Types of Dialyzer

TYPE OF DIALYZERS, CLEARANCE TYPE OF DIALYZERS, CLEARANCE AND BIOCOMPATIBILITYAND BIOCOMPATIBILITY

BYBY

HAJI HUSIN HARUN (MA)HAJI HUSIN HARUN (MA)

DIALYSIS MANAGER HEMODIALYSIS UNITDIALYSIS MANAGER HEMODIALYSIS UNIT

HOSPITAL SELAYANGHOSPITAL SELAYANG

DIALYZERDIALYZERA dialyzer is composed of a dialysis A dialyzer is composed of a dialysis

membrane and supporting structure. There membrane and supporting structure. There are four components:are four components:

Blood compartmentBlood compartmentDialysate compartmentDialysate compartmentSemi permeable membrane separating (1) Semi permeable membrane separating (1)

and (2)and (2)Membrane support structureMembrane support structure

MembraneMembrane

A membrane can be described A membrane can be described as an imperfect barrier as an imperfect barrier between two solutionbetween two solution

TYPES OF DIALYZERTYPES OF DIALYZER

Kiil dialyzerKiil dialyzer Coil dialyzerCoil dialyzer Parallel Plate dialyzer (PPD)Parallel Plate dialyzer (PPD) Hollow fibre dialyzerHollow fibre dialyzer

The hollow fibre dialyzer is the most popular of the The hollow fibre dialyzer is the most popular of the above four types and is composed of a group of above four types and is composed of a group of between 8000 to 12,000 fibre like structures between 8000 to 12,000 fibre like structures (capillaries) with an internal diameter of 200 microns(capillaries) with an internal diameter of 200 microns

HistoryHistory

Organ centered specialties including Organ centered specialties including NephrologyNephrologywas developed in Europewas developed in Europe

It took more than a decade such developmentIt took more than a decade such developmentcame to this countrycame to this country

Early FiftiesEarly Fifties

Historical Perspective on the Development Historical Perspective on the Development of Artificial Organsof Artificial Organs

1854 - Graham used an ox bladder membrane (principles of dialysis)

1855 - Fick, used a collodion membrane 1923 - Haas, first in Vivo dialysis in man (collodion tubes) 1938 - first cellophane artificial kidney - Thalhemer 1943 - Rotating drum dialyzer by Kolff 1946 - First complete artificial kidney (dialysis and ultrafiltration

by Alwall 1946 1955 - First disposable twin-coil dialyzer by Kolff and

Watschinger

Development of dialysis during a Development of dialysis during a century down to the 1950scentury down to the 1950s• In the years before world war 1, In the years before world war 1,

Abel and collaborators developed Abel and collaborators developed a designed of hemodialyser - a designed of hemodialyser - named ‘artificial kidney’named ‘artificial kidney’

• Similar to modern capillary kidneySimilar to modern capillary kidney

• Consisting of a system hand-Consisting of a system hand-made collodion tubes for study in made collodion tubes for study in animal experimentanimal experiment

• Clotting was prevented by means Clotting was prevented by means of hirudin extracted from the of hirudin extracted from the heads of leechesheads of leeches

• Experiments were discontinued Experiments were discontinued owing to the warowing to the war

• George Haas (German George Haas (German Physician) tried hemodialysis Physician) tried hemodialysis in uremic patient in Giessenin uremic patient in Giessen

• In second part of the 1920s, In second part of the 1920s, he performed six dialysis in he performed six dialysis in six casessix cases

• The blood was passed The blood was passed through of six hand made through of six hand made aggregates of Abel’s type in aggregates of Abel’s type in order to increase surface order to increase surface areaarea

Development of dialysis during a Development of dialysis during a century down to the 1950s century down to the 1950s (cont)(cont)

Fundamental technical in Fundamental technical in hemodialysishemodialysis

• In 1938, Wilhelm In 1938, Wilhelm Thalmer studies on Thalmer studies on fractionated dialysis of fractionated dialysis of dog in apparatus made dog in apparatus made of cellophane tubingof cellophane tubing

• Cellophane was to Cellophane was to become the key of become the key of further developmentfurther development

The first dialyser with sufficient The first dialyser with sufficient capacity for therapycapacity for therapy• Well known rotating drum Well known rotating drum

dialyser published by Kolff in dialyser published by Kolff in 19431943

• Blood enters and leaves the Blood enters and leaves the cellophane tubing (30 -40 m cellophane tubing (30 -40 m in length) through rotating in length) through rotating couplingcoupling

• Total area of the membrane Total area of the membrane (S.A) approximately 2.4 sqm(S.A) approximately 2.4 sqm

• The lower part of the drum is The lower part of the drum is immersed in an open tank immersed in an open tank containing approximately containing approximately 100 litres of dialysis fluid100 litres of dialysis fluid

• Figure 5Figure 5 shows the shows the modified Kolff - Brigham modified Kolff - Brigham dialyser, equipped with dialyser, equipped with a hood to prevent a hood to prevent evaporationevaporation

The first dialyser with sufficient The first dialyser with sufficient capacity for therapy capacity for therapy (cont)(cont)

Dialysers of special historical interest Dialysers of special historical interest constructed in the late 1940sconstructed in the late 1940s

Parallel-flow dialyser Parallel-flow dialyser described by Skeggs and described by Skeggs and Leonards of Claveland in Leonards of Claveland in 1948, which is the forerunner 1948, which is the forerunner of modern plate kidneys. It of modern plate kidneys. It was not disposablewas not disposable

The blood flows between two The blood flows between two sheets of cellophane sheets of cellophane membrane sandwiched membrane sandwiched between grooved rubber between grooved rubber pads carrying the dialysis pads carrying the dialysis fluidfluid

• End of 1940s, Von End of 1940s, Von Garrelts of Stockholm Garrelts of Stockholm constructed the first constructed the first compact coil kidneycompact coil kidney

• It is the forerunner of It is the forerunner of the later types of coil the later types of coil devices.devices.

Dialysers of special historical interest Dialysers of special historical interest constructed in the late 1940s constructed in the late 1940s (cont)(cont)

First artificial kidney which First artificial kidney which allowed hemodialysis as well as allowed hemodialysis as well as ultrafiltration by pressure made ultrafiltration by pressure made in 1942in 1942

The cellophane tubing is wound The cellophane tubing is wound round a vertical stationary round a vertical stationary cylinder of metal netting and cylinder of metal netting and rest in a track made of a thin rest in a track made of a thin metal wiremetal wire

It is submerged in a glass tank It is submerged in a glass tank closed with a lid.closed with a lid.

The dialysis fluid, moved by a The dialysis fluid, moved by a propeller, circulate around the propeller, circulate around the tubing.tubing.

Artificial kidneys for hemodialysis and/or Artificial kidneys for hemodialysis and/or ultrafiltrationultrafiltration

TYPES OF DIALYZERTYPES OF DIALYZER

• Kiil dialyzer• Coil dialyzerCoil dialyzer• Parallel Plate dialyzer (PPD)Parallel Plate dialyzer (PPD)• Hollow fibre dialyzerHollow fibre dialyzer

The hollow fibre dialyzer is the most popular of the The hollow fibre dialyzer is the most popular of the above four types and is composed of a group of above four types and is composed of a group of between 8000 to 12,000 fibre like structures between 8000 to 12,000 fibre like structures (capillaries) with an internal diameter of 200 microns(capillaries) with an internal diameter of 200 microns

Kiil dialyzerKiil dialyzer

• Used by HKL 1964Used by HKL 1964• Assemble by dialysis Assemble by dialysis

staff before HD sessionstaff before HD session• Treatment timeTreatment time

– 8 hrs to 10 hrs8 hrs to 10 hrs

• Problem - massive Problem - massive blood leakblood leak

• High mortality rateHigh mortality rate

Semi Automatic (Biosystem Mark 300)Semi Automatic (Biosystem Mark 300)

Haemodialysis

Patient on HD using Kiil dialyserPatient on HD using Kiil dialyser

Coil dialyzerCoil dialyzer

• Use by HKL from 1975 to 1978

• HKL used till 1978HKL used till 1978

Coil dialyzerCoil dialyzer

Hollow Fibre DialyzerHollow Fibre Dialyzer

Anatomy of a Hemofilter

Hollow Fibre membrane

Blood in

Blood out

Dialysate in

Dialysate Out

Cross Section

Outside the Fibre (effluent)Inside the Fibre (blood)

Dialysate out

Dialysate in

Hollow fibre dialyser

Characteristics of a dialyzer

Hollow fibre artificial kidney (dialyzer)

Blood inlet

Dialysate port & inlet

Dialysate port & outlet

Blood outlet

End cap

Potting material

Fibre

• Fibre : - diameter - length - thickness

Design : individual fibre ,allows better membrane transporttherefore allows efficient clearance

diameter ( in microns)

thickness(measured in microns)

Membrane structure:

1. symmetric – pores on both sides of membrane are same in size

2. Asymmetric – pores on dialysate side of membrane are larger in size.

Anatomy of the KidneysAnatomy of the Kidneys


TYPES OF MEMBRANE USED IN TYPES OF MEMBRANE USED IN HOLLOW FIBRE DIALYZERHOLLOW FIBRE DIALYZER

• Regenerated CelluloseRegenerated Cellulose– CuphrophaneCuphrophane

– Cuprammonium rayon (CAR)Cuprammonium rayon (CAR)

– Safonified cellulose esther (SCE)Safonified cellulose esther (SCE)

• Substitute Cellulose Substitute Cellulose – Cellulose acetateCellulose acetate

– HemophaneHemophane

• SyntheticsSynthetics– Polyacrylonitrile (PAN)Polyacrylonitrile (PAN)

– Polymethylmethacrylate (PMMA)Polymethylmethacrylate (PMMA)

– Polysuphone (PS)Polysuphone (PS)

– Polycarbonate (PC)Polycarbonate (PC)

– Polyamide (PA)Polyamide (PA)

Regenarated Cellulose MembraneRegenarated Cellulose Membrane

• Cuphrophan• e.g. Terumo

NotesNotes• Cuphrophane has been used for more Cuphrophane has been used for more

than 20 yrs, there is most experience with than 20 yrs, there is most experience with this membrane & it constitutes 45% of this membrane & it constitutes 45% of usage.usage.

• Some of the hydroxyl group of cellulose Some of the hydroxyl group of cellulose polysaccharide has been substituted to e.g polysaccharide has been substituted to e.g acetate, to make modified cellulosic acetate, to make modified cellulosic membranes - about 30% of current total membranes - about 30% of current total usage.usage.

• Cupramonium Rayon Cupramonium Rayon membranemembrane

• e.g: Asahie.g: Asahi


• Safonified Safonified cellulose esther cellulose esther (SCE)(SCE)

• e.g: C-DAKe.g: C-DAK


Substitute CelluloseSubstitute Cellulose

• Cellulose acetate Cellulose acetate membranemembrane

• e.g: CDAK 4000e.g: CDAK 4000

• Cellulose acetateCellulose acetate

Substitute CelluloseSubstitute Cellulose

• Polysulfone• Polyamide

Synthetics MembraneSynthetics Membrane

Synthetics membraneSynthetics membrane

• PolyamidePolyamide• High fluxHigh flux• S.A 2.1 mS.A 2.1 m22,, 1.7 m1.7 m22

• e.g Gambroe.g Gambro


DIALYZER FLUXDIALYZER FLUX

• Low (standard) flux dialyzerLow (standard) flux dialyzer– Substances larger then 8000 daltons do not across the membraneSubstances larger then 8000 daltons do not across the membrane– Small “marker” molecules such as urea and creatinine pass through Small “marker” molecules such as urea and creatinine pass through

freelyfreely– Pores are small and this is reflected by the low ultrafiltration Pores are small and this is reflected by the low ultrafiltration

coefficient (between 2 to 9 ml/mmHG/hour)coefficient (between 2 to 9 ml/mmHG/hour)– Mainly cellulosic and some sinthetic membraneMainly cellulosic and some sinthetic membrane

• Intermidiate FluxIntermidiate Flux– UF coefficient 10 - 19 ml/mmHg/hourUF coefficient 10 - 19 ml/mmHg/hour– Sythetic membranes and altered cellulosicSythetic membranes and altered cellulosic

• Polyacrylonitrile (PAN)Polyacrylonitrile (PAN)• PolysulfonePolysulfone• Polymethylmethacrylate (PMMA)Polymethylmethacrylate (PMMA)

DIALYZER FLUX (cont)DIALYZER FLUX (cont)

• High Flux DialyzerHigh Flux Dialyzer– Substances larger then 8000 daltons cross the Substances larger then 8000 daltons cross the

membranemembrane– A high performing high flux dialyzer has sieving A high performing high flux dialyzer has sieving

coefficient forcoefficient for beta 2-beta 2-microglobulin > 0.6microglobulin > 0.6

– Ultrafiltration coefficient are generally > 20 Ultrafiltration coefficient are generally > 20 ml/mmHg/hour reflecting the larger pore size (20 - 80 ml/mmHg/hour reflecting the larger pore size (20 - 80 ml/mmHg/Hour)ml/mmHg/Hour)

– Mainly hemofiltersMainly hemofilters

SIEVING COEFFICIENTSIEVING COEFFICIENT

• Defined as membrane permeability to Defined as membrane permeability to solutes during ultrafiltrationsolutes during ultrafiltration– Small solutes pass through without problemsSmall solutes pass through without problems– Permeability decreased with increasing Permeability decreased with increasing

molecular weight sizemolecular weight size– Always expressed as a percentageAlways expressed as a percentage

ADVANTAGES OF HOLLOW FIBRE ADVANTAGES OF HOLLOW FIBRE DIALYZERDIALYZER

Low or small priming volumeLow or small priming volume Handy, small and compactHandy, small and compact Increase clearance of middle moleculesIncrease clearance of middle molecules Good ultrafiltration rate (UFR)Good ultrafiltration rate (UFR) No rebuilding No rebuilding Reduced risk of leakageReduced risk of leakage

Clearance (K) of a substanceClearance (K) of a substance

• The volume of blood (or plasma) from which a substance is The volume of blood (or plasma) from which a substance is completely clear by the dialyzer per unit time (ml/min). The completely clear by the dialyzer per unit time (ml/min). The clearance values provided by the manufacturer for urea clearance values provided by the manufacturer for urea (molecular weight 60d)or creatinine (molecular weight 112) etc. (molecular weight 60d)or creatinine (molecular weight 112) etc. are in vitro values and slightly over estimated.are in vitro values and slightly over estimated.

• The formula used to calculate clearance (CL) is:The formula used to calculate clearance (CL) is:

CL = CL = A - VA - V x Qb ml/min x Qb ml/min

AA

A = arterial sample (urea)A = arterial sample (urea)

V = venous sample (urea)V = venous sample (urea)

Clearance (K) of a substance Clearance (K) of a substance (cont)(cont)

Dialyzer ClearanceDialyzer Clearance

The clearance of solutes (in ml) removed in one minute at blood The clearance of solutes (in ml) removed in one minute at blood flow of 200 ml/min and 300 ml/minflow of 200 ml/min and 300 ml/min

Example TAF 10 Terumo C10L) dialyzerExample TAF 10 Terumo C10L) dialyzer

Blood flow (QBlood flow (Qbb) 200ml/min) 200ml/min Blood flow (Q Blood flow (Qbb) 300ml/min) 300ml/min

UreaUrea 171171 216216 CreatinineCreatinine 142142 170170 PhosphatePhosphate 118118 149149 Vit B12Vit B12 4545 4646

Clearance (K) of a substance Clearance (K) of a substance (cont)(cont)

• Urea Reduction Rate (URR)Urea Reduction Rate (URR)

• The formula used to calculate URR is:The formula used to calculate URR is:

URR = URR = Pre urea - Post ureaPre urea - Post urea x 100% x 100%

Pre ureaPre urea

Pre urea samplePre urea sample = arterial sample before commencing HD= arterial sample before commencing HD

Post UreaPost Urea = arterial sample toward end of HD session= arterial sample toward end of HD session

ResultsResults

< 60%< 60% -- Not goodNot good

> 60%> 60% -- PreferablePreferable

MoleculeMolecule A stable configuration of atomic nuclei and electron e.g.; water (H2O) consists of two

hydrogen atoms and one oxygen atoms.

Molecular Weight

The weight of the sum of the atoms (dalton) e.g.:

Sodium - 23

Calcium - 40

Urea - 60

Creatinine - 113

Phosphates - 120

Uric acid - 168

Aluminium - 700

Phosphorus - 838

• Molecular Weight (cont)Molecular Weight (cont)

Vit B12Vit B12 -- 13551355

InulinInulin -- 50005000

HeparinHeparin -- 8000 - 120008000 - 12000

Vit B2Vit B2 -- 1100011000

AlbuminAlbumin -- 6800068000

GlobulinGlobulin -- 180000180000

RBC / WBCRBC / WBC -- > above> above

Molecular WeightsMolecular Weights100,000 ___

50,000 ___

10,000 ___

5,000 ___

1,000 ___

500___

100___

• Glucose (180)

• Uric Acid (160)

• Creatinine (113)

• Phosphate (80)

50___

• Potassium (35)

• Phosphorus (31)

• Sodium (23)

• Urea (60)

10___

5___ 0___

“Large”• Albumin (55,000 - 60,000)

• Inulin (6,200)

• Beta, Microglobulin (11,800)

• Vitamin B12 (1,355)

• Aluminium/desfroxamine complex (700) “middle”

“small”

NotesNotes• All membranes are * hydrophillic except All membranes are * hydrophillic except

PA,PS,PMMA,PAN which are ** hydrophobic. The later PA,PS,PMMA,PAN which are ** hydrophobic. The later are apolar, adsorb protein, are porous and have high are apolar, adsorb protein, are porous and have high coefficiency.coefficiency.

• Synthetic polymer (biocompatible membranes) account Synthetic polymer (biocompatible membranes) account for 25% of usage and have been use for about 10 yrs.for 25% of usage and have been use for about 10 yrs.

• Most membrane are similar clearance for small Most membrane are similar clearance for small molecules but synthetic one have increased clearance molecules but synthetic one have increased clearance of middle molecules and higher UF coefficient.of middle molecules and higher UF coefficient.

* absorbing and wet the membrane smoothly

** Incapable of desolving in water

Characteristic of a dialyzerCharacteristic of a dialyzer

• MembraneMembrane– TypeType– Wall Thickness (permeability)Wall Thickness (permeability)– Surface area ( The area of the membrane Surface area ( The area of the membrane

exposed to the blood - effectivenessexposed to the blood - effectiveness• PerformancePerformance

– UFR (the amt of fluid remove in a given UFR (the amt of fluid remove in a given period of time at a given pressure.period of time at a given pressure.

– Clearance (the vol of blood completely Clearance (the vol of blood completely cleared of a substance in a certain timecleared of a substance in a certain time

– Stable Performance ( as well during the Stable Performance ( as well during the treatment as from batch to batch)treatment as from batch to batch)


• Overall designOverall design– Flow geometryFlow geometry– Internal resistance (the pressure drop in the blood and Internal resistance (the pressure drop in the blood and

dialysis fluid during passage through the dialyzerdialysis fluid during passage through the dialyzer– Size & weight (important for handling and storage)Size & weight (important for handling and storage)

• VolumeVolume– Priming volume (the vol of the blood compartment)Priming volume (the vol of the blood compartment)– Compliance (the volume increase of the blood Compliance (the volume increase of the blood

compartment at increasing pressures (ml/mmHg)compartment at increasing pressures (ml/mmHg)– RBV (the amount of blood left in the dialyzer after RBV (the amount of blood left in the dialyzer after

rinseback.rinseback.

• MaterialMaterial– SterileSterile– BiocompatibleBiocompatible


Components MaterialComponents Material• Membrane typeMembrane type ::• Potting materialPotting material :Polyurethane (PUR):Polyurethane (PUR)• Housing,cap Housing,cap ;Polycabonate (PC);Polycabonate (PC)• Sterile PlugSterile Plug :Polyprophylene (PP):Polyprophylene (PP)

Sterilisation methodsSterilisation methods :Ethylene Oxide (ETO):Ethylene Oxide (ETO)

:Gamma (Wet):Gamma (Wet)

:Steam:Steam

Other factors causes bio-Other factors causes bio-incompatibilityincompatibility

• Types of dialysateTypes of dialysate• Other materials in the circuit e.g. Other materials in the circuit e.g.

Bloodlines, blood accessBloodlines, blood access• ETO, steam or gamma ray sterilization ETO, steam or gamma ray sterilization • ReuseReuse• SterilantSterilant

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Types of Dialyzer