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Children 2015, 2(3), 358-370; doi:10.3390/children2030358

Controversies in the Mechanism of Total Parenteral Nutrition Induced Pathology

1
Department of Pediatrics, St. Louis University School of Medicine, Cardinal Glennon Children's Medical Center, SSM Cardinal Glennon Hospital 1465 South Grand Blvd., St. Louis, MO 63104, USA
2
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine
*
Author to whom correspondence should be addressed.
Academic Editor: Sari Acra
Received: 3 June 2015 / Revised: 11 July 2015 / Accepted: 14 July 2015 / Published: 31 July 2015
(This article belongs to the Collection Controversies in Pediatric Digestive Diseases)
View Full-Text   |   Download PDF [207 KB, uploaded 31 July 2015]

Abstract

Over 30,000 patients are permanently dependent on Total Parenteral Nutrition (TPN) for survival with several folds higher requiring TPN for a prolonged duration. Unfortunately, it can cause potentially fatal complications. TPN infusion results in impairment of gut mucosal integrity, enhanced inflammation, increased cytokine expression and trans-mucosal bacterial permeation. It also causes endotoxin associated down regulation of bile acid transporters and Parenteral Nutrition Associated Liver Disease (PNALD), which includes steatosis, disrupted glucose metabolism, disrupted lipid metabolism, cholestasis and liver failure. Despite multiple theories, its etiology and pathophysiology remains elusive and is likely multifactorial. An important cause for TPN related pathologies appears to be a disruption in the normal enterohepatic circulation due to a lack of feeding during such therapy. This is further validated by the fact that in clinical settings, once cholestasis sets in, its reversal occurs when a patient is receiving a major portion of calories enterally. There are several other postulated mechanisms including gut bacterial permeation predisposing to endotoxin associated down regulation of bile acid transporters. An additional potential mechanism includes toxicity of the TPN solution itself, such as lipid mediated hepatic toxicity. Prematurity, leading to a poor development of bile acid regulating nuclear receptors and transporters has also been implicated as a causative factor. This review presents the current controversies and research into mechanisms of TPN associated injury. View Full-Text
Keywords: liver; gut; neonatal; parenteral nutrition liver; gut; neonatal; parenteral nutrition
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kumar, J.A.; Teckman, J.H. Controversies in the Mechanism of Total Parenteral Nutrition Induced Pathology. Children 2015, 2, 358-370.

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