Alcohol-Related Pancreatic Damage Mechanisms and Treatment MINOTI V. A PTE, M.D., M. MED. SCI.; JEREMY S. WILSON, M.D., PH.D.; AND MARK A. KORSTEN, M.D. Pancreatitis is a potentially fatal inflammation of the pancreas often associated with long-term alcohol consumption. Symptoms may result from blockage of small pancreatic ducts as well as from destruction of pancreatic tissue by digestive enzymes. In addition, by-products of alcohol metabolism within the pancreas may damage cell membranes. Research on the causes of pancreatitis may support more effective disease management and provide hope for a potential cure. KEY WORDS: alcoholic pancreatitis; prevalence; pathogenesis; diagnosis; treatment n association between alcohol THE HEALTHY PANCREAS glucose) levels: insulin and glucagon. abuse and pancreatic injury Poorly regulated blood glucose can A was reported as early as 1878 The pancreas lies deep within the produce symptoms associated with (Friedreich 1878). Alcoholic pancre- abdomen, behind the stomach. The diabetes. The hormones produced by atitis is a potentially fatal illness that pancreas serves two major functions these cells are released directly into may be short term (i.e., acute) or long (figure 1). First, certain cells (i.e., islet the bloodstream. Second, another term (i.e., chronic). The relationship cells) dispersed throughout the pan- specialized group of cells (i.e., acinar between acute and chronic pancreatitis creas play the role of an endocrine cells) secrete digestive enzymes into is complex. Symptoms shared by acute gland by producing two crucial hor- the small intestine through tubes (i.e., and chronic pancreatitis include dis- mones that regulate blood-sugar (i.e., ducts). In support of its digestive abling abdominal pain and interference function, the pancreas also secretes with normal pancreatic functions. MINOTI V. APTE, M.D., M. MED. SCI., bicarbonate through these same ducts. Although the prevalence of alcoholic is a research officer and JEREMY S. Pancreatic bicarbonate, a chemical pancreatitis in the population is un- WILSON,M.D., PH.D., is an associate similar to household baking soda, known, clinicians usually agree that professor at the Gastrointestinal helps adjust and maintain the rela- both acute and chronic alcoholic pan- Unit, Pancreatic Research Group, tively weak acidity required for the creatitis are responsible for a signifi- Prince of Wales Hospital, Randwick, action of intestinal digestive enzymes. cant amount of illness and death in the Australia. Pancreatitis arises in the acinar United States. This article discusses cells. However, inflammatory damage the extent of the problem, clinical MARK A. KORSTEN, M.D., is director of can destroy all parts of the pancreas— aspects, diagnosis, development (i.e., gastrointestinal endoscopy at the the islet cells as well as the acinar cells. pathogenesis), and treatment of both Alcohol Research Center, Mount Any disorder that affects the digestion acute and chronic alcohol-related Sinai School of Medicine, New York, of food or the subsequent metabolism pancreatitis. New York. of digested food in the bloodstream is VOL. 21, NO. 1, 1997 13 alcohol or smoking on other organs such as the liver. Pancreas The increased risk of pancreatic A cancer reported in heavy alcohol users (i.e., people who consume 10 to 12 standard drinks per day)1 by earlier studies has not been confirmed by more recent investigations. One com- plicating factor in some of the studies is cigarette smoking, which is com- monly associated with alcohol abuse. Pancreatic ducts B When the effect of cigarette smoking Acini was controlled for statistically, no association was found between alco- Islets hol abuse and pancreatic cancer. It has been suggested that the specific risk of pancreatic cancer among alcoholics To Small may be limited to those alcoholics intestine who develop chronic pancreatitis (Ahlgren 1996). This notion is not un- Duodenum reasonable, given that an excess rela- tive risk of pancreatic cancer has been Islet cells found in nonalcoholic types of pancre- atitis, including a hereditary form of the disease (Andren-Sandberg and Acinar cells Lowenfels 1997). The relationship of alcohol-related pancreatitis to pancre- Duct cells atic cancer, however, is less clear, again because of possible contributing Figure 1 The human pancreas. (A) View of the pancreas showing clusters of factors, such as malnutrition and acinar cells (i.e., acini), islet cells (i.e., islets), and pancreatic ducts. (B) smoking. An enlargement of a secretory region of the pancreas. Acini secrete digestive enzymes into the small intestine, islets secrete the hormones insulin and glucagon into the bloodstream to regulate blood glucose MEDICAL ASPECTS concentration, and duct cells secrete bicarbonate to regulate small intestine acidity. Alcoholic pancreatitis usually occurs in men in their forties. Initial symp- toms include vomiting as well as likely to have serious consequences for ences in the populations studied. For acute abdominal pain, which may be the entire body. example, in a Veterans Affairs hospital localized to the back and upper ab- (where the prevalence of alcoholism domen and is relieved by leaning among patients is high) (Steinberg and forward. In mild cases, the pain may THE EXTENT OF THE PROBLEM Tenner 1994), the number of cases of last 2 to 3 days; the short-term prog- alcohol-related pancreatitis is likely to be nosis in such cases is very good. In Since Friedreich’s initial observation, higher than that in a rural community severe cases, however, the pain may many studies have confirmed that exces- hospital. persist for several weeks and the risk sive alcohol intake is associated with The mortality rate of patients with of death rises to about 30 percent. pancreatic damage. However, the pro- alcoholic pancreatitis is about 36 Less commonly, pancreatitis can be portion of cases of pancreatitis attributed percent higher than that of the general completely painless and is only diag- to alcohol varies widely among countries population. Approximately 50 percent and even among different studies in the of patients with alcoholic pancreatitis nosed from symptoms of insufficient same country. In the United States, for die within 20 years of onset of the pancreatic function, such as diabetes instance, the reported incidence of pan- disease. Only 20 percent of deaths and steatorrhea (excess fat in feces). creatitis attributed to alcohol ranges from occurring before a patient’s life ex- 1 5 to 90 percent. This huge variation may A standard drink is roughly equivalent to the pectancy are attributed to pancreatitis amount of alcohol contained in 12 ounces of be related to the difficulties in accurately or its complications; most of these beer, 5 ounces of wine, or one and a half identifying alcohol abuse and to differ- deaths are attributed to the effects of ounces of 80-proof distilled spirits. 14 ALCOHOL HEALTH & RESEARCH WORLD Alcohol-Related Pancreatic Damage One complication of pancreatitis is sional episodes, or acute “flareups.” prospective study has reported that localized masses of dead tissue and This notion was based on results of changes in the pancreas related to old blood walled off between the tissue analyses and x-ray studies taken chronic pancreatitis were more likely to pancreas and surrounding organs (i.e., from alcoholics during their first at- occur in alcoholics who had recurrent pseudocysts). If a pseudocyst becomes tack of pancreatitis that seemed to acute inflammation of the pancreas infected, it can invade the pancreas reveal signs of already existing chron- (Ammann and Muellhaupt 1994). In and become an abscess. ic pancreatitis. Among these signs addition, a post mortem study of 247 Approximately 5 to 6 years after were shrinkage of tissue (i.e., atro- patients with fatal alcoholic pancreatitis the onset of the disease (especially in phy), replacement of healthy tissue by demonstrated that in 53 percent of the patients who continue to drink), evi- scar tissue (i.e., fibrosis), and harden- patients, no evidence existed of chronic dence of chronic pancreatic disease ing of tissue caused by calcium de- changes in the pancreas. Experiments develops as a result of progressive posits (i.e., calcification) (figure 2). show that repeated episodes of acute destruction of pancreatic tissue (i.e., Furthermore, autopsy studies demon- pancreatitis in rats produce chronic parenchyma). Patients seek medical strated evidence of pancreatic fibrosis changes in the pancreas, including fat attention for persistent pain (which in alcoholics who had no history of deposits, atrophy, and fibrosis (Elsasser often leads to narcotic addiction from clinical pancreatitis. et al. 1992). excessive use of pain medication), In recent years, the view that alco- weight loss, diabetes, and maldiges- holic pancreatitis is a form of chronic DIAGNOSIS OF ALCOHOLIC tion of food (a result of inadequate pancreatitis has been challenged. Opin- PANCREATITIS production of digestive enzymes by ion is now reverting to the hypothesis the pancreas). Abstinence from alco- first put forward in 1946 by Comfort A clinical diagnosis of pancreatitis is hol has been shown to slow the rate of and colleagues, who suggested that usually made on the basis of an attack progression of the disease and de- repeated attacks of acute pancreatic of severe abdominal pain and tender- crease the severity of abdominal pain. inflammation resulted in chronic pan- ness, accompanied by a rise in the Until recently, it was generally