In humans, the most common causes of EPI are chronic pancreatitis and cystic fibrosis, the former a longstanding inflammation of the pancreas altering the organ's normal structure and function that can arise as a result of malnutrition, heredity, or (in the western world especially), behaviour (alcohol use, smoking), and the latter a recessive hereditary disease most common in Europeans and Ashkenazi Jews where the molecular culprit is an altered, "CFTR"-encoded chloride channel. In children, another common cause is Shwachman-Bodian-Diamond syndrome, a rare autosomal recessive genetic disorder resulting from mutation in the SBDS gene.

EPI is often treated with pancreatic enzyme replacement products (PERPs) such as pancrelipase, that are used to break down fats (via a lipase), proteins (via a protease), and carbohydrates (via amylase) into units that can be digested by those with EPI. Pancrelipase is typically porcine derived and requires large doses. A novel treatment called Sollpura (Liprotamase) is under trial that uses biotechnology derived enzymes to help treat EPI.

Although there can be various causes of dog pancreatitis, such as drugs, fatty diet, trauma, etc., the pathophysiology is very complex. Pancreatitis can be idiopathic; no real causation factor can be found. Obese animals as well as animals fed a diet high in fat may be more prone to developing acute and chronic pancreatitis. Certain breeds of dogs are considered predisposed to developing pancreatitis including miniature schnauzers, Cocker Spaniels, and some terrier breeds. Miniature Schnauzers as a breed tend toward developing hyperlipidemia, an excess of circulating fats in the blood. The breed which appears to be at risk for the acute form of pancreatitis is the Yorkshire Terrier, while Labrador Retrievers and miniature Poodles seem to have a decreased risk for the acute form of the disease. It is suggested that genetics may play a part in the risk factor. Dogs suffering from diabetes mellitus, Cushing's disease (hyperadrenocorticism), hypothyroidism and epilepsy are at increased risk for pancreatitis. Diabetes and hypothyroidism are also associated with hyperlipidemia. Those with other types of gastrointestinal conditions and dogs who have had previous pancreatitis attacks are also at increased risk for the disorder.

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome. It is caused by a progressive loss of the pancreatic cells that make digestive enzymes. Chronic pancreatitis is the most common cause of EPI in humans. Loss of digestive enzymes leads to maldigestion and malabsorption of nutrients.

The pancreas is central in the pathophysiology of both major types of diabetes mellitus. In type 1 diabetes mellitus, there is direct damage to the endocrine pancreas that results in insufficient insulin synthesis and secretion. Type 2 diabetes mellitus, which begins with insulin resistance, is characterized by the ultimate failure of pancreatic β cells to match insulin production with insulin demand.

Blind loop syndrome is a complication of surgical operations of the abdomen, as well as inflammatory bowel disease or scleroderma. Another cause is jejunoileal diverticula.

A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.

There are no approved treatments for canine pancreatitis. Treatment for this disease is supportive, and may require hospitialization to attend to the dog's nutritional and fluid needs, pain management, and addressing any other disease processes (infection, diabetes, etc.) while letting the pancreas heal on its own. Treatment often involves "resting" the pancreas for a short period of time by nil per os/nothing per os (NPO)/nil by mouth (NBM), in which the patient receives no food or fluids by mouth, but is fed and hydrated by intravenous fluids and a feeding tube. Dehydration is also managed by the use of fluid therapy. However, a specialist from Texas A&M University has stated "There is no evidence whatsoever that withholding food has any beneficial effect." Other specialists have agreed with his opinion.

Canine pancreatitis is complex, often limiting the ability to approach the disease.

In adults in the United Kingdom, the estimated average total direct and indirect costs of chronic pancreatitis is roughly £79,000 per person on an annual basis. Acute recurrent pancreatitis and chronic pancreatitis occur infrequently in children, but are associated with high healthcare costs due to substantial disease burden. Globally, the estimated average total cost of treatment for children with these conditions is approximately $40,500 annually.

The overgrowth of bacteria in the small intestine is prevented by various mechanical and chemical factors which include the constant peristaltic movement of contents along the length of the gastrointestinal tract and the antibacterial properties of gastric secretions, pancreatic secretions and bile.

It follows that a disruption of any of these factors could lead to bacterial overgrowth and indeed BLS has been found to occur in persons with anatomical anomalies that result in stagnation. BLS has also been associated with achlorhydria, dysmotility, fistulae, and strictures. Chronic or high dose opioid therapy may contribute to BLS by reducing gastric motility.

Due to the disruption of digestive processes by the overgrowth of intestinal bacteria malabsorption of bile salts, fat and fat-soluble vitamins, protein and carbohydrates results in damage to the mucosal lining of the intestine by bacteria or via the production of toxic metabolites.

In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US. In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963-74) over time.

In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease (such as infection) being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups.

There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy (HRT), diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing panreatitis are not known exactly; but it is possible that statins has direct toxic effect on the pancreas or through the long term accumulation of toxic metabolites. Meanwhile, ACE inhibitors causes angioedema of the pancreas through the accumulation of bradykinin. Oral contraceptives/HRT causes arterial thrombosis of the pancreas through the accumulation of fat (hypertriglyceridemia). Diuretics such as furosemide has direct toxic effect on the pancreas. Meanwhile, thiazide diuretics causes hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones. HIV infection itself can cause a person to more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. There are various oral hypoglycemic agents that contributes to pancreatitis including metformin. But, glucagon-like peptide-1 (GLP-1) is more strongly associated with pancreatits by promoting inflammation.

Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis.

treatment of HP resemble that of chronic pancreatitis of other causes. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction.(PMC1774562)

There is a 2-3:1 male-to-female predilection in primary sclerosing cholangitis. PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of inflammatory bowel disease (IBD). PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC.

The main purpose of the gastrointestinal tract is to digest and absorb nutrients (fat, carbohydrate, protein, micronutrients (vitamins and trace minerals), water, and electrolytes. Digestion involves both mechanical and enzymatic breakdown of food. Mechanical processes include chewing, gastric churning, and the to-and-fro mixing in the small intestine. Enzymatic hydrolysis is initiated by intraluminal processes requiring gastric, pancreatic, and biliary secretions. The final products of digestion are absorbed through the intestinal epithelial cells.

Malabsorption constitutes the pathological interference with the normal physiological sequence of digestion (intraluminal process), absorption (mucosal process) and transport (postmucosal events) of nutrients.

Intestinal malabsorption can be due to:

- Mucosal damage (enteropathy)

- Congenital or acquired reduction in absorptive surface

- Defects of specific hydrolysis

- Defects of ion transport

- Pancreatic insufficiency

- Impaired enterohepatic circulation

Locoregional complications include pancreatic pseudocyst (Most common, occurring in up to 25% of all cases) and phlegmon / abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.

The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.

PSC is strongly associated with inflammatory bowel disease (IBD), in particular ulcerative colitis (UC) and to a lesser extent Crohn's disease. As many as 5% of patients with IBD are co-diagnosed with PSC and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital.

Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis (hepatic osteodystrophy) and hypothyroidism are also associated with PSC.

Orlistat (also known by trade names Xenical and Alli) is a diet pill that works by blocking the enzymes that digest fat. As a result, some fat cannot be absorbed from the gut and is excreted in the feces instead of being metabolically digested, sometimes causing oily anal leakage. Vytorin (ezetimibe/simvastatin) tablets can cause steatorrhea in some people.

Symptoms can manifest in a variety of ways and features might give a clue to the underlying condition. Symptoms can be intestinal or extra-intestinal - the former predominates in severe malabsorption.

- Diarrhoea, often steatorrhoea, is the most common feature. Watery, diurnal and nocturnal, bulky, frequent stools are the clinical hallmark of overt malabsorption. It is due to impaired water, carbohydrate and electrolyte absorption or irritation from unabsorbed fatty acid. The latter also results in bloating, flatulence and abdominal discomfort. Cramping pain usually suggests obstructive intestinal segment e.g. in Crohn's disease, especially if it persists after defecation.

- Weight loss can be significant despite increased oral intake of nutrients.

- Growth retardation, failure to thrive, delayed puberty in children

- Swelling or oedema from loss of protein

- Anaemias, commonly from vitamin B, folic acid and iron deficiency presenting as fatigue and weakness.

- Muscle cramp from decreased vitamin D, calcium absorption. Also lead to osteomalacia and osteoporosis

- Bleeding tendencies from vitamin K and other coagulation factor deficiencies.

Impaired digestion or absorption can result in fatty stools.

Possible causes include exocrine pancreatic insufficiency, with poor digestion from lack of lipases, loss of bile salts, which reduces micelle formation, and small intestinal disease producing malabsorption. Various other causes include certain medicines that block fat absorption, or indigestible or excess oil/fat in diet.

The absence of bile secretion can cause the feces to turn gray or pale. Other features of fat malabsorption may also occur such as reduced bone density, difficulty with vision under low light levels, bleeding, bruising and slow blood clotting times.

First described by Smith (1953), and elaborated upon by Cameron et al. (1976), internal pancreatic fistulas can result in pancreatic ascites, mediastinital pseudocysts, enzymatic mediastinitis, or pancreatic pleural effusions, depending on the flow of pancreatic secretions from a disrupted pancreatic duct or leakage from a pseudocyst.

Marked recent weight loss is a major clinical manifestation, and unresponsiveness of the ascites to diuretics is an additional diagnostic clue.

The cause of pancreatic pseudocyst can occur due to a variety of reasons, among them pancreatitis (chronic), pancreatic neoplasm and/or pancreatic trauma.

The annual incidence of chronic pancreatitis is 5 to 12 per 100,000 persons, the prevalence is 50 per 100,000 persons.

Pancreatic diseases that affect digestion refers to disorders affecting the exocrine pancreas, which is a part of the pancreas involved in digestion.

One of the most common conditions of the exocrine pancreas is acute pancreatitis, which in the majority of cases relates to gallstones that have impacted in the pancreatic part of the biliary tree, or due to acute or chronic alcohol abuse or as a side-effect of ERCP. Other forms of pancreatitis include chronic and hereditary forms. Chronic pancreatitis may predispose to pancreatic cancer and is strongly linked to alcohol use. Other rarer diseases affecting the pancreas may include pancreatic pseudocysts, exocrine pancreatic insufficiency, and pancreatic fistulas.

Pancreatic disease may present with or without symptoms. When symptoms occur, such as in acute pancreatitis, a person may suffer from acute-onset, severe mid-abdominal pain, nausea and vomiting. In severe cases, pancreatitis may lead to rapid blood loss and systemic inflammatory response syndrome. When the pancreas is unable to secrete digestive enzymes, such as with a pancreatic cancer occluding the pancreatic duct, result in jaundice. Pancreatic disease might be investigated using abdominal x-rays, MRCP or ERCP, CT scans, and through blood tests such as measurement of the amylase and lipase enzymes.