Contr. Nephrol., vol. 17, pp. 44-50 (Karger, Basel 1979)
The Peritoneal Dialysis System KariD. Nolph Department of Medicine, University of Missouri Medical Center and VA Hospital, Columbia, Mo.
Introduction Peritoneal dialysis represents an internal hemodialysis system (an intracorporeal hemodialyzer). I will review our current understanding of the blood path, the membrane, and the dialysis compartment of this dialyzer.
Larger vessels coursing through the peritoneum on their way to viscera probably do not participate in solute exchange during peritoneal dialysis. Small arterioles (10 Ilfll in diameter) branch into numerous parallel capillaries particularly near reflections over viscera. In many microcirculatory systems, 5 or more capillaries can be identified branching from each arteriole (1-3). In a non-vasodilated state, the majority of these capillaries may be non-perfused secondary to tonic effects of so-called precapillary sphincters. With vasodilatation, the numbers of capillaries perfused increases. Some work suggests that longer, more permeable capillaries open in vasodilated states (3). Thus, the peritoneal blood path has the unique capabilities of varying the number of capillaries perfused and thus changing mean pore size and total pore area. Peritoneal lymphatics may also contribute to solute exchange. Because of low flow rates, their contributions have been assumed to be minor. This remains to be established. Although total splanchnic blood flow in humans may exceed 1,200 ml/min (4), effective peritoneal capillary blood flow relative to peritoneal dialysis exchange is unknown. Studies in animals and man looking at diffusion of gases during peritoneal dialysis suggest that effective peritoneal capillary blood flow may be at least 2-3 times peritoneal urea clearances and approach 60-70 mIl
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The Peritoneal Dialysis 'Blood Path'
The Peritoneal Dialysis System
45
Table L The peritoneal 'blood path'
Splanchnic blood flow> 1,200 ml/min (4) 'Effective' capillary flow unknown - indirect evidence suggests 60-70 ml/min (5, 6) Peritoneal capillaries branch in parallel from small arterioles (mainly near viscera) (1-3) Most (80%) of capillaries may be non-perfused because of precapillary sphincters except with vasodilatation (1- 3) 5. Vasodilators may increase number of capillaries perfused and increase endothelial area 1. 2. 3. 4.
(2)
6. Capillaries perfused only with vasodilatation may be more permeable (2, 3)
min in humans (5, 6). Since effective total pore area is probably very small, Popovich has predicted that peritoneal capillary blood flow in this range should cause little to no limitations on small solute clearances (6). For gases, effective capillary blood flow as reflected by transport studies should approach total intracellular and extracellular blood water flow. The same should be nearly true for highly diffusible solutes like urea which can rapidly cross red cell walls. For large solutes, such as inulin confined to the extracellular fluid space, effective capillary flow should reflect effective plasma water flow and be several times less than the effective flow for solutes distributed intracellularly. Nevertheless, even for large extracellular solutes such as inulin, effec-tive plasma water flow rates as low as 10-20 ml/min should have little or no limitation on clearances usually in the 5-ml/min range. Multiple vasoactive substances may influence the number of capillaries perfused and, therefore, markedly alter endothelial area and permeability (1, 7). Thus, the size and transport characteristics of the blood path may be influenced by vasoactive components of dialysis solutions, the activity of the sympathetic nervous system, circulating vasoactive hormones, and vasoactive drugs (1). Table I summarizes some of the essential features of the blood path of the peritoneum.
It has been assumed that peritoneal dialysis affects the composition of body fluids mainly by the net exchange of solutes and fluid between peritoneal capillary blood and dialysis solution via the peritoneal membrane interstitium. Some direct exchange may occur between dialysis solution and intracellular fluid of the peritoneal mesothelium; also, exchange may occur across peritoneal
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The Peritoneal Dialysis Membrane
46
lymphatics. The latter implies that peritoneal dialysis to some extent may be lymph dialysis as well as hemodialysis; transcapillary exchange has been deemed quantitatively more important because of presumably higher effective flow rates. Exchange between peritoneal capillaries and the peritoneal cavity involves diffusion of solutes and/or the convective transport of water and solutes through two cell layers, namely capillary endothelium and peritoneal mesothelium. Studies of passive transport through biological membranes suggest that solutes up to molecular weights of 30,000 or more may traverse primarily the interstitium, Le. intercellular channels (8-10). Although peritoneal dialysis may to some extent alter the intracellular fluid composition of mesothelial and endothelial cells, there is little to suggest that transcellular movement of solutes or water contributes significantly to exchange. For example, the clearance of urea, a highly diffusible solute distributed intracellularly (60 daltons), is usually no more than 3-4 times that of inulin clearance (5,200 daltons), a solute confmed to the extracellular space (1). If effective peritoneal capillary blood flow is indeed 60-70 ml/min or more, and if urea could readily cross endothelial and mesothelial cell walls, then it seems reasonable that urea clearances should be even nearer to effective peritoneal capillary flow at high Qo and many more times higher than inulin clearance (since inulin moves only through intercellular spaces). Since equilibrated intraperitoneal dialysate approaches the composition of interstitial fluid, significant contributions of mesothelial intracellular solutes such as potassium are not apparent. Even with hypertonic exchanges, there is no evidence that mobilization of the intracellular potassium pool occurs to any significant extent (11). At high Qo, membrane resistance appears the major limitation on small and large solute clearances (6). This may result from the small number of capillaries involved and a relatively sparse number of endothelial intercellular channels (12, 13). However, relatively high ratios of large to small solute clearances coupled with significant protein losses suggest that mean pore size is quite high. As above, it also suggests that smaller transcellular pores are not available to any significant extent for the net transport of smaller solutes such as urea. Thus, the membrane is characterized as one of low total pore area, but relatively high mean pore size. If endothelial intercellular channels really are the major determinants of total pore area and mean pore size, the vasoactive substances which increase the number of capillaries perfused may markedly alter total pore area and, if capillaries perfused only during vasodilation are more permeable, mean pore size should increase as well (3). It is known that vasoactive substances such as nitroprusside favor greater increases in clearances of larger solutes than of smaller solutes for predictions at infinite Qo (2). Inulin clearances have been reported to be more than double with intraperitoneal nitroprusside while urea
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Nolph
The Peritoneal Dialysis System
47
Table II. The peritoneal membrane
6. 7. 8. 9.
Two cell layers: capillary endothelium and peritoneal mesothelium Solutes thought to traverse mainly endothelial and mesothelial intercellular channels Relatively low number of pores (total pore area) but large mean pore size (6, 24) Mesothelial surface area 1-2 m 2 (24, 25) Effective pore area (dog and rabbit studies): 4% of endothelial surface, 0.6% of visceral mesothelial surface, 0.2% of parietal peritoneal mesothelial surface (12,13,18) Mean pore radius (dog) 0.58 /.1m (13) Low total pore area most likely major limitation on solute transport at high QD (6) Unexplained resistance to convective transport of electrolytes (11, 14, 15) Cell metabolism may influence charge and dimensions of 'pores' (18)
clearances increase no more than 25% (1, 2). This would suggest that increases in effective peritoneal capillary blood flow with vasodilatation are minor in their effect compared to increases in area and/or permeability. It is possible that with vasodilatation, capillary area increases more than flow, resulting in a decrease in flow per area and a relative increase in the significance of previously minor flow limitations on small solute clearances. Even in the absence of a concentration gradient for net diffusion, solutes can be removed by convection with ultrafiltration (14-16). Under these conditions, the net removal of non-charged small solutes such as urea per unit volume of ultrafiltrate has been reported to be similar to extracellular fluid concentrations (16). Even for non-charged solutes as large as inulin, net sieving coefficients (the ratio of the solute removed per unit volume of ultra filtrate in the absence of a concentration gradient for diffusion compared to the concentration in extracellular fluid) have been reported as high as 0.80 (16). Paradoxically, the convective removal of sodium and potassium is relatively inefficient (11, 14, 15). Net sieving coefficients of 0.50 or less have been reported (11, 14, 15). There is the possibility that intercellular surface charges interfere with convective transport of electrolytes. Transcellular movement of water without electrolytes could explain low net sieving coefficients for electrolytes, but not the relatively high sieving coefficients for large non-charged solutes. Molecular interaction between solutes carried downstream with ultrafiltration and glucose moving upstream may be involved (17). It has been shown that substances which alter the metabolism of peritoneal cells can alter the transport characteristics of the membrane (18). The state of cell health may determine the dimensions and charges of intracellular channels. Table II summarizes features of the peritoneal membrane. Some reported values for effective pore area and mean pore size are shown; these are from animal or isolated membrane studies and similar values for humans are unknown.
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1. 2. 3. 4. 5.
Nolph
48
Table III. Peritoneal dialysis solutions and the 'dialysate compartment' 1. Average and range of dialysate channel width unknown - may contribute significantly to membrane resistance 2. Even at very high QD, urea clearance rarely exceeds 30-40 ml/min (6,19,26,27) 3. Currently available solutions cause initial vasoconstriction and delayed vasodilatation in rats (22) 4. Dialysate temperature, osmolality, and buffer anion composition may account for vasoactivity (22, 23) 5. Dialysis solution may thus influence microcirculation and peritoneal transport characteristics 6. Long dwell exchanges make continuous dialysis possible (21)
The peritoneal cavity comfortably tolerates 2-3 liters in most adults. The average width of dialysate channels is unknown, but presumably some are very wide. Compared to extracorporeal systems, dialYSis solution is relatively stagnant during dwell times unless a continuous flow system is utilized. Usually, 2 liters are cycled into and from the peritoneal cavity every hour manually, or every half hour with automated cyclers. High continuous flow systems have been studied (19). Usually some discomfort is seen at flow rates approaching 8-121/h. Recently, frequent intermittent flow of small volumes (several hundred ml) on top of an intraperitoneal reservoir has been studied ('reciprocating' flow) (20). Continuous ambulatory peritoneal dialYSis uses intermittent cycles of 4-8 h in duration in a continuously repeated fashion as a technique of chronic dialysis (21). Thus, the peritoneal dialyzer offers many opportunities for different types of dialysis solution flow. Overall, the higher the QD the higher the small solute clearances up to the point of membrane limitation as discussed above. Long dwell continuous exchanges offer the opportunity for continuous 'steady state' dialysis. Currently available solutions cause initial vasoconstriction in rat microcirculatory beds when applied topically (22). The initial vasoconstriction lasts 3-5 min and is followed by a delayed vasodilation. Nitroprusside prevents the initial vasoconstriction and causes immediately dilatation of approximately the same magnitude as the delayed vasodilatation with solutions alone. The fact that intraperitoneal nitroprusside increases clearances in humans suggests that the vasoconstrictive phase with standard solutions may be significant, or that nitroprusside has other direct effects on permeability independent of its vasodilatory effects. Although the low pH of commercially available solutions may account for pain on instillation in some patients, the low pH does not seem to account
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Peritoneal Diillysis Solution and the Diillysate Compartment (table III)
The Peritoneal Dialysis System
49
for the vasoactivity of the solutions. Recent studies to be mentioned elsewhere in this issue suggest that non-bicarbonate buffer anions and high glucose concentrations may be responsible for the vasoactive components of dialysis solutions. Dialysis solution temperature has also been shown to effect clearances (23). This may similarly relate to effects on the status of the microcirculation.
2 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16
Nolph, K.D.; Ghods, A.J.; Brown, P.; Stone, J.C. van; Miller, F.N.; Wiegman, D.L., and Harris, P.D.: Factors affecting peritoneal dialysis efficiency. Dial. Transpl. 6: 52-90 (1977). Nolph, K.D.; Ghods, A.J.; Brown, P.; Miller, F.; Harris, P.; Pyle, K., and Popovich, R.: Effects of nitroprusside on peritoneal mass transfer coefficients and microvascular physiology. Trans. Am. Soc. artif. internal Organs 23: 210-218 (1977). Renkin, E.M.: Exchange of substances through capillary walls. Circulatory and respiratory mass transport; in Wolstenholme, Ciba Found. Symp., pp. 50-66 (Little, Brown, Boston 1969). Wade, O.L.; Combes, B.; Childs, A.W.; Wheeler, H.O.; Cournand, A., and Bradley, S.E.: The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin. Sci. 15: 457-463 (1956). Aune, S.: Transperitoneal exchange. II. Peritoneal blood flow estimated by hydrogen gas clearance. Scand. J. Gastroent. 5: 99 (1970). Nolph, K.D.; Popovich, R.P.; Ghods, A.J., and Twardowski, Z.J.: Determinants of low clearances of small solutes during peritoneal dialysis. Kidney into 13: 117-123 (1978). Nolph, K.D.; Ghods, A.J.; Stone, J. van, and Brown, P.A.: The effects of intraperitoneal vasodilators on peritoneal clearances. Trans. Am. Soc. artif. internal Organs 22: 586-594 (1976). Karnovsky, M.J.: The ultrastructural basis of capillary permeability studies with peroxides as a tracer. J. Cell BioI. 35: 213-235 (1967). Cotran, R.S.: The fine structure of the microvasculature in relation to normal and altered permeability; in Reeve and Guyton, Physical bases of circulatory transport: regulation and exchange, pp. 249-275 (Saunders, Philadelphia 1967). Karnovsky, M.J.: The ultrastructural basis of transcapillary exchanges; in Biological interfaces: flows and exchanges, pp. 64-95 (Little Brown, Boston 1968). Brown, S.T.; Ahearn, D.J., and Nolph, K.D.: Potassium removal with peritoneal dialysis. Kidney into 4: 67-69 (1973). Nagel, W. and Kuschinsky, W.: Study of the permeability of isolated dog mesentery. Eur. J. clin. Invest. 1: 149-154 (1970). Gosselin, R.E. and Berndt, W.O.: Diffusional transport of solutes through mesentery and peritoneum. J. theor. BioI. 3: 487-495 (1962). Nolph, K.D.; Hano, J.E., and Teschan, P.E.: Peritoneal sodium transport during hypertonic peritoneal dialysis: physiologic mechanisms and clinical implications. Ann. intern. Med. 70: 931-941 (1969). Ahearn, D.J. and Nolph, K.D.: Controlled sodium removal with peritoneal dialysis. Trans. Am. Soc. artif. internal Organs 28: 423-428 (1972). Henderson, L.W. and Nolph, K.D.: Altered permeability of the peritoneal membrane after using hypertonic peritoneal dialysis fluid. J. clin. Invest. 48: 992-1001 (1969).
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References
Nolph
18 19 20 21 22 23 24 25 26 27
Nolph, K.D.; Hopkins, C.A.; New, D.; Antwiler, G.D., and Popovich, R.P.: Differences in solute sieving with osmotic vs. hydrostatic ultrafiltration. Trans. Am. Soc. artif. internal Organs 22: 618-626 (1976). Erbe, R.W.; Greene, J.A., jr., and Weller, J.M.: Peritoneal dialysis during hemorrhagic shock. J. appl. Physiol. 22: 131-135 (1967). Stephen, R.L.; Atkin-Thor, E., and Kolff, W.I.: Recirculating peritoneal dialysis with subcutaneous catheter. Trans. Am. Soc. artif. internal Organs 22: 575-585 (1976). Stephen, R.L.; Jacobsen, S.C.; Kablitz, c.; Kirkham, R., and Kolff, W.J.: Reciprocating peritoneal dialysis. Proc. 11th Annu. Contractors' Conf. Artifical Kidney-Chronic Uremia Program, NIH, vol. 11, pp. 32-35 (1978). Popovich, R.P.; Moncrief, J.W.; Nolph, K.D.; Ghods, A.J.; Twardowski, Z.J., and Pyle, W.K.: Continuous ambulatory peritoneal dialysis. Ann. intern. Med. 88: 449-456 (1978). Miller, F.N.; Nolph, K.D.; Harris, P.D.; Rubin, J.; Wiegman, D.L., and Joshua, LG.: Effects of peritoneal dialysis solutions on human clearances and rat arterioles (abstr.). Amer. Soc. artif. internal Organs 7: 37 (1978). Gross, M. and McDonald, H.P., jr.: Efects of dialysate temperature and flow rate on peritoneal clearance. J. Am. med. Ass. 202: 215-217 (1967). Henderson, L. W.: The problem of peritoneal membrane area and permeability. Kidney int. 3: 409-410 (1973). Henderson, L.: Peritoneal dialysis; Massey and Sellers, Clinical aspects of uremia and dialysis, pp. 566-570 (Thomas, Springfield 1976). Tenckhoff, H.; Ward, G., and Boen, S.T.: The influence of dialysate volume and flow rate on peritoneal clearance. Proc. Eur. Dial. Transplant Ass. 2: 113-117 (1965). Goldschmidt, Z.H.; Pote, H.H.; Katz, M.A., and Shear, L.: Effect of dialysate volume on peritoneal dialysis kinetics. Kidney int. 5: 240-245 (1975).
K.D. Nolph, MD, Department of Medicine, University of Missouri Medical Center and VA Hospital, Columbia, MO 65211 (USA)
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17
50
The Peritoneal Dialysis System KariD. Nolph Department of Medicine, University of Missouri Medical Center and VA Hospital, Columbia, Mo.
Introduction Peritoneal dialysis represents an internal hemodialysis system (an intracorporeal hemodialyzer). I will review our current understanding of the blood path, the membrane, and the dialysis compartment of this dialyzer.
Larger vessels coursing through the peritoneum on their way to viscera probably do not participate in solute exchange during peritoneal dialysis. Small arterioles (10 Ilfll in diameter) branch into numerous parallel capillaries particularly near reflections over viscera. In many microcirculatory systems, 5 or more capillaries can be identified branching from each arteriole (1-3). In a non-vasodilated state, the majority of these capillaries may be non-perfused secondary to tonic effects of so-called precapillary sphincters. With vasodilatation, the numbers of capillaries perfused increases. Some work suggests that longer, more permeable capillaries open in vasodilated states (3). Thus, the peritoneal blood path has the unique capabilities of varying the number of capillaries perfused and thus changing mean pore size and total pore area. Peritoneal lymphatics may also contribute to solute exchange. Because of low flow rates, their contributions have been assumed to be minor. This remains to be established. Although total splanchnic blood flow in humans may exceed 1,200 ml/min (4), effective peritoneal capillary blood flow relative to peritoneal dialysis exchange is unknown. Studies in animals and man looking at diffusion of gases during peritoneal dialysis suggest that effective peritoneal capillary blood flow may be at least 2-3 times peritoneal urea clearances and approach 60-70 mIl
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 5/2/2018 1:39:02 PM
The Peritoneal Dialysis 'Blood Path'
The Peritoneal Dialysis System
45
Table L The peritoneal 'blood path'
Splanchnic blood flow> 1,200 ml/min (4) 'Effective' capillary flow unknown - indirect evidence suggests 60-70 ml/min (5, 6) Peritoneal capillaries branch in parallel from small arterioles (mainly near viscera) (1-3) Most (80%) of capillaries may be non-perfused because of precapillary sphincters except with vasodilatation (1- 3) 5. Vasodilators may increase number of capillaries perfused and increase endothelial area 1. 2. 3. 4.
(2)
6. Capillaries perfused only with vasodilatation may be more permeable (2, 3)
min in humans (5, 6). Since effective total pore area is probably very small, Popovich has predicted that peritoneal capillary blood flow in this range should cause little to no limitations on small solute clearances (6). For gases, effective capillary blood flow as reflected by transport studies should approach total intracellular and extracellular blood water flow. The same should be nearly true for highly diffusible solutes like urea which can rapidly cross red cell walls. For large solutes, such as inulin confined to the extracellular fluid space, effective capillary flow should reflect effective plasma water flow and be several times less than the effective flow for solutes distributed intracellularly. Nevertheless, even for large extracellular solutes such as inulin, effec-tive plasma water flow rates as low as 10-20 ml/min should have little or no limitation on clearances usually in the 5-ml/min range. Multiple vasoactive substances may influence the number of capillaries perfused and, therefore, markedly alter endothelial area and permeability (1, 7). Thus, the size and transport characteristics of the blood path may be influenced by vasoactive components of dialysis solutions, the activity of the sympathetic nervous system, circulating vasoactive hormones, and vasoactive drugs (1). Table I summarizes some of the essential features of the blood path of the peritoneum.
It has been assumed that peritoneal dialysis affects the composition of body fluids mainly by the net exchange of solutes and fluid between peritoneal capillary blood and dialysis solution via the peritoneal membrane interstitium. Some direct exchange may occur between dialysis solution and intracellular fluid of the peritoneal mesothelium; also, exchange may occur across peritoneal
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 5/2/2018 1:39:02 PM
The Peritoneal Dialysis Membrane
46
lymphatics. The latter implies that peritoneal dialysis to some extent may be lymph dialysis as well as hemodialysis; transcapillary exchange has been deemed quantitatively more important because of presumably higher effective flow rates. Exchange between peritoneal capillaries and the peritoneal cavity involves diffusion of solutes and/or the convective transport of water and solutes through two cell layers, namely capillary endothelium and peritoneal mesothelium. Studies of passive transport through biological membranes suggest that solutes up to molecular weights of 30,000 or more may traverse primarily the interstitium, Le. intercellular channels (8-10). Although peritoneal dialysis may to some extent alter the intracellular fluid composition of mesothelial and endothelial cells, there is little to suggest that transcellular movement of solutes or water contributes significantly to exchange. For example, the clearance of urea, a highly diffusible solute distributed intracellularly (60 daltons), is usually no more than 3-4 times that of inulin clearance (5,200 daltons), a solute confmed to the extracellular space (1). If effective peritoneal capillary blood flow is indeed 60-70 ml/min or more, and if urea could readily cross endothelial and mesothelial cell walls, then it seems reasonable that urea clearances should be even nearer to effective peritoneal capillary flow at high Qo and many more times higher than inulin clearance (since inulin moves only through intercellular spaces). Since equilibrated intraperitoneal dialysate approaches the composition of interstitial fluid, significant contributions of mesothelial intracellular solutes such as potassium are not apparent. Even with hypertonic exchanges, there is no evidence that mobilization of the intracellular potassium pool occurs to any significant extent (11). At high Qo, membrane resistance appears the major limitation on small and large solute clearances (6). This may result from the small number of capillaries involved and a relatively sparse number of endothelial intercellular channels (12, 13). However, relatively high ratios of large to small solute clearances coupled with significant protein losses suggest that mean pore size is quite high. As above, it also suggests that smaller transcellular pores are not available to any significant extent for the net transport of smaller solutes such as urea. Thus, the membrane is characterized as one of low total pore area, but relatively high mean pore size. If endothelial intercellular channels really are the major determinants of total pore area and mean pore size, the vasoactive substances which increase the number of capillaries perfused may markedly alter total pore area and, if capillaries perfused only during vasodilation are more permeable, mean pore size should increase as well (3). It is known that vasoactive substances such as nitroprusside favor greater increases in clearances of larger solutes than of smaller solutes for predictions at infinite Qo (2). Inulin clearances have been reported to be more than double with intraperitoneal nitroprusside while urea
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 5/2/2018 1:39:02 PM
Nolph
The Peritoneal Dialysis System
47
Table II. The peritoneal membrane
6. 7. 8. 9.
Two cell layers: capillary endothelium and peritoneal mesothelium Solutes thought to traverse mainly endothelial and mesothelial intercellular channels Relatively low number of pores (total pore area) but large mean pore size (6, 24) Mesothelial surface area 1-2 m 2 (24, 25) Effective pore area (dog and rabbit studies): 4% of endothelial surface, 0.6% of visceral mesothelial surface, 0.2% of parietal peritoneal mesothelial surface (12,13,18) Mean pore radius (dog) 0.58 /.1m (13) Low total pore area most likely major limitation on solute transport at high QD (6) Unexplained resistance to convective transport of electrolytes (11, 14, 15) Cell metabolism may influence charge and dimensions of 'pores' (18)
clearances increase no more than 25% (1, 2). This would suggest that increases in effective peritoneal capillary blood flow with vasodilatation are minor in their effect compared to increases in area and/or permeability. It is possible that with vasodilatation, capillary area increases more than flow, resulting in a decrease in flow per area and a relative increase in the significance of previously minor flow limitations on small solute clearances. Even in the absence of a concentration gradient for net diffusion, solutes can be removed by convection with ultrafiltration (14-16). Under these conditions, the net removal of non-charged small solutes such as urea per unit volume of ultrafiltrate has been reported to be similar to extracellular fluid concentrations (16). Even for non-charged solutes as large as inulin, net sieving coefficients (the ratio of the solute removed per unit volume of ultra filtrate in the absence of a concentration gradient for diffusion compared to the concentration in extracellular fluid) have been reported as high as 0.80 (16). Paradoxically, the convective removal of sodium and potassium is relatively inefficient (11, 14, 15). Net sieving coefficients of 0.50 or less have been reported (11, 14, 15). There is the possibility that intercellular surface charges interfere with convective transport of electrolytes. Transcellular movement of water without electrolytes could explain low net sieving coefficients for electrolytes, but not the relatively high sieving coefficients for large non-charged solutes. Molecular interaction between solutes carried downstream with ultrafiltration and glucose moving upstream may be involved (17). It has been shown that substances which alter the metabolism of peritoneal cells can alter the transport characteristics of the membrane (18). The state of cell health may determine the dimensions and charges of intracellular channels. Table II summarizes features of the peritoneal membrane. Some reported values for effective pore area and mean pore size are shown; these are from animal or isolated membrane studies and similar values for humans are unknown.
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 5/2/2018 1:39:02 PM
1. 2. 3. 4. 5.
Nolph
48
Table III. Peritoneal dialysis solutions and the 'dialysate compartment' 1. Average and range of dialysate channel width unknown - may contribute significantly to membrane resistance 2. Even at very high QD, urea clearance rarely exceeds 30-40 ml/min (6,19,26,27) 3. Currently available solutions cause initial vasoconstriction and delayed vasodilatation in rats (22) 4. Dialysate temperature, osmolality, and buffer anion composition may account for vasoactivity (22, 23) 5. Dialysis solution may thus influence microcirculation and peritoneal transport characteristics 6. Long dwell exchanges make continuous dialysis possible (21)
The peritoneal cavity comfortably tolerates 2-3 liters in most adults. The average width of dialysate channels is unknown, but presumably some are very wide. Compared to extracorporeal systems, dialYSis solution is relatively stagnant during dwell times unless a continuous flow system is utilized. Usually, 2 liters are cycled into and from the peritoneal cavity every hour manually, or every half hour with automated cyclers. High continuous flow systems have been studied (19). Usually some discomfort is seen at flow rates approaching 8-121/h. Recently, frequent intermittent flow of small volumes (several hundred ml) on top of an intraperitoneal reservoir has been studied ('reciprocating' flow) (20). Continuous ambulatory peritoneal dialYSis uses intermittent cycles of 4-8 h in duration in a continuously repeated fashion as a technique of chronic dialysis (21). Thus, the peritoneal dialyzer offers many opportunities for different types of dialysis solution flow. Overall, the higher the QD the higher the small solute clearances up to the point of membrane limitation as discussed above. Long dwell continuous exchanges offer the opportunity for continuous 'steady state' dialysis. Currently available solutions cause initial vasoconstriction in rat microcirculatory beds when applied topically (22). The initial vasoconstriction lasts 3-5 min and is followed by a delayed vasodilation. Nitroprusside prevents the initial vasoconstriction and causes immediately dilatation of approximately the same magnitude as the delayed vasodilatation with solutions alone. The fact that intraperitoneal nitroprusside increases clearances in humans suggests that the vasoconstrictive phase with standard solutions may be significant, or that nitroprusside has other direct effects on permeability independent of its vasodilatory effects. Although the low pH of commercially available solutions may account for pain on instillation in some patients, the low pH does not seem to account
Downloaded by: Université René Descartes Paris 5 193.51.85.197 - 5/2/2018 1:39:02 PM
Peritoneal Diillysis Solution and the Diillysate Compartment (table III)
The Peritoneal Dialysis System
49
for the vasoactivity of the solutions. Recent studies to be mentioned elsewhere in this issue suggest that non-bicarbonate buffer anions and high glucose concentrations may be responsible for the vasoactive components of dialysis solutions. Dialysis solution temperature has also been shown to effect clearances (23). This may similarly relate to effects on the status of the microcirculation.
2 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16
Nolph, K.D.; Ghods, A.J.; Brown, P.; Stone, J.C. van; Miller, F.N.; Wiegman, D.L., and Harris, P.D.: Factors affecting peritoneal dialysis efficiency. Dial. Transpl. 6: 52-90 (1977). Nolph, K.D.; Ghods, A.J.; Brown, P.; Miller, F.; Harris, P.; Pyle, K., and Popovich, R.: Effects of nitroprusside on peritoneal mass transfer coefficients and microvascular physiology. Trans. Am. Soc. artif. internal Organs 23: 210-218 (1977). Renkin, E.M.: Exchange of substances through capillary walls. Circulatory and respiratory mass transport; in Wolstenholme, Ciba Found. Symp., pp. 50-66 (Little, Brown, Boston 1969). Wade, O.L.; Combes, B.; Childs, A.W.; Wheeler, H.O.; Cournand, A., and Bradley, S.E.: The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin. Sci. 15: 457-463 (1956). Aune, S.: Transperitoneal exchange. II. Peritoneal blood flow estimated by hydrogen gas clearance. Scand. J. Gastroent. 5: 99 (1970). Nolph, K.D.; Popovich, R.P.; Ghods, A.J., and Twardowski, Z.J.: Determinants of low clearances of small solutes during peritoneal dialysis. Kidney into 13: 117-123 (1978). Nolph, K.D.; Ghods, A.J.; Stone, J. van, and Brown, P.A.: The effects of intraperitoneal vasodilators on peritoneal clearances. Trans. Am. Soc. artif. internal Organs 22: 586-594 (1976). Karnovsky, M.J.: The ultrastructural basis of capillary permeability studies with peroxides as a tracer. J. Cell BioI. 35: 213-235 (1967). Cotran, R.S.: The fine structure of the microvasculature in relation to normal and altered permeability; in Reeve and Guyton, Physical bases of circulatory transport: regulation and exchange, pp. 249-275 (Saunders, Philadelphia 1967). Karnovsky, M.J.: The ultrastructural basis of transcapillary exchanges; in Biological interfaces: flows and exchanges, pp. 64-95 (Little Brown, Boston 1968). Brown, S.T.; Ahearn, D.J., and Nolph, K.D.: Potassium removal with peritoneal dialysis. Kidney into 4: 67-69 (1973). Nagel, W. and Kuschinsky, W.: Study of the permeability of isolated dog mesentery. Eur. J. clin. Invest. 1: 149-154 (1970). Gosselin, R.E. and Berndt, W.O.: Diffusional transport of solutes through mesentery and peritoneum. J. theor. BioI. 3: 487-495 (1962). Nolph, K.D.; Hano, J.E., and Teschan, P.E.: Peritoneal sodium transport during hypertonic peritoneal dialysis: physiologic mechanisms and clinical implications. Ann. intern. Med. 70: 931-941 (1969). Ahearn, D.J. and Nolph, K.D.: Controlled sodium removal with peritoneal dialysis. Trans. Am. Soc. artif. internal Organs 28: 423-428 (1972). Henderson, L.W. and Nolph, K.D.: Altered permeability of the peritoneal membrane after using hypertonic peritoneal dialysis fluid. J. clin. Invest. 48: 992-1001 (1969).
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References
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Nolph, K.D.; Hopkins, C.A.; New, D.; Antwiler, G.D., and Popovich, R.P.: Differences in solute sieving with osmotic vs. hydrostatic ultrafiltration. Trans. Am. Soc. artif. internal Organs 22: 618-626 (1976). Erbe, R.W.; Greene, J.A., jr., and Weller, J.M.: Peritoneal dialysis during hemorrhagic shock. J. appl. Physiol. 22: 131-135 (1967). Stephen, R.L.; Atkin-Thor, E., and Kolff, W.I.: Recirculating peritoneal dialysis with subcutaneous catheter. Trans. Am. Soc. artif. internal Organs 22: 575-585 (1976). Stephen, R.L.; Jacobsen, S.C.; Kablitz, c.; Kirkham, R., and Kolff, W.J.: Reciprocating peritoneal dialysis. Proc. 11th Annu. Contractors' Conf. Artifical Kidney-Chronic Uremia Program, NIH, vol. 11, pp. 32-35 (1978). Popovich, R.P.; Moncrief, J.W.; Nolph, K.D.; Ghods, A.J.; Twardowski, Z.J., and Pyle, W.K.: Continuous ambulatory peritoneal dialysis. Ann. intern. Med. 88: 449-456 (1978). Miller, F.N.; Nolph, K.D.; Harris, P.D.; Rubin, J.; Wiegman, D.L., and Joshua, LG.: Effects of peritoneal dialysis solutions on human clearances and rat arterioles (abstr.). Amer. Soc. artif. internal Organs 7: 37 (1978). Gross, M. and McDonald, H.P., jr.: Efects of dialysate temperature and flow rate on peritoneal clearance. J. Am. med. Ass. 202: 215-217 (1967). Henderson, L. W.: The problem of peritoneal membrane area and permeability. Kidney int. 3: 409-410 (1973). Henderson, L.: Peritoneal dialysis; Massey and Sellers, Clinical aspects of uremia and dialysis, pp. 566-570 (Thomas, Springfield 1976). Tenckhoff, H.; Ward, G., and Boen, S.T.: The influence of dialysate volume and flow rate on peritoneal clearance. Proc. Eur. Dial. Transplant Ass. 2: 113-117 (1965). Goldschmidt, Z.H.; Pote, H.H.; Katz, M.A., and Shear, L.: Effect of dialysate volume on peritoneal dialysis kinetics. Kidney int. 5: 240-245 (1975).
K.D. Nolph, MD, Department of Medicine, University of Missouri Medical Center and VA Hospital, Columbia, MO 65211 (USA)
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