Mechanisms of alcoholic pancreatitis

Abstract

Alcoholic pancreatitis is a major complication of alcohol abuse. The risk of developing pancreatitis increases with increasing doses of alcohol, suggesting that alcohol exerts dose-related toxic effects on the pancreas. However, it is also clear that only a minority of alcoholics develop the disease, indicating that an additional trigger may be required to initiate clinically evident pancreatic injury. It is now well established that alcohol is metabolized by the pancreas via both oxidative and non-oxidative metabolites. Alcohol and its metabolites produce changes in the acinar cells, which may promote premature intracellular digestive enzyme activation thereby predisposing the gland to autodigestive injury. Pancreatic stellate cells (PSCs) are activated directly by alcohol and its metabolites and also by cytokines and growth factors released during alcohol-induced pancreatic necroinflammation. Activated PSCs are the key cells responsible for producing the fibrosis of alcoholic chronic pancreatitis. Efforts to identify clinically relevant factors that may explain the susceptibility of some alcoholics to pancreatitis have been underway for several years. An unequivocal, functionally characterized, association is yet to be identified in clinical studies, although in the experimental setting, endotoxin has been shown to trigger overt pancreatic injury and to promote disease progression in alcohol-fed animals. Thus, while the molecular effects of alcohol on the pancreas have been increasingly clarified in recent years, identification of predisposing or triggering factors remains a challenge.

Alcoholic pancreatitis: New insights into the pathogenesis and treatment

“…Although there is a tremendous association between alcohol abuse and pancreatitis, relatively few individuals who abuse alcohol develop alcoholic pancreatitis. This fact indicates that alcoholic pancreatitis is not caused by chronic alcohol abuse alone [16][17][18] . Instead, it appears that the pancreas is sensitized to injury by alcohol consumption, and external or environmental factors trigger initiation of this disease.…”

“…These findings have lead to the suggestion that these cytokines and growth factors act on pancreatic stellate cells in an autocrine manner, thereby perpetuating their activation [16] . This autocrine loop may help to explain both the apparent inability of the pancreas to fully recover from injury in the continued presence of ethanol, and the extremely common association between alcohol abuse and chronic pancreatitis [3,14] .…”

The inhibitory effects of Nardostachys jatamansi on alcoholic chronic pancreatitis

“…Many clinicians routinely advise patients to abstain from alcohol, however this has no benefit for the patient. Previous studies that have tried to reverse ACP by stopping alcohol consumption, they could not find a significant improvement (2,24). In contrast to humans, the murine AP and ACP model generally recover the diseases after the absence of stimuli (25,26).…”

“…The resulting symptoms of abdominal pain, steatorrhea, and weight loss may be debilitating, complicated by psychosocial problems, loss of work, narcotic addiction, and consumption of health-care resources (2). CP is mainly associated with alcohol abuse (3).…”

Pancreatic Acinar and Island Vascular Apparatus Associated with Acute and Chronic Inflammatory Processes

“…In case of acute pancreatitis we observed isolated cells in the vicinity of intense necrotic lesions, this aspect being maintained in the vicinity of fibrosis zones in chronic pancreatitis ( figure 11 and 12). These argirophils may provide the reticular fibril-genesis for vascular apparatus of the parenchyma [23].…”