Hemodialysis and the Hemodialysis and the

Artificial Kidney Artificial Kidney

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

'
=

t
=
'

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

t
+

'
+

'
=
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
H
H
=

t
=

'

And using the definition of E

'
=

'
=
D B
M
M
M M
M
M
C C
D
C C
D
N
H
E
H
)
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
H H H
H H H
H
!
!
! @
!

d
@
1
K
o
is the overall mass transfer coefficient
It includes two fluid films and the membrane
Note also that K Note also that K
oo
can be defined in terms can be defined in terms
of resistances to mass transfer of resistances to mass transfer
Note also that K Note also that K
oo
can be defined in terms can be defined in terms
of resistances to mass transfer 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 This is a model based on molecular
mass transfer mass transfer
Gives concentrations and flux Gives concentrations and flux
We are interested in the amount of We are interested in the amount of
waste that can be removed in a waste that can be removed in a
period of time (efficiency of the period of time (efficiency of the
system) system)
To do this we need to do an overall To do this we need to do an overall
balance on the dialyzer balance on the dialyzer
This is a model based on molecular This is a model based on molecular
mass transfer mass transfer
Gives concentrations and flux Gives concentrations and flux
We are interested in the amount of We are interested in the amount of
waste that can be removed in a waste that can be removed in a
period of time (efficiency of the period of time (efficiency of the
system) system)
To do this we need to do an overall To do this we need to do an overall
balance on the dialyzer balance on the dialyzer
Consider a differential element of the Consider a differential element of the
dialyzer dialyzer
Consider a differential element of the Consider a differential element of the
dialyzer 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 K
oo
describes performance of dialyzer describes performance of dialyzer
Combines Combines
diffusivity of molecule diffusivity of molecule
permeability of membrane permeability of membrane
effects of flow (convection etc) effects of flow (convection etc)
Similar model to that obtained in heat Similar model to that obtained in heat
transfer transfer
K K
oo
describes performance of dialyzer describes performance of dialyzer
Combines Combines
diffusivity of molecule diffusivity of molecule
permeability of membrane permeability of membrane
effects of flow (convection etc) effects of flow (convection etc)
Similar model to that obtained in heat Similar model to that obtained in heat
transfer transfer
Performance Performance - -Clinical Clinical
Approach Approach
Performance Performance - -Clinical Clinical
Approach Approach
Clearance / dialysance Clearance / dialysance - - more clinical more clinical
than fundamental than fundamental
Clearance / dialysance Clearance / dialysance - - more clinical more clinical
than fundamental 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 C
* *
is volume of blood completely is volume of blood completely
cleared of solute per unit time cleared of solute per unit time
Maximum value of Q Maximum value of Q
B B
C C
* *
is volume of blood completely is volume of blood completely
cleared of solute per unit time cleared of solute per unit time
Maximum value of Q Maximum value of Q
B B
Dialysance Dialysance Dialysance Dialysance
Defined by: Defined by: Defined by: 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 Extraction ratio
Measurement of efficiency Measurement of efficiency
Extraction ratio Extraction ratio
Measurement of efficiency Measurement of efficiency
Di Bi
Bo Bi
C C
C C
E

=
Can show
) . J
) . J
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 If z is small (Q
B B
<Q <Q
D D
) ) If z is small (Q If z is small (Q
B B
<Q <Q
D 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 Analysis for countercurrent flow
Similar analysis for cocurrent flow Similar analysis for cocurrent flow
with slightly different results with slightly different results
Countercurrent flow more commonly Countercurrent flow more commonly
used used
Analysis for countercurrent flow Analysis for countercurrent flow
Similar analysis for cocurrent flow Similar analysis for cocurrent flow
with slightly different results with slightly different results
Countercurrent flow more commonly Countercurrent flow more commonly
used used
Assume Assume
QQ
B B
= 200 mL/minute = 200 mL/minute
QQ
D D
= high = high
A = 1.0 m A = 1.0 m
2 2
urea K urea K
oo
= 0.017 cm/minute = 0.017 cm/minute
Assume Assume
QQ
B B
= 200 mL/minute = 200 mL/minute
QQ
D D
= high = high
A = 1.0 m A = 1.0 m
2 2
urea K urea K
oo
= 0.017 cm/minute = 0.017 cm/minute
) )
min / ml 113
833 . 0 exp 1 200
833 . 0
*
=
=
=
C
Q
A K
B
o
Time required for treatment Time required for treatment
Model patient as CSTR (exit conc. = Model patient as CSTR (exit conc. =
conc. in tank conc. in tank - - well mixed) well mixed)
Mass balance on patient Mass balance on patient can show can show
Time required for treatment Time required for treatment
Model patient as CSTR (exit conc. = Model patient as CSTR (exit conc. =
conc. in tank conc. in tank - - well mixed) well mixed)
Mass balance on patient Mass balance on patient can show 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 Integrate to yield Integrate to yield 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: Consider:
C C
urea urea
0 0
= 150 mg/dL = 150 mg/dL
Require C Require C
urea urea
= 50 mg/dL = 50 mg/dL
Using previous data we find that Using previous data we find that
required t is approximately 8 h required t is approximately 8 h
Consider: Consider:
C C
urea urea
0 0
= 150 mg/dL = 150 mg/dL
Require C Require C
urea urea
= 50 mg/dL = 50 mg/dL
Using previous data we find that Using previous data we find that
required t is approximately 8 h required t is approximately 8 h
Hemofiltration Hemofiltration Hemofiltration Hemofiltration
Cleansing by ultrafiltration Cleansing by ultrafiltration
Materials removed from the blood by Materials removed from the blood by
convection convection
Analogous to glomerulus of natural Analogous to glomerulus of natural
kidney kidney
Cleansing by ultrafiltration Cleansing by ultrafiltration
Materials removed from the blood by Materials removed from the blood by
convection convection
Analogous to glomerulus of natural Analogous to glomerulus of natural
kidney kidney
Features Features
Same equipment as hemodialysis Same equipment as hemodialysis
Leaky membrane required Leaky membrane required
Water lost is replaced either before or Water lost is replaced either before or
after filter (physiologic solution) after filter (physiologic solution)
No dialysate needed No dialysate needed
Clearance less dependent on molecular Clearance less dependent on molecular
weight weight - - better for middle molecules better for middle molecules
Generally faster than hemodialysis Generally faster than hemodialysis
Features Features
Same equipment as hemodialysis Same equipment as hemodialysis
Leaky membrane required Leaky membrane required
Water lost is replaced either before or Water lost is replaced either before or
after filter (physiologic solution) after filter (physiologic solution)
No dialysate needed No dialysate needed
Clearance less dependent on molecular Clearance less dependent on molecular
weight weight - - better for middle molecules better for middle molecules
Generally faster than hemodialysis Generally faster than hemodialysis
Hemoperfusion / Hemoperfusion /
Hemoadsorption Hemoadsorption
Hemoperfusion / Hemoperfusion /
Hemoadsorption Hemoadsorption
Blood passed over bed of activated Blood passed over bed of activated
charcoal charcoal
Waste materials adsorbed on charcoal Waste materials adsorbed on charcoal
No dialysate No dialysate
Relatively simple Relatively simple
Little urea removal, no water removal Little urea removal, no water removal
Used in combination with hemodialysis / Used in combination with hemodialysis /
hemoperfusion hemoperfusion
Blood passed over bed of activated Blood passed over bed of activated
charcoal charcoal
Waste materials adsorbed on charcoal Waste materials adsorbed on charcoal
No dialysate No dialysate
Relatively simple Relatively simple
Little urea removal, no water removal Little urea removal, no water removal
Used in combination with hemodialysis / Used in combination with hemodialysis /
hemoperfusion hemoperfusion