Lecture Outline
•Introduction •History of Hemodialysis •Back To Basics: Mechanism of Solute Removal •Hemodialysis Circuit •Hemodialysis Circuit •Modalities of Renal Replacement Therapies Intermittent hemodialysis –High flux dialysis –Hemodiafitration •Summary
History of hemodialysis
John J. Abel & colleagues at Johns Hopkins develops a dialysis system and tests it on animals.
1913
Georg Haas, German physician dialyzes patients with ARF in Giessen, Patient died
Dutchman Willem Kolff
The first hollow-fiber dialyzers
SkeggsLeonards developed the parallel plate dialyzer,
Production of disposable parallel plate dialyzers in Europe. Hollow fiber kidneys were developed
History of hemodialysis
192319451948
John J. Abel & colleagues at Johns Hopkins develops a dialysis system and tests it on animals.
1913
Georg Haas, German physician dialyzes patients with ARF in Giessen, Patient died
Willem Kolff achieves a breakthrough when a patient with ARF survives therapy for the first time.
History of hemodialysis
1960’s Haemodialysis was performed for 8-10 hours, every other day
Early dialysis machines were cumbersome
Dialysis membranes
1980’s … Dialysis hours rapidly contracted to a ‘standard’ 4 hrs per session, 3 times per week
NCDS 1983
1970’s: Drive for shorter dialysis with high urea clearance rate lead to high efficiency dialysis
Equipment/expertise was improving fast
1990’s…. The use of conventional low efficiency membrane has declined.
The search for more biocompatible features & the desire
1980’s1990’s
Dialysis ‘membranes’ were re-usable ‘slabs’ called Kiil plates
Dialysis was confined to only a few centers
Dialysis was available to only a few people
1970’s
NCDS 1983 Urea considered to be an appropriate surrogate marker for small molecule clearance
Kt/V was introduced
Increased the dialysis membrane surface area (KoA)
They succeeded in reducing dialysis time to ~4 hrs, 3 times/wk
1990’s…. The use of conventional low efficiency membrane has declined.
The search for more biocompatible features & the desire
1980’s1990’s
Dialysis ‘membranes’ were re-usable ‘slabs’ called Kiil plates
Dialysis was confined to only a few centers
Dialysis was available to only a few people
1970’s
NCDS 1983 Urea considered to be an appropriate surrogate marker for small molecule clearance
Kt/V was introduced
Increased the dialysis membrane surface area (KoA)
They succeeded in reducing dialysis time to ~4 hrs, 3 times/wk
features & the desire to remove amyloidogenic B2 M has led to high flux dialysis
BASIC CONCEPTS
Mechanisms of Solute and fluid Removal
•Diffusion
•Ultra-filtration
•Convection
•Adsorption
Mechanisms of Solute Removal: DIFFUSION
Solute transport in hemodialysis Primary mechanism: diffusion
Small solute pass through the dialysis membrane down a concentration gradient from a higher plasma concentration to a lower dialysate concentration
Mechanisms of Solute Removal: DIFFUSION
Ultrafiltration
•Movement of FLUIDSthrough a membrane caused by pressure gradient
•Positive, negative and osmotic pressure from non•Positive, negative and osmotic pressure from nonpermeable
Ultrafiltration - removal of fluid from patients blood
Mechanisms of Solute Removal: CONVECTION
CONVECTION Convection is a process where solutes pass across the semipermeable membrane along with the solvent (“solvent drag”) in response to a positive
Mechanisms of Solute Removal: CONVECTION
response to a positive transmembrane pressure
CONVECTION (“ ““ “solvent-drag” ”” ”)
Fluid Flux is a pre-requisite for the removal of solutes, whereas concentration gradient is not.
Note: All these slides have beautiful pictures which will take time for me to incorporate here. Perhaps one day I will add videos or other visuals to make it more easy to understand.
Solute Classes by Molecular Weight
Theres large for example albumin, middle and small for example urea
Mechanisms of Solute Removal: DIFFUSION/CONVECTION
Clearance for Diffusion and Convection
Clearance Profiles by Modality
HEMODIALYSIS CIRCUIT
Hemodialysis Circuit
Main Functions of Hemodialysis Machines
Blood Related functions:
To transport blood from the patient via blood pump to dialyser and back to the patient safely Dialysate Related functions Dialysate Related functions
To prepare dialysis fluid by heating, deaerating and appropriate proportioning of dialysate and treated water and ensuring conductivity and temp of dialysate is maintained
Components of Hemodialysis Machine
The standard machine consists of: •Blood pump •Heparin infusion pump •Dialysis solution delivery system •Dialysis solution delivery system •Heating and degassing •Ultra-filtration controller
Components of Hemodialysis Machine
Monitoring Devices: Blood circuit •Arterial pressure monitoring •Venous pressure monitoring •Venous pressure monitoring •Air bubble detector
Components of Hemodialysis Machine
Monitoring Devices: Dialysis solution circuit •Conductivity •Temperature •Temperature •Bypass valve •Blood leak detector •UF controller
Options available for hemodialysis machine
•Bicarbonate dialysate
•Sodium profiling
•Ultrafiltration controller
•High Flux dialyser
•Hemodiafiltration (HDF)
Criteria to determine if Hemodialysis Machine is safe for use
•Air bubble detector should be able to detect micro bubbles /air passing through the devise and clamp immediately
•All audible and visual alarms should be in working order order
•Blood and dialysate flow rates should be accurate
•Conductivity and temp readings should be within acceptable limits
•All monitoring devices should be in good working order
Definition Definition Efficiency/Flux/Permeability
Efficiency
•Measure of urea clearance
•KoA=urea mass transfer co-efficient
•High efficiency is achieved by increasing surface •High efficiency is achieved by increasing surface area (A) of dialysis membrane
Efficiency
Qb =200 300 400 urea (ml/min) 195 267 315
Polyflux 21 s: KoA 1238 ml/min Qd=500 ml/min
Low efficiency: KoA <450 div="" min="" ml="">
High efficiency: KoA >450 mL/min
Flux
•Measure of UF capacity
•based on the ultrafiltration coefficient (Kuf)
•Kuf= the volume removed (in ml) perhour per mmHg of applied transmembrane pressure(TMP) of applied transmembrane pressure(TMP)
•Low flux: •Kuf < 15mL/h/mm Hg
•High flux: •Kuf > 20 mL/h/mm Hg
Permeability
•Measure of the clearance of the middle molecular weight
molecule (eg, B2-microglobulin)
•General correlation between flux and permeability •General correlation between flux and permeability
•Low permeability: B2-microglobulin clearance <10 div="" min="" ml="">
•High permeability: B2-microglobulin clearance >20 mL/min
General correlation exists between the (water) flux and the (middle molecular weight molecule) permeability of dialysis membrane but the are not synonymous
FLUX , EFFICIENCY, PERMEABILITY
A : numerous small pores –allows water flux but not B2 M
B: fewer pores with pore size large enough to allow B2-M transport
The KUf of the 2 membranes are equivalent
Low Efficiency (Conventional) Versus Versus High Efficiency
Efficiency of dialysis
Rate of small solute transfer across membrane
•KoA Urea –urea mass transfer co-efficient. –urea mass transfer co-efficient. –Theoretical maximum urea clearance at infinite blood and dialysate flow rate
Dialyzer urea clearance as a function of KoA and Qb
High Efficiency Dialysis : Technical Requirements
•High Efficiency Dialyser
–Large surface area (A)
–High mass transfer coeeficient (K0) –High mass transfer coeeficient (K0)
•High Blood Flow
•High Dialysate Flow
•Bicarbonate dialysate
CONVENTIONAL/HIGH EFFICIENCY
CharacteristicLow EfficiencyHigh Efficiency
KoA (ml/min)
<500 nbsp="">600
Urea Clearance (ml/min)
<200 nbsp="">200
Blood Flow (ml/min)
<350 nbsp="">350
Dialysate Flow (ml/min)
<500 nbsp="">500
Bicarbonate Dialysate
optimal necessary
Benefits of high efficiency dialysis:
Higher clearance of small solutes, such as urea compared with conventional dialysis without increase in treatment time
•Better control of chemistry •Better control of chemistry
•Potentially reduced morbidity
•Potentially higher patient survival rates
CAUSES OF FAILURE OF HIGH EFFICIENCY DIALYSIS
Access-related
•Low blood flow rate
•High recirculation rate
Time-related
•Patient not adherent to prescribed time
•Staff not adherent to prescribed time
Failure to adjust time for conditions such as alarm, dialysate bypass, and hypotension
Low Flux Versus Versus High Flux
FLUX ,EFFICIENCY AND PERMEABILITY
Flux •Measure of UF capacity •based on the ultrafiltration coefficient (Kuf) •Kuf= the volume removed (in ml) perhour per mmHg •Kuf= the volume removed (in ml) perhour per mmHg of applied transmembrane pressure(TMP) •Low flux: •Kuf < 15mL/h/mm Hg •High flux: •Kuf > 20 mL/h/mm Hg
Hemodialysis
Solute transport in conventional hemodialysis
•Primary mechanism: Diffusion
Low flux dialyser
Hemodialysis Typical Prescription
Conventional HD treatment : 3x per week, 4 hrs/session
Blood pump250-350 ml/min
Dialysate Flow500 ml/min –700 ml/min
Ultrafiltration : 3% of dry weight
Up to 3.9 lit over 4 hrs
Lecture Outlines
•History of hemodialysis •Back To Basic: Mechanism of Solute Removal •Term Definition: Flux/ Permeability •High Flux Hemodialysis –Technical Requirement –Technical Requirement –Potential Benefit •Hemofiltration/Hemodiafiltration (HF/HDF) –Technical Requirement –Potential Benefit •Summary
High Flux
•High flux membranes are all High Efficiency membranes ( as defined by KoA urea)
•In addition, larger pore size and water permeability •In addition, larger pore size and water permeability lead to a high ultrafiltration (Kuf) co-efficient
•Kuf = volume removed in ml/hr/mmHg of applied TMP
High Flux Dialysis
High permeability to solutes: larger pore size High permeability to water: UF co-efficient (Kuf) Large surface area (high KoA)
Kuf •= volume removed in ml/hr/mmHg of applied TMP •Low flux: Kuf < 15mL/hr/mm Hg •High flux: Kuf > 20mL/hr/mm Hg
Characteristic Conventional (High Efficiency)
High flux
KoA (ml/min)
>600 >600
Urea Clearance>200 >200
Urea Clearance (ml/min) >200 >200
Kuf ( ml/mm Hg/h) variable >20
B2 M Clearance (ml/min) variable >20
High Flux Dialysis
Low Flux & high efficiency
ManufacturerModelMembraneKoAKUfSurface Area
TorayB3 1.6 Apolymethylacrylate71881.0
FreseniusF8polysulfone71671.0
BaxterPSN 210polysynthane1044102.0
High Flux
ManufacturerModelMembraneKoAKUfSurface Area
GambroPolyflux 14spolyamide711.7
GambroPolyflux 21spolyamide1238832
FreseniusF80polysulfone945651.8
High Flux: Characteristics
Because of high KUf, high flux HD requires an automated UF control system to avoid accidental profound intravascular volume depletion (which is standard in current HD machines)
High Flux Dialysis
Potential“reverse filtration”: movement of fluid from dialysate to the blood compartment,
•Therefore, need pyrogen free water
•The dialysis membranes are impermeable to intact Endotoxin to intact Endotoxin
•However, their fragments (some of which still are pyrogenic) may be small enough to traverse the membrane.
•Although the membrane is impermeable to bacteria and blood cells, a mechanical break in the membrane could result in bacteremia.
High Flux Dialyser
•Automated UF control system
•Potential “reverse filtration”: movement of fluid
from dialysate to the blood compartment, use of
pyrogen free dialysate is preferred
Potential benefit high flux dialysis:
β2microglobulin clearance
β2microglobulin
100 amino acids •Single polypeptide chains, globular structure β ββ β2microglobulin globular structure •11 815 Dalton •Daily production = 150-200 mg (3 mg/kg/D) •Normal serum level = 1.2-2.7 mg/l •95% metabolized by the kidneys
Potential benefit of high flux dialysis: Dialysis related amyloidosis
RR of carpal tunnel syndrome in patients receiving high flux treatment is 40% lower than those receiving conventional therapy
Until slide 56 of 71...now its become slow again.
To be continued...
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