Hemodialysis and the Artificial Kidney

1. Hemodialysis and the Artificial Kidney

2. Here I generally say that we can extrapolate to Hamilton. I am trying to remember the numbers but I am thinking that the clinic at St. Joe�s deals with 100+ patients at any one time. I will ask Peter Marguetts, a doctor at St. Joes to come in and chat with the class and he can give them a better idea.Here I generally say that we can extrapolate to Hamilton. I am trying to remember the numbers but I am thinking that the clinic at St. Joe�s deals with 100+ patients at any one time. I will ask Peter Marguetts, a doctor at St. Joes to come in and chat with the class and he can give them a better idea.

3. 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

4. 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

5. Primary urine is filtered from the blood into the renal corpuscles - steps in processing occur as the urine flows through the intermediate regions of the tubule to the collecting duct Bowmans capsule - adapted for a high rate of capillary filtration Glomerular filter is freely permeable to water, mineral ions (Na+, K+, Ca++) and to small organic molecules such as glucose. A substantial fraction of high molecular weight proteins (with MW up to 20 000) are also filtered but proteins with MW greater than 40 000 are filtered only in trace amounts. Glomerular capillaries are about 10 x more permeable than other capillaries in the body Kidneys receive 1580 L of blood per day (or a plasma flow of 870 L/day). If the filtered fraction is 20%, then the glomerular filtration rate is 174 L/day or about 60 times the plasma volume which is about 3L. Forces - 45 mm Hg on arterial side, opposing 10 mm Hg Osmotic forces due to presence of plasma proteins - 25 mm Hg in the direction of reabsorption - therefore net force of 10 mm Hg Proximal tubule 174 L/day in, 60 L/day out - Cells actively remove Na+ from urine resulting in reabsorption of water- other substances are actively secreted by active transport Distal tubule - proximal tubule has no effect on the water to solute ratio- fluid entering is isotonic to plasma - Loop of Henle and distal tubule produce lower osmotic pressure than plasma - almost impermeable to water, reabsorption of Na+ and Cl-Primary urine is filtered from the blood into the renal corpuscles - steps in processing occur as the urine flows through the intermediate regions of the tubule to the collecting duct Bowmans capsule - adapted for a high rate of capillary filtration Glomerular filter is freely permeable to water, mineral ions (Na+, K+, Ca++) and to small organic molecules such as glucose. A substantial fraction of high molecular weight proteins (with MW up to 20 000) are also filtered but proteins with MW greater than 40 000 are filtered only in trace amounts. Glomerular capillaries are about 10 x more permeable than other capillaries in the body Kidneys receive 1580 L of blood per day (or a plasma flow of 870 L/day). If the filtered fraction is 20%, then the glomerular filtration rate is 174 L/day or about 60 times the plasma volume which is about 3L. Forces - 45 mm Hg on arterial side, opposing 10 mm Hg Osmotic forces due to presence of plasma proteins - 25 mm Hg in the direction of reabsorption - therefore net force of 10 mm Hg Proximal tubule 174 L/day in, 60 L/day out - Cells actively remove Na+ from urine resulting in reabsorption of water- other substances are actively secreted by active transport Distal tubule - proximal tubule has no effect on the water to solute ratio- fluid entering is isotonic to plasma - Loop of Henle and distal tubule produce lower osmotic pressure than plasma - almost impermeable to water, reabsorption of Na+ and Cl-

6. Mechanism of formation of concentration urine according to the two solute hypothesis. The osmolarity of the interstitial fluid at different levels of the medulla is shown to scale at the left. The urine leaving the proximal tubule is isotonic. As the urine travels in the descending limb of the loop of Henle, water leaves the descending limb, drawn by the increasing osmotic pressure of the interstitial fluid in the medulla. As a result, the urine in the descending limb becomes progressively more concentrated. As the urine passes through the thin ascending limb, NaCl diffuses out as the osmoti pressure of the interstitial fluid decreases. In the thick, ascending limb, more salt is removed by active reabsorption. The urine entering the distal tubule is more dilute than plasma and the urea has been concentrated by the reabsorption of water. Urea and water move down their concentration gradients as the urine passes through the collecting duct. The remaining solutes in the urine are concentrated further by water reabsorption and a urine as concentrated as the interstitial fluid at the innermost part of the medulla. Mechanism of formation of concentration urine according to the two solute hypothesis. The osmolarity of the interstitial fluid at different levels of the medulla is shown to scale at the left. The urine leaving the proximal tubule is isotonic. As the urine travels in the descending limb of the loop of Henle, water leaves the descending limb, drawn by the increasing osmotic pressure of the interstitial fluid in the medulla. As a result, the urine in the descending limb becomes progressively more concentrated. As the urine passes through the thin ascending limb, NaCl diffuses out as the osmoti pressure of the interstitial fluid decreases. In the thick, ascending limb, more salt is removed by active reabsorption. The urine entering the distal tubule is more dilute than plasma and the urea has been concentrated by the reabsorption of water. Urea and water move down their concentration gradients as the urine passes through the collecting duct. The remaining solutes in the urine are concentrated further by water reabsorption and a urine as concentrated as the interstitial fluid at the innermost part of the medulla.

7. Curve 1: Filtered load of glucose as a function of the plasma glucose concentration. The filtered load varies in direct proportion to the plasma concentration Curve 2: The rate of glucose reabsorption as a function of plasma glucose concentration. = filtration rate until Tm, transport maximum is reached Curve 3: Rate of glucose excretion Use this to explain why sometimes patients with diabetes have sugar in their urine. The body can only reabsorb a certain amount � above this amount, it is excreted.Curve 1: Filtered load of glucose as a function of the plasma glucose concentration. The filtered load varies in direct proportion to the plasma concentration Curve 2: The rate of glucose reabsorption as a function of plasma glucose concentration. = filtration rate until Tm, transport maximum is reached Curve 3: Rate of glucose excretion Use this to explain why sometimes patients with diabetes have sugar in their urine. The body can only reabsorb a certain amount � above this amount, it is excreted.

8. Secretion - same pathways and ideas Removal of such things as drugs. Amount removed is often much higher than would be expected because the body is able to actively transport some substances out of the body.Secretion - same pathways and ideas Removal of such things as drugs. Amount removed is often much higher than would be expected because the body is able to actively transport some substances out of the body.

9. Actively Secreted Substances Hydroxybenzoates Hippurates Neutrotransmitters (dopamine) Bile pigments Uric acid Antibiotics Morphine Saccharin

10. Reabsorbed Substances Glucose Amino acids Phosphate Sulfate Lactate Succinate Citrate

12. Filtration and Reabsorption of Water by the Kidneys

13. 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

14. 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

15. Top is a typical dialyzer model Bottom is peritoneal dialysis. In this model, the natural membranes of the body are used to filter the wastes. Top is a typical dialyzer model Bottom is peritoneal dialysis. In this model, the natural membranes of the body are used to filter the wastes.

17. Membrane Material Permeable to waste products Impermeable to essential blood components Sufficiently strong Compatible with blood What kind of properties should the material possess from an engineering standpoint?What kind of properties should the material possess from an engineering standpoint?

18. 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

19. 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) How does adding glucose to the dialysate work in terms of water removal?How does adding glucose to the dialysate work in terms of water removal?

20. Membrane Materials Wettability - usually hydrophilic for transport of dissolved materials Permeability Mechanical strength Blood compatibility Discuss wettability - what is wettable? How might this affect the transport properties of the membrane?Discuss wettability - what is wettable? How might this affect the transport properties of the membrane?

21. Recall from mass transfer: First term represents diffusive mass transfer, second term represents convective mass transfer What are the units of these terms? J - g/cm2s PM - cm/s Jv - cm3/cm2 sFirst term represents diffusive mass transfer, second term represents convective mass transfer What are the units of these terms? J - g/cm2s PM - cm/s Jv - cm3/cm2 s

22. 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 Why do we need a small priming volume? Why do we want a low flow resistance on the blood side?Why do we need a small priming volume? Why do we want a low flow resistance on the blood side?

23. 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 Thin, stagnant films are assumed to be adjacent to fully mixed bulk regions. Of course this is not literally true -rather the degree of mixing decreases gradually as we move from bulk towards the surface. Mass transfer near the wall only occurs by diffusion since mixing is minimal and there is no fluid motion perpendicular to the surface Draw in concentration profiles for each of the different layers - Remember partitioning between different phases Linear profiles are normal for steady state diffusion across a thin filmThin, stagnant films are assumed to be adjacent to fully mixed bulk regions. Of course this is not literally true -rather the degree of mixing decreases gradually as we move from bulk towards the surface. Mass transfer near the wall only occurs by diffusion since mixing is minimal and there is no fluid motion perpendicular to the surface Draw in concentration profiles for each of the different layers - Remember partitioning between different phases Linear profiles are normal for steady state diffusion across a thin film

24. Assume linear profiles in the films and in the membrane Define a partition coefficient a Why would the partition coefficient between the blood and membrane phases and between the membrane and dialysate phases be equal?Why would the partition coefficient between the blood and membrane phases and between the membrane and dialysate phases be equal?

26. 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

29. Note also that Ko can be defined in terms of resistances to mass transfer Also note that CB and CD will vary with position - CB is high at the arterial end and low at the exit. CD will depend on whether using cocurrent or countercurrent flow.Also note that CB and CD will vary with position - CB is high at the arterial end and low at the exit. CD will depend on whether using cocurrent or countercurrent flow.

30. 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

31. Consider a differential element of the dialyzer dW is the mass transferred in a differential element per unit timedW is the mass transferred in a differential element per unit time

34. W = DCxQW = DCxQ

35. 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

36. Performance -Clinical Approach Clearance / dialysance - more clinical than fundamental

37. C* is volume of blood completely �cleared� of solute per unit time Maximum value of QB

38. Dialysance Defined by:

39. Extraction ratio Measurement of efficiency E is fraction of solute entering which is removed NT gives measure of mass transfer capabilities of dialyzerE is fraction of solute entering which is removed NT gives measure of mass transfer capabilities of dialyzer

40. If z is small (QB<QD)

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

42. Assume QB = 200 mL/minute QD = high A = 1.0 m2 urea Ko = 0.017 cm/minute

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

44. Integrate to yield

45. Consider: Curea0 = 150 mg/dL Require Curea = 50 mg/dL Using previous data we find that required t is approximately 8 h Expect to know and to be able to use these relationshipsExpect to know and to be able to use these relationships

46. Hemofiltration Cleansing by ultrafiltration Materials removed from the blood by convection Analogous to glomerulus of natural kidney

47. 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

48. 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