Loss of Pancreatic enzymes leads to maldigestions and malabsorption which may lead to:

- steatorrhea

- weight loss

- fatigue

- flatulence and abdominal distention (bacterial fermentation of unabsorbed food)

- edema (hypoalbuminemia)

- anemia (Vitamin B12, iron, folate deficiency)

- bleeding disorders (Vitamin K malabsorption)

- Metabolic bone disease (Vitamin D deficiency)

- neurologic manifestation

- hypocalcemia

HP is characterised by attacks of epigastric pain, which are often associated with nausea and vomiting. Symptoms may start shortly after birth but onset varies periodically, with some patients not exhibiting symptoms until adulthood. There is usually progression to chronic pancreatitis with endocrine and exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54% to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis. Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.

The epidemiology of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences. For example, HP typically has an earlier age of pancreatitis onset; although malabsorption and diabetes mellitus occur at a later stage in the disease progression.

Hereditary pancreatitis (HP) is an inflammation of the pancreas, attributed to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb "et al" isolated the first responsible mutation in the trypsinogen gene ("PRSS1") on the long arm of chromosome seven ("7q35").

The term "hereditary pancreatitis" is used when a genetic biomarker is identified, and "familial pancreatitis" otherwise.

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.

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor.

The clinical signs can vary from mild gastrointestinal upset to death, with most dogs presenting with common gastrointestinal signs of upset, such as vomiting, anorexia, painful abdomen, hunched posture, diarrhea, fever, dehydration, and lack of energy, with vomiting being the most common symptom. These signs are not specific just for pancreatitis and may be associated with other gastrointestinal diseases and conditions.

Acute pancreatitis can trigger a build-up of fluid, particularly in abdominal and thoracic (chest) areas, acute renal failure, and cause inflammation in arteries and veins. The inflammation triggers the body's clotting factors, possibly depleting them to the point of spontaneous bleeding. It is this form which can be fatal in animals and in humans.

Chronic pancreatitis can be present even though there are no clinical signs of the disease.

Pancreatitis can result in exocrine pancreatic insufficiency, if the organ's acinar cells are permanently damaged; the pancreatic enzymes then need replacement with pancrelipase or similar products. The damage can also extend into the endocrine portion of the pancreas, resulting in diabetes mellitus. Whether the diabetes is transient (temporary) or permanent depends on the severity of the damage to the endocrine pancreas beta cells.

The primary physiological effect of glucagonoma is an overproduction of the peptide hormone glucagon, which leads to an increase in blood glucose levels through the activation of anabolic and catabolic processes including gluconeogenesis and lipolysis respectively. Gluconeogenesis produces glucose from protein and amino acid materials. It also increases lipolysis, which is the breakdown of fat. The net result is hyperglucagonemia, decreased blood levels of amino acids (hypoaminoacidemia), anemia, diarrhea, and weight loss of 5 to15 kg.

Necrolytic migratory erythema (NME) is a classical symptom observed in patients with glucagonoma and is the presenting problem in 70% of cases. Associated NME is characterized by the spread of erythematous blisters and swelling across areas subject to greater friction and pressure, including the lower abdomen, buttocks, perineum, and groin.

Diabetes mellitus also frequently results from the insulin and glucagon imbalance that occurs in glucagonoma. Diabetes mellitus is present in 80% to 90% of cases of glucagonoma, and is exacerbated by preexisting insulin resistance.

Canine pancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden while chronic pancreatitis is characterized by recurring or persistent form of pancreatic inflammation. Cases of both can be considered mild or severe.

Endocrine insufficiency of the pancreas occurs with JBS, though it is sometimes less common and less pronounced than the more prominent effects on exocrine function. The islets of Langerhans are ducts in the pancreas where endocrine activity such as the release of hormones glucagon, somatostatin and insulin takes place. Pancreatic endocrine insufficiency in JBS can be associated with either a buildup of connective tissue in the islet regions, congenital replacement of the islets with fatty tissue, or improper nerve signalling to the islets. Endocrine dysfunction of the pancreas often results in diabetes mellitus. Both insulin resistance and diabetes have been observed with JBS, and it is suggested that diabetes should be considered as a complication of JBS and its course.

Ductular output of fluids and electrolytes is preserved in the pancreas of many with JBS, as well as moderate to normal levels of functioning bicarbonate.

Endocrine abnormalities in other areas have also been present with the disorder. These include hypothyroidism, growth hormone deficiency and hypopituitarism. Findings affecting pituitary function in some JBS patients have included such anomalies as the formation of a glial hamartoma (a neoplasm, or tumor composed of glial cells) on a lobe of the pituitary gland, as well congenital underdevelopment of the anterior pituitary. Growth failure and associated short stature (dwarfism) in JBS can be attributed to growth hormone deficiency caused by diminished anterior pituitary function, with malabsorption of fats playing a subsequent role.

The most prominent effect of JBS is pancreatic exocrine insufficiency. Varying degrees of decreased secretion of lipases, pancreatic juices such as trypsin, trypsinogen and others, as well as malabsorption of fats and disruptions of glucagon secretion and its response to hypoglycemia caused by insulin activity are major concerns when JBS is diagnosed. Associated with developmental errors, impaired apoptosis, and both prenatal and chronic inflammatory damage, necrosis and fibrosis of the pancreatic acini (clusters of pancreatic exocrine gland tissue, where secretion of pancreatic juice and related enzymes occurs), pancreatic exocrine insufficiency in JBS can additionally stem from congenital replacement of the acini with fatty tissue. Near total replacement of the entire pancreas with fatty tissue has also been reported. This is a progressive, sometimes fatal consequence of the disorder.

Pancreatitis is inflammation of the pancreas. There are two forms of pancreatitis, which are different in causes and symptoms, and require different treatment:

- Acute pancreatitis is a rapid-onset inflammation of the pancreas, most frequently caused by alcoholism or gallstones.

- Chronic pancreatitis is a long-standing inflammation of the pancreas.

Accessory pancreas is a rare condition in which small groups of pancreatic cells are separate from the pancreas. They may occur in the mesentery of the small intestine, the wall of the duodenum, the upper part of the jejunum, or more rarely, in the wall of the stomach, ileum, gallbladder or spleen. The condition was first described by Klob in 1859.

Accessory pancreas is a small cluster of pancreas cells detached from the pancreas and sometimes found in the wall of the stomach or intestines.

X-ray computed tomography (CT scan) findings of cysts in the pancreas are common, and often are benign. In a study of 2,832 patients without pancreatic disease, 73 patients (2.6%) had cysts in the pancreas. About 85% of these patients had a single cyst. Cysts ranged in size from 2 to 38 mm (mean, 8.9 mm). There was a strong correlation between the presence of cysts and age. No cysts were identified among patients less than 40 years of age, while 8.7 percent of the patients aged 80 to 89 years had a pancreatic cyst.

Cysts also may be present due to intraductal papillary mucinous neoplasm.

Autoimmune pancreatitis (AIP) is an increasingly recognized type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.

Type 1 AIP is now regarded as a manifestation of IgG4-related disease, and those affected have tended to be older and to have a high relapse rate. Type 1 is associated with pancreatitis, Sjogren syndrome, Primary sclerosing cholangitis and Inflammatory bowel disease. Patients with Type 2 AIP do not experience relapse, tend to be younger and not associated with systemic disease. AIP occurring in association with an autoimmune disorder has been referred to as "secondary" or "syndromic" AIP. AIP does not affect long-term survival.

Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in acute pancreatitis.

AIP is relatively uncommon and is characterized by the following features:

1. Scleral Icterus (yellow eyes), jaundice (yellow skin) which is usually painless, usually without acute attacks of pancreatitis.

2. Relatively mild symptoms, such as minimal weight loss or nausea.

3. Increased serum levels of gamma globulins, immunoglobulin G (IgG) or IgG4.

4. The presence of serum autoantibodies such as anti-nuclear antibody (ANA), anti-lactoferrin antibody, anti-carbonic anhydrase II antibody, and rheumatoid factor (RF).

5. Contrast-enhanced CT demonstrates a diffusely enlarged (sausage-shaped) pancreas.

6. Diffuse irregular narrowing of the main pancreatic duct, and stenosis of the intrapancreatic bile duct on endoscopic retrograde cholangiopancreatography (ERCP).

7. Rare pancreatic calcification or cyst formation.

8. Marked responsiveness to treatment with corticosteroids.

Two-thirds of patients present with either obstructive painless jaundice or a "mass" in the head of the pancreas mimicking carcinoma. It is mandatory to rule out carcinoma prior to making a diagnosis of AIP.

Nesidioblastosis is a controversial medical term for hyperinsulinemic hypoglycemia attributed to excessive function of pancreatic beta cells with an abnormal microscopic appearance. The term was coined in the first half of the 20th century. The abnormal histologic aspects of the tissue included the presence of islet cell enlargement, islet cell dysplasia, beta cells budding from ductal epithelium, and islets in apposition to ducts.

By the 1970s, nesidioblastosis was primarily used to describe the pancreatic dysfunction associated with persistent congenital hyperinsulinism and in most cases from the 1970s until the 1980s, it was used as a synonym for what is now referred to as congenital hyperinsulinism. Most congenital hyperinsulinism is caused by different mechanisms than excessive proliferation of beta cells in a fetal pattern and the term fell into disfavor after it was recognized in the late 1980s that the characteristic tissue features were sometimes seen in pancreatic tissue from normal infants and even adults, and is not consistently associated with hyperinsulinemic hypoglycemia.

However, the term has been resurrected in recent years to describe a form of "acquired" hyperinsulinism with beta cell hyperplasia found in adults, especially after gastrointestinal surgery.

Evidence of physiologic mechanisms purporting that weight loss surgery conveys the ability to induce a more contemporary presentation of nesidioblastosis remains elusive and is of intense interest to diabetes researchers.

Substantial numbers of patients with intestinal malabsorption present initially with symptoms or laboratory abnormalities that point to other organ systems in the absence of or overshadowing symptoms referable to the gastrointestinal tract. For example, there is increasing epidemiologic evidence that more patients with coeliac disease present with anemia and osteopenia in the absence of significant classic gastrointestinal symptoms. Microcytic, macrocytic, or dimorphic anemia may reflect impaired iron, folate, or vitamin B12 absorption. Purpura, subconjunctival hemorrhage, or even frank bleeding may reflect hypoprothrombinemia secondary to vitamin K malabsorption. Osteopenia is common, especially in the presence of steatorrhea. Impaired calcium and vitamin D absorption and chelation of calcium by unabsorbed fatty acids resulting in fecal loss of calcium may all contribute. If calcium deficiency is prolonged, secondary hyperparathyroidism may develop. Prolonged malnutrition may induce amenorrhea, infertility, and impotence. Edema and even ascites may reflect hypoproteinemia associated with protein losing enteropathy caused by lymphatic obstruction or extensive mucosal inflammation. Dermatitis and peripheral neuropathy may be caused by malabsorption of specific vitamins or micronutrients and essential fatty acids.

Prior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium). Meconium may completely block the intestines and cause serious illness. This condition, called meconium ileus, occurs in 5–10% of newborns with CF. In addition, protrusion of internal rectal membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and increased intra–abdominal pressure due to coughing.

The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. These secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis.

The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Resultant hypoproteinemia may be severe enough to cause generalized edema. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K.

In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation. Older individuals with CF may develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.

Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF. It is mainly associated with "severe" CFTR mutations, where both alleles are completely nonfunctional (e.g. ΔF508/ΔF508). It occurs in 10% to 15% of patients with one "severe" and one "mild" CFTR mutation where little CFTR activity still occurs, or where two "mild" CFTR mutations exist. In these milder cases, sufficient pancreatic exocrine function is still present so that enzyme supplementation is not required. Usually, no other GI complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development. Despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications.

Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Over time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting. Liver disease is the third-most common cause of death associated with CF.

Early signs of abnormality include polyhydramnios (an excess of amniotic fluid), low birth weight, and feeding intolerance immediately after birth.

DIOS is sometimes classified by the degree of obstruction as incomplete or complete DIOS.

Depending on the nature of the disease process causing malabsorption and its extent, gastrointestinal symptoms may range from severe to subtle or may even be totally absent. Diarrhea, weight loss, flatulence, abdominal bloating, abdominal cramps, and pain may be present. Although diarrhea is a common complaint, the character and frequency of stools may vary considerably ranging from over 10 watery stools per day to less than one voluminous putty-like stool, the latter causing some patients to complain of constipation. On the other hand, stool mass is invariably increased in patients with steatorrhea and generalized malabsorption above the normal with 150–200 g/day. Not only do unabsorbed nutrients contribute to stool mass but mucosal fluid and electrolyte secretion is also increased in diseases associated with mucosal inflammation such as coeliac disease. In addition, unabsorbed fatty acids, converted to hydroxy-fatty acids by colonic flora, as well as unabsorbed bile acids both impair absorption and induce secretion of water and electrolytes by the colon adding to stool mass. Weight loss is common among patients with significant intestinal malabsorption but must be evaluated in the context of caloric intake. Some patients compensate for fecal wastage of unabsorbed nutrients by significantly increasing their oral intake. Eliciting a careful dietary history from patients with suspected malabsorption is therefore crucial. Excessive flatus and abdominal bloating may reflect excessive gas production due to fermentation of unabsorbed carbohydrate, especially among patients with primary or secondary disaccharidase deficiency. Malabsorption of dietary nutrients and excessive fluid secretion by inflamed small intestine also contribute to abdominal distention and bloating. Prevalence, severity, and character of abdominal pain vary considerably among the various disease processes associated with intestinal malabsorption. For example, pain is common in patients with chronic pancreatitis or pancreatic cancer and Crohn disease, but it is absent in many patients with coeliac disease or postgastrectomy malabsorption.

Signs and symptoms of pancreatic pseudocyst include abdominal discomfort and indigestion.

The main signs and symptoms of cystic fibrosis are salty-tasting skin, poor growth, and poor weight gain despite normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital absence of the vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies. As the children grow, they exercise to release mucus in the alveoli. Ciliated epithelial cells in the person have a mutated protein that leads to abnormally viscous mucus production. The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers, and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.

In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin K–dependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present.

It is typically associated with abnormal embryological development, however adult cases can develop. It can result from growth of a bifid ventral pancreatic bud around the duodenum, where the parts of the bifid ventral bud fuse with the dorsal bud, forming a pancreatic ring. It can also result if the ventral pancreatic bud fails to fully rotate, so it remains on the right or if the dorsal bud rotates in the wrong direction, such that the duodenum is surrounded by pancreatic tissue. Blockage of the duodenum develops if inflammation (pancreatitis) develops in the annular pancreas.