BMEN #: Engineering Principles of Human

Physiology and Anatomy

Lecture 3
23/06/2023
Compartmental Analysis and Modelling
Compartmental Modeling/Analysis
• When analyzing systems of the body characterized by a transfer of
solute from one compartment to another, such as the respiratory
and circulatory systems, it is convenient to describe the system as a
series of compartments.

• Compartmental analysis differs from physiological modeling in that

it is concerned with maintaining correct chemical levels in the body
and their correct fluid volumes.
Identifiable Compartments
• Cell volume that is separated from the extracellular space by the cell
membrane

• Interstitial volume that is separated from the plasma volume by the

capillary walls that contain the fluid that bathes the cells

• Plasma volume contained in the circulatory system that consists of

the fluid that bathes blood cells
State Variables
• Variables tracked in compartmental analysis
• Quantity/concentration of a substance (solute)
• Temperature
• Pressure

• Substances of interest
• Exogenous: a drug or tracer
• Endogenous: glucose, an enzyme or hormone such as insulin.
Concepts & Attributes
• The process of transfer of substance from one compartment to another is based
on mass conservation

• Compartmental models can be

• Linear/nonlinear
• Continuous/discrete
• Time-varying
• Stochastic

• Compartmental analysis provides a uniform theory that can be systematically

applied to many of the body’s systems.

• Compartmental analytical techniques are widely used in studying

pharmacokinetics, chemical reaction engineering, fluid transport, and even
semiconductor design and fabrication.
Mathematical Basics - Fick's Law
• The time course of the transfer of a solute between two
compartments separated by a thin membrane is examined using
Fick’s law of diffusion as given by:
𝑑𝑞 𝑑𝑐
= −𝐷𝐴
𝑑𝑡 𝑑𝑥
where
𝑞 = quantity of solute
𝐴 = membrane surface area
𝑐 = concentration
𝐷 = diffusion coefficient
𝑑𝑥 = membrane thickness
Mathematical Basics - Fick's Law
• It is more convenient to work in
concentrations rather than quantity since
most measurements are in concentrations

• Hence, the following relationship is used in

moving between quantity and 𝑽𝟏
concentration. 𝑽𝟐
𝒄𝟏 𝒄𝟐
𝒒𝟏 𝒒𝟐
𝑄𝑢𝑎𝑛𝑡𝑖𝑡𝑦
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 =
𝑉𝑜𝑙𝑢𝑚𝑒 𝚫𝒙

• Consider the system of two compartments

shown in the figure
Mathematical Basics - Fick's Law
where
𝑉1 and 𝑉2 are the volumes of compartments I and II
𝑞1 and 𝑞2 are the quantities of solute in compartments I and II
𝑐1 and 𝑐2 are the concentrations of solute in compartments I and II
and an initial amount of solute, 𝑄𝑜 , is dumped into compartment I.

The rate of change of solute in compartment I is given by

𝑑𝑞1 𝑑𝑐1 𝐷𝐴 𝑐1 − 𝑐2
= −𝐷𝐴 = −
𝑑𝑡 𝑑𝑥 Δ𝑥
Mathematical Basics - Fick's Law
Let's convert the quantity of solute into concentration by,
𝑞1 = 𝑉1 𝑐1

and after differentiating above equation, we have

𝑑𝑞1 𝑑𝑐1
= 𝑉1
𝑑𝑡 𝑑𝑡

and substituting this into the Fick’s law equation yields

𝑑𝑐1 𝐾 𝑐1 − 𝑐2 𝐷𝐴
= − where 𝐾 = (transfer rate)
𝑑𝑡 𝑉1 Δ𝑥
Mathematical Basics - Fick's Law
Due to conservation of mass,
𝑞1 + 𝑞2 = 𝑄𝑜
and after converting to concentrations gives
𝑉1 𝑐1 + 𝑉2 𝑐2 = 𝑉1 𝐶𝑜
where 𝐶𝑜 is the initial concentration in compartment I due to the initial
amount of solute dumped into the compartment.

The concentration in compartment II is found from above equation as

𝑉1 𝐶𝑜 −𝑉1 𝑐1
𝑐2 =
𝑉2
Mathematical Basics - Fick's Law
𝑑𝑐1 𝐾
which when substituted into = − 𝑐1 − 𝑐2 gives
𝑑𝑡 𝑉1
𝑑𝑐1 𝐾 𝐾𝐶0 𝐾𝑐1
=− 𝑉2 𝑐1 − 𝑉1 𝐶0 + 𝑉1 𝑐1 = − 𝑉1 + 𝑉2
𝑑𝑡 𝑉1 𝑉2 𝑉2 𝑉1 𝑉2
𝑑𝑐1 𝑉1 + 𝑉2 𝐾𝐶0
+𝐾 𝑐1 =
𝑑𝑡 𝑉1 𝑉2 𝑉2
Mathematical Basics - Fick's Law
𝑑𝑐1 𝑉1 + 𝑉2 𝐾𝐶0
+𝐾 𝑐1 =
𝑑𝑡 𝑉1 𝑉2 𝑉2

• First order differential equation, with

𝐾𝐶𝑂
𝑓 𝑡 = (forcing function)
𝑉2

𝑐1 0 = 𝐶𝑂 (initial condition)
Mathematical Basics - Fick's Law
• Assume for simplicity 𝑉1 = 𝑉2

𝑑𝑐1 2𝐾 𝐾𝐶0
+ 𝑐1 =
𝑑𝑡 𝑉1 𝑉1
2𝐾𝑡
−𝑉
𝑐1𝑛 = 𝐵1 𝑒 1

2𝐾 𝐾𝐶𝑂 𝐶𝑂
𝐵 = or 𝐵2 =
𝑉1 2 𝑉1 2
Mathematical Basics - Fick's Law
• Thus the complete solution (for 𝑡 ≥ 0) is
2𝐾𝑡 𝐶𝑂
−
𝑐1 = 𝑐1𝑛 + 𝑐1𝑓 = 𝐵1 𝑒 𝑉1 +
2

• To find 𝐵1 the initial condition is used

2𝐾𝑡 𝐶𝑂 𝐶𝑂
−𝑉 ฬ
𝑐 0 =𝐶 =𝐵 𝑒 1
1 𝑂 1 𝑡=0
+ = 𝐵1 +
2 2

• The complete solution

2𝐾𝑡
𝐶𝑂 𝑉1 𝐶𝑂 −𝑉1 𝑐1 𝐶𝑂 −
𝑐1 = 𝑒 −2𝐾𝑡/𝑉1 − 1 𝑐2 = = 1 −𝑒 𝑉1
2 𝑉2 2
Basics of Compartmental Modelling
• Compartmental modeling involves describing a system by breaking it
down
• a finite number of compartments
• each compartment connected with a flow of solute from one compartment to
another

• Given a system described by a group of compartments, some

exchange of solute (i.e., a radioactive tracer, a molecule such as
glucose or insulin, or a gas such as oxygen or carbon dioxide) is
expected between compartments by diffusion.
Basics of Compartmental Modelling
• Compartmental analysis predicts the concentrations of solutes
under consideration in each compartment as a function of time
using conservation of mass:
accumulation equals input minus output

• Boxes are used to define a compartment and the flow of solute

between compartments defined by arrows.
Basics of Compartmental Modelling
• The following assumptions are made when describing the transfer of
a solute by diffusion between any two compartments:

• The volume of each compartment remains constant.

• Any solute q entering a compartment is instantaneously mixed throughout

the entire compartment.

• The rate of loss of a solute from a compartment is proportional to the amount

of solute in the compartment times the transfer rate, 𝐾, given by 𝐾𝑞.
Examples – One compartment model
Solution
• Using conservation of mass, the differential equation describing the rate of change of the
quantity of Iodine(131) in the compartment is given by

𝐴𝑐𝑐𝑢𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛 = 𝑖𝑛𝑝𝑢𝑡 – 𝑜𝑢𝑡𝑝𝑢𝑡

where
𝑑𝑞
𝑎𝑐𝑐𝑢𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛 =
𝑑𝑡

𝑖𝑛𝑝𝑢𝑡 = 0

𝑜𝑢𝑡𝑝𝑢𝑡 = 𝐾1 𝑞 + 𝐾2 𝑞
thus
𝑑𝑞
= − 𝐾1 + 𝐾2 𝑞
𝑑𝑡
A more realistic example
• Consider the more realistic
compartmental model shown in the
figure with ingestion of a solute in the
digestive system, and removal of
solute via metabolism and excretion
in urine.

• By including a digestive system

component
• the solute is not instantaneously
delivered into the plasma but is slowly
released from the digestive system into
the plasma.
Solution
• The conservation of mass is written for each compartment, thus

𝑑𝑞1
= 𝐾3 𝑞2 − 𝐾1 + 𝐾2 𝑞1
𝑑𝑡

𝑑𝑞2
= −𝐾3 𝑞2
𝑑𝑡

Solve for 𝑞2 and substitute into first equation

Multi-compartmental models
• Real models of the body involve many more compartments than
described in the previous section, such as cell volume, interstitial
volume, and plasma volume.
• Each of these volumes can be further compartmentalized.
• For instance, the interstitial volume can be defined with
compartments including the GI tract, mouth, liver, kidneys, and other
unidentified compartments.
• Each of these compartments has its own transfer rate for moving the
solute from one compartment to another.
Multi-compartmental models
• In general, concern about how the solute moves from and into a compartment is not a
focus, only the amount of solute that is transferred
• The concepts described in the previous section can be applied to a model with any
number of compartments.
• Each compartment is characterized by a conservation of mass differential equation
describing the rate of change of solute.
• Thus, for the case of N compartments, there are N equations of the general form
𝑑𝑄𝑖
= 𝑖𝑛𝑝𝑢𝑡 – 𝑜𝑢𝑡𝑝𝑢𝑡
𝑑𝑡
• where 𝑄𝑖 is the quantity of solute in compartment 𝑖.
• For a linear system, the transfer rates are constants.
Assignment