Hemodialysis and the Artificial Kidney

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Hemodialysis and the Artificial Kidney
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• Kidney failure - affects 200 000 patients
  worldwide
• 15 000 in Canada
• Hamilton?

Arterial blood
Venous blood
Waste
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• 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

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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

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Actively Secreted Substances

• Hydroxybenzoates
• Hippurates
• Neutrotransmitters (dopamine)
• Bile pigments
• Uric acid
• Antibiotics
• Morphine
• Saccharin

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Reabsorbed Substances

• Glucose
• Amino acids
• Phosphate
• Sulfate
• Lactate
• Succinate
• Citrate

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Filtration and Reabsorption of Water by the
Kidneys
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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

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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

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• Membrane Material
• Permeable to waste products
• Impermeable to essential blood components
• Sufficiently strong
• Compatible with blood

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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

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• 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)

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Membrane Materials

• Wettability - usually hydrophilic for transport
  of dissolved materials
• Permeability
• Mechanical strength
• Blood compatibility

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• Recall from mass transfer

Js solute flux PM diffusive permeability Dc
concentration difference c average membrane
conc ss reflection coefficient Jv volume flux
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Design Considerations

• Should be
• Efficient in removing toxic wastes
• Efficient in removing water (ultrafiltration or
  osmosis)
• Small priming volume (lt500 mL)
• Low flow resistance on blood side
• Convenient, disposable, reliable, cheap

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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
dm
db
dd
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• Assume linear profiles in the films and in the
  membrane
• Define a partition coefficient a

At steady state, the fluxes in the membrane and
in the films are equal
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At steady state, the fluxes in the membrane and
in the films are equal
N - weight of solute removed /time area Ds are
diffusion coefficients
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• 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 CB and CD

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Overall concentration difference
Also
And using the definition of a
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Ko is the overall mass transfer coefficient It
includes two fluid films and the membrane
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• Note also that Ko can be defined in terms of
  resistances to mass transfer

Analogous to electricity (and like heat
transfer), resistances in series are additive RB
represents limitation for small molecules RM
represents limitation for large molecules RD can
be neglected when high flowrate on dialysate side
is used
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• 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

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• Consider a differential element of the dialyzer

QD,CD
CDdCD
dW
CBdCB
QB,CB
dx (dA)
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Equating the dWs
Integrate assuming constant Ko
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• Ko describes performance of dialyzer
• Combines
• diffusivity of molecule
• permeability of membrane
• effects of flow (convection etc)
• Similar model to that obtained in heat transfer

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Performance -Clinical Approach

• Clearance / dialysance - more clinical than
  fundamental

QB, CBi
CBo
CDo
QD, CDi
Clearance defined as
W- weight of solute removed/time
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• C is volume of blood completely cleared of
  solute per unit time
• Maximum value of QB

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Dialysance

• Defined by

Allows for possible presence of solute in inlet
dialysate
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• Extraction ratio
• Measurement of efficiency

Can show
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• If z is small (QBltQD)

Assuming Cdi 0
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• Analysis for countercurrent flow
• Similar analysis for cocurrent flow with slightly
  different results
• Countercurrent flow more commonly used

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• Assume
• QB 200 mL/minute
• QD high
• A 1.0 m2
• urea Ko 0.017 cm/minute

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• Time required for treatment
• Model patient as CSTR (exit conc. conc. in tank
  - well mixed)
• Mass balance on patient can show

CBo
CBi
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• Integrate to yield

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• Consider
• Curea0 150 mg/dL
• Require Curea 50 mg/dL
• Using previous data we find that required t is
  approximately 8 h

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Hemofiltration

• Cleansing by ultrafiltration
• Materials removed from the blood by convection
• Analogous to glomerulus of natural kidney

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• 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

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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