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Front Physiol. 2018 Oct 1;9:1360. doi: 10.3389/fphys.2018.01360. eCollection 2018.

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination.

Author information

1
Institute for Translational Medicine, Medical School, University of Pecs, Pecs, Hungary.
2
Momentum Gastroenterology Multidisciplinary Research Group, Hungarian Academy of Sciences-University of Szeged, Szeged, Hungary.
3
First Department of Medicine, University of Szeged, Szeged, Hungary.
4
Institute of Bioanalysis, Medical School, University of Pecs, Pecs, Hungary.
5
Department of Gastroenterology, First Department of Medicine, University of Pecs, Pecs, Hungary.
6
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
7
Department of Translational Medicine, First Department of Medicine, University of Pecs, Pecs, Hungary.
8
Department of Pathophysiology, University of Szeged, Szeged, Hungary.
9
Institute of Surgical Research, University of Szeged, Szeged, Hungary.
10
Department of Laboratory Medicine, University of Szeged, Szeged, Hungary.
11
Momentum Epithel Cell Signaling and Secretion Research Group, Hungarian Academy of Sciences-University of Szeged, Szeged, Hungary.

Abstract

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

KEYWORDS:

acid-base balance; acidosis; experimental pancreatitis; meta-analysis; mortality

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