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This document was created by Alex Yartsev ([email protected]); if I have used your data or images and forgot to reference you, please email me. THE VARIOUS BASIC SCIENTIFIC LAWS important to physiology MOLES A mole is 6 x 1023 molecules of something. It’s the standard SI unit for expressing an amount of a substance. A mole of NaCl is the weight of 1 mole of Na and 1 mole of Cl; which weigh 23 and 35.5 grams ( thus, 58.5 grams) A millimole is one thousands of a mole. Thus a millimole of Na+ in solution weighs 23 milligrams. Thus, a litre of normal blood contains 3.22 grams of sodium DALTONS A dalton is a unit of measuring the molecular mass of a substance. It’s the ratio of the mass of the molecule you are measuring to the weight of 1/12th of a carbon atom (which, if its carbon 12 (12C), has the atomic weight of around 12.) Measuring large molecules requires kilodaltons. A dalton is a dimensionless ratio. Thus, for some reason it is incorrect to say that a protein weighs 64 kDa. You say, “this protein’s molecular mass is 64 kDa”. EQUIVALENTS These are electrical equivalents; 1 equivalent (eq) of a substance is one mole of the substance divided by its valence. Thus, lets take ionized sodium. One mole of it will dissociate into 1 eq because it has the valence of 1. Thus, 1eq of sodium weighs 23 grams. Calcium, however, has a valence of 2 ( Ca++) and so 1 eq of calcium only weighs 20 grams (whereas a mole of calcium weighs 40 grams). TO CONFUSE THINGS FURTHER: There are also chemical equivalents, which are totally different to electrical equivalents. A gram equivalent is the weight of a substance which is chemically equivalent to 8 grams of oxygen. It’s the mass of a given substance that will supply or react with 1 mole of hydrogen ions in an acid base equation, for example. It determines the normality (N) of a solution; for example a 1N solution of hydrochloric acid will have 1 gram equivalent of hydrogen and 1 gram equivalent of chloride ions (which actually weighs 35.5 grams). This is of interest to chemists, but rarely to doctors. pH AND BUFFERING pH is the negative (inverse) base 10 logarithm of the H+ concentration in water. Acids donate more H+ , thus increase the H+ concentration, and thus DECREASE the pH (see, its inverse) At 25o , the pH of pure water is 7.0 (i.e. the H+ concentration is 10-7 moles per litre) for every pH unit below 7, the H+ concentration is increased tenfold stomach juice is pH 1.5 – 2 pancreatic juice is around 8.0 normal plasma has to stay slightly alkaline, around pH 7.35 – 7.45. Otherwise enzyme activity goes to hell. This is because the enzymes are made of amino acids, and keep their shape only because the amino acids interact – ionized ends of amino acids attract other ionized ends and thus the protein bends and twists. Acidic amino acids have carboxyl functional groups, and basic amino acids have amine functional groups in their side chains. Changes in pH cause the amino acids to become relatively more or less acidic; they cause them to be more or less ionized. This causes the enzyme protein to lose its shape; and this is bad because it is the distinct shape of the enzyme which makes it specific to its substrate. The substrate’s charge properties will also be affected by the pH, and so nothing is going to work unless the pH is just right BUFFERING - a BUFFER is something that can absorb or release H+ ions to keep the pH of a solution constant. There are numerous buffers in body fluids, but they all buffer the same H+ concentration (this is called the Acid Dissociation Constant; the larger the the ISOHYDRIC PRINCIPLE) value, the stronger the acid i.e. the more of the acid Most acids in the body are weak acids (i.e. they molecules have donated their protons. don’t completely dissociate in solution; some acid remains floating around- like H2CO3 which prefers to The pKa is the pH at which concentration of ionized and remain as H2CO3 and not dissociate into H+ and non-ionised forms is equal. HCO3 The buffering capacity of a weak acid is best when the pKa of that acid is equal to the pH of the solution. Carbonic acid (H2CO3) is a weak acid – pKa around 6.36 – and thus only partly dissolved: If H+ is added, the solution becomes more acidic and the carbonic acid absorbs some H+ (equation shifts left) to maintain equilibrium. If OH- is added, the extra H+ in the carbonic acid solution combines with the OH- and forms H2O, so the acidity drops -so to maintain equilibrium, the carbonic acid dissociates some more, releasing H+ ions (equation shifts to the right) pKa: - - REFERENCES: Ganong’s review of medical physiology, 23rd ed: Section 1; as well as Guyton and Hall (11th edition), and, sadly, Wikipedia. This document was created by Alex Yartsev ([email protected]); if I have used your data or images and forgot to reference you, please email me. DIFFUSION If asked in a viva exam situation, one would be forced to say that DIFFUSION IS A PROCESS BY WHICH A GAS OR SUBSTANCE IN A SOLUTION EXPANDS, BECAUSE OF THE MOTION OF ITS PARTICLES, TO FILL ALL THE AVAILABLE VOLUME. How fast will it do this? - the higher its concentration, the faster it will diffuse the farther it has to travel, the slower it will diffuse (proportionally to the square of the distance) the wider an area it is diffusing across, (the wider the membrane) the faster it will diffuse THIS IS FICK’S LAW OF DIFFUSION: (high concentration minus low concentration) x Area x Permability coefficient Thickness OSMOSIS - - if you dissolve something in water, the concentration of water in that solution is LOWER than in pure water. Thus, if given half a chance, pure water will attempt to diffuse into this solution, from a higher concentration of pure water into the area of lower concentration (where water is impure and something is dissolved) Thus, in a viva, one is compelled to spout that OSMOSIS IS THE DIFFUSION OF SOLVENT MOLECULES INTO A REGION WHERE THERE IS A HIGHER CONCENTRATION OF SOLUTE. This can be prevented- if you apply pressure to the impure solution, pure solvent will be discouraged from going there. THE PRESSURE REQUIRED TO PREVENT SOLVENT MIGRATION IS THE OSMOTIC PRESSURE Osmotic pressure depends on the number of particles of solute in solution, rather than their type. It doesn’t matter what is dissolved. Like the partial pressure of a gas, it is a constant, modified only by temperature and volume. In an ideal situation, at constant temperature, the osmotic pressure is proportionate to the number of particles per unit volume of solution. For this reason, the concentration of osmotically active particles is expressed as OSMOLES. o one osmole (Osm) is the gram-molecular weight of a substance divided by the number of particles it releases in solution o for non-ionising substances like glucose, it is the number of molecules that matters o for ionizing sustances like NaCl, each ion is a particle; so 1 mole of NaCl forms 2 osmoles o of course, in body fluids, ions interact, and so the actual number is slightly less than 2. The freezing point of normal human plasma is -0.54 Co o o o The osmolal concentration of a substance is measured by the degree to which it depresses the freezing point of the solution: 1 mol of an ideal solution depresses the freezing point by 1.86 Co The OSMOLARITY is the number of osmoles per litre of solution The OSMOLALITY is the number of osmoles per kilogram of solvent. Thus, osmolarity is affected by temperature and volume of the solution, while osmolality is not. Seeing as 1 litre of water weighs 1kg, osmolality can also be expressed as osmoles per litre when discussing substances dissolved in body fluids. TONICITY The normal osmolal concentration of plasma is 290 mOsm/L. One might expect it to be around 300, but some of the ions interact, forming complexes and reducing the total number of dissolved particles. The osmotic pressure against pure water is 7.3 atmospheres. SOLUTIONS WHICH ARE AROUND 300 mOsm ARE SAID TO BE ISOTONIC. All but 20 mOsm of plasma are contributed by Na+ and Cl-, with a little help from HCO3Proteins contribute 2 mOsm; urea contributes 5 mOsm and glucose contributes 5mOsm REFERENCES: Ganong’s review of medical physiology, 23rd ed: Section 1; as well as Guyton and Hall (11th edition), and, sadly, Wikipedia. This document was created by Alex Yartsev ([email protected]); if I have used your data or images and forgot to reference you, please email me. NON-IONIC DIFFUSION This applies to substances which are lipid-soluble in their undissociated form; and are thus able to dissolve through the lipid cell membrane and get to the other side – where they dissociate. DONNAN EFFECT and the Gibbs-Donnan equation Cells are full of ions which occasionally aren’t able to diffuse out of the cells. However, these ions are still osmotically active, and have a charge. Donnan and Gibbs state that in the presence of a non-diffusable ion, the diffusable ones will distribute themselves so that their concentration ratios will be equal; i.e. (sum of concentrations of diffusable ions inside) = (sum of concentrations of diffusable ions outside) Cell BUT: there end up being more osmotically active solutes inside the cell. Thus, water is constantly attracted into the cell by osmosis. The cell needs to constantly pump ions out of Proteins: constant source of negative itself to reduce the number of osmotically active change and osmotic activity particles inside itself. Cl- 9 mmol -70mV Cl- 125 mmol K+ 150 mmol Na+ 15mmol -90mV K+ 5.5 mmol +60mV Na+ 150mmol IF IT WERE NOT FOR Na+/K+ ATPase, ALL OF OUR CELLS WOULD SWELL UP AND EXPLODE. Because of the constant pumping, the concentration of ions inside vs. the concentration outside is unequal; and because the ions are charged, AN ELECTRICAL POTENTIAL DIFFERENCE EXISTS BETWEEN THE INSIDE AND THE OUTSIDE FORCES ACTING ON IONS Chloride ions are present in a higher concentration outside the cell; they would diffuse inside if they could, but they are REPELLED by a net negative charge inside the cell (provided by the proteins in there). The diffusion force sucking it in is balanced by the repulsion force pushing it out. The membrane potential at which this equilibrium exists is the equilibrium potential. The equilibrium potential for Cl- is -70millivolts. K+ is the reverse: it is being attracted inside the cell by the negative charge, but sucked back out of the cell by the concentration gradient. For Na+, the chemical gradient promotes suction into the cell (where there is less sodium). The electrical gradient is also sucking it into the cell (because the charge is nicely negative in there). One might expect the cell to fill up with an absurd amount of sodium. Thankfully, owing to the constant thankless efforts of the Na+/K+ ATPase, the intracellular concentration of sodium is kept at a steady low 15mmol. MEMBRANE POTENTIAL At equilibrium, there is a slightly increased concentration of anions on the inside. This condition is maintained by the the Na+/K+ ATPase. The difference in concentration is miniscule, but it creates a potential difference across the membrane – about 70 mV in total. The condition of this electrical difference is present only around the membrane (everywhere else the charges are mixed well enough). REFERENCES: Ganong’s review of medical physiology, 23rd ed: Section 1; as well as Guyton and Hall (11th edition), and, sadly, Wikipedia.