TYPE OF DIALYZERS, CLEARANCE AND BIOCOMPATIBILITY

BY HAJI HUSIN HARUN (MA) DIALYSIS MANAGER HEMODIALYSIS UNIT HOSPITAL SELAYANG

DIALYZER
A dialyzer is composed of a dialysis membrane and supporting structure. There are four components: Blood compartment Dialysate compartment Semi permeable membrane separating (1) and (2) Membrane support structure

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

TYPES OF DIALYZER
Kiil dialyzer Coil dialyzer Parallel Plate dialyzer (PPD) Hollow fibre dialyzer The hollow fibre dialyzer is the most popular of the above four types and is composed of a group of between 8000 to 12,000 fibre like structures (capillaries) with an internal diameter of 200 microns

H ory istory ist

Early Fifties

Organ centered specialties including Nephrology was developed in Europe I t took more than a decade such development came to this country

Historical Perspective on the Development of 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 century down to the 1950s

In the years before world war 1, Abel and collaborators developed a designed of hemodialyser - named artificial kidney Similar to modern capillary kidney Consisting of a system hand-made collodion tubes for study in animal experiment Clotting was prevented by means of hirudin extracted from the heads of leeches Experiments were discontinued owing to the war

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

George Haas (German Physician) tried hemodialysis in uremic patient in Giessen In second part of the 1920s, he performed six dialysis in six cases The blood was passed through of six hand made aggregates of Abels type in order to increase surface area

Fundamental technical in hemodialysis

In 1938, Wilhelm Thalmer studies on fractionated dialysis of dog in apparatus made of cellophane tubing Cellophane was to become the key of further development

The first dialyser with sufficient capacity for therapy

Well known rotating drum dialyser published by Kolff in 1943 Blood enters and leaves the cellophane tubing (30 -40 m in length) through rotating coupling Total area of the membrane (S.A) approximately 2.4 sqm The lower part of the drum is immersed in an open tank containing approximately 100 litres of dialysis fluid

The first dialyser with sufficient capacity for therapy (cont)

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

Dialysers of special historical interest constructed in the late 1940s

Parallel-flow dialyser described by Skeggs and Leonards of Claveland in 1948, which is the forerunner of modern plate kidneys. It was not disposable The blood flows between two sheets of cellophane membrane sandwiched between grooved rubber pads carrying the dialysis fluid

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

End of 1940s, Von Garrelts of Stockholm constructed the first compact coil kidney It is the forerunner of the later types of coil devices.

Artificial kidneys for hemodialysis and/or ultrafiltration

First artificial kidney which allowed hemodialysis as well as ultrafiltration by pressure made in 1942 The cellophane tubing is wound round a vertical stationary cylinder of metal netting and rest in a track made of a thin metal wire It is submerged in a glass tank closed with a lid. The dialysis fluid, moved by a propeller, circulate around the tubing.

TYPES OF DIALYZER
Kiil dialyzer Coil dialyzer Parallel Plate dialyzer (PPD) Hollow fibre dialyzer

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

Kiil dialyzer
Used by HKL 1964 Assemble by dialysis staff before HD session Treatment time
8 hrs to 10 hrs

Problem - massive blood leak High mortality rate

Semi Automatic (Biosystem Mark 300)

Haemodialysis

Patient on HD using Kiil dialyser

Coil dialyzer
Use by HKL from 1975 to 1978

Coil dialyzer
HKL used till 1978

Hollow Fibre Dialyzer

Anatomy of a Hemofilter
Blood in Cross Section Dialysate in

Hollow Fib re membran e

Hollow fibre dialyser

Dialysate out
Dialysate Out

Blood out

Outside the Fibre (efflu ent) Insi de the Fibre (blood )

Dialysate in

Characteristics of a dialyzer
Hollow fibre artificial kidney (dialyzer) Blood inlet Potting material Dialysate port & outlet Fibre Dialysate port & inlet End cap Blood outlet

diameter ( in microns)

Fibre : - diameter
- length - thickness

(measured in microns)

thickness

Design : individual fibre ,allows better membrane transport therefore allows efficient clearance 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 Kidneys

Anatomy of the Kidneys

TYPES OF MEMBRANE USED IN HOLLOW FIBRE DIALYZER

Regenerated Cellulose
Cuphrophane Cuprammonium rayon (CAR) Safonified cellulose esther (SCE)

Substitute Cellulose
Cellulose acetate Hemophane

Synthetics
Polyacrylonitrile (PAN) Polymethylmethacrylate (PMMA) Polysuphone (PS) Polycarbonate (PC) Polyamide (PA)

Regenarated Cellulose Membrane Cuphrophan e.g. Terumo

Notes
Cuphrophane has been used for more than 20 yrs, there is most experience with this membrane & it constitutes 45% of usage. Some of the hydroxyl group of cellulose polysaccharide has been substituted to e.g acetate, to make modified cellulosic membranes - about 30% of current total usage.

Regenarated Cellulose Membrane

Cupramonium Rayon membrane e.g: Asahi

Regenarated Cellulose Membrane

Safonified cellulose esther (SCE)

e.g: C-DAK

Substitute Cellulose
Cellulose acetate membrane e.g: CDAK 4000

Substitute Cellulose
Cellulose acetate

Synthetics Membrane
Polysulfone Polyamide

Synthetics membrane
Polyamide High flux S.A 2.1 m2, 1.7 m2 e.g Gambro

Anatomy of the Kidneys

DIALYZER FLUX
Low (standard) flux dialyzer
Substances larger then 8000 daltons do not across the membrane Small marker molecules such as urea and creatinine pass through freely Pores are small and this is reflected by the low ultrafiltration coefficient (between 2 to 9 ml/mmHG/hour) Mainly cellulosic and some sinthetic membrane

Intermidiate Flux
UF coefficient 10 - 19 ml/mmHg/hour Sythetic membranes and altered cellulosic
Polyacrylonitrile (PAN) Polysulfone Polymethylmethacrylate (PMMA)

DIALYZER FLUX (cont)

High Flux Dialyzer
Substances larger then 8000 daltons cross the membrane A high performing high flux dialyzer has sieving coefficient for beta 2-microglobulin > 0.6 Ultrafiltration coefficient are generally > 20 ml/mmHg/hour reflecting the larger pore size (20 - 80 ml/mmHg/Hour) Mainly hemofilters

SIEVING COEFFICIENT
Defined as membrane permeability to solutes during ultrafiltration
Small solutes pass through without problems Permeability decreased with increasing molecular weight size Always expressed as a percentage

ADVANTAGES OF HOLLOW FIBRE DIALYZER

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

Clearance (K) of a substance

The volume of blood (or plasma) from which a substance is completely clear by the dialyzer per unit time (ml/min). The clearance values provided by the manufacturer for urea (molecular weight 60d)or creatinine (molecular weight 112) etc. are in vitro values and slightly over estimated. The formula used to calculate clearance (CL) is: CL = A - V x Qb ml/min A A = arterial sample (urea) V = venous sample (urea)

Clearance (K) of a substance (cont)

Dialyzer Clearance The clearance of solutes (in ml) removed in one minute at blood flow of 200 ml/min and 300 ml/min Example TAF 10 Terumo C10L) dialyzer Blood flow (Qb) 200ml/min Urea Creatinine Phosphate Vit B12 171 142 118 45 Blood flow (Qb) 300ml/min 216 170 149 46

Clearance (K) of a substance (cont)

Urea Reduction Rate (URR) The formula used to calculate URR is: URR = Pre urea - Post urea x 100% Pre urea Pre urea sample = arterial sample before commencing HD Post Urea = arterial sample toward end of HD session Results < 60% Not good > 60% Preferable

Molecule
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 Urea60 Creatinine 113 Phosphates 120 Uric acid 168 Aluminium 700 Phosphorus 838

 Molecular Weight (cont) Vit B12 Inulin Heparin Vit B2 Albumin Globulin RBC / WBC 1355 5000 8000 - 12000 11000 68000 180000 > above

Molecular Weights
100,000 ___ 50,000 ___ 10,000 ___ 5,000 ___ 1,000 ___ 500___
Glucose (180) Vitamin B12 (1,355) Aluminium/desfroxamine complex (700) Albumin (55,000 - 60,000) Beta, Microglobulin (11,800) Inulin (6,200)

Large

middle

100___

Uric Acid (160) Creatinine (113) Phosphate (80)

50___

Urea (60) Potassium (35) Phosphorus (31) Sodium (23)

small

10___ 5___ 0___

Notes
All membranes are * hydrophillic except PA,PS,PMMA,PAN which are ** hydrophobic. The later are apolar, adsorb protein, are porous and have high coefficiency. Synthetic polymer (biocompatible membranes) account for 25% of usage and have been use for about 10 yrs. Most membrane are similar clearance for small molecules but synthetic one have increased clearance of middle molecules and higher UF coefficient.

* absorbing and wet the membrane smoothly ** Incapable of desolving in water

Characteristic of a dialyzer
Membrane Type Wall Thickness (permeability) Surface area ( The area of the membrane exposed to the blood - effectiveness Performance UFR (the amt of fluid remove in a given period of time at a given pressure. Clearance (the vol of blood completely cleared of a substance in a certain time Stable Performance ( as well during the treatment as from batch to batch)

Characteristic of a dialyzer
Overall design
Flow geometry Internal resistance (the pressure drop in the blood and dialysis fluid during passage through the dialyzer Size & weight (important for handling and storage)

Volume
Priming volume (the vol of the blood compartment) Compliance (the volume increase of the blood compartment at increasing pressures (ml/mmHg) RBV (the amount of blood left in the dialyzer after rinseback.

Material
Sterile Biocompatible

Characteristic of a dialyzer
Components Material Membrane type Potting material Housing,cap Sterile Plug : :Polyurethane (PUR) ;Polycabonate (PC) :Polyprophylene (PP)

Sterilisation methods :Ethylene Oxide (ETO) :Gamma (Wet) :Steam

Other factors causes bioincompatibility

Types of dialysate Other materials in the circuit e.g. Bloodlines, blood access ETO, steam or gamma ray sterilization Reuse Sterilant

 The holl

Thank You