other and thus make a sort of contact combination. Failure of adsorption means that the electrical changes are similar so that they repel each other, during the process of adsorption much kinetic energy is lost and this kinetic energy appears as heat of adsorption.

36. Physiological importance: In Physiology adsorption plays a great role
Physiological importance: In Physiology adsorption plays a great role. Some of them as follow:
1.Enzyme action: Both the enzymes and substrate are colloid in nature is hastened.
2. The combination between toxin and antitoxin, by which they neutralize each other.
3. Various adsorption compounds formed in the body such as lecithin with protein (found in the brain) and such others. The blue compound formed by adding iodine with starch is an adsorption compound.

37. DIFFUSION
Diffuse means spreading. Diffusion is a passive movement of substance in the body proceeds usually.
Diffusion refers to the movement of a chemical substance from an area of a high concentration to an area of low concentration. Molecules of substance are continuously in motion. This motion is least in solid, maximum in gases and intermediate in the liquids.

40. For example:
1.Diffusion process enables the transfer of oxygen from the alveoli to the lungs (high concentration) through the alveolar and capillary walls into the blood (low concentration).
2. Sugar molecules heaped of the bottom of a cup of coffee that has not been steered well, in time become evenly distributed throughout the liquid by diffusion.

41. The process of diffusion is speeded up if the temperature rises and the concentration of diffusing substance is increased.
Diffusion can also occur across the semi permeable membrane. Such as the plasma membrane; in this case, only those molecules able to cross the membrane can diffuse through.
For example, the capillary wall is effectively a semi permeable membrane; although water can travel freely in either direction across it, the large protein in the plasma and red blood cells are too big to cross and so remain in blood.

42. Types of Diffusion 1.Simple Diffusion
a. Simple Diffusion through lipid layer
b. Simple Diffusion through protein layer
2. Facilitated Diffusion

43. Simple diffusion 1.Simple diffusion through the lipid bilayer:
Nonpolar, hydrophobic molecules diffuse freely through the lipid bilayer of the plasma membrane of the cells without the help of membrane transport protein. Such molecules include O2, CO2 and nitrogen gases; fatty acids steroids and fat soluble vitamins (A, E, D & K), small alcohol and ammonia. As we already know two small uncharged polar molecules – water and urea – can diffuse through the lipid bilayer.

44. Diffusion through the lipid bilayer is important in the movement of oxygen and carbon dioxide between blood and body cells and between blood and air within the lungs during breathing. It also is the route for absorption of some nutrients and excretion of some waste of body cells.

46. 2. Simple diffusion through protein layer:
2. Simple diffusion through protein layer: The protein layer of all the cell membrane is permeable to water soluble substance. Many electrolytes diffuse through protein layer.
Protein channels:
The pores are present in the central lipid layer are entirely lined up by the integral protein molecules. These pores are the hypothetical pores and form the channels for the diffusion of water, electrolytes and other substance which can not pass through the lipid layer. As the channels are lined by protein molecules, these are called as protein channels fro water soluble substance.

47. Regulation of the channel:
1.Ungated channel: Some protein channels are continuously open are called as ungated channel.
2.Gated channel: The closed channels are called gated channels. , they open only when required.

48. For example:
1.In voltage gated channel open whenever there is a change in the electrical potential. In the muscles, during the excitation contraction coupling, the action potential spread through the transverse tubules of the sarcotubular system. When the action potential reaches the cisternae, large number of calcium ions diffuses from ciaternae into sarcoplasm.
2.Ligand gated channels open in the presence of some hormonal substance, during the transmission of impulse through the neuromuscular junction, acetylcholine releases from the vesicles. This acetylcholine molecules cause opening of Sodium channel in post synoptic membrane Na ions diffuse into neuromuscular junction from ECF.

49. 3. Facilitated Diffusion
The water soluble substance having large molecules cannot diffuse through the protein channels. Such substances pass through the cell membrane with the help of some carrier proteins. This type of diffusion is called facilitated diffusion.
By this process the substance are transported across the cell membrane faster than the simple diffusion. For example Glucose and Amino Acids.(Because the diameter of the molecule is larger than diameter of channels).

51. Factors affecting rate of diffusion
1. Permeability of cell membrane: Rate of diffusion is directly proportional to the permeability of cell membrane.
2. Temperature: Rate of diffusion is directly proportional to the body temperature.
3. Concentration of electrical gradients: Rate of diffusion is directly proportional to the concentration of gradients.
4. Solubility of the substance: IT is directly proportional to the rate of diffusion.

52. 5. Thickness of cell membrane: Rate of diffusion
5.Thickness of cell membrane: Rate of diffusion is inversely proportional to the thickness of membrane.
6.Size of molecules: Rate of diffusion is inversely proportional to the Size of molecules.
7.Size of ions: Rate of diffusion is inversely proportional to the Size of ions.
8.Charge of the ions: Rate of diffusion is inversely proportional to the Charge of the ions.
9.Surface area: Rate of diffusion is directly proportional to the Surface area.

53. Physiological importance:
1. Admixture of food stuff with digestive juices.
2. Absorption from the intestine.
3. Exchange between plasma and red cells.
4. Exchange of capillary bed; e.g. food stuffs, oxygen etc. pass out fro the blood stream (high concentration) to the tissue fluid (low concentration) and then to the tissue cells (lowest concentration) where they are used up.
5. Admixture of gases in the lungs.

54. OSMOSIS
Definition: The diffusion of water through a semi permeable membrane is called osmosis. It is a passive process.
In other words water moves through a semi permeable (selective) permeable membrane from area of lower solute concentration to an area of high solute concentration.
Osmotic pressure:
The force under which a solvent moves from a solution of lower solute concentration to a solution of higher solute concentration when a selectively permeable membrane separates this solution is called osmotic pressure.

55. Example: Osmotic pressure plays a great role in physiology:
1. Absorption from intestine.
2.Exchange in the capillary bed. Continuous osmotic exchange is going on between blood, tissue fluid, tissue cells and lymph.
3. Regulation of urine formation.
4. Clinical use: injection of isotonic, hypotonic, and hypertonic saline and other solution are given in suitable cases by way of treatment.

56. Tonicity: Tonicity and its effects on red cells
A solution’s tonicity (tonic tension) is a measure of the solution’s ability to change the volume of cell by altering their water content.
The term tonicity is used to compare the osmotic pressure of the solution with the plasma.
Tonicity and its effects on red cells
For example a red blood cell maintains its normal shape and volume is isotonic solution. The concentration of solute that can not cross the plasma membrane on the both side of the membrane.
In hypotonic solution a solution that has a lower concentration of solute then the cytosol inside the RBCs.
In hypertonic solution has a higher concentration of solutes then does the cytosol inside RBCs.

58. Colloid
Definition: Colloid is not a substance but it is a state of substance which depends upon the molecular size. OR
Colloid may be defined as a substance, (e.g. gelatin, or cell cytoplasm), which by reason of the size of its molecules, is slowly diffusible rather than soluble in water (its hydrates being gelatinous is consistence), and is incapable of passing through an animal membrane (a semi permeable membrane). In this substance the solute particles are proportionally larger than the solvent molecules.

59. # When sugar, urea, NaCl, etc be dissolved in water the result is clear permanent true solution.
True solution: It is a homogenous solution which contains small solute particles (molecules or ions) dispersed throughout a solvent.
But if protein, starch, glycogen etc. be placed in water they will make a thick opalescent unstable solution. Graham (1861) called the first type as the crystalloidal solution, because solute particles form crystals and pass through parchment membrane and called the second group – colloidal solution. (Colloidal solution is a heterogeneous solution which contains particles of intermediate size) for the solute particles in this case show reverse properties.

60. Modern idea indicates that the difference between the true solution and the colloidal solution depends on the size of solute molecules in the solvent. If the Size is greater than 200 mµ they remain as a suspension and if less than 1 mµ as true solution. The size of the molecules in colloidal solution varies from mµ.

61. To understand the difference between a crystalloidal and colloidal solution, one should remember that the force which keep the solute particle in solution are roughly as follows:
1. Inherent movement of the solute particles i.e. their diffusibility.
2. Inherent movement of the solvent molecules which continuously dash against the solute particles and thus help to keep them in solution.
3. Electric charge – Positive or Negative – carried by the particles which by constant attraction and repulsion also help uniform solution.
4. Hydration of the solute particles and so on.

62. If the solute particles be very small all these force will be acting to their maximum and the result will be permanent true solution.
Now if the solid particles be gradually made larger and larger their own movement will be gradually reduced and ultimately will be almost nil. The first factor, mentioned above, will therefore be completely out of the field. The other forces, such as the dashing by the solvent molecules, electric charge, etc. will then try to keep the large solute particles. Somehow in solution and will be able to do so up to certain extent. Such a solution will be unstable and heterogeneous – a sort of pseudo solution. This is a colloid.

63. Types of Colloid Dispersed Material Dispersed in Gas
Dispersed in Liquid
Dispersed in Solid
Gas (bubbles)
Not possible
Foams: soda pop; whipped cream; beaten egg whites
Solid foams: plaster; pumice
Liquid (droplets)
Fogs: mist; clouds; hair sprays
Emulsions: milk; blood; mayonnaise
butter; cheese
Solid (grains)
Smokes: dust; industrial smoke
Sols and gels: gelatin; muddy water; starch solution
Solid sol: pearl; colored glass; porcelain; paper

64. Soda pop Butter Pearl
Milk
Pumice Gelatin Cheese

65. Emulsoid and Suspensoid
Colloid fall into two classes – Emulsoid (Emulsion) or lyophilic colloids and suspensoid or lyophobic colloids. In emulsions and solutes have a great affinity for the solvent so they are called lyophilic and when the solvents are water, they are hydrophilic colloids. In suspensoids, there is no affinity between the solute and the solvent. A large quantity of electrolyte is required to precipitate an Emulsoid which is reversible. In case of suspensoid a very small amount is required for such precipitation which is irreversible.

66. Examples of suspensoids are colloidal solution of inorganic salts, metals etc. and those of Emulsoids are polysaccharides, proteins etc. and are of great physiological importance.
Emulsoids being more stable can impart their own stability to suspensoids. In other words when suspension of solid particles are made in a solvent which is already are emulsions the resulting suspensoids will be relatively more stable. This is called the protective action of emulsoids. For instance, blood is a suspension of red cells (7.2µ) in plasma, which in itself is an emulsion of proteins in water. This makes blood relatively stable suspensoid

67. Sol and Gel: 1.Liquid --- Sol 2.Solid. --- Gel.
A colloid may remain in two states,
1.Liquid Sol
2.Solid Gel.
These two states are reversible.
Sol can be transformed into Gel by altering temperature, H ions concentration, and salt concentration.
During this process, a relatively small amount of solute particles runs together and sets into a semisolid mass, entangling in its mashes a fairly large amount of the solvent in the form of isolated droplets.

68. The explanation is as follows:
Being heterogeneous, colloid solution has two distinct component- called phases.
1. The solvent, being continuous is called the continuous phase.
2. The solute being discontinuous or dispensed is known as dispersed phase.
The two phases are interchangeable. When the solute is more or less solid and the solvent is liquid – it becomes a Sol.
If ,on the other hand, the solvent is more or less solid and the solute be liquid it makes a Gel.
For instance, a hot solution of agar-agar is a liquid- a Sol. On cooling, it sets into a semisolid jelly- a Gel. Milk is Sol, Butter is a Gel.

69. Properties of Colloids:
1.Brownian movement: Due to the impact of the solvent molecules, the colloid particles are continuously moving about.
2.Ferday-Tyndall phenomenon: When a beam of light is passed through a colloidal solution ad observed at right angle, the track of light, which is invisible in a true solution, may be visible here as a white line. This is caused by dispersal of light rays by the colloidal particles.
3.Electrical phenomenon:
Colloid particles carry electric charge- may be +ve or –ve.
Isoelectric pH- By addition o salts, weak acids, weak alkaline etc. the hydrogen ion concentration of the medium can be adjusted to an electric pH where the electric charge of the colloid ions will be completely neutralized.

70. Separation of colloids:
4. Coagulation: This also is a property of the colloid. Here the intra molecular change tales place. The coagulum cannot be redissolved.
5. Osmotic pressure: Colloid exerts some osmotic pressure, but the particles being large, it is proportionally much smaller.
6. Imbibition of water: Emulsoid particles can imbibe a good amount of water.
7. Adsorption: This also is a colloid phenomenon.
Separation of colloids:
1.Dialysis.
2.Isoelectric precipitation.
3.Adsorption: By suitable methods, colloids can be isolated by adsorption.
4.Ultrafiltration: By this process the colloidal and crystalloid molecules can be separated from each other.

71. Physiological importance:
1.Cell protoplasm: In every cell exists in a colloid state mostly as Emulsoid.
2.Milk, plasma and lymph: are all emulsoids. Blood is a suspension of red cells in plasma.
3.Interfacial reaction: Being dispersed in the form of minute particles, colloids afford a very large surface area for various reaction to occur, such as adsorption, surface tension, enzyme action etc.
4.Imbibition of water: Since emulsoids readily imbibe water, a good deal of water remains stored in the body in this way.
5.Blood clotting: It is essentially a colloidal process- in which a Sol is converted into a Gel.

72. HYDROTROPHY
Definition: Certain substances have property of making water insoluble substance soluble in water. This is called hydrotrophy or hydrotropic action.
Introduction: How this action is brought about is not definitely known. It is said that the hydrotropic substance form loose compounds with the insoluble substance and thereby makes them soluble and diffusible through membranes. This view is supported by the fact that a qualitative relation often found between them. For instance, when glycocholic acid forms hydrotropic compound with oleic acid they have a molecular ratio of 3:1.

73. Hydrotropic substances of physiological Importance are:
- Bile salts and such other compounds of cholic acid.
- Lecithin, soaps of higher fatty acid, phenylacetic acid, benzoic acid, hippuric etc.
- Hydrotropic substances of unknown nature are also found in the intestinal juice, in the intestinal mucosa in the blood plasma and possible on other tissue and body fluids.
Example: The insoluble substances which are made soluble in this way are:
Fats, certain phospholipids, steroids specially cholesterol, insoluble soaps, uric acid and inorganic salts of Ca, Mg, and possibly of Fe, Cu, Mn etc.

74. Physiological importance:
1.In the bile (in the liver, gall bladder, common bile duct) cholesterol and certain other compound are kept in solution with the help of bile salts.
2.In the intestine the insoluble soaps, sterols, fatty acids, inorganic salts etc. make hydrotropic compounds with bile salts and other hydrotropic substance present in the intestinal juice and mucosa and are thus easily absorbed.
3.In the blood, plasma and other body fluid (and possibly in the tissue) there are number of hydrotropic substance which keep many otherwise insoluble substance in solution, for instance, sterol, Ca and other inorganic salts, uric acid etc.

75. DONNAN EQUILIBRIUM
Definition: The products of the same pair of ions on two side of the permeable membrane became same is called Donnan equilibrium.
Introduction: When a saline solution and distilled water are separated be a permeable membrane final equilibrium will be reached when the concentration of the salt on both side will be same. But if there be any non diffusible ion on one side, a different phenomenon will be seen.

76. Example: Suppose NaP is an ionisable compound of which P is non diffusible. If this compound is kept on one side and NaCl on the other side Na and Cl ions will freely pass out but not P. When the final equilibrium will be reached it will be seen that the product of Na and Cl on one side is equal to the product of the same two ions on the other side.
For example:
Initial state Final state
Na : Na Na : Na
P : Cl Cl : Cl
: P :
In the final stage Na x Cl (left) = Na x Cl (right)

77. In the final state Na of the left side is greater than total Na of the right side and total Cl of the right side are greater than total Cl of the left side.
Similarly, if NaP be on the left side and H2O on the right side, in the final state the reaction on the right side will be alkaline due to Na and OH ions. If a compound Cl-P is on the left and H2O on the right, in the final state the reaction on the right side will be acidic due to H and Cl ions.

78. It is obvious that in the final state there will be a great difference in the nature and quantity of diffusible ions on two sides of the membrane which will lead to a difference of electric potential and chemical reaction on the two sides, since, in our body there are many compounds of NaP type, Donnan equilibrium is of great importance. It explains how difference of electric potential can be established on two sides of a membrane, how stomach can secrete a strongly acidic juice and pancreas can secrete an alkaline juice. The Phenomenon of chloride shift can also be explained from this standpoint.

79. ACID –BASE AND pH
Acid: Acid may be defined as a substance which when dissolved in water produces hydrogen ions (H+) or a electronegative element.
Base: similarly a base or a alkali is a substance which produces hydroxyl ions (OH-) when dissolved in water. That is a electronegative element.
Neutral: During neutralization equal numbers of hydrogen ions of acid and hydroxyl ions of base unite to form water.

80. pH: The pH is another term for hydrogen ion concentration
pH: The pH is another term for hydrogen ion concentration. The negative logarithm of hydrogen ion concentration is taken for calculating the pH.
pH = log 1/ H+
An increase in H+ concentration decrease the pH (acidosis) and a reduction in H+ concentration increases the pH (alkalosis)
In a healthy person the pH of ECF is 7.40.
Hydrogen ion concentration and pH
H+ (nm/l) pH

81. Regulation of Acid Base balance: body is under constant threat of acidosis because of the production of large amount of acid. Generally, two types of acids are produced in the body.
1. Volatile acids: They are derived from CO2. Large quantity of CO2 is produced during the metabolism of carbohydrate and lipids.
2. Non volatile acids: During the metabolism of other nutritive substance such as protein the nonvolatile acids are produced.

82. Three different mechanisms of regulation of acid base balance:
1. Acid base buffer system which binds free H+ ions.
2. Respiratory mechanism which eliminate CO2.
3. Renal mechanism which excrete H+ and conserve the bases.

83. Acid base buffer system
Definition: It is the combination of weak acid and a base which prevents the changes in pH leading to acidosis or alkalosis.
Types of buffer system:
1. Bicarbonate
2. Phosphate
3. Protein

84. Mechanism of action of Bicarbonate buffer system:
Bicarbonate buffer system: This buffer system is present in ECF (Plasma). It consists of the protonated substance carbonic acid (H2CO3) which is a weak acid and the unprotonated substance bicarbonate which is a weak base. Bicarbonate is in the form of salt i.e. Sodium Bicarbonate.
Mechanism of action of Bicarbonate buffer system:
Bicarbonate buffer system prevents the fall of pH in a fluid to which a strong acid like HCl is added.
Normally when HCl is mixed with a fluid the pH of the fluid decreases quickly because the strong HCl dissociates into H+ and Cl-.

85. But if bicarbonate buffer system (NaHCO3) is added to the fluid with the HCl the pH is not altered much. This is because, the H+ ions dissociated from HCl combines with HCO3- of NaHCO3 and form a weak H2CO3. This H2CO3 is in turn dissociated into CO3 and H2O.
HCl + NaHCO H2CO3 + NaCl
H2O + CO2

86. It also prevents the increase in pH in a fluid to which a strong base like NaOH is added.
Normally when a base (NaOH) is added to a fluid, pH increased, it prevented by adding H2CO3 which dissociated into H+ and HCO3-. The hydroxyl group (OH) of NaOH combines with H+ and form H2O and Na+ combines with HCO3- and form NaHCO3. NaHCO3 is a weak base and it prevents the increase in pH by strong NaOH.
NaOH H2CO3 H2O + NaHCO3
(Strong base) (Weak base)

87. As sodium bicarbonate is a very weak base, its association with H+ ions is poor. So the rise in pH of the fluid is very mild.
Importance: Buffer system plays important role in maintaining the pH of body fluid than the other buffer system. It is because the concentration of two components (bicarbonate and CO2).
The concentration of bicarbonates ions is regulated by kidneys and the concentration of CO2 is regulated by the respiratory system.

88. 2. Phosphate buffer system
This system consist of a weak acid, the dihydrogen phosphate (H2PO4 - protonated substance) in the form of NaH2PO4 (sodium dihydrogen phosphate) and the base, Hydrogen phosphate (HPO4 - unprotonated substance) in the form of Disodium hydrogen phosphate (Na2HPO4)
Phosphate buffer system is useful in the ICF (in red blood cells or other cells) as concentration of phosphate is more in ICF than in ECF.

89. Mechanism: When a strong acid like HCl is mixed with a fluid containing a phosphate buffer, Sodium dihydrogen phosphate (NaH2PO4 weak acid) is formed. This permits only a mild change in the pH of the fluid.
HCl + Na2HPO NaH2PO4 + NaCl
(Strong acid) (Weak acid)
If a strong base such as NaOH is added to fluid containing phosphate buffer, a weak base called disodium hydrogen phosphate (Na2HPO4) is formed. This prevents the change in pH.
NaOH + NaH2PO4 NaHPO4 + H2O
(Strong base) (Weak base)

90. Importance: phosphate buffer system is more powerful
Importance: phosphate buffer system is more powerful. Which is close to the pH of the body fluid, 7.4 In addition to ICF, phosphate buffer is useful in tubular fluid of kidney also. It is because more phosphate ions are found in tubular fluid.

91. 3. Protein buffer system:
The protein buffer system is present in the blood both in the plasma and erythrocytes.
Importance: The protein buffer system in plasma is more powerful because of their high concentration in plasma.
Protein buffer in erythrocytes (hemoglobin): Hb has about 6 times more buffering capacity than the plasma proteins.
When a Hb molecules becomes deoxygenated in the capillaries, it easily binds with H+, which are related when CO2 enters the capillaries. Thus Hb prevents CO2 enters more CO2 enters the capillaries.

92. Regulation of acid base balance by respiratory mechanism:
The lungs play an important role in the maintaining of acid base balance by removing CO2. This CO2 combines with water to form carbonic acid. Since carbonic acid is unstable it slits into H+ and HCO3- ions.
CO2 + H2O H2CO H++ HCO3-

93. The entire reaction is reversed in lungs when CO2 diffuse from blood into the alveoli of lungs.
H+ + HCO H2CO3 H2O + CO2
And CO2 is blown off by ventilation.
When metabolic activities increases, more amount of CO2 is produced in the tissues and concentration of H+ increases as seen above. The increased H+ concentration increases pulmonary ventilation by acting on the chemo receptors. Due to hyperventilation the excess of CO2 is removed from the body.

94. Regulation of acid base balance by renal mechanism:
Kidney maintains the acid base balance of the body by the secretion of H+ and by the retention of HCO3- ions.

95. Acidosis: The acidosis is produced by
Disturbances of acid base status: Regulation in pH (increase in H+ concentration) below normal range is called acidosis and
increase in pH (decrease in H+ concentration) above the normal range is called alkalosis.
Acidosis: The acidosis is produced by
In crease in Partial pressure of CO2 in the body fluid particularly in arterial blood.
Decrease in Bicarbonate concentration.
It has Respiratory acidosis and Metabolic acidosis.

96. Respiratory acidosis
Metabolic Acidosis 1. 2. 3. 4. 5. 6.
Air way obstruction due to bronchitis, bronchospasm, emphysema etc.
Lungs diseases like fibrosis, pneumonia etc.
Respiratory center depression by anesthetics, sedatives, tumor etc.
Extra pulmonary thoracic disease like flat chest, kyphosis and scoliosis.
Neural diseases like poliomyelitis, paralysis of respiratory muscles.
Lactic acidosis as in circulatory shock.
Ketoacidosis as in diabetes mellitus.
Uric acidosis as in renal failure
Acid poisoning.
Renal tubular acidosis due to decrease H+ excretion.
Loss of excess HCO3- due to diarrhea and pancreatic or intestinal disease.

97. Alkalosis:
The alkalosis is produced by
-Decrease in partial pressure of CO2 in the arterial blood.
-Increase in bicarbonate concentration.

98. Respiratory alkalosis
Metabolic alkalosis 1. 2. 3.
Hypoxia as in high altitude, severe anemia in pulmonary diseases like edema and embolism.
Increased respiratory due to cerebral disturbances, voluntary hyperventilation and psychological and emotional trauma.
Vomiting and congenital diarrhea.
Endocrine disorder such as Cushing syndrome and Conh’s syndrome.
Diuretic therapy.

99. Bibliography
GERARD J.TORATORA, BRYAN DERRICSON- PRINCIPALS OF ANATOMY & PHYSIOLOGY
ROSS & WILSON- ANATOMY & PHYSIOLOGY
GYATON – MEDICAL PHYSIOLOGY
A.K.DAS – MEDICAL PHYSIOLOGY
BIJLANI – UNDERSTANDING MEDICAL PHYSIOLOGY
C.C.CHATERJEE – HUMAN PHYSIOLOGY
K.SAMBULINGUM & PREMA SAMBULINGUM – ESSENTIAL OF MEDICAL PHYSIOLOGY
Picture downloads from Internet.

100. THANKS