Dialyzer

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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
History
istory
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 Abel’s 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
Hollow fibre
Dialysate in
dialyser
Hollow Fib re membran e

Dialysate
out
Dialysate Out

Outside the Fibre (efflu ent)


Insi de the Fibre (blood )
Blood out

Dialysate
in
diameter ( in microns)
Characteristics of a dialyzer
Hollow fibre artificial kidney (dialyzer)
thickness
Blood inlet • Fibre : - diameter (measured
in microns)
Potting material - length
- thickness
Dialysate port & outlet

Fibre Design : individual fibre ,allows


better membrane transport
therefore allows efficient
Dialysate port & inlet clearance
End cap
Membrane structure:
Blood outlet
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 Blood flow (Qb) 300ml/min


 Urea 171 216
 Creatinine 142 170
 Phosphate 118 149
 Vit B12 45 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
Urea- 60
Creatinine - 113
Phosphates - 120
Uric acid - 168
Aluminium - 700
Phosphorus - 838
• Molecular Weight (cont)

Vit B12 - 1355


Inulin - 5000
Heparin - 8000 - 12000
Vit B2 - 11000
Albumin - 68000
Globulin - 180000
RBC / WBC - > above
Molecular Weights
100,000 ___
• Albumin (55,000 - 60,000)
50,000 ___

10,000 ___ • Beta, Microglobulin (11,800) “Large”


• Inulin (6,200)
5,000 ___

• Vitamin B12 (1,355)


1,000 ___
• Aluminium/desfroxamine complex (700) “middle”
500___

• Glucose (180)
• Uric Acid (160)
100___
• Creatinine (113)
• Phosphate (80)
50___ • Urea (60)
• Potassium (35) “small”
• Phosphorus (31)
• Sodium (23)
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 :Polyurethane (PUR)
• Housing,cap ;Polycabonate (PC)
• Sterile Plug :Polyprophylene (PP)

Sterilisation methods :Ethylene Oxide (ETO)


:Gamma (Wet)
:Steam
Other factors causes bio-
incompatibility
• 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

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