Quantitative Histomorphometry of the Healthy Peritoneum

Abstract

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1–60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7–12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches.

Reduced Microvascular Density in Omental Biopsies of Children with Chronic Kidney Disease

“…Omental biopsies were performed in children initiating PD as part of an ongoing study evaluating morphological characteristics of the peritoneal membrane and the omentum [20]. Data of CKD patients had been recorded at the time of catheter insertion for PD by participating centers and was retrieved from the online database.…”

Recommendations for pathological diagnosis on biopsy samples from peritoneal dialysis patients

“…The inflammation and endothelial injury caused by peritonitis or other factors are believed to cause high vascular permeability and fibrin exudation based on PD related vasculopathy in progressive EPS cases. Repetitive peritonitis also causes angiogenesis, with vessels expanding beyond the three distinct vascular layers found in normal peritoneum [17,57]. IL-6 is thought to be a mediator of increased solute transport related to infection, seen in an IL-6 KO peritonitis model [58], and supported by clinical findings of elevated level of IL-6 in PD effluent [59].…”

“…The 4 um sections are cut and stained with hematoxylin & eosin (H&E) and Masson's trichrome stain. To identify vessels or lymph vessels, cluster of differentiation (CD) 31 (or CD34) and podoplanin staining is added to the procedure [16,17]. Podoplanin staining is also useful to identify mesothelial cells, or podoplanin positive fibroblasts or "fibroblast-like cells (FLC)" [18,19].…”

“…The vascular network of parietal peritoneum is mainly located between the submesothelial interstitial layer and peritoneal adipose tissue and is composed of small artery, arteriole, capillary, post-capillary venule and veins ( Figure 1A-b), occasionally with lymphatic vessels. Of note is that the vascular population varies dependent on age and mesothelial location; blood and lymph vessel density in parietal peritoneum is higher in infant age [17], lymphatic vessels are more abundant in the visceral peritoneum than the parietal [19,25].…”

“…One prospective observational study, "Neutral solution, Extraneal use, and current PD outcome in Japan (NEXT-PD)" [99] showed that multidisciplinary approaches including the use of biocompatible PD solution, reduction of high glucose solutions, introduction of an incremental prescription style [100], combination therapy (PD and hemodialysis) [101], and planned PD discontinuation for long-term cases with membrane damage [101] contributed to a decreased incidence of EPS [99,102]. One systematic pathological analysis on healthy peritoneum including a wide range of ages (0.1-60 years old) showed that age dependent vascular and lymph blood vessel densities form three distinct layers together with nerve fibers, related to SMC thickness without inflammation, pro-fibrosis and mesothelial cell translocation [17]. Another systematic review of peritoneal vascular anatomy and function also highlights that the peritoneal vascular plexus and vascularization is under the influence of neurological factors as well as other physical, chemical, and hormonal factors [103].…”