Integration of the Peritoneal Transport System

The complexity of the peritoneal transport barrier requires an integrated approach toward its description. Figure 3 is a useful conceptual model when the system is modeled mathematically. Quantitative flows of blood and lymph must be assigned to all of the various pathways in this illustration. Rates of mass transfer with individual mass transfer coefficients and surface contact areas must be assigned to each tissue group. The system in Figure 3 must then be integrated into a total-body system with multiple compartments for each organ system. Quantitative values for the various parameters have been suggested by Flessner and Dedrick (see Further Reading).

The distributed model concept of Figure 1 requires tissue-specific transport coefficients that cannot be obtained from the compartmental model of Figure 3. Solutes transport from the cavity through the peritoneum, which has been shown to be an insignificant barrier, through the tissue inter-stitium and are absorbed either directly into the distributed blood system throughout the subperitoneal tissues or into the lymphatic vessels, if macromolecules. Characteristics of the interstitium and its variability during a large-volume dialysis or chemotherapeutic procedure must be taken into account. In addition, the vascular system is highly reactive to hypertonic solutions often used in dialysis. Therefore in the early stages of dialysis, there may be a localized vasodi-lation in the layers of the tissue closer to the anatomic peritoneum. However, after 15 to 20 minutes, this tends to disappear and a rather uniform rate of blood flow appears to be the rule. Rates of small-solute transport appear to be the same whether in the direction from the cavity to the blood or from the blood to the cavity. Larger solutes, however, experience an asymmetry in their transport. They leave the blood vessels via large pores and transport through the tissue inter-stitium to the peritoneal cavity. However, if administered into the peritoneal cavity, they transport across the peritoneum and through the interstitium, but cannot be reabsorbed directly across the endothelium; they must be taken up by lymphatics. The restrictive properties of the peritoneal interstitium must be taken into account when describing the transport. Although a small portion of the peritoneal surface area is made up of solid organs such as the liver and spleen, the vast majority of the tissue microcirculation can be represented by vessels of the muscle.

The cells illustrated in Figure 5 need to be considered as a system. Although each of these cell types can be studied in vitro, it is only through their interaction that the clinically observed pathology is created. It is also only through this interaction that an improved understanding of the complex process of chronic inflammation will come about. The integrated cellular system within the peritoneal tissue reacts to multiple stimuli. In bacterial peritonitis, the interaction of the organisms with the macrophages and the mesothelium results in a rapid response of the local inflammatory cascade. This affects the underlying tissue space in the short term but appears to be rapidly reversed if the infection is brought under control. On the other hand, chronic inflammation occurs at a very slow rate and is due to the exposure of the peritoneum to noncompatible dialysis solutions. It is not known whether any solutions other than an isotonic salt solution could be truly compatible with these cells. The macrophages and the mesothelial cells are both stimulated by dialysis solutions to produce a myriad of cytokines, prostaglandins, and matrix proteins, such as collagen and hyaluronan. Hyaluronan is secreted into the peritoneal cavity and is deposited within the tissue. This along with fibronectin and other macromolecules that escape the inflamed endothelium results in a thickening and scarring of the submesothelial peritoneum. Stimulation of tissue fibrob-last results in greater deposition of matrix materials with further scarring. Parenchymal cells such as skeletal muscle may just be innocent bystanders, but their true role has not been elucidated. It is anticipated that the system in Figure 5 will become more complex and more specific over the next several years.

To truly understand the peritoneal transport system in living human beings who utilize this for solute and water excretion over many years, one must combine Figures 1 and 5. Overlying the physiologic transport resistances of the various portions of the tissue space is a highly reactive cellular system of resident macrophages, mesothelial cells, fibroblasts, and endothelial cells. All of these combine in an integrated system of inflammatory response, which has the capacity to bring about over time marked alterations in the peritoneal transport system and its functional characteristics. It is anticipated that many advances will be made in the description of these changes and how to combat them and improve intraperitoneal therapies.

Glossary

Distributed model: A conceptual and integrative model of transperitoneal transport in which the microvasculature is distributed uniformly in the tissue.

Intraperitoneal chemotherapy: Regional treatment of peritoneal metastases with intraperitoneal solutions containing high concentrations of chemotherapeutic agents.

Peritoneal dialysis: A therapeutic technique used to remove waste metabolites and excess water from patients with kidney failure.

Three-pore model: A classic conceptual model of transendothelial transport.

Further Reading

Chambers, R., and Zwiefach, B. W. (1946). Functional activity of the blood capillary bed, with special reference to visceral tissue. Ann. N. Y. Acad. Sci. 46, 683-694. This is the classic description of the topography of the mesenteric circulation. Flessner, M. F. (1991). Peritoneal transport physiology: Insights from basic research. J. Am. Soc. Nephrol. 2, 122-135. This integrative review of the peritoneal transport system includes discussion of the role of the peritoneum, interstitium, lymphatics, and blood circulation. It includes quantitative data obtained in a rat model. Flessner, M. F., and Dedrick, R. L. (2000). Intraperitoneal chemotherapy. In Textbook of Peritoneal Dialysis (R. Gokal, R. Khanna, R. Th. Krediet, and K. D. Nolph, eds.), pp. 809-827. Dordrecht: Kluwer Academic.

This chapter reviews the details of the multicompartment model of intraperitoneal drug delivery and presents equations and parameter values for various drugs of interest.

Rippe, B., Rosengren, B. I., and Venturoli, D. (2001). The microcirculation in peritoneal dialysis. Microcirculation 8, 303-320. This is a detailed review of the three-pore model of transcapillary transport in the peritoneum. Included are the detailed equations used to describe the pore model.

White, R., and Granger, D. N. (2000). The peritoneal microcirculation in peritoneal dialysis. In Textbook of Peritoneal Dialysis (R. Gokal, R. Khanna, R. Th. Krediet, and K. D. Nolph, eds.), pp. 107-134. Dordrecht: Kluwer Academic. This is a detailed description of the peritoneal microvasculature, including effects of vasoactive substances on blood flow and leukocyte interactions with the endothelium during states of inflammation.

Capsule Biography

Dr. Flessner's background combines biomedical engineering with medicine. He has been the Director of Nephrology and the John Bower Professor of Nephrology and Hypertension, University of Mississippi Medical Center, since 2001. He is supported by grants from the NIH and the American Heart Association to study intraperitoneal immunotherapy and chronic inflammation in the peritoneal cavity.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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