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Alcohol-induced pancreatic injury

https://doi.org/10.1016/S1521-6918(03)00050-7Get rights and content

Abstract

Alcoholic pancreatitis is a major complication of alcohol abuse. Until recently, it was generally accepted that alcoholic pancreatitis was a chronic disease from the outset. However, evidence is now emerging in support of the ‘necrosis–fibrosis’ hypothesis that alcoholic pancreatitis begins as an acute process and that repeated episodes of acute injury lead to the changes of chronic pancreatitis (acinar atrophy and fibrosis) resulting in exocrine and endocrine dysfunction. The treatment of acute pancreatitis follows the regimen of bed rest, nasogastric suction, analgesia and intravenous support. The role of additional therapeutic measures such as prophylactic antibiotics, antioxidants and enteral nutrition in severe cases has not yet been precisely defined. The treatment of chronic pancreatitis involves attention to its three cardinal features: pain, maldigestion and diabetes. With respect to the pathogenesis of alcoholic pancreatitis, the focus of research over the past 30 years has shifted from the sphincter of Oddi and ductular abnormalities to the acinar cell itself. It has now been established that the acinar cell is capable of metabolizing alcohol and that direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to injury in the presence of an appropriate trigger factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. This chapter summarizes the natural history, clinical features, current trends in treatment as well as recent advances in our understanding of the pathogenesis of alcoholic pancreatitis.

Section snippets

Natural history and clinical features

The traditionally accepted view of alcoholic pancreatitis was that it was a form of chronic pancreatitis from the beginning, punctuated during its course by acute exacerbations.6., 7. This notion was based on studies showing that histological and radiological evidence of chronic pancreatitis (atrophy, fibrosis and calcification) could be found in the pancreas of many alcoholics at the time of their first clinical attack of pancreatitis.8., 9. Furthermore, an autopsy study demonstrated evidence

Diagnosis

A clinical diagnosis of acute pancreatitis is usually made on the basis of an attack of severe abdominal pain and tenderness, accompanied by a rise in the levels of amylase and lipase (pancreatic digestive enzymes) in the blood to more than three times the upper limit of normal. In recent years, there has been increasing use of serum lipase levels in the diagnosis of acute pancreatitis. Serum lipase is more specific for a pancreatic origin and levels remain elevated for a longer period than

Pathology

Most of the morphological and histological changes observed in alcoholic pancreatitis have been reported in pancreatic tissue obtained at autopsies or during surgical resection. It is possible therefore that the advanced forms of pancreatitis are over represented in such reports. In mild acute pancreatitis, the only gross change may be oedema of the gland, while in severe acute pancreatitis overt necrosis, haemorrhage, abscess formation and fluid collections may be evident. The gland of chronic

Treatment

The mainstays of treatment of an acute attack of alcoholic pancreatitis are bed rest, analgesia, fasting, nasogastric suction (if nausea and vomiting are problematical) and intravenous fluids.60 Most patients with mild pancreatitis recover quickly and do not require any additional support. In severe pancreatitis, nutritional support is required; this is usually provided via the intravenous route (parenteral nutrition). The enteral route had not been commonly used for nutritional support in

Pathogenesis

An understanding of the mechanism(s) responsible for the injurious effects of alcohol on the pancreas is an essential step towards the development of novel therapeutic strategies to prevent alcoholic pancreatitis or improve its outcome. Studies on the pathogenesis of alcoholic pancreatitis have often been hampered by the lack of suitable animal models of the disease and the difficulty in obtaining human pancreatic tissue for analysis. Nevertheless, significant advances have been made in recent

Current concept of the pathogenesis of alcoholic pancreatitis

The clinical and experimental evidence of alcohol-related pancreatic injury available in the literature has led us to propose the concept of the Drinker's Pancreas (Figure 2).

We postulate that the effects of alcohol, its metabolites (generated via both oxidative and non-oxidative pathways within the acinar cell) and its metabolic by-products (reactive oxygen species) lead to: (i) increased content of digestive and lysosomal enzymes (via increased synthesis and possibly decreased secretion in

Summary

Alcoholic pancreatitis is thought to begin as an acute necroinflammatory/autodigestive process in a susceptible individual and to progress with repeated episodes. The clinical spectrum of the disease includes acute pancreatitis (acute abdominal pain and raised serum levels of pancreatic enzymes) and chronic pancreatitis (abdominal pain, maldigestion, diabetes). Acute and chronic features can coincide.

Treatment of acute episodes is as for acute pancreatitis of other aetiologies and includes bed

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