BMEn 3101 Spring 2012

Biomedical Transport Processes

HW 2
assigned Fri Jan 27, due Fri Feb 3

Please solve all problems on separate pieces of paper.
Please include the names, recitation sections, and student ID numbers of all contributing students.
All contributing students must sign the first page.
Unless otherwise indicated, the total value for a HW problem is the same in all assignments

1. Compartmental Modeling of the Body. The body can be modeled as a network of compartments
connected by blood vessels. The simplest compartment is a well-mixed blood compartment between two
organs. The blood flows in and out of the compartment of volume V with volumetric flow rate Q
<vol/t>. The inlet blood concentration of a drug, d, of interest is C
di
and the outlet concentration is C
do
.
Note that the well-mixed assumption means the drug concentration in the compartment is everywhere the
same and equal to C
do
. An illustration follows.
Q, C
di
Q, C
do




i) In a test using a non-metabolizable drug analog, at time t=0, C
di
is decreased from value C
d
*
(where is
was maintained for a long time) to 0 and held at 0. C
do
(t) is measured. Q and V are known,
a) Derive the equation for C
do
as a function of time, i.e. C
do
(t).
b) Sketch C
do
(t).
c) What is the half-time that describes the change in C
do
(t)?
ii) In a subsequent test, a drug that is potentially metabolizable used in the same test.
a) How would you know if it is metabolized?
b) If it is metabolized, how would you know if it follows a 1
st
-order rate of metabolism?
c) If it follows a 1
st
-order rate, how can you determine the rate constant k
1
from the t
1/2
of C
do
(t)?
d) Assuming the metabolism is enzyme-mediated and described by Michaelis-Menton kinetics, how
would you know the enzyme is operating in a 1
st
-order regime rather than a 0
th
order regime?
e) If it is operating neither in a 1
st
-order regime or a 0
th
order regime, how does that affect how you
would determine the t
1/2
?

2. Oxygen transport in a pulmonary capillary. Assume the average blood velocity is 0.07 cm/s, the
capillary length is 300 m and the capillary diameter is 3 m. The diffusivity of oxygen in blood is 2
x10
-5
cm
2
/s. At the outlet of the capillary, the hemoglobin is essentially fully saturated corresponding to
an oxygen concentration in blood of 150 M, and the concentration gradient is 5250 M/cm.

a) What is the convective flux of oxygen at the capillary outlet?
b) What is the convective flow of oxygen at the capillary outlet?
c) What is the diffusive flux of oxygen at the capillary outlet?
d) What is the diffusive flow of oxygen at the capillary outlet?
e) What is the total flow of oxygen at the capillary outlet?
f) Based on the Peclet number, what is the dominant mode of transport for axial transport? Does this
agree with your answers above?
g) What is the average time it takes for oxygen to be transported the length of the capillary?
h) What is the average time it takes for oxygen to be transported from the luminal surface of the capillary
to the center of the capillary?
V


i) Based on these calculations, do you consider the pulmonary capillary to be well designed for
oxygenation? Explain.



3. Diffusive and convective fluxes during pressure-driven membrane transport. The following
equation describes the steady-state concentration profile from z = 0 to L across a membrane of thickness
L for a species i being transported due to its diffusion and its convection with the flowing solvent. The
convection is associated with a solvent velocity v
z
driven by a pressure difference across the membrane.
C
0
and C
L
denote C
i
at z = 0 and L (the surfaces of the membrane), respectively.


( )
( ) ( )
( )
|
|
.
|

\
|

Pe
Pe
C
L
z
i
exp 1
exp 1
C C - C =
L o o


i) Plot the dimensionless concentration (C
i
(z)-C
L
)/( C
0
-C
L
) vs. dimensionless position z/L for Pe = 0, 0.5,
1, 5, 50
ii) Derive an equation for the diffusive flux of i from the above expression
iii) Derive an equation for the convective flux of i from the above expression
iv) Plot the fluxes from (i) and (ii) at z= 0 as a function of Pe for Pe = 0.1 10, and the values DC
o
/L = 3
and DC
L
/L =1, which have units <moles/sec>.
v) Explain why these plots makes sense.

4. Protein diffusivity estimation.

A proteins diffusion coefficient in ddH
2
O is measured to be 1.2x10
-7
cm
2
/s. When it is measured in
PBS, the value is 0.1x10
-7
cm
2
/s.

i) One hypothesis is the protein denatures from its globular (spherical) form to an extended
cylindrical rod-like form because electrostatic bonds are being screened by the salt in PBS.
What are the dimensions of the rod if that is the case? State any assumptions.
ii) What are possible confounding factors excluded by this hypothesis?

5. Single particle tracking of G-actin in cells. G-actin is labeled with a fluorescent label (fluorescein)
and its 3-D motion in a living cell is tracked, yielding the following data based on the measured
displacement d:
t <s> <d
2
> <m
2
>
720 4.32
1440 8.64

a) What is the estimated G-actin diffusivity?
b) How long would it take a G-actin molecule to diffuse on average from the center to the plasma
membrane of the cell, modeled as a sphere of 100m?
c) The actual time it takes for G-actin to be transported through the cell is far less than what is
estimated by diffusion. Give at least one reason why that is.