Hemodialysis and the

Artificial Kidney
Kidney failure - affects 200 000
patients worldwide
15 000 in Canada
Hamilton?
Arterial blood
Venous blood
Waste
What sort of things are excreted?
Urea - 30 g/day
Creatinine - 2 g/day
Salt - 15 g/day
Uric Acid - 0.7 g/day
Water - 1500 mL/day
Unknown
Kidney failure
accumulation of waste
acidosis, edema, hypertension, coma
Kidney Structure and Function:
Nephrons
Functional units of the kidney
1.2 million per kidney
Filtration and removal of wastes
Reabsorption of water, proteins, other
essentials into the blood
Actively Secreted Substances
Hydroxybenzoates
Hippurates
Neutrotransmitters (dopamine)
Bile pigments
Uric acid
Antibiotics
Morphine
Saccharin
Reabsorbed Substances
Glucose
Amino acids
Phosphate
Sulfate
Lactate
Succinate
Citrate
Filtration and Reabsorption
of Water by the Kidneys
L/day mL/min
Filtration 170 120
Resorption 168.5 119
Urine
Excretion
1.5 1
What does this mean in
terms of dialysis?
Purpose - removal of wastes from the
body
Kidney should be the ideal model for
hemodialysis
Water retention / removal
Salt retention / removal
Protein retention
Artificial Kidney
Removes waste products from the
blood by the use of an extracorporeal
membrane process
Waste products pass from the blood
through the membrane into the
dialysate
Membrane Material
Permeable to waste products
Impermeable to essential blood
components
Sufficiently strong
Compatible with blood
Mechanisms of Transport
through the Membrane
Diffusion (true dialysis)
movement due to concentration gradient
If concentration is higher in the blood and the
species can pass through the membrane,
transport occurs until the concentrations are
equal
Slow
If dialysate concentration is higher, the flow
goes toward the blood
Convection
Massive movement of fluid across
membrane
Fluid carries dissolved or suspended
species that can pass through the
membrane
Usually as a result of fluid pressure
(both positive and suction pressure)
Principal means of water and electrolyte
removal (ultrafiltration)
Can also remove water by adding
glucose to dialysate (osmotic gradient)
Membrane Materials
Wettability - usually hydrophilic for
transport of dissolved materials
Permeability
Mechanical strength
Blood compatibility
Recall from mass transfer:
( )
( )
v s
v s M s
J c
dx
dc
D
J c c P J
o
o
+ =
+ A =
1
1
J
s
= solute flux
P
M
= diffusive permeability
Ac = concentration difference
c = average membrane conc
o
s
= reflection coefficient
J
v
= volume flux
Design Considerations
Should be:
Efficient in removing toxic wastes
Efficient in removing water
(ultrafiltration or osmosis)
Small priming volume (<500 mL)
Low flow resistance on blood side
Convenient, disposable, reliable, cheap
Performance - Engineering
Approach
Use of film theory model
resistance to mass transfer in fluids is
in thin stagnant films at solid surfaces
Leads to concept of mass transfer
coefficients
Blood Dialysate
o
m
o
b
o
d

Assume linear profiles in the films
and in the membrane
Define a partition coefficient o

=
'
'
=
D
M
B
M
C
C
C
C
o
At steady state, the fluxes in the membrane and in the films
are equal
At steady state, the fluxes in the membrane and in the films
are equal
M
M M
M
D
D D
D
B
B B
B
C C
D
C C
D
C C
D N
o o o

'
=

=
'

=
N - weight of solute removed /time area
Ds are diffusion coefficients
Recall from mass transfer that
concentrations in the membrane and in
the films are difficult to measure
When the system is at steady state we
can manipulate this equation along with
the partition coefficient to give an
equation that is based on the easily
measurable concentrations C
B
and C
D

Overall concentration difference
|
.
|

\
|

+
|
.
|

\
|

'
+
|
.
|

\
|
'
=
D D D B B B D B
C C C C C C C C
Also
D
D
D D
B
B
B B
D
N
C C
D
N
C C
o
o
=
|
.
|

\
|

=
|
.
|

\
|
'

And using the definition of o

|
.
|

\
|

'
=
|
.
|

\
|

'
=
D B
M
M
M M
M
M
C C
D
C C
D
N
o
o
o
( )
D
D
M
M
B
B
o
D B o
D
D
M
M
B
B
D B
M
M
D B
D D D
K
C C K N
D
N
D
N
D
N
C C
D
N
C C
o
o
o o
o
o
o o
o
o
+ + =
=
+ + =
=
|
.
|

\
|

'

1
K
o
is the overall mass transfer coefficient
It includes two fluid films and the membrane
Note also that K
o
can be defined in terms
of resistances to mass transfer
D M B
o
R R R R
K
+ + = =
1
Analogous to electricity (and like heat transfer),
resistances in series are additive
R
B
represents limitation for small molecules
R
M
represents limitation for large molecules
R
D
can be neglected when high flowrate on dialysate
side is used
This is a model based on molecular
mass transfer
Gives concentrations and flux
We are interested in the amount of
waste that can be removed in a
period of time (efficiency of the
system)
To do this we need to do an overall
balance on the dialyzer
Consider a differential element of the
dialyzer
Q
B
,C
B

C
B
+dC
B

dx
(dA)
dW
Q
D
,C
D

C
D
+dC
D

( )
B B D D
D B o
dC Q dC Q dW
dA C C K dW
= =
=
and
( ) ( )
( )
D
B
D B
B
D B B D B B
D
B
D B B B
D
B
D B D D
D
B
D
B
Q
Q
C C d
Q dW
C C d Q dC dC Q
Q
Q
dW
dC Q dC Q dW
Q
Q
dW
dC Q dC Q
Q
Q
dW
Q
Q

=
= =
|
|
.
|

\
|

=
|
|
.
|

\
|

=
|
|
.
|

\
|
=
|
|
.
|

\
|

1
1
&
Equating the dWs
( )
( )
( )
( )
dA
Q Q
K
C C
C C d
dA C C K
Q
Q
C C d
Q
D B
o
D B
D B
D B o
D
B
D B
B
|
|
.
|

\
|
=

1 1
1
Integrate assuming constant K
o

( )
( )
( ) ( )
( )
mean o
Di Bo
Do Bi
Di Bo Do Bi
o
Di Do Bo Bi
D B
D B
o
Di Bo
Do
i
B
C A K W
C C
C C
C C C C
A K W
W
C C
W
C C
Q Q
Since
A
Q Q
K
C C
C C
log
ln
1 1
1 1
ln
A =
(
(
(
(
(

|
|
.
|

\
|

=
|
|
.
|

\
|
=
(

K
o
describes performance of dialyzer
Combines
diffusivity of molecule
permeability of membrane
effects of flow (convection etc)
Similar model to that obtained in heat
transfer
Performance -Clinical
Approach
Clearance / dialysance - more clinical
than fundamental
Q
B
, C
Bi

C
Bo

Q
D
, C
Di

C
Do

Clearance defined as:
Bi Bi
Bo Bi
B
C
W
C
C C
Q C =

=
*
W- weight of solute removed/time
C
*
is volume of blood completely
cleared of solute per unit time
Maximum value of Q
B

Dialysance
Defined by:
Di Bi Di Bi
Bo Bi
B
C C
W
C C
C C
Q D

=
(

=
*
Allows for possible presence of solute in inlet dialysate
Extraction ratio
Measurement of efficiency
Di Bi
Bo Bi
C C
C C
E

=
Can show
( ) | |
( ) | |
D
B
B
o
T
T
T
Q
Q
z
Q
A K
N
z N z
z N
E
=
=


=
1 exp
1 exp 1
If z is small (Q
B
<Q
D
)
( )
(

|
|
.
|

\
|
=
|
|
.
|

\
|
=
|
|
.
|

\
|
=

~
B
o
B
B
o
Bi Bo
B
o
Bi
Bo Bi
T
Q
A K
Q C
Q
A K
C C
Q
A K
C
C C
N E
exp 1
exp
exp 1
exp 1
*
Assuming C
di
= 0
Analysis for countercurrent flow
Similar analysis for cocurrent flow
with slightly different results
Countercurrent flow more commonly
used
Assume
Q
B
= 200 mL/minute
Q
D
= high
A = 1.0 m
2

urea K
o
= 0.017 cm/minute

( ) ( )
min / ml 113
833 . 0 exp 1 200
833 . 0
*
=
=
=
C
Q
A K
B
o
Time required for treatment
Model patient as CSTR (exit conc. =
conc. in tank - well mixed)
Mass balance on patient can show
C
Bi

C
Bo

( )
|
|
.
|

\
|
=
=
B
o
Bi Bo
Bi Bo B
Bi
B
Q
A K
C C
that know and
C C Q
dt
dC
V
exp
Integrate to yield
0 at
1 exp
exp
0
= =
(
(
(
(
(

|
|
.
|

\
|

=
t C C
V
t
Q
A K
Q
C
C
Bi Bi
B
B
o
B
Bi
Bo
Consider:
C
urea
0
= 150 mg/dL
Require C
urea
= 50 mg/dL
Using previous data we find that
required t is approximately 8 h
Hemofiltration
Cleansing by ultrafiltration
Materials removed from the blood by
convection
Analogous to glomerulus of natural
kidney
Features
Same equipment as hemodialysis
Leaky membrane required
Water lost is replaced either before or
after filter (physiologic solution)
No dialysate needed
Clearance less dependent on molecular
weight - better for middle molecules
Generally faster than hemodialysis
Hemoperfusion /
Hemoadsorption
Blood passed over bed of activated
charcoal
Waste materials adsorbed on charcoal
No dialysate
Relatively simple
Little urea removal, no water removal
Used in combination with hemodialysis /
hemoperfusion