Transcript of Basics of peritoneal dialysis
- 1. Basics of Peritoneal Dialysis Dr. Vishal Golay
14-03-2012
- 2. Topic overview History of evolution of CAPD. Anatomy of the
peritoneum. Physiology of the peritoneum with respect to CAPD.
Peritoneal Equilibrium Test.
- 3. If you would understand anything,observe its beginning and
its development. -Aristotle
- 4. History of Peritoneal Dialysis The basics of dialytic
therapy was laid down by Thomas Graham (1805-1869). He described
the Grahams Law, investigated on osmotic forces, separated fluids
by dialysis and also differentiated crystalloids from colliods.
Father of modern dialysis. Ren Dutrochet (1776-1846): introduced
the term osmosis which explains ultrafiltration. Grandfather of
dialysis.
- 5. Recklinghausen, Wegner, Beck, Kollossow (Later half of 19th
century) described the mesothelium, transport of solutes and water
across the peritoneum & also described the pathways of
transport. Starling & Tubby(1894) described that solute
transport was primarily between PC and blood (lymphatic transport
was negligible). Cunningham, Putnam & Engel (Early 20th
century) described the role of peritoneal
- 6. First attempt at PD Georg Ganter (Germany, 1923) was the
first person who applied PD in humans. He published his work in his
paper: On the elimination of toxic substances from the blood by
dialysis. Interestingly, he made many observations that are still
valid: An adequate access was needed. Infection was the most imp.
complication. Large volume of fluid was needed (1-1.5L). Dwell time
was needed for equilibrium. Hypertonic solutions were needed to
promote fluid
- 7. Early attempts at PD Howard Frank, Arnold Seligman &
Jacob Fine (USA, 1946): intermittently continuous irrigation of the
peritoneal cavity. Arthur Grollman : used only one plastic catheter
and his PD was done
- 8. Modern Era of PD Morton Maxwell Special PD fluid:
Na-140mEq/L, Cl- (1959): made 101mEq/L, Ca-4mEq/L, many new
Mg-1.5mEq/L, Dextrose- developments that 15g/L, Lactate-45mEq/L
paved way for modern PD. Nylon catheter Paul Doolan (1959):
PVC
- 9. Advent of the era of PD Richard Ruben (San Fransisco, 1959):
he was the first to initiate long term IPD in CRF. The first
patient was Mae Stewart, 33/F. Boen (Seattle, 1962): First long
term PD programme. First automated PD machine. Repeated puncture
method using the Boens button.
- 10. Advent of the era of CAPD Tenckhoff (1968): Developed the
revolutionary Tenckhoff catheter that changed the PD practice
worldwide. Moncreif & Popovich (Austin, Texas; 1975): initiated
patients on continuous mode of PD and named it CAPD. Ann Intern Med
1978; 88(4): 449-55 Oreopoulos (Toronto Western Hospital, 1977):
Adapted the M&P method to their programme and used the plastic
bags (wearable bag system with the spike system).
- 11. Advent of the era of CAPD Uberto Buoncristiani (Italy,
1980): he paved way for the most accepted modern form of CAPD, the
Y-set with the flush before fill technique giving rise to the
latest sytem: the disconnect system, that significantly reduced
incidence of peritonitis. Bazzato (1980): Double bag system.
Diaz-Buxo (1981): developed APD/CCPD
- 12. Anatomy of the peritoneum
- 13. Peritoneum is a serous membrane, derived from the
mesenchyma. It is composed of the parietal and visceral peritoneum
that lines the peritoneal space. The total surface area of the
peritoneum in adults is 1-2m and the peritoneal space contains
50-100mL of fluid.
- 14. Visceral peritoneum: Comprises 80% of the TSA. Supplies by
the SMA and drains into the portal circulation.Parietal Peritoneum:
Comprises 20% of the TSA. Supplied by the lumbar, intercostal &
epigastric arteries and drains into the IVC.
- 15. Natural functions of theperitoneum Facilitate motion
Minimize friction. To conduct vessels and nerves to the viscera.
Solute transfer and exchange. Regulation of fluid dynamics and
UF.
- 16. Interstitium Blood vessels Mesothelium
- 17. Mesothelium It consists of a single layer of flattened
cuboidal cells (30,000cells/cm) lying on a basement membrane.
Microvilli present on the luminal side increases the effective
surface area of the peritoneal cavity up to 40m. Tight junctions
and desmosomes are present between the mesothelial cells. Transport
through the mesothelium occurs via endocytosis, transcytosis
and
- 18. Interstitium Consists of cells (pred. fibroblast) &
fibers (pred. collagen) embedded in an amorphous substance.
Thickness of the interstitium varies from 1-2m to 30m. This
thickness influences transport characteristics as this also defines
the distance between the mesothelium and bvs. Movement of solute is
determined by the difference in concentration per unit distance
(Ficks law of diffusion). GAGs and glycoproteins also influence
solute
- 19. Peritoneal microcirculation. -Resistance vessels.
-Regulation of blood flow to capillaries.Solute and fluid exchange(
principle site) -Leukocyte adhesion -Permeability under
inflammatory conditions
- 20. Peritoneal blood flow 50-100mL/min. Peritoneal clearance is
not blood flow limited as long as blood flow is >30% of normal.
Similarly UF also does not appear to be blood flow limited.
Vasoactive agents can affect peritoneal clearance by means of
capillary recruitment & increasing the micropore diameters. PDF
is also vasoactive and causes increased blood flow and capillary
recruitment
- 21. In addition to the vascular network, there is also a system
of lymphatics that drain the peritoneum. There are direct stomatas
in the diaphragmatic peritoneum as well as lymphatics in the
abdominal wall.
- 22. Physiology of Peritoneal Dialysis
- 23. Barriers of peritoneal transportThere are three main
barriers to peritoneal transport of solutes and fluid:1.
Mesothelium.2. Interstitial tissue.3. Blood vessels (endothelium
& basement membrane)The parietal peritoneum is more important
intransport than the visceral as only 25-30% ofthe VP it is in
contact with the peritoneal fluid.
- 24. Bidirectionaltransport
- 25. DiffusionConvection Absorption Mechanism s in PD
- 26. Models of Peritoneal transport :The PylePopovich model In
this model, the physiological reality is simplified by considering
just two homogeneous compartments (body and dialysate) separated by
an ideal homoporous semi-permeable membrane with constant
characteristics and nil thickness. By applying irreversible
thermodynamic laws, an equation describing the mass transfer rate
is obtained. The mathematics was simple but multiple samplings were
necessary making this a
- 27. Models of Peritoneal transport :The three pore model. It
was evident that transport of solutes and fluid was taking place
across various clefts between the endothelial cells. However, it
was being noted that there was a discrepancy between the Sieving
coeff and the Reflection coeff which gave rise to the theoretical
possibility of the presence of water conductive ultrasmall pores
that tended to sieve back solutes. For homoporous membrane, this
relationship is S=1-RC. However for glucose, S is 0.6-0.7 and RC is
0.02-0.05.
- 28. The three pore model. Large Inter-endothelial
cleftsAquaporin-1 Inter-endothelial cleft
- 29. Yang et al. Am J Physiol 276: C76 C81,1999
- 30. Models of Peritoneal transport : The distrubuted model. The
previous two models gave a simplistic 1D view of the peritoneal
transport but EFFECTIVE PERITONEAL SURFACE mathematical
calculations were AREA easy. However, the distributed model gives a
2D concept including the distribution of
- 31. The distrubuted model. The distributed model is closest
model to describe the transport physiology. But it is severely
limited by the cumbersome calculations of partial differential
equations with several variable parameters for a time-dependent
solution which makes it difficult to be applied in the bedside and
is thus limited as a research tool.
- 32. Problems with themathematical models They are empiric in
nature and do not describe the physiological situation. It does not
take into account the presence of absorption of fluid into the
tissues. These models assume that there is no tissue surrounding
the capillaries while it is not so. The role of the interstitium is
totally neglected. The changes in the gradients with time as well
as with the distance from the cavity is not fully represented.
- 33. The two aspects of peritonealtransport 1. Solute clearance.
Diffusive. Convective. 2. Fluid removal (Ultrafiltration)
- 34. Factors that influence solutediffusion Concentration
gradient. Effective peritoneal surface area. Intrinsic membrane
permeability characteristics. Solute characteristics. Blood flow
(no significant role). Dwell time and total volume of the
dialysate.
- 35. Kinetics of diffusive solute transport According to the
Ficks Law, Js=(Df/x).A.C Where Js=rate of solute transport,
Df=diffusion coefficient, x=diffusion distance, A=Surface area,
C=concentration gradient. (Df/x).A is the Permeability surface area
cross MTAC isor the Mass Transferto the Coefficient product
theoretically equal Area diffusive (MTAC) clearance of a solute per
unit time when thedialysate flow is infinitely high so that the
solute gradient is always maximal. Or in EnglishTheoretical maximal
clearance of a solute at
- 36. This MTAC is calculated by theHenderson and Nolph equation:
MTAC=(Vt/t)ln((P-D0)/(P-Dt))
- 37. Size-selectivity of diffusion. The second important
influence on the kinetics of diffusion after the concentration
gradient is the size of the diffusing solute (inverse
relationship). This is often expressed by the term restriction
coefficient , in which a value of 1.0 implies absence of a size
restriction barrier. Thus, the higher the value of the restriction
coefficient, the lower the size-selective permeability of the
peritoneum.
- 38. In summary, MTAC values of small molecular weight
substances are representative of the functional surface area.
Restriction coefficient on the other hand is a representation of
the size-selectivity. MTAC values: 1. Urea=17mL/min. 2.
Creatinine=10mL/min The D/P ratio has a good correlation with the
MTAC values
- 39. Determinants of convectivetransport Sieving occurs due to
the presence of the ultrasmall pores which holds back the solutes
and thus limiting the convective clearance due to UF. This is
measured by the Sieving coefficient (S) which represents the ratio
between the concentration of the solute in the ultrafiltrate and
its concentration in the plasma, assuming that net diffusion is
zero. S ranges from 0(complete seiving) to 1(no sieving).
- 40. Determinants of Ultrafiltration Concentration gradient of
the osmotic agent. Peritoneal surface area. Hydraulic conductance
of the membrane. Reflection coefficient of the osmotic agent.
Hydrostatic pressure gradient.
- 41. Transcapillary Ultrafiltration Transport of water across
the capillary wall occurs through the small pore system and though
aquaporin-1. Small pores=transport by hydrostatic & colloid
osmotic pressure. Aquaporin-1=dependent on the osmotic=colloid
osmotic UFR=UFC(P- +Refl coeff. gradient. pressure gradient.
O=crystalloid osmolality O) gradientUFC is the product of the
hydraulic conductivityand surface area and ranges from
0.04-0.08
- 42. Reflection coefficient measures how effectively the osmotic
agent diffuses out of the dialysis solution into peritoneal
capillaires. Its value ranges from 0 to 1. Lower the value, faster
the gradient is lost. Glucose has a RC of approx. 0.03 while
icodextrin has a RC close to 1. Hydrostatic pressure of the
capillaries is around 20mmHg, intraperitoneal pressure is around
7mmHg which exceeds 20mmHg while walking.
- 43. Differences in kinetics of glucose and icodextrin
Glucose(1.5 Icodextrin Peritoneal %) capillariesHydrostatic
pressure 8 (9) 8 (9) 17(gradient)Colloid osmotic 0 (-21) 66 (45)
21pressure (gradient)Osmolality 347, 285 305 486(4.25%)Crystalloid
osmotic 24, -12pressure gradient. 105(4.25%)Net pressure 12mmHg(93)
42mmHggradient
- 44. Differences in kinetics ofglucose and icodextrin Thus from
this we can conclude that icodextrin, due to to its high molecular
weight induces colloid osmosis even when it is a iso-hypoosmotic
solution. This movement of fluid takes place through the small pore
system. Due to the hypo-osmolality of this solution, no movement of
fluid takes place through the ultra- small pores and hence there is
No Sieving with Icodextrin. In addition it tends to maintain the
colloid oncotic gradient for a longer time as it is not absorbed
due to it high reflection coefficient.
- 45. Application of physiologyFluid removal in clinical practice
can be enhanced by1. Maximizing the osmotic gradient. 1. Higher
tonicity dwells. 2. Shorter duration dwells (eg. APD). 3. Higher
dwell volumes.2. Using osmotic agents with higher reflection
coefficients (eg. Icodextrin).3. Increasing urine output (eg.
Duiretics)
- 46. Application of physiologyPeritoneal Clearance of solute
which is the net result of diffusion plus convective clearance
minus the absorption can be increased by:1. Maximizing time on PD
(no dry dwells).2. Maximizing concentration gradient. 1. Frequent
exchanges 2. Larger dwell volumes3. Maximizing effective peritoneal
surface area.4. Maximizing fluid removal.
- 47. Calculation of peritonealclearance Peritoneal clearance is
equal to the total daily dialysate volume multiplied by its solute
concentration and divided by the plasma concentration of the
solute. Peritoneal clearance(Kt)=24hour dialysate volume XD/P
Residual urine Kt is also calculated in the same way and added to
peritoneal Kt. It is normalized to V to get the Kt/V. (multiplty by
7 to get weekly Kt/V).
- 48. PeritonealEquilibriation Test (PET)
- 49. Introduced by Twardowski et al. in 1987. It is a
semiquantitative assessment of peritoneal membrane transport
function in patients on peritoneal dialysis. The solute transport
rates are assessed by the rates of their equilibration between the
peritoneal capillary blood and dialysate.
- 50. Uses of PET1. Defining the baseline membrane
characteristics of the patient to determine the best PD regimen.2.
Assessment of inadequate dialysis and make necessary changes in
regimen.3. Detecting Ultrafiltration Failure (UFF).
- 51. The standardized PET test An overnight 8 to 12 hour
pre-exchange is performed. While the patient is in an upright
position, the overnight exchange is drained (drain time not to
exceed 25 minutes). Two liters of 2.5% dialysis solution are
infused over 10 minutes with the patient in the supine position.
The patient is rolled from side to side after every 400 mL
infusion. After the completion of infusion (0 time) and at 120
minutes dwell time, 200 mL of dialysate is drained. A 10 mL sample
is taken and the remaining 190 mL is infused back into the
peritoneal cavity.
- 52. A serum sample is obtained at 120 minutes. At the end of
the dwell (240 minutes), the dialysate is drained in the upright
position (drain time not to exceed 20 minutes). The drain volume is
measured and a 10 mL sample is taken from the drain. All the
samples are sent for solute measurement (creatinine, urea, and
glucose). The serum and dialysate creatinine concentrations are
corrected for a high glucose level, which contributes to
non-creatinine chromogens during the creatinine assay. The Dt/D0
glucose, and the D/P ratios for creatinine, urea, and others, are
calculated.
- 53. Timing of PET First PET is done after 4-8 weeks of PD. If
there is peritonitis, PET should be done 1 month after the
resolution of peritonitis as there is a increased small solute
transport and reduced UF during peritonitis. KDOQI does not
recommend repeating PET. However, it may be useful to repeat the
4.25% modified PET annually to anticipate problems.
- 54. Transporter typesHigh(Fast) transporters have Highest D/P
ratios for Creat, Urea & Na Low net UF & D/Do values. Lower
serum albumin values. Thus they do better with shorter
dwells/APDLow(slow) transporters have Low D/P ratios for Creat,
urea &Na. Good net UF and high D/Do values. Albumin losses are
lower. They do better with longer dwells.
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