BIOMECHANICS: Interstitial Fluid Flow

COURSE: BIOMECHANICS
CHAPTER 5: The interstitium
LECTURER: ASSOC. PROF. DR. TICH THIEN TRUONG

OBJECTIVES OF CHAPTER 5
1. Apply Darcy’s law to estimate the flow rate from capillaries
to lymphatics.
2. Apply Darcy’s law to estimate the clearance time of
edematous (swollen) tissue flow.
3. Determine the effective tissue elasticity.
Contents
5.1. Interstitial fluid flow.

5.2. Problems.
5.1. Interstitial fluid flow
The net flow rate from capillaries to lymphatics is
determined by the driving potential (the difference in p − π
between the capillaries and the lymphatics), as well as the
hydrodynamic resistance of the intervening interstitium.
Interstitial flow resistance is therefore very important in fluid
homeostasis, or maintaining proper tissue hydration.
Intuition suggests that interstitial flow resistance should
depend on tissue structure, or more specifically on:
 the local concentrations of ECM components
 the local number of cells per unit tissue volume
 the manner in which cells and ECM components are packed
together.
Cells and ECM components are packed together in a
random manner. Because of this random character, it is
challenging to describe detailed flow patterns on a cellular or
subcellular length scale.
However, it is possible to characterize and quantify tissue
composition if a statistical approach is used, in which larger
tissue regions containing many cells are considered. In this
case, the average flow rate through the interstitium can be
related to average interstitial composition by using porous
media theory.
Since it is usually the average flow through a tissue area
that is of practical interest, this approach is entirely adequate.
These flow patterns are important in fluid clearance but can also
have important biological effects.
5.1.1. Darcy’s law
At this point, it is necessary to take a small diversion to
describe the essentials of porous media theory. A porous
material consists of a solid matrix permeated by a network of
pores, usually having a very complex topology. Porous media
theory is typically used to describe flow through the material
when it is too complex or difficult to describe the flow through
each pore on an individual basis.
The basic law describing average flow through the tissue
is due to Darcy. In a series of experiments, Darcy forced fluid
through porous bodies having crosssectional area A and flow-
wise length L. The pressure difference driving flow was p , the
working fluid had viscosity  , and the resulting flow rate Q was
measured (Fig. 5.1). Empirically, Darcy found that his data were
correlated by the relationship
Q K p
 (5.1)
A  L
Where, K is a material property called
the permeability (or hydraulic
permeability), having dimensions of
length squared. The permeability is a
purely local property of the porous
material: that is, it does not depend on
the overall size of the sample being
considered. It characterizes the ease
with which fluid can pass through the
porous material.
Darcy’s law is valid only for slow (low Reynolds number)

single-phase flow of a Newtonian fluid through a porous matrix.
However, that is precisely the situation that occurs when fluid flows
through the interstitium, and we therefore take Equation (5.1) as
the starting point of a quantitative description of flow in tissue.
Noting that Q/A is the average (or superficial) velocity of the
fluid in the porous material, and that p / L is the pressure
gradient in the flow-wise (x) direction, Equation (5.1) can be written
as
K dp
u (5.2)
 dx
where u is the superficial velocity in the x direction
Equation (5.2) can be generalized to three-dimensional

flows by replacing (scalar) u and dp/dx with the superficial velocity
vector u and the pressure gradient p , respectively, to obtain
K
u p (5.3)

Equation (5.3) states that the mean fluid transport rate (u) is
proportional to the driving potential p , with proportionality constant
K/
5.1.2. Clearance of edema
We will apply Darcy’s law to estimate the clearance time of

edematous (swollen) tissue, such as a bruise. Everyone is familiar
with the concept of bruising: after sustaining blunt trauma,
localized swelling and discoloration results, which is cleared over
the course of several days.
Physiologically, the trauma causes a series of events
leading to a loss of capillary endothelial integrity. This allows fluid,
plasma proteins, and formed elements to enter the interstitium.
The excess fluid produces local swelling (edema).
Once the capillary endothelium heals, the surrounding
tissue is left in an overhydrated state. Because significant amounts
of plasma protein are present in the edematous tissue, the oncotic
pressure in the interstitium is close to that in the capillary, so little
fluid drainage occurs into the capillaries.
Rather, fluid leaves the edematous tissue by draining into
the lymphatic capillaries.We seek to estimate how long it will take
the tissue to drain as a function of the properties of the interstitium.
Evidently a given tissue region will contain many lymphatic
capillaries, and, all other things being equal, fluid will drain into the
closest lymphatic capillary. Assuming that all capillaries are similar,
it is therefore sufficient to consider a single lymphatic capillary,
which we assume is responsible for draining fluid from a
cylindrically shaped region (or domain) of radius R
The entire tissue can be conceptually broken up into such
regions, each one draining into its central capillary. The radius of
each region will be a function of the number of capillaries per unit
volume: more capillaries mean that each capillary must drain a
smaller region (smaller R) and mutatis mutandis.
To analyze this problem, it is necessary to understand the
driving force that causes fluid to leave the tissue. All tissues have
an equilibrium or homeostatic level of hydration.
The tissue is overhydrated, which causes the ECM
components (particularly the proteoglycans) to swell beyond their
equilibrium value. Thermodynamically, it is favorable for the
proteoglycans to contract and return to their equilibrium
configuration; in so doing, fluid must be driven out of the tissue.
The closest analogy is a sponge that has had water injected
into it under pressure, causing it to swell excessively. In this case
the elastic fibers making up the solid matrix of the sponge have
been stretched beyond their equilibrium lengths. These fibers try to
contract elastically, which is manifested as a tendency of the
sponge to expel water, and which can be quantified through the
concept of an excess pressure within the sponge.
In order to characterize this effect, we denote the tissue
swelling pressure by pswell, and note that this quantity will depend
on how much water is in the tissue. The hydration of the tissue can
be characterized by the tissue porosity, ε, defined as
fluid volumein tissue

 (5.4)
total tissue volume
It is expected that the swelling pressure will increase with
increasing tissue porosity, and we denote this rate of increase by
the parameter  (the effective tissue elasticity)
dpswell
 (5.5)
d
For present purposes, we will assume that  is a constant, which
depends on tissue composition but which can be taken as known.
Returning to the edema clearance problem, the physics of the
process can now be clearly understood. The problem is
fundamentally unsteady, with the rate of fluid clearance from the
tissue being proportional to the changing tissue hydration. Fluid
drainage is driven by the swelling pressure within the tissue, which
forces the water out of the interstitium and into the capillary.
However, fluid drainage is opposed by the flow resistance
of the interstitium, such that the net rate at which the tissue drains
results from a balance between tissue swelling and interstitial
hydrodynamic resistance.
Although it is possible to analyze this problem in a detailed
quantitative manner (see below), it is simpler to use dimensional
analysis to obtain the time scale for edema clearance,
The value of  is expected to depend on the size of the
region to be drained (characterized by domain radius R), the
effective tissue elasticity  and the flow resistance of the
interstitium, characterized by  / K
Its value will also depend on the radius of the capillary,  , but we
assume that this dependence is not a strong one
From these parameters one   group can be formed,
namely:
K 
1   (5.6)
 R 2
Since there is only one   group, it must be constant,

which indicates that
R 2
 (5.7)
K
This makes physical sense: the clearance time increases if
a larger region must be drained or if fluid viscosity increases, and
the clearance time decreases if tissue permeability increases or if
tissue elasticity is large.
It is of interest to estimate the value of  based on this
analysis. Making the assumption that the proportionality constant
implied by Equation (5.7) is one, andbusing the following values:
  0.007 g /  cm.s 
R  5.5 102  cm 
  5.83 104  s 
K  8 10 4
 cm 
2
  4540 dynes / cm 2
This accords with practical experience: if we raise a bruise it

persists for a day or so.
Detailed parameter derivation
Here we justify some of the parameter values selected in
the above calculation, as well as deriving the form of the equation
that governs tissue swelling. We begin with the governing
equation.
Consider a small tissue-containing region of volume V.
• The void volume within the region is V  dV the mass flux
of fluid out
• The fluid mass within the region isV  dV of the cube
Conservation of mass written in integral form then states
V
 dV    u.nˆ dV  0
S
(5.8)
Where: n̂ is the outward normal to the region’s surface S; u is the

superficial velocity.
Assuming that ρ is constant, using Gauss’ theorem, and
taking the volume V as arbitrary gives an unsteady differential
equation representing conservation of mass under pressure,
causing it to swell excessively.
In this case the elastic fibers making up the solid matrix of
the sponge have been stretched beyond their equilibrium lengths.
These fibers try to contract elastically, which is manifested as a
tendency of the sponge to expel water, and which can be
quantified through the concept of an excess pressure within the
sponge.

 .u  0 (5.9)
t
Combining Equations (5.9) and (5.3) yields
 K 2
  ptissue  0 (5.10)
t 
Finally, we use the definition of the effective tissue elasticity  :
dptissue
d 

ptissue K 2
  ptissue  0 (5.11)
t 
It is convenient to non-dimensionalize the above equation by
defining a nondimensional pressure, time, and radial position by
ptissue  p0
pˆ tissue  (5.12)
pi  p0
tˆ  t /  (5.13)
rˆ  r / R (5.14)
where p0 is the equilibrium (homeostatic) pressure in the tissue, pi

is the initial tissue pressure (when the tissue is in the swollen state
and fluid begins to drain), and  is a time scale given by
 R2
 (5.15)
K
With this set of non-dimensional parameters, the governing
equation for the tissue pressure becomes
pˆ tissue ˆ 2
  pˆ tissue (5.16)
tˆ
If we make the (admittedly simplistic) assumption that tissue
pressure is uniform within the circular domain at t = 0, then the
initial condition is pˆ tissue  1 at t = 0 for all  / R  rˆ  1 . By virtue of the
fact that we divided the entire tissue into cylindrical domains, with
one capillary per domain, there is little fluid drainage across the
outer surface of a cylindrical domain. This can be expressed by a
no-flux boundary condition
pˆ tissue
 0 at rˆ  1 (5.17)
rˆ
A second boundary condition is required, which is obtained from
the reasonable assumption that the lymphatic capillary is freely
draining (i.e., that the capillary walls have little flow resistance), in
which case the tissue pressure immediately adjacent to the
capillary is homeostatic. Mathematically, this is expressed as
pˆ tissue  0 at rˆ   / R
Equation (5.16) has a separable solution in terms of Bessel
functions of order zero and decaying exponentials, with time
scale  .
 R2
This confirms that   is the relevant time scale for tissue
K
drainage
We now turn attention to estimating the radius of the cylindrical
region R and the effective tissue elasticity  . Estimation of R is
somewhat difficult, since there are few quantitative data on
lymphatic capillary distribution. Casely-Smith estimated that there
is 0.4 ml of lymph in the heart, which has a mass of approximately
300 g.
Therefore, the volume fraction of lymphatics in the heart is roughly
0.4/300 = 0.0013, assuming that the density of heart tissue is
approximately 1 g/cm3.
Taking a typical lymphatic capillary diameter of 20 μm,
R  20 m / 0.0013  550  m
It is unclear as to whether data for the heart can be applied to the

interstitium.
Estimation of  is somewhat more complex and requires further
examination of the physics behind tissue elasticity.
Recall that ptissue arises because the interstitium has become
“overhydrated” and the proteoglycans have become
overstretched.
We ignore the contribution to  from physical extension of
collagen and elastin and assume that the proteoglycans are
entangled with other tissue components. This implies that
proteoglycans become hydrated at the same rate as the entire
tissue, which seems reasonable.
By analogy with the theory of rubber elasticity, the quantity ptissue −
po is equal to πo − πtissue, where πtissue refers to the osmotic
pressure generated by tissue proteoglycans and πo is the
equilibrium (homeostatic) value of πtissue. Defining the solid tissue
volume fraction   1   allows us to write
dptissue d  tissue
  (5.18)
d dtot
It seems reasonable to assume that the ratio of proteoglycans to
total solid tissue is constant.
PG d tissue cPG d tissue
  (5.19)
tot dPG tot dcPG
where cPG is the concentration of proteoglycans in the tissue
The major contribution to proteoglycan osmotic pressure comes
from their glycosaminoglycan components. Johnson stated that
the osmotic pressure of the most common glycosaminoglycan,
hyaluronan, is given by
  A2 c 2 (5.20)
A2  7 M 0.1S 0.5 (5.21)
where A2 is expressed in mmHg/(g/100 ml).

We assume a molecular weight M of 500 kDa and physiologic
salinity S of 150 mM:
  4500 dynes / cm 2 .
5.2. Problems
Problem 1.
When analyzing porous materials, it is handy to have a way of
estimating the permeability of a material without actually having to
force fluid through it. A simple relationship that allows us to
estimate permeability from these variables is the Carman–
Kozeny equation.
1. Consider a block of cross-
sectional area A and flow-wise
length L, which is permeated by N
pores, each of length l and radius
R. Assuming that Poiseuille’s law
holds in each pore, show that the
total flow rate passing through the
block, Q, is given by:
N  R 4 p where p is the pressure drop from front to
Q
8 l back.
5.2. Problems
Problem 1.
When analyzing porous materials, it is handy to have a way of
estimating the permeability of a material without actually having to
force fluid through it. A simple relationship that allows us to
estimate permeability from these variables is the Carman–
Kozeny equation.
2. Compare this result with Darcy’s
law to show that the permeability,
K, can be given by:
3
K 2 2  *
2 S
where  ,  , S are the tortuosity, porosity, and specific surface,
respectively, defined by.
l total pore volume total pore wall area
  ;  ;S 
L total block volume total block volume
5. Question?

BIOMECHANICS: Interstitial Fluid Flow

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COURSE: BIOMECHANICS

CHAPTER 5: The interstitium

LECTURER: ASSOC. PROF. DR. TICH THIEN TRUONG

5.1. Interstitial fluid flow.

Darcy’s law is valid only for slow (low Reynolds number)

Equation (5.2) can be generalized to three-dimensional

We will apply Darcy’s law to estimate the clearance time of

fluid volumein tissue

Since there is only one   group, it must be constant,

This accords with practical experience: if we raise a bruise it

Where: n̂ is the outward normal to the region’s surface S; u is the

where p0 is the equilibrium (homeostatic) pressure in the tissue, pi

It is unclear as to whether data for the heart can be applied to the

A2  7 M 0.1S 0.5 (5.21)

where A2 is expressed in mmHg/(g/100 ml).

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