Gallbladder and Pancreatic Disease and Dysfunction an Overview

Reading Time: 15 minutes

Blausen_0701_PancreaticTissueDr Carrie Decker ND discusses the role of the pancreas and gall bladder in human digestion and health and explores some common problems, signs and symptoms and makes some recommendations for treatment and functional interventions.

Normal pancreatic and gallbladder function:

Digestive secretions of the gallbladder and pancreas are necessary for appropriate digestion of food substances. The digestion of foodstuff begins in the oral cavity with the process of chewing mixing foods with saliva, and salivary amylase initiates digestion by beginning to breakdown carbohydrates into smaller molecules. Subsequent to this, the food particles continue to be broken down by mechanical action and the acidic pH of the stomach. The partially digested substances, mixed into a semi-fluid mass called chyme, leave the stomach and enter the duodenum where bile from the gallbladder and pancreatic enzymes are both added via the ductal system of the biliary tree.

The central nervous system also plays an important role in the digestive process. Normal function of the pancreas and gallbladder requires input from the central nervous system in response to food intake. Postprandial release of cholecystokinin (CCK) plays a central role in the activation of intestinal feedback control of gastrointestinal function, and is stimulated by parasympathetic nerve fibres of the vagus nerve. Actions of CCK include stimulation of the exocrine pancreas and postprandial gallbladder emptying as well as inhibition of gastric emptying and acid secretion.[1],[2] CCK also acts via vagal afferent pathways to inhibit food intake.

Gallbladder dysfunction:

Biliary dysfunction can include multiple issues, which if not resolved can lead to pathology such as gallstones. Bile that is supersaturated with excess amounts of cholesterol or bilirubin leads to a sludge of precipitates.[3] Bile salts are an important part of the bile as they act as detergents to solubilise lipids. They also aid in the absorption of dietary lipids in the intestine. When there is excess cholesterol or bilirubin relative to bile salts, it will precipitate and can lead to the formation of stones. Gallbladder hypomotility or bile stasis also is a factor that leads to stone formation. Gallbladder stones can lead to obstruction of the biliary tree via which gallbladder and pancreas enzymes are secreted into the duodenum, causing emergency events such as acute cholecystitis or acute pancreatitis.

Gallbladder hypomotility or poor bile ejection can be associated with certain disease conditions, or may be a functional issue. Gallbladder tone is regulated by smooth muscle activity, hormones, and neurotransmitters released from intrinsic neurons and extrinsic sympathetic nerves.[4] Gallbladder hypomotility has been shown to be associated with polyneuropathy of diabetes mellitus, as well as other conditions such as spinal cord injuries which affect nervous system function.[5],[6] Animal studies have shown that the lack of CCK induces gallbladder hypomotility, prolonging the time that excess cholesterol resides in the gallbladder. [7] Biliary dyskinesia is a motility disorder that also may affect gallbladder function or the sphincter of Oddi, which connects the biliary tree to the duodenum. This also may lead to symptoms similar to gallstones as well as pancreatitis.[8]

Risk factors for gallstone formation include being of the female sex, obesity, rapid weight loss, pregnancy, oestrogen therapies, diabetes mellitus, and a family history of gallbladder disease.[9] Individuals with Crohn’s disease or haemolytic disorders such as sickle cell disease or hereditary spherocytosis also have an increased risk for forming gallstones.[10] Native Americans are an ethnic group with a higher risk for gallstones, while African Americans have been observed to have the lowest risk.[11] Historically, haemolytic disease was primary risk factor in children, while now gallstone disease in children is more often associated with obesity.[12]

Symptoms of gallbladder dysfunction and gallstones may include right upper quadrant pain, nausea, changes in stool colour or fat malabsorption, and acutely with obstruction there may be vomiting. Symptoms commonly occur after a meal or snack with increased fat content. More often than not the presence of gallstones will be asymptomatic and they are an incidental finding on abdominal imaging. Laboratory studies are usually normal in individuals with uncomplicated gallstone disease. With acute cholangitis (obstruction and infection of biliary tract) there may be elevations in the white blood cell count, serum alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, and possibly aminotransferases. Patients with acute cholecystitis (gallbladder inflammation) typically have elevated white blood cell counts, possibly with mild elevations in serum aminotransferases and bilirubin. “Murphy’s sign,” a sensation of discomfort with deep inspiration when pressure is applied along the right lower rib margin at the mid-clavicular line, is usually is positive with acute cholecystitis.[13]

Pancreatic dysfunction:

Pancreatic exocrine insufficiency (PEI), although often not discussed in the medical realm outside of the context of cystic fibrosis or acute and chronic pancreatitis, may exist in many individuals who do not have these conditions. Although it is possible to detect mild changes in pancreatic exocrine function with early pancreatic disease, overt maldigestion of fat and protein does not occur until approximately 90 percent of pancreas glandular function has been lost.[14] Symptoms of mild PEI can include bloating, cramping, increased flatulence, and diarrhea. As mentioned, malabsorption also may occur depending on severity. As the early symptoms are common complaints associated with irritable bowel syndrome (IBS), it often may be diagnosed as such without further workup to determine the aetiology of these symptoms.

Risk factors for PEI in addition to cystic fibrosis and acute or chronic pancreatitis include age, smoking, small intestine infection, diabetes mellitus, coeliac disease, inflammatory bowel disease, and excess alcohol intake. [15],[16],[17],[18],[19],[20] Lower levels of pancreatic elastase also have been shown in some individuals with IBS.[21] Increased rates of chronic pancreatitis have been found in association with autoimmune disease, with increased autoantibodies to pancreatic antigen being found in individuals with Sjögren’s syndrome and idiopathic chronic pancreatitis.[22] As an increased frequency of autoimmune related pancreatitis has been observed over the last 10 years, it has been suggested that chronic pancreatitis due to autoimmune disease will continue to rise.[23] Sphincter of Oddi dysfunction also can lead to pancreatic insufficiency and chronic pancreatitis.[24] As vagal stimulation of CCK also stimulates pancreatic exocrine function, poor vagal tone also can contribute to pancreatic insufficiency.

There are a variety of techniques utilised to assess pancreatic exocrine function. Measurement of pancreatic exocrine function by faecal chymotrypsin or elastase-1 are commonly available, non-invasive diagnosis techniques that have been well studied for the diagnosis of pancreatic exocrine insufficiency. A direct correlation of pancreatic elastase-1 concentrations have been shown between pancreatic exocrine fluid and stool, and this marker has been shown to be highly sensitive for the diagnosis of moderate to severe pancreatic exocrine insufficiency.[25],[26] Although faecal chymotrypsin and elastase-1 are both relatively stable through intestinal transit, elastase-1 has been shown to be a more sensitive marker of pancreatic exocrine insufficiency and levels are not affected by the use of digestive enzymes.[27]

Supporting gallbladder and pancreatic health and function:

A deficiency of ascorbic acid (vitamin C) is associated with the development of gallstones, and supplementation may exert a protective effect.[28],[29] Increased consumption of fruits, vegetables, nuts, polyunsaturated and monounsaturated fats, and coffee has also been shown to reduce the risk of gallstone formation in different populations.[30],[31],[32],[33] Increased physical activity has also been shown to reduce the incidence of symptomatic gallstones independent of obesity and recent weight loss, while individuals with a sedentary lifestyle are at increased risk of having a cholecystectomy.[34]

Taurine deficiency has been shown in animal studies to lead to increased cholesterol gallstone formation, while supplementation with taurine reduced the incidence of gallstones, likely due to enhanced cholesterol degradation and the excretion of bile acid.[35],[36],[37] Ox bile, taken as a supplement, supports the production and flow of bile, which may lead to a reduction in stone formation as well as improving symptoms of fat malabsorption. Dietary fat and stomach acid secretion promotes gallbladder emptying, which may improve symptoms on a long term basis if they are related to stasis and poor ejection.[38]

The presence of larger asymptomatic gallstones may be treated by cholecystectomy as it is associated with increased risk of gallbladder cancer. Because of the high incidence of gallstones in populations with haemolytic disorders and after gastric bypass, gallbladder removal is recommended in these populations.[39] However, overall, only about 30% of patients with asymptomatic cholelithiasis have been observed to require surgery during their lifetime.[40]

Abstinence from alcohol and tobacco, as well as treatment of hyperglycemia and small intestine bacterial overgrowth if present also will impact pancreatic exocrine function and related symptoms.[41],[42] Antioxidant therapies have been shown to reduce the pain and oxidative stress associated with chronic pancreatitis.[43] Support for an acidic stomach pH also may play a role in normalising pancreatic exocrine function of a functional nature, while supplementation of pancreatic enzymes including lipase, proteases, and amylase with meals is recommended to improve absorption of nutrients as well as digestive symptoms.[44],[45]

For individuals with documented PEI, the initial dose of enzyme supplementation has been recommended to be is 25,000 units of lipase per meal possibly increasing to 90,000 units of lipase per meal.35,[46]  Supplementation of papain (papaya) and bromelain (pineapple) also may be used to support the digestion of protein.[47] Pancreatin, a mixture of digestive enzymes secreted by the pancreas, also has been shown to be effective, but preparations have been shown to vary.[48],[49] Even in absence of testing that indicates PEI, a trial of supplementation with enzymes may be found to improve symptoms and if so may indicate insufficiency. If symptoms are exaggerated, discontinue supplementation until further investigations have been completed, as some patients with PEI will describe an increase in gastric distress with exogenous pancreatic enzymes.

Supporting parasympathetic balance may improve a variety of digestive complaints as the vagus nerve plays a significant role in digestion including gallbladder ejection and pancreas exocrine function.[50],[51] Poor vagal tone has also been documented in individuals with functional dyspepsia.[52]

Consumption of fat may play a role in digestive function via the parasympathetic nervous system as well. Increased enteral fat has been shown to reduce release of inflammatory mediators by acting as a stimulant of parasympathetic outflow via the vagus nerve, mediated by CCK release.[53],[54] Other interventions which support parasympathetic balance and improved digestion include making time for meals, chewing food thoroughly, engaging in a meditative or mindfulness practice including at meal times, eating meals in less stressful settings (away from the laptop or work environment), as well as other stress management techniques.

References

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