**4. Pathology**

NEC primarily affects the ileum and colon, the commonest location being ileocecal area [22]. The entire gastrointestinal tract may be involved in severe cases. On gross examination, the bowel loops are distended with areas of hemorrhage, congestion, necrosis, and pneumatosis (**Figure 1**). On microscopic examination, signs of inflammation, mucosal edema, bacterial invasion, submucosal and intramural gas bubbles, and ischemic transmural necrosis are seen. Intestinal perforation may happen when the entire thickness of bowel is involved leading to pneumoperitoneum, peritonitis, and portal venous gas (**Figure 2**). Microscopically, the predominant feature is coagulation necrosis, suggesting an ischemic origin of NEC. The aggregated inflammatory cells are both acute and chronic, such as neutrophils, lymphocytes, and macrophages representing an appropriate response to pathogenic bacterial invasion and tissue necrosis. Epithelial regeneration, granulation tissue formation and fibrosis may be seen suggesting reparative histological process [23]. Common pathogens isolated in NEC are Enterobacteriaceae including *Escherichia*, *Salmonella*, *Enterobacter*, and *Klebsiella* (68%); staphylococcal species (26%); clostridium species (4%); viruses including rota, echo, corona, and toro (11%); and candida (1%). No organism is isolated in 3% of cases.

#### **Figure 1.**

*Macroscopic appearance of necrotizing enterocolitis showing necrotic bowel loops. [Courtesy of Renu Sharma, MD, Professor of Pediatrics, University of Florida at Jacksonville, USA].*

**29**

*Necrotizing Enterocolitis*

**5. Pathogenesis**

*Schematic presentation of pathogenesis of NEC.*

**Figure 2.**

The pathogenesis of NEC is complex, multifactorial, and incompletely defined.

Immaturity of neonatal intestinal mucosal barrier and mucosal immune system is characterized by decreased mucus coat, altered mucus protein, reduced Ig A, and abnormal epithelial membrane and tight junctions [4, 26, 27]. Preterm intestinal

The disorder is believed to be a composite result of intestinal immaturity, aberrant immunological response, and gut microbial dysbiosis [3, 4, 23, 24]. It almost never occurs when the intestinal immune system is mature and intact, even when other risk factors are present. Experimental NEC does not occur in sterile environment. Research support the hypothesis that NEC in the preterm infant results from a multifactorial process that requires the concurrent presence of an immature intestinal tract and immune system leading to increased susceptibility, factors causing disruption of the normal intestinal bacterial microbiome with growth of potentially pathogenic bacteria, and an exaggerated inflammatory host response with the release of cytokines and chemokines (**Figure 2**). A genetically determined predisposition to necrotizing enterocolitis has been also proposed implying the contribution of genetic polymorphisms in the pro-inflammatory cytokines associated with NEC [25]. The combination of compromised intestinal epithelial barrier; underdeveloped and anomalous immune defense; abnormal mesenteric vascular development, tone, and flow; and altered luminal microbiota shaped by formula feedings, antibiotic exposure, and cesarean delivery presumably leads to intestinal inflammation and gangrene. NEC is triggered when several risk factors heighten neonatal intestinal inflammation and an irreversible borderline is surpassed.

**5.1 Intestinal immaturity, dysbiosis, and barrier dysfunction**

*DOI: http://dx.doi.org/10.5772/intechopen.85784*
