DIFFUSION I Thomas Graham (1805 1869) Grahams law The diffusion of a spontaneous intermixture of two gases in contact is affected

d by an interchange of position of infinitely minute volumes, being, in the case of each gas, inversely proportional to the square root of the density of the gas.
Air Diffusion Test gas

Grahams experiment He noted the increase and decrease in volume with different test gases

Adolf Fick (1799 1869) Physician and physiologist. Suggested that the spreading of warmth in a conductor and the diffusion of the dissolved material were both left to the influence of molecular forces basic to same law. He accordingly applied the heat conducting law of Joseph Fourier (1768 1830) to diffusion which states that the flux of heat is directly proportional to the temperature gradient that causes it. or

J Z = D

dC . dz

Mathematical description of diffusion processes may be macroscopic (via entropy, non-equilibrium thermodynamics) or microscopic (via kinetic theory of gases and collisions of molecules).
Kinetic Theory of Gases

Avogadros number = 6.023 10 23 . 1 mole of gas occupies 22.4 l. 6.023 10 23 3 In 1 cm of gas there are = 2.689 1019 molecules. 3 22.4 10
Now the molecular separation, or average distance, between molecules 1 = 3.34 10 7 cm . = 3 2.689 1019

A separation of 3.34 10 7 cm would 1 = 2.994 10 6 give 7 3.34 10 molecules along each edge of the cube.

(2.994 10 )

6 3

= 2.68 1019 molecules.

Average molecular diameter for a simple gas 2 5 10 8 cm average separation is about 10 the diameter. At ordinary temperature and pressure, average velocity is ca. 104 cm/s. Many collisions actual diffusion velocities much slower ca. 1 cm/s.

Simple Kinetic Theory of Gases

Assumes molecules rigid, non-interacting spheres, all moving at the same speed, which undergo elastic collisions. From this, it can be calculated that each molecule will undergo 2nd 2 u collisions per second.
No.of molecules per unit volume Speed of molecule Diameter of molecule

This gives a mean free path, , of

u 1 = . 2nd 2 u 2nd 2

Furthermore, with this simple model of diffusion, it is possible to calculate the diffusion coefficient 1 D = u . 3 Thus, i) Obtain diffusion constant in terms of microscopic behaviour of system. ii) Note diffusion constant increases when the velocity increases and/or the mean free path increases.

Rigorous Kinetic Theory of Gases

Refinement of simple theory. i) Interactions between molecules according to certain force field: Lennard-Jones Potential. ii) Velocities distributed according to Maxwells velocity distribution function. Mathematics complicated and known as Chapman-Enskog theory.

Molecules attract r>rm Molecules repel r<rm rm r

(r) 0 -

Collision diameter

Binary and Multicomponent Diffusion

Binary diffusion refers to the situation when there are only two species present. Multicomponent diffusion refers to the situation when there are more than two species present. Ficks Law applies to binary diffusion, but not necessarily to multicomponent diffusion. Arnold and Toors experiment:
50% CH4 50% Ar 50% H2 50% Ar In starting position, no gradient for Ar and therefore according to Ficks Law this should not move.

70 Ar 60 (%) 50

In practice, H2 diffuses into the methane section quicker than the methane diffuses into the H2 section which concentrates the Ar on the H2 side. 30 60

Time (min)

For most of our physiological modelling, we assume we can apply the results for binary diffusion, although strictly speaking physiological systems are normally multicomponent.

Ficks (first) Law of Diffusion

When diffusion occurs in one direction, z, only can be written as:

dC Jz = D dz

D Jz

When diffusion occurs in more than one direction, Ficks law has to be written in vector form: J = -D C C means grad C =

dC dz

C C C i+ j+ k x y z

in cartesian co-ordinates Underline means it is a vector books use bold letters for vectors

(Essentially this is just three equations rolled into one).

Ficks Second Law of Diffusion

Ficks first law does not contain time as a variable. Thus, when unsteady, or time varying, concentrations occur, Ficks first law cannot be used alone, and Ficks second law must be used, which is: C 2C =D 2 t z or C = D 2 C t
2

(one dimensional diffusion)

(multi-dimensional diffusion N.B. still a scalar equation)

2C 2C 2C C= 2 + 2 + 2 x y z
Cartesian co-ordinates. 5

Derivation of Ficks Second Law of Diffusion

One-dimensional diffusion. Consider a box, dimensions dx, dy, dz, with a concentration gradient in the z direction:

dy Jz

Jz+dz

dx

dz

Flux due to diffusion into the box = Jz per unit area. Flux due to diffusion out of the box J z+dz per unit area. Amount of substance in the box = CdV, where: dV = volume of box (=dxdydz) C = concentration of substance in the box.

Rate of change of amount of substance in box =

(CdV ) t

This is equal to difference in diffusional fluxes across boundaries

(CdV) = J z dxdy J z+dz dxdy t Dividing through by volume (which is constant) we obtain: C J z J z+dz J z in the limit. = = t dz z
Combining this equation with the first derivative of Ficks law and eliminating

J z yields: z

Differentiating Ficks first law with respect to z yields

C 2C =D 2 t z

J z 2C = D 2 z z

Applying the Diffusion Equations to Physiological Problems Kroghs Cylinder

Krogh had been studying the distribution of capillaries in various vascular beds. His basic problem was, if I know a partial pressure/concentration of oxygen in the blood perfusing the capillary and if I know the oxygen consumption of the tissue surrounding the capillary, can I calculate the way the partial pressure of oxygen drops off as one moves further away from the capillary.
Analytic approach

Consider a capillary of radius rc, surrounded by a cylinder of tissue radius, rt.

rc rt

Now consider a small cylindrical piece of tissue taken from this tissue. The thickness of this piece of tissue is dr in the radial direction, and dz in the longitudinal direction. The internal radius is r, and external radius is r+dr. From this, the volume of the tissue piece, dV = (r + dr)2dz r2dz = (2rdr + dr2)dz the internal surface area = 2 rdz the external surface area = 2 (r + dr)dz the end-on surface area (one end only) = (r + dr)2 - r2 = 2rdr + dr2

dz

r dr

Kroghs Cylinder continued

Let the flux per unit area into the tissue from inside = Jr Let the flux per unit area out of the tissue from outside = Jr+dr Let the flux per unit area into the tissue end-on = Jz Let the flux per unit area out of the tissue end-on = Jz+dz
Jz+dz

Let the metabolic consumption per unit volume of the tissue be & M. Let the concentration within the tissue segment be C.

Jr+dr Jz Jr

We may write down the rate of change of amount of substance as (CdV ) . t We may also write down the rate change of amount of substance by writing down the sum of all fluxes into and out of the tissue segment, and including the oxygen consumption:
(CdV ) = J r 2rdz J r +dr 2(r + dr )dz +J z (2rdr + dr 2 ) t & J z +dz (2rdr + dr 2 ) MdV. Dividing through by volume dV (which also equals (2rdr+dr2)dz) gives: C 2rdz(J r J r +dr ) 2drdzJ r +dr (2rdr + dr 2 )(J z J z+dz ) & = + M t (2rdr + dr 2 )dz (2rdr + dr 2 )dz Let dr 0, dz 0, (and dr2 becomes negligible) J J z+dz & C J r J r +dr 1 = J r +dr + z M dr r t dz J 1 J C & = r J r +dr z M. t r r z

Kroghs Cylinder continued

J r C 2C = D r 2 Ficks first law gives J r = D r r r r

Also J z = D z

J C 2C z = D z 2 z z z J r J and z in our equation gives: r z

Mathematicians may note that this is Ficks second law in cylindrical polar coordinates, with rotational movement neglected and metabolism added in.

Substituting these expressions Jr,

2C 1 C C 2C & + Dz 2 M = Dr 2 + r t r r z

This is a partial differential equation. Solving it involves getting an explicit expression for C, in terms of r and z, and getting rid of all differential terms. To do this, an initial set of conditions (boundary conditions) is required. The solution published by Krogh was under a particularly simple set of conditions. C 1. Assumed the concentrations were steady state = 0. t 2C 2. Neglected axial movement Dz 2 = 0. z 3. Conditions were C=co when r=rc (i.e. the concentration is co in the capillary). C = 0 when r=rt (i.e. no diffusion gradient at edge of tissue r cylinder + hence no oxygen diffusion beyond tissue cylinder). The equation becomes

d 2 C 1 dC & M 0 = Dr 2 + dr r dr or

& d 2 C 1 dC M + = dr 2 r dr D r

Notice that the s have become straight ds because C is a function of only one variable once z is neglected. 9

Kroghs Cylinder continued

The equation

d 2C dr 2

& 1 dC M = can be solved by a method known at the r dr D r integrating factor method.

1 First multiply through by exp dr = r (the integrating factor). r Notice the left-hand side is now & d 2 C dC Mr d dC = r 2 + r dr D r dr dr dr Integrating both sides with respect to r yields: & dC M 2 Where K1 is a constant which can be found r + K1 r = dr 2D r from the initial condition dC / dr = 0 when r = r t. Substituting for dC / dr and r yields: & 2 & 2 Mrt Mrt 0= + K1 or K1 = 2D 2D r r Thus: & 2 & 2 Mr rdC Mr t = dr 2D 2D r r & 2 & Mrt 1 dC Mr = dr 2D 2D r r r Integrating both sides again with respect to r yields: & & 2 Mr 2 Mr t ln r + K where K2 is a constant which can be found C= 2 4D 2D from the initial condition C=co at r=rc. r r Substituting for C and r yields: & & 2 Mr 2 Mrc t ln r + K co = c 2 4D 2D r r & & 2 Mr 2 Mrc t ln r K 2 = co + c 4D 2D r r & & & 2 Mr 2 & 2 Mr 2 Mrc Mr t ln r t ln r + c + Thus: C = c o 4D 2D 4D 2D r r r r How did Krogh do it? In his paper in 1919, he states The 2 2 r2 & mathematician M.K. Erlang r M r rc t ln C = co + has shown me the kindness 2 rc D 4 r to work out such a formula, which runs .
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Kroghs Cylinder Continued Numerical Approach

Analytic approach taken above is quite complicated even for the simplest problem. Once we allow axial diffusion back into the differential equation and allow concentrations to vary with time, or allow slightly more complex geometries, obtaining analytic solutions becomes much harder or else impossible. Fortunately computers now offer alternative numerical methods which can be applied much more widely. Assume whole Krogh cylinder made up of short concentric cylinders, so that each one is like our previous tissue segment:

n lengthwise elements, index, j.

m concentric elements, index, i.

For any of these elements, say the ith concentric, jth lengthwise, element, we may use the equations derived for the change in concentration with time from the small element considered in the analytic approach. Thus,

C ij t +

J r ij 2rijdz ij J ( r +dr ) ij 2(r + dr ) ij dz ij dVij

2 2

J z ij (2rijdrij + drij ) J ( z+dz )ij (2rijdrij + drij ) dVij

& M

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Kroghs Cylinder Continued

Instead of letting dz 0 and dr 0, however, we keep dz and dr at their small, finite, chosen values. The unknowns remaining on the right-hand side of the equation are thus J(r)ij, J(r+dr)ij, J(z)ij and J(z+dz)ij. Each of these we may calculate using Ficks law and the starting concentrations in the current and neighbouring compartments. i.e. J r ij
J ( r +dr ) J z ij
ij ij

= -Dr (Cij Ci-1,j)/drij

= -Dr (Ci+1,j Cij)/drij = -Dr (Cij Ci,j-1)/dzij

J ( z+dz ) = -Dr (Ci,j+1 Ci,j)/dzij These values for J(r)ij, J(r+dr)ij, J(z)ij and J(z+dz)ij may be substituted into the C ij right-hand side of the equation above to obtain a value for . Values t C for may be calculated in a similar way for all other components. Once t all these values are known, we can calculate the change in concentration following a small increment in time, T. Once elapsed, the concentration in ij component is given by: Cij, t+ t = Cij, t +

C ij,t t

The whole process may then be repeated with these new concentrations. Method known as the finite difference method. Very long-winded. But method mathematically simple and very general. Method becomes more accurate with more and smaller components and shorter time intervals.

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REFERENCES

Chang, H.K. (1987). Diffusion of gases. In: handbook of Physiology: The Respiratory Sustem. Section 3, volume IV, Gas Exchange. Farhi, L.E. and Tenney, S.M. (eds). American Physiological Society, Bethesda, pp.33-50. Krogh, A. (1919). The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. Journal of Physiology, 52: 409-415. Roca, J., Hogan, M.C., Story, D., Bebout, D.E., Haab, P., Gonzalez, R., Veno, O. and Wagner, P.D. (1989). Evidence for tissue diffusion & limitation of VO 2 max in normal humans. Journal of Applied Physiology, 67: 291-299.

Experimental study of diffusion limitation in muscles of humans

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