1. Hemodialysis and the Artificial Kidney

2. Kidney failure - affects 200 000 patients worldwideKidney failure - affects 200 000 patients worldwide –15 000 in Canada –Hamilton? Kidney failure - affects 200 000 patients worldwideKidney failure - affects 200 000 patients worldwide –15 000 in Canada –Hamilton? Arterial blood Venous blood Waste

3. What sort of things are excreted?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 failureKidney failure –accumulation of waste –acidosis, edema, hypertension, coma What sort of things are excreted?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 failureKidney failure –accumulation of waste –acidosis, edema, hypertension, coma

4. Kidney Structure and Function: Nephrons Functional units of the kidneyFunctional units of the kidney 1.2 million per kidney1.2 million per kidney Filtration and removal of wastesFiltration and removal of wastes Reabsorption of water, proteins, other essentials into the bloodReabsorption of water, proteins, other essentials into the blood Functional units of the kidneyFunctional units of the kidney 1.2 million per kidney1.2 million per kidney Filtration and removal of wastesFiltration and removal of wastes Reabsorption of water, proteins, other essentials into the bloodReabsorption of water, proteins, other essentials into the blood

9. Actively Secreted Substances HydroxybenzoatesHydroxybenzoates HippuratesHippurates Neutrotransmitters (dopamine)Neutrotransmitters (dopamine) Bile pigmentsBile pigments Uric acidUric acid AntibioticsAntibiotics MorphineMorphine SaccharinSaccharin HydroxybenzoatesHydroxybenzoates HippuratesHippurates Neutrotransmitters (dopamine)Neutrotransmitters (dopamine) Bile pigmentsBile pigments Uric acidUric acid AntibioticsAntibiotics MorphineMorphine SaccharinSaccharin

10. Reabsorbed Substances GlucoseGlucose Amino acidsAmino acids PhosphatePhosphate SulfateSulfate LactateLactate SuccinateSuccinate CitrateCitrate GlucoseGlucose Amino acidsAmino acids PhosphatePhosphate SulfateSulfate LactateLactate SuccinateSuccinate CitrateCitrate

12. Filtration and Reabsorption of Water by the Kidneys

13. What does this mean in terms of dialysis? Purpose - removal of wastes from the bodyPurpose - removal of wastes from the body Kidney should be the ideal model for hemodialysisKidney should be the ideal model for hemodialysis Water retention / removalWater retention / removal Salt retention / removalSalt retention / removal Protein retentionProtein retention Purpose - removal of wastes from the bodyPurpose - removal of wastes from the body Kidney should be the ideal model for hemodialysisKidney should be the ideal model for hemodialysis Water retention / removalWater retention / removal Salt retention / removalSalt retention / removal Protein retentionProtein retention

14. Artificial Kidney Removes waste products from the blood by the use of an extracorporeal membrane processRemoves waste products from the blood by the use of an extracorporeal membrane process Waste products pass from the blood through the membrane into the dialysateWaste products pass from the blood through the membrane into the dialysate Removes waste products from the blood by the use of an extracorporeal membrane processRemoves waste products from the blood by the use of an extracorporeal membrane process Waste products pass from the blood through the membrane into the dialysateWaste products pass from the blood through the membrane into the dialysate

17. Membrane MaterialMembrane Material –Permeable to waste products –Impermeable to essential blood components –Sufficiently strong –Compatible with blood Membrane MaterialMembrane Material –Permeable to waste products –Impermeable to essential blood components –Sufficiently strong –Compatible with blood

18. Mechanisms of Transport through the Membrane Diffusion (true dialysis)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 Diffusion (true dialysis)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

19. ConvectionConvection –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) ConvectionConvection –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)

20. Membrane Materials Wettability - usually hydrophilic for transport of dissolved materialsWettability - usually hydrophilic for transport of dissolved materials PermeabilityPermeability Mechanical strengthMechanical strength Blood compatibilityBlood compatibility Wettability - usually hydrophilic for transport of dissolved materialsWettability - usually hydrophilic for transport of dissolved materials PermeabilityPermeability Mechanical strengthMechanical strength Blood compatibilityBlood compatibility

21. Recall from mass transfer:Recall from mass transfer: J s = solute flux P M = diffusive permeability  c = concentration difference c = average membrane conc  s = reflection coefficient J v = volume flux

22. Design Considerations Should be: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 Should be: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

23. Performance - Engineering Approach Use of film theory modelUse 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 Use of film theory modelUse 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 BloodDialysate mm bb dd

24. Assume linear profiles in the films and in the membraneAssume linear profiles in the films and in the membrane Define a partition coefficient Define a partition coefficient  Assume linear profiles in the films and in the membraneAssume linear profiles in the films and in the membrane Define a partition coefficient Define a partition coefficient  At steady state, the fluxes in the membrane and in the films are equal

25. N - weight of solute removed /time area D’s are diffusion coefficients

26. Recall from mass transfer that concentrations in the membrane and in the films are difficult to measureRecall 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 DWhen 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 Recall from mass transfer that concentrations in the membrane and in the films are difficult to measureRecall 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 DWhen 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

27. Overall concentration difference Also And using the definition of 

28. K o is the overall mass transfer coefficient It includes two fluid films and the membrane

29. Note also that K o can be defined in terms of resistances to mass transferNote also that K o can be defined in terms of resistances to mass transfer 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

30. This is a model based on molecular mass transferThis is a model based on molecular mass transfer Gives concentrations and fluxGives concentrations and flux We are interested in the amount of waste that can be removed in a period of time (efficiency of the system)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 dialyzerTo do this we need to do an overall balance on the dialyzer This is a model based on molecular mass transferThis is a model based on molecular mass transfer Gives concentrations and fluxGives concentrations and flux We are interested in the amount of waste that can be removed in a period of time (efficiency of the system)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 dialyzerTo do this we need to do an overall balance on the dialyzer

31. Consider a differential element of the dialyzerConsider 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

33. Equating the dW’s Integrate assuming constant K o

35. K o describes performance of dialyzerK o describes performance of dialyzer CombinesCombines –diffusivity of molecule –permeability of membrane –effects of flow (convection etc) Similar model to that obtained in heat transferSimilar model to that obtained in heat transfer K o describes performance of dialyzerK o describes performance of dialyzer CombinesCombines –diffusivity of molecule –permeability of membrane –effects of flow (convection etc) Similar model to that obtained in heat transferSimilar model to that obtained in heat transfer

36. Performance -Clinical Approach Clearance / dialysance - more clinical than fundamentalClearance / dialysance - more clinical than fundamental Q B, C Bi C Bo Q D, C Di C Do Clearance defined as: W- weight of solute removed/time

37. C * is volume of blood completely “cleared” of solute per unit timeC * is volume of blood completely “cleared” of solute per unit time Maximum value of Q BMaximum value of Q B C * is volume of blood completely “cleared” of solute per unit timeC * is volume of blood completely “cleared” of solute per unit time Maximum value of Q BMaximum value of Q B

38. DialysanceDialysance Defined by:Defined by: Allows for possible presence of solute in inlet dialysate

39. Extraction ratioExtraction ratio –Measurement of efficiency Extraction ratioExtraction ratio –Measurement of efficiency Can show

40. If z is small (Q B <Q D )If z is small (Q B <Q D ) Assuming C di = 0

41. Analysis for countercurrent flowAnalysis for countercurrent flow Similar analysis for cocurrent flow with slightly different resultsSimilar analysis for cocurrent flow with slightly different results Countercurrent flow more commonly usedCountercurrent flow more commonly used Analysis for countercurrent flowAnalysis for countercurrent flow Similar analysis for cocurrent flow with slightly different resultsSimilar analysis for cocurrent flow with slightly different results Countercurrent flow more commonly usedCountercurrent flow more commonly used

42. AssumeAssume –Q B = 200 mL/minute –Q D = high –A = 1.0 m 2 –urea K o = 0.017 cm/minute AssumeAssume –Q B = 200 mL/minute –Q D = high –A = 1.0 m 2 –urea K o = 0.017 cm/minute

43. Time required for treatmentTime required for treatment –Model patient as CSTR (exit conc. = conc. in tank - well mixed) –Mass balance on patient – can show Time required for treatmentTime required for treatment –Model patient as CSTR (exit conc. = conc. in tank - well mixed) –Mass balance on patient – can show C Bi C Bo

44. Integrate to yieldIntegrate to yield

45. Consider: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 Consider: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

46. HemofiltrationHemofiltration Cleansing by ultrafiltrationCleansing by ultrafiltration Materials removed from the blood by convectionMaterials removed from the blood by convection Analogous to glomerulus of natural kidneyAnalogous to glomerulus of natural kidney Cleansing by ultrafiltrationCleansing by ultrafiltration Materials removed from the blood by convectionMaterials removed from the blood by convection Analogous to glomerulus of natural kidneyAnalogous to glomerulus of natural kidney

47. FeaturesFeatures –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 FeaturesFeatures –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

48. Hemoperfusion / Hemoadsorption Blood passed over bed of activated charcoalBlood passed over bed of activated charcoal Waste materials adsorbed on charcoalWaste materials adsorbed on charcoal No dialysateNo dialysate Relatively simpleRelatively simple Little urea removal, no water removalLittle urea removal, no water removal Used in combination with hemodialysis / hemoperfusionUsed in combination with hemodialysis / hemoperfusion Blood passed over bed of activated charcoalBlood passed over bed of activated charcoal Waste materials adsorbed on charcoalWaste materials adsorbed on charcoal No dialysateNo dialysate Relatively simpleRelatively simple Little urea removal, no water removalLittle urea removal, no water removal Used in combination with hemodialysis / hemoperfusionUsed in combination with hemodialysis / hemoperfusion