1 • Dialyzer clearance is expression of A. The performance of a dialyzing process B. The volume of blood totally cleared of a given substance per unit time C. The blood solute flux rate per minute D. Both A & B E. Both B & C 2 • Which one of the following does not influence dialyzer urea clearance A. B. C. D. E. Blood flow rate Dialysate flow rate Membrane permeability Surface area of the dialyzer Blood concentration of urea 3 • Factors affecting the rate of diffusion in hemodialysis include all of these EXCEPT A. B. C. D. E. Surface area of dialyzer Membrane size Hydrostatic pressure in blood compartment Membrane pore size distribution Concentration gradient between blood and dialysate 4 • Diffusive resistance include all of the following EXEPT A. B. C. D. Blood film layer thickness Membrane permeability Dialysate film thickness Solute drag 5 • The blood dialysate flow configuration that maintains the optimum blood dialysate concentration gradient A. B. C. D. Concurrent flow Countercurrent flow Crosscurrent flow Recirculation flow 6 • Ultrafiltration during hemodialysis is due to A. Dialysate flow rate B. Blood flow rate C. Osmotic pressure gradient between blood and dialysate D. Hydrostatic pressure gradient between blood and dialysate E. None of above 7 • Ultrafiltration coefficient (KUF) refers to A. The resistance to water removal B. Amount of water removed from blood per unit time as a function of pressure difference C. The amount of water removed per unit time D. The resistance of dialyzer to solute removal 8 • Mass transfer coefficient refers to A. B. C. D. E. Amount of fluid removed per unit time Amount of solute removed per unit time The resistance offered to solute removal The resistance offered to fluid removal None of them 9 • Sieving coefficient depends on all of following EXEPT A. B. C. D. Molecular weight cutoff the membrane Ultrafiltration rate Surface area Diffusion 10 • Factors affecting the net flux include A. B. C. D. E. Membrane surface area Membrane permeability Blood dialysate flow configuration A&B All of the above Functions of the Kidneys • Excretory – Excretion of waste products • Regulatory – Fluid – Electrolytes – Acid base • Hormonal – Rennin – Erythropoietin – 1,25 OH D3 • Metabolic Functions of the Kidneys • Excretory • Regulatory – Electrolytes – Acid base – Fluid • Hormonal – Renin – Erythropoiten – 1,25 OH D3 • Metabolic Solute removal or solute shift Water removal Basic Principals of Dialysis • Principles related to solute removal (mass transfer) – Diffusion – Convection – (Clearance, dialysance, net flux, KoA, sieving coefficient) • Principles related to water removal – Ultrafiltration – Osmosis – (TMP, Ultrafiltration coefficient-KUF) Principles of Dialysis What is Diffusion ? • Movement of the solute through semi permeable membrane from one side to the other on the basis of concentration gradient Diffusion – Random Molecule Movement ` Diffusion – Random Molecule Movement Diffusive resistance ` Diffusion – Random Molecule Movement Diffusive resistance ` Diffusion – Random Molecule Movement Diffusive resistance ` Mass transfer area coefficient KoA Diffusive resistance ` - MW of solute - Pore size, number & distribution - Temperature on either side - Membrane thickness - Diffusive resistance - Membrane surface area – A - Concentration gradient Ko KoA • The rate at which the solutes diffuse through the membrane – overall permeability -transport coefficient expressed as cm2/minute – Ko • KoA is Ko x surface area – • Mass transport area coefficient – ml/min Net flux • Js = KoA ( C ) • Js = Rate of solute movement in mg/min also called as net Flux • Ko = Membrane and solute specific constant cm2/min • A = membrane area cm2 • C = Concentration gradient Ficks A, Annals Physiol 95: 59-74 1855 Ultrafiltration A B Ultrafiltration A B Ultrafiltration Transmembrane pressure (TMP) = Positive pressure A + Negative pressure B Ultrafiltration Pressure (UFP) = TMP – Oncotic Pressure A A B Ultrafiltration Coefficient (KUF) • Hydraulic permeability of the membrane X UFP. Hydraulic permeability • Surface area • Number and size of pores UFP = TMP-Oncotic pressure • Expressed as milliliter of fluid moved per hr per mmHg of ultrafiltration pressure Ultrafiltration & Convection Osmosis Osmosis & Convention Kidney Urine Dialyzer Dialysate Diffusion- KoA Diffusive resistance ` Diffusion in Dialyzer Diffusive force = Concentration gradient Blood Dialysate Countercurrent & Concurrent Js= KoA x log mean concentration gradient Membrane Countercurrent Blood-Dialysate Flow Diffusive force Blood Membrane Dialysate Diffusion in Dialyzer Diffusive force Blood Dialysate Membrane Diffusion in Dialyzer For adequate diffusion Dialysate flow 2-2.5 time blood flow Js= KoA x log mean concentration gradient Dialysate Flow Unstirred layer effect Effect of Dialysate Flow Rate on Membrane Diffusion Blood Flow & Diffusion Wide blood channel Blood Flow & Diffusion Blood Flow & Diffusion Slow Blood Flow Membrane Limited Diffusion Flow Limited Diffusion Effect of Blood Flow on Clearance Dialyzer design Older hollow fiber dialyzer Dialysate out Dialysate out Blood out Blood & dialysate flow geometry Blood in Header Dialysate out Hollow fiber Casing or jacket Dialysate in Dialysate Blood out Blood flow velocity Header modification Blood flow and dialysate flow rate Improved header design Spiral blood flow inlet Smooth cut vs rough cut surface Blood flow velocity Placement of fibers, straight fibers Placement of fibers - Mourie Design Space yarn between fibers Comparison of dialysate flow The densitometry profiles achieved in the three different hemodialyzers are graphically reported (top panels). Claudio Ronco et al. JASN 2002;13:S53-S61 Clearances Wavy (undulated fibers) vs straight OLDER DIALYZER Dialysate entry port Dialysate entry port Pores size and distribution Mass transfer area coefficient-KoA of Dialyzer • Product of overall mass transfer coefficient (Ko) for a given solute x dialyzer surface area (A) • Expressed as ml/min Diffusion in Hollow Fiber Dialyzer • Concentration gradient – – – – – Blood flow rate – channel width Dialysate flow rate - channel width Directions of blood and dialysate flow Molecular weight of solute Shape, size of molecule • Membrane property – – – – – of Dialyzer for Surface area-number of pores particular salute Size of pores ie. KoA urea Distribution of pores At particular blood and dialysate flow rate Thickness of membrane Temperature of solution Dialyzer KoA Calculated from clearance, blood flow, dialysate flow Qb.Qd Ln KoA = Qb - Qd 1-Kd/Qb 1-Kd/Qd Kd: Dialyzer clearance Qb: Blood flow Qd: dialysate flow KoA: Mass transfer area coefficient • Diffusion is greater for small molecules as compared to larger molecules • Low flux: molecular wt cut off = 10000 deltons • High flux: molecular weight cut off = 30000 deltons Distribution of pore size A B Categorization of molecules Sieving coefficient • It refers to the amount of solute removed by convection • A sieving coefficient = Concentration in the ultrafiltrate Concentration in blood A sieving coefficient of 0.5 for a solute means that 50% of that solute will pass through membrane during ultrafiltration Sieving coefficient • Depends on – Molecular weight cutoff of the membrane – Ultrafiltration rate – Membrane surface area Sieving coefficient Dialysance Rate of removal Dialysance = Concentration gradient Clearance & Dialysance Rate of removal Clearance = mean of inflow & outflow concentration Rate of removal per min= Blood flow x (inflow concentration - outflow concentration Blood flow Ml/min Inflow Concentration Outflow Concentration Dialysance Dialysate Blood flow Ml/min Sodium Urea Sodium On line urea clearance = Sodium dialysance Functions of the Kidneys • Excretory Solute removal (Urea,creatinine etc.) • Regulatory – Electrolytes – Acid base – Fluid • Hormonal • – Renin – Erythropoiten – 1,25 OH D3 Catabolic Solute shift Water removal Dialysance Dialysate Blood flow Ml/min Sodium Potassium Sodium Potassium Calcium Calcium Bicarbonate Magnesium Bicarbonate Magnesium Shift of solute per minute = Blood flow per minute (Inflow – outflow concentration) Difference of concentration in blood & dialysate Effect of Pore Distribution & Solute MW on KoA A = Low flux cellulose membrane, B= High flux membrane Low Flux Cellulose Membrane High Flux Membranes Erythrocyte Diffusion Barriers Urea Creatinine Phosphate Effect of Hematocrit on Clearance Effect of Flow on Membrane Filtration • Flux – Measure of ultrfiltration capacity – Low or high flux dialyzers based on KUF – Low flux when KUF < 10 ml/hr/mmHg – High flux when KUF > 20 ml/hr/mmHg • Permeabilty – Related to middle molecular clearance – Low & high permeability=B2 microglobulin clearance < 10 and > 20 ml/min • Efficacy • Related to urea clearance of dialyzer urea clearance – KoAurea – Low efficacy – KoAurea < 500 ml/min – High efficacy – KoAurea > 600 ml/min RRTs – Principles of Dialysis Diffusion Convection Ultrafiltration Osmosis Conventional Hemodialtsis +++ + + + High Efficiency HD ++++ + + + High Flux Dialysis +++ +++ +++ + Hemofiltration - ++++ ++++ - Hemodialfiltra tion +++ ++++ ++++ + Peritoneal Dialysis +++ - - ++