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Neonatal Necrotising Enterocolitis in Premature Neonates

Neonatal Necrotising Enterocolitis (NEC) in Premature Neonates: Pathogenesis and clinical findings Prematurity risk factors ↓ Intestinal motility ↑ Intestinal stasis allows bacteria more time to proliferate Bacterial overgrowth in gut ↓ Goblet cells in intestinal epithelium ↓ Intestinal mucus layer production leads to impaired mechanical defense against pathogenic bacteria Immature tight junctions in intestinal epithelium ↑ Permeability of intestinal epithelial barrier ↑ Toll-like receptor 4 (TLR4) expression on intestinal epithelial cells Aberrant bacterial colonization of gut Impaired gut barrier allows for ↑ bacterial translocation across intestinal epithelium TLR4 on intestinal mesentery endothelial cells bind lipopolysaccharides (LPS) on Gram-negative gut bacteria Immune cells release proinflammatory mediators (TNF, IL-12, IL-18) Cytokines mediate ↑ enterocyte apoptosis (including enteric stem cells) and ↓ enterocyte proliferation Intestinal mucosa healing is impaired, leading to local inflammation & injury TLR4 on intestinal epithelial cells binds LPS from Gram-negative gut bacteria Authors: Rachel Bethune Naima Riaz Reviewers: Nicola Adderley Michelle J. Chen Kamran Yusuf* Jean Mah* * MD at time of publication Endothelial nitric oxide synthase expression is reduced Vasoconstriction from ↓ NO reduces blood flow to intestines Prolonged ↓ in O2 perfusion results in irreversible intestinal mucosal cell death (necrosis) Gas escapes into abdominal cavity Leakage of intestinal contents irritates parietal peritoneum Bacteria enter bloodstream Pneumo- peritoneum Abdominal distention Peritonitis Sepsis Blood from tissue damage mixes with intestinal contents Bloody stool Intestinal sensory neurons detect damage and send signals to medullary vomiting centre Bilious vomiting Damaged intestinal cells are unable to absorb nutrients Short gut syndrome Persistent intestinal mucosal injury creates penetrating lesions through intestinal wall Intestinal perforation Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published May 6, 2019; updated Mar 21, 2024 on www.thecalgaryguide.com