664  Chapter 10  |  Systems of Linear Differential Equations

A system of differential equations describing the amount of measured in mg. (See also Exercise 16 in the Review Sec-
antibody in each compartment is tion of this chapter.)
(a) Use a change of variables to obtain a homogene-
dx1
− G 1 k21 x2 2 k12 x1 2 kx1 ous system of differential equations describing the
dt situation.
dx2 (b) What is the general solution to the differential equa-
− k12 x1 2 k21 x2 tions in part (a)?
dt
(c) What is the general solution obtained in part (b) in
where G is the rate of generation of antibodies, k is the rate terms of the original variables x1 and x2?
at which the drug treatment removes antibody from the Source: Adapted from K. Suzuki et al., “Anti-DNA Antibody Kinetics Fol-
bloodstream, and kij is the rate of flow of antibody from lowing Selective Removal by Adsorption using Dextran Sulphate Cellulose
compartment i to j. The variables x1 and x2 are the amounts Columns in Patients with Systemic Lupus Erythematosus,” Journal of Clini-
of antibody in the bloodstream and organs, respectively, cal Apheresis 11 (1996): 16–22.

■ Project  Pharmacokinetics of Antimicrobial Dosing

The term pharmacokinetics refers to the change in drug concentration within the body
during treatment. Figure 1 gives an example of the serum concentration (in mgymL) of
the antimicrobial drug panobacumab in a patient during three consecutive infusions. The
concentration increases nearly instantaneously during an infusion and it then declines
through metabolism until the next infusion occurs.
Serum panobacumab

40
(g/mL)

30

20

10

0 200 400 600 t

Figure 1 (hours)

Mathematical models are routinely used to determine the drug dose and time between
infusions required to achieve a desired peak serum level. A common model is a two-
compartment mixing model. One compartment is the blood serum, and the other is the
remainder of the body. The drug is infused directly into the serum and is metabolized
from there. It also flows back and forth between the serum and the rest of the body (see
Figure 2). Following the approach used in Exercises 7.4.45–48, we can obtain the fol-
Serum lowing system of linear differential equations:

dx1 k21 k12 k10

− x2 2 x1 2 x1
dt V2 V1 V1
(1)
dx2 k12 k21
Figure 2
− x1 2 x2
dt V1 V2

where x1 and x2 are the amounts in the serum and body, respectively (in mgymL), kij are
rate constants, and Vi is the effective volume of compartment i (in mL). The initial condi-
tion for the model is x1 s0d − d and x2 s0d − 0, where d is the drug dose that is infused.
Models like (1) often provide an excellent fit to data, as shown in Figure 3.

Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
 Section 10.4  |  Systems of Nonlinear Differential Equations   665

Serum panobacumab
40

(g/mL)
30

20
Model prediction
10

0 200 400 600 t

Figure 3 (hours)

1. 
Explain the terms in Equations 1 and the assumptions that underlie them.
As an example, suppose that k10 yV1 − 2, k12 yV1 − 1, and k21 yV2 − 2. Find the
2. 
general solution to Equations 1.
3. 
Show that the general solution we obtained in Problem 2 can be written as
wstd ? c, where
u u
e 1t 0 c1
wstd − £ v1 v2 § c d      c − c d
0 e 2t c2
u u

with i and vi being the eigenvalues and eigenvectors of the coefficient matrix.
4. 
Using our result from Problem 3, show that the solution to the initial-value
problem can be written as xstd − Bstdx0 , where Bstd − wstdw 21 s0d and x0 is the
vector of initial values (that is, its components are d and 0).
x¡ 5.  I f drug infusions continue repeatedly at fixed intervals, the level of drug in the
10 serum eventually displays periodic behavior, as shown in Figure 4. Suppose
 is the time between infusions. If the amount of drug in the serum and body
6 immediately after an infusion is denoted by the vector y, then from Problem 4
 the amounts immediately before the next infusion are Bsdy. Immediately after
2
the next infusion the amounts are Bsdy 1 x0. (Why?) Further, if the amounts
0 10 20 30 40 t in each compartment are displaying periodic behavior, then immediately after
infusion they must be at the same level as they were immediately after the previ-
Figure 4 ous infusion; that is, Bsdy 1 x0 − y. Use this last equation to find the function
relating peak serum level to the dose and infusion constants d and .

10.4 Systems of Nonlinear Differential Equations

Systems of linear differential equations form the basis for analyzing the stability proper-
ties of equilibria of systems of nonlinear differential equations. The approach is illus-
trated in this section. As with the rest of this chapter, we focus on two-dimensional
systems.

■ Linear and Nonlinear Differential Equations

In the preceding sections we studied autonomous systems of differential equations hav-
ing the form
dx1 dx2
(1) − a11 x1 1 a12 x2 1 t1    − a21 x1 1 a22 x2 1 t2
dt dt

Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.

change of variables ystd − e kt T std. Solve the differential
equation using this technique.
45–48  Mixing problems  Mixing problems arise in many
areas of science. They typically involve a tank of fixed capac-
ity filled with a well-mixed solution of some substance (such as
salt). Solution of a given concentration enters the tank at a fixed
rate and the mixture, thoroughly stirred, leaves at a fixed rate.
We will focus on examples where the inflow and outflow rates
are the same, so that the volume of solution in the tank remains
constant. If ystd denotes the amount of substance in the tank at
time t, then y9 − srate ind 2 srate outd.
r . b
(L/min) (amount/L)
ry
yª=rb _ V
Volume=V
45. A tank contains 1000 L of brine with 15 kg of dissolved
salt. Pure water enters the tank at a rate of 10 Lymin. The
solution is kept thoroughly mixed and drains from the tank
at the same rate. How much salt is in the tank (a) after
t minutes? (b) After 20 minutes?
46. Dialysis treatment  removes urea and other waste products
from a patient’s blood by diverting some of the blood flow
externally through a machine called a dialyzer. Suppose that
a patient’s blood volume is V mL and blood is diverted
through the dialyzer at a rate of K mLymin. At the start of
treatment the patient’s blood contains cs0d − c0 mgymL of
urea.
(a) Formulate the process of dialysis as an initial-value
problem.
(b) What is the concentration of urea in the patient’s blood
after t minutes of dialysis? Compare your answer to
Exercise 1.5.53.
47. A vat with 500 gallons of beer contains 4% alcohol (by
volume). Beer with 6% alcohol is pumped into the vat at a
rate of 5 galymin and the mixture is pumped out at the same
rate. What is the percentage of alcohol after an hour?
48. Lung ventilation  A patient is placed on a ventilator to
remove CO 2 from the lungs. Suppose that the rate of ven-
tilation is 100 mLys, with the percentage of CO 2 (by
volume) in the inflow being zero. Suppose also that air is
absorbed by the lungs at a rate of 10 mLys and gas con-
sisting of 100% CO 2 is excreted back into the lungs at the
same rate. The volume of a typical pair of lungs is around
4000 mL. If the patient starts ventilation with 20% of lung
volume being CO 2, what volume of CO 2 will remain in the
lungs after 30 minutes?
Copyright 2015 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s).
Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.
Section 7.4 | Separable Equations   457
49. When a raindrop falls, it increases in size and so its mass at
time t is a function of t, namely, mstd. The rate of growth of
the mass is kmstd for some positive constant k. When we
apply New­ton’s Law of Motion to the raindrop, we get
smvd9 − tm, where v is the velocity of the raindrop
(directed downward) and t is the acceleration due to gravity.
The terminal velocity of the raindrop is lim t l ` vstd. Find an
expression for the terminal velocity in terms of t and k.
50. Homeostasis  refers to a state in which the nutrient content
of a consumer is independent of the nutrient content of its
food. In the absence of homeostasis, a model proposed by
Sterner and Elser is given by
dy 1 y
−
dx  x

where x and y represent the nutrient content of the food and
the consumer, respectively, and  is a constant with  > 1.
(a) Solve the differential equation.
(b) What happens when  − 1? What happens when
 l `?
y(t)
r .
V Source: Adapted from R. Sterner et al., Ecological Stoichiometry: The Biol-
ogy of Elements from Molecules to the Biosphere (Princeton, NJ: Princeton
(L/min) (amount/L)
University Press, 2002).
51. Tissue culture  Let Astd be the area of a tissue culture at
time t and let M be the final area of the tissue when growth
is complete. Most cell divisions occur on the periphery of
the tissue and the number of cells on the periphery is pro-
portional to sAstd. So a reasonable model for the growth of
tissue is obtained by assuming that the rate of growth of the
area is jointly proportional to sAstd and M 2 Astd.
(a) Formulate a differential equation and use it to show that
the tissue grows fastest when Astd − 13 M.
CAS (b) Solve the differential equation to find an expression
for Astd. Use a computer algebra system to perform the
integration.
52. According to Newton’s Law of Universal Gravitation, the
gravitational force on an object of mass m that has been pro-
jected vertically upward from the earth’s surface is
mtR 2
F−
sx 1 Rd2

where x − xstd is the object’s distance above the surface at
time t, R is the earth’s radius, and t is the acceleration due
to gravity. Also, by Newton’s Second Law,
F − ma − m sdvydtd and so
dv mtR 2
m −2
dt sx 1 Rd2
(a) Suppose a rocket is fired vertically upward with an
initial velocity v 0. Let h be the maximum height above
the surface reached by the object. Show that
Î
2tRh
v0 −
R1h
[Hint: By the Chain Rule, m sdvydtd − mv sdvydxd.]