Basic principles of hemodialysis final

1. Hesham Elsayed
Professor of Nephrology
Ain shams university – Cairo Egypt
BASIC PRINCIPLES OF
HEMODIALYSIS

2. HD : a Filtration Therapy
Enhance
the
Clearance
HD
Removal by
Filtration
Removal by
Adsorption
Flux HDF
17 %
Solute
permeability
Solute
Dragging

3. Principles of Hemodialysis
Hemodialysis is a treatment which aims to
1- Remove accumulated metabolic waste products and
2-To correct blood electrolyte composition by means of an
exchange between patient's blood and a dialysate fluid
Across a semi-permeable membrane in a countercurrent
mechanism .
3-To remove excess fluids by means of ultrafiltration

4. Basic Principals of Dialysis
Principles related to solute removal
(mass transfer)
Diffusion
Convection
Principles related to water removal
Ultrafiltration

5. Membrane
Blood
Dialysate
Countercurrent Blood-Dialysate
Flow
Dialysate Flow QD
2 X QB
The counter-current approach is used for intermittent
haemodialysis to provide maximum diffusive gradient as fresh
dialysate fluid is continuously exposed to solute-laden blood
Hemodialysis utilizes counter current flow, where the dialysate is flowing in the opposite
direction to blood flow in the extracorporeal circuit. Counter-current flow maintains the
concentration gradient across the membrane at a maximum and increases the efficiency of
the dialysis
Blood Flow QB

6. In the end , the concentration gradient
remains the same; the solute-depleted
blood is exposed to clean dialysate, and
the concentration gradient remains
unchanged.
in the middle , the concentration gradient
remains the same; the blood is depleted of
solute at the same rate as the dialysate is
enriched by it.
In the first part , the exiting dialysate fluid
is already concentrated, but less so than the
blood. Thus there is still a concentration
gradient.
Countercurrent Blood-Dialysate Flow
Magnitude of the
concentration
gradient
the
Urea
100
mg/dl
50
25

7. Always a
concentration
Gradient

8. Blood & dialysate flow
Blood in
Blood out
Dialysate out
Dialysate in
Hollow fiber
Casing or jacket
Dialysate
Header
Diffusion
process all
through the
Dialyzer length
Maximumspeed

9. Recirculation
Affect the
clearance

10. Blood Flow QB ml/min
Dialysate Flow QD ml/min
Where
QBi is Blood flow inlet in ml/min
QBo is Blood flow outlet in ml/min
QDi is Dialysate flow inlet in ml/min
QDo is Dialysate outflow in ml/min
Where
CBi is concentration of solute in Blood inlet in
mg/dl
CBo is concentration of solute in Blood outlet in
mg/dl
CDi is concentration of solute in Dialysate inlet in
mg/dl
CDo is concentration of solute in Dialysate outlet
in mg/dl

11. Clearance from
Plasma then from
RBCS
Urea diffuse easily
Creatinine less
diffuse from RBC

12. CA: filter inlet concentration
CD: dialysate concentration
QD: dialysate flow
CV: filter outlet concentration

13. Clearance of
molecules

14. Effect of Hematocrit from 20 – 40 %
Urea diffuse from Plasma and Blood , creatinine less and Phosphate Much less
- 8% - 13%

15. Calculation of Clearance
 Dialyzer clearance
Urea pre = 200
Urea post = 20
Clearance = 180 ml /min
Whole session clearance
Urea pre predialysis = 200
Urea post Dialysis = 40
URR = 80%

16. 1/34
Dialyzer
Flux
Surface area m2

17. Diffusion and Backdiffusion
Movement of
molecules from the
blood side is called
Clearance or diffusion
Movement of
molecules from the
Dialysate side is called
BackDiffusion
Removal of Toxins
Removal of excess K+
Backdiffusion of
Bicarbonate
Glucose and Calcuim

18. Semipermeable Membrane
HD will allow certain molecules to pass in Both directions while
it retains other molecules to pass
Albumin and Cells
will not pass

19. Diffusion
 Diffusion is defined as the spontaneous passive transport of
solutes from blood to dialysate (and vice versa, i.e., backdiffusion)
across the dialysis membrane through a concentration gradient .
Equilibrium
Diffusion is Bi-directional
From Blood to Dialysate = Diffusion or
Clearance
From Dialysate to Blood = Back-Diffusion

20. Basic Principals of Dialysis
Diffusion
The rate of diffusive transport depends upon:
1- The diffusion coefficients of the solute in blood, in membrane
and in dialysate.
2-The concentration difference across the Membrane.
3-The surface area of the membrane.
The transport rate of solute is inversely proportional to the
Molecular Wright (MW)
So smaller solute can diffuse easier than bigger molecules .

21. Basic Principals of Dialysis
Diffusion
solute movement against concentration gradient
`
Blood side Dialysate side
Semipermeable
Membrane
Larger solute difuse
slower
Small solutes diffuse
easier

22. Diffusion – Random Molecule Movement
Diffusive resistance
`
Diffusion process is
slower in :
1- Bigger molecules .
2-Thicker Dialysis
membrane
3-low Temperature
4-Low concentration
gradient

23. Dialyzer KoA
 The mass transfer area coefficient (KoA),
expressed in mL/min, for a given solute is the
clearance of the dialyzer at infinitely high blood
and dialysate flow rates on a theoretical basis.
 Therefore, KoA is a measure of the maximum
solute removal capacity of the dialyzer and has
been considered as an intrinsic property of the
dialyzer membrane.

24. Dialyzer KoA
KoA =
Qb.Qd
Qb - Qd
Ln
1-Kd/Qb
1-Kd/Qd
Calculated from clearance, blood flow, dialysate flow
Kd: Dialyzer clearance
Qb: Blood flow
Qd: dialysate flow
KoA: Mass transfer area coefficient

25. Mass transfer area coefficient KoA
Diffusive resistance
`
- MW of solute
- Membrane Pore size, number &
distribution
Membrane thickness
- Diffusive resistance
- Membrane surface area – A
- Concentration gradient
Ko

26. Basic Principals of Dialysis
Convection
Convection is the simultaneous transport of solvent and
solutes from the blood compartment to the dialysate
compartment (and vice versa, i.e.,backfiltration) across
the dialysis membrane

27. HFD versus HDF
Removal of
MM
•Diffusion
•convection
High
Flux
•Diffusion
•Augmented
convection
HDF

28. HDF Dose
Depends on :
 1-Blood volume
processed.
 2- UF and substitution
volume
Volume of
processed Blood
Volume of
convection
volume
QBSV

29. Basic Principals of Dialysis
Convection
The convective process requires a fluid movement
caused by a transmembrane pressure gradient
Solute flux
Depends on
Ultrafiltration Rate (Qf)
Solute concentration in plasma water (Cb)
And Sieving coefficient of the solute (SC)
Removal
rate
Through a
pressure gradient

30. B2m RR% is a linear with substitution volume
45%
50%
58%
65%
70%
78%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
0 40 60 80 100 120
ml/min

31. Basic Principals of Dialysis
Adsorption
 increasing size of middle-sized proteins and
other compounds, relatively more clearance is
achieved by membrane adsorption compared
with loss into the dialysate.
 A high adsorptive capacity, one of the main
features of some dialysis membranes like
polymethylmethacrylate (PMMA) can adsorb
more LMW proteins than others

32. Basic Principals of Dialysis
Adsorption
 Removing PBUT from the blood by means of diffusion and
convection (containing the albumin loss) is virtually
impracticable; however, PBUT can be removed by using the
adsorptive properties of particular biomaterials.
PMMA
High
adsorption
capacity

33. Clark, W. R. et al. J Am Soc Nephrol 2002;13:S41-S47
Effect on membrane function by protein adsorption
With time membrane
clogging by proteins will
close the membrane
pores a phenomenon
called
“Protein Fouling”

34. Basic Principals of Dialysis
Ultrafiltration
 Ultrafiltration is the movement of water across a semi-
permeable membrane because of a pressure gradient
(hydrostatic, osmotic or oncotic).
 UFR = rate of water removal / hour
 QUF of dialyzer = UF capacity / mmHg eg 10 – 80
TMP = UFR / QUF
LF = 1000/10 = 100 mmHg is required
HF = 1000 / 50 = 20 mmHg is required
Volumetric
HD
Machine

35. Basic Principals of Dialysis
Ultrafiltration
Blood pressure within the hollow fibers is positive,
while the pressure outside the hollow fibers is lower.
The difference between the blood pressure in the
hollow fibers and the surrounding pressure is the
TransMembrane Pressure (TMP).
The TMP determines the ultrafiltrate production

36. Basic Principals of Dialysis
Ultrafiltration
Transmembrane pressure
(TMP) =
Positive pressure in Blood side + Negative pressure
in Dialysate side in mmHg
Maximum UF
Higher pressure
Lower UF
Lower pressure

37. Back Filtration
A situation where there is a
transport of fluid from the
dialysis fluid side into the blood
side is called backfiltration.
This is a phenomenon
encountered with High Flux
Dialysis .
And is due to excessive UF
through the first half of dialyzer
that follow a pressure drop in
the second distal part of the
dialyzer

38. HD Backfiltration
Pressure Drop
Back filtration volume is risky for
Pyrogen transfer `… volume ??

39. Basic Principals of Dialysis
Ultrafiltration
The magnitude
of net
filtration in
Haemodialysis
is determined
by
1- The
hydraulic
permeability
of the dialyzer
2-The surface
area of the
membrane,
and by the
geometry of
the dialyzer .
3-the
hydrostatic
and oncotic
forces acting
on the blood
and dialysate
sides of the
membrane.

40. Ultrafiltration and Back Filtration
in different modalities
Low Flux dialyzer has
low KUF so need more
TMP
Backfiltration occur
due to obligatory fluid
loss and pressure drop
HDF remove excess fluids
so needs high TMP all
through the dialyzer
length

41. Ultrafiltration and Back Filtration
High Flux Dialysis

42. HD clearance of solutes
In a clinical setting, the removal
of a solute is measured in terms
of clearance,
the term being defined as the
volume of blood or plasma from
which the solute is completely
removed in unit time. ml/min.

43. HD clearance of solutes
During transit across the dialyzer, most
solutes are removed from plasma water
(about 93% of blood volume, depending on
plasma protein concentration).
the clearance of the solute decreases as the
hematocrit increases (since the plasma
volume decreases).
There is a difference between the
manufacture data ( in vitro test ) from the
actual data in clinics ( in vivo test ).

44. HD clearance of solutes
• Solute Generates slowly
then transport within
the body
Generation
• Generation is slow
enough for equilibration
to occur between
extracellular (interstitial
and plasma) and cellular
water
Equilibration • During HD blood levels
fall sharply but blood re-
equilibrates as urea is
recruited from the body
HD clearance

45. HD clearance of solutes
Diffusion
K = CLEARANCE FOR A GIVEN SOLUTE IN ML/MIN
QB = Blood flow rate ml/min
CBi = cpncentration of solute at Blood inlet mg/dl
CBo = concentration of solute at blood outlet mg/dl

46. HD clearance of solutes
convection

47. HD clearance of solutes
Dialyzer Flux or permeability
• Flux
• Measure of ultrafiltration capacity
• Permeability
• Measure of the clearance of the middle molecular weight molecule (eg,
B2-microglobulin)
• General correlation between flux and permeability
• Efficiency
• Low and high efficiency are based on the urea KoA value
• Low efficiency: KoA <500 mL/min
• High efficiency: KoA >600 mL/min

48. Solute Removal during HD
Hemodialysis Kinetics
Diffusion , convection and Solute Flux index
Body distribution
Intravascular Intracellular / interstitial
Protein bound
Free Bound and %
Solute MW
Small Medium

49. Sieving coefficient
It refers to the amount of solute removed
by convection
A sieving coefficient S =
Concentration in the ultrafiltrate
Concentration in blood
A membrane cutoff is defined when the SC
of a certain solute is below 0.1

50. The solute sieving coefficient of dialyzer
Only High Flux membrane
can remove middle
molecules

51. Factors influencing low-molecular-weight
solute clearance during hemodialysis
Dialyzer related factors :
1- Surface area.
2- membrane type and its diffusive permeability
3-membrane porosity.
4-dialyzer rheology or fiber configuration.
Dialysis related factors :
QB ,QD, Dialysis time .
Patient related factors :
1-Vascular access type.
2-Recirculation%
3-Patient Haematocrite.

52. Clearance by Diffusion in Dialyzer
 Concentration gradient
Blood flow rate
Dialysate flow rate
Directions of blood and dialysate flow
Molecular weight of solute
Shape, size of molecule
Membrane property
Surface area-number of pores
Size of pores
Distribution of pores
Thickness of membrane
of Dialyzer for
particular salute
ie. KoA urea
At particular blood and dialysate
flow rate

53. Increasing Blood flow
Up to a
limit
Clearance of solute is
not linear to the
increased QB

54. Effect of Blood Flow on Clearance

55. Clearance depends on solute MW

56. Dialysate flow rate QD ml/min
At low blood flow rates (<200 mL/min), no difference exists in urea clearance rates between the two
different Qd conditions, because equilibrium in urea concentrations between blood and dialysate is
readily achieved. When the blood flow rate is high (>300 mL/min), the higher Qd maintains a higher
concentration gradient for diffusion of urea, and therefore, the urea clearance rate is higher.

57. Causes of low clearance values despite
use of high efficient dialysis
Vascular access related :
Low Blood flow
High Recirculation rates
Time Related factors :
Not adherent to prescribed dialysis time.
Failure to adjust prescribed time due to repeated
alarms , Hypotension episodes and Dialysate Bypass

58. Improving clearance by better Blood & dialysate
flow geometry
Blood in
Blood out
Hollow fiber
Casing or jacket
Dialysate
Header
Blood to Dialysate matching
to increase the clearance

59. Blood Flow speed is higher in the
center
Dialysate Flow is higher in the
periphery

60. Dialyzer geometry to enhance the performance
Improvement of Blood / Dialysate flow matching
spacer yarns consist of multifilament threads
integrated into the fiber bundles
Improves dialysate distribution throughout the
dialyzer
Micro Undulation technology for better blood-
dialysate matching

61. The Japanese classification of
Dialyzer permeability
 The classification of dialyzers refers to five types,
classified to a clearance (in vitro) of β2-microglobulin
 β2microglobulin (in vitro)
 I < 10 mL/min
 II < 30 mL/min
 III< 50 mL/min
 IV 50-70 mL/min
 V ≧70 mL/min
Worldwide classification
High flux
UFR > 20 mL/mmHg/hr
β2MG sieving coefficient (SC)
>0.6

62. Increasing Flux Risks :
ET transfer
Albumin Loss
Dialysis Membrane Is NOT a One Way Street

63. Hemodiafiltration
2
ET
Filters

64. H2O water soluble molecules
F
mmHg
mmHgB
B
B
D
B
D
mmHgB
mmHg
D
B
D
low-flux
high-flux
Therapy types
Hemodialysis Hemofiltration Hemodiafiltration

65. Methods of delivery of substitution fluids (SF)

66. Convective transport is achieved by an effective
convection volume of at least 20% of the total blood
volume processed
FF % = UFR/ QB = > 25 %

67. Filtration
Fraction
UFR/QB
Nephrol Dial Transplant
(2013) 0: 1–8

68. Pre
dilution
Post
dilution
25 Liters/
session
50 Liters/
session

69. Sterile
Bags
SF

71. Post-
Dilution
HDF
SF> 20
L
Back filtration
On demand
High TMP
`Pre Dilution on Demand
Flushing 200 ml saline
Maintain UF
capacity

72. Mixed
Dilution
HDF
SF> 40 L

73. 
Dialyzer
Hemoconcentration
Vascular Access
Blood Flow
Dialysis Machine
Blood Purif 2015;40(suppl 1):
Hematocrit
Protocrit
Pressure control
Volume control
Main Limiting Factors in Achieving High Convective Volume or Qi

74. Thank you
for your
Attention
Questions
?