Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of

digestive enzyme Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of anima ...

s made by the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...

. EPI is found in humans afflicted with

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Ot ...

and

Shwachman–Diamond syndrome Shwachman–Diamond syndrome (SDS), or Shwachman–Bodian–Diamond syndrome, is a rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities and short stature. After cystic fibro ...

, and is common in dogs. EPI is caused by a progressive loss of the pancreatic cells that make digestive enzymes; loss of digestive enzymes leads to maldigestion and

malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...

of nutrients from normal digestive processes.

Chronic pancreatitis 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 pa ...

is the most common cause of EPI in humans and

cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

s. In dogs, the most common cause is ''pancreatic acinar atrophy'', arising as a result of genetic conditions, a blocked

pancreatic duct The pancreatic duct, or duct of Wirsung (also, the major pancreatic duct due to the existence of an accessory pancreatic duct), is a duct joining the pancreas to the common bile duct. This supplies it with pancreatic juice from the exocrine pancr ...

, or prior infection. The

exocrine pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocr ...

is a portion of this organ that contains clusters of ducts (acini) producing

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochemi ...

anion, a mild alkali, as well as an array of digestive enzymes that together empty by way of the interlobular and main pancreatic ducts into the

duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...

(upper small intestine). The hormones cholecystokinin and

secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the du ...

secreted by the stomach and duodenum in response to distension and the presence of food in turn stimulate the production of digestive enzymes by the exocrine pancreas. The alkalization of the duodenum neutralizes the acidic

chyme Chyme or chymus (; from Greek χυμός ''khymos'', "juice") is the semi-fluid mass of partly digested food that is expelled by a person's stomach, through the pyloric valve, into the duodenum The enzymes include

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

s (

trypsinogen Trypsinogen () is the precursor form (or zymogen) of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by ent ...

and

chymotrypsinogen Chymotrypsinogen is an inactive precursor (zymogen) of chymotrypsin, a digestive enzyme which breaks proteins down into smaller peptides. Chymotrypsinogen is a single polypeptide chain consisting of 245 amino acid residues. It is synthesized in th ...

), hydrolytic enzymes that cleave

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...

(the

lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually ...

phospholipase A2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyc ...

and lysophospholipase, and cholesterol esterase), and amylase to digest starches. EPI results from progressive failure in the exocrine function of the pancreas to provide its

s, often in response to a genetic condition or other disease state, resulting in the inability of the animal involved to properly digest food.

Signs and symptoms

Loss of pancreatic enzymes leads to maldigestion and malabsorption, which may in turn lead to: *

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

(

Vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...

deficiency) * bleeding disorders (

Vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...

malabsorption) *

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

( hypoalbuminemia) * fatigue * flatulence and abdominal distention (bacterial fermentation of unabsorbed food) * hypocalcemia * metabolic bone disease ( Vitamin D deficiency) * neurologic manifestation *

steatorrhea Steatorrhea (or steatorrhoea) is the presence of excess fat in feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may o ...

* weight loss

Causes

In humans, the most common causes of EPI are

chronic pancreatitis 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 pa ...

and

, 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 Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...

. According to WebMD, "Crohn's disease and celiac disease can also lead to EPI in some people". In children, another common cause is Shwachman-Bodian-Diamond syndrome, a rare autosomal recessive genetic disorder resulting from mutation in the SBDS gene.

Diagnosis

The three main tests used in considering a diagnosis of EPI are: fecal elastase test, fecal fat test, and a direct pancreatic function test. The latter is a limitedly used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions.

Treatment

EPI is often treated with pancreatic enzyme replacement products (PERPs) such as pancrelipase, that are used to break down fats (via a

), proteins (via a

), and carbohydrates (via amylase) into units that can be digested. Pancrelipase is typically porcine derived and requires large doses.

Other animals

Causes and pathogenesis

is the most common cause of EPI in

s. In dogs, where the condition has been deemed common, the usual cause is by ''pancreatic acinar atrophy'', arising as a result of genetic conditions, a blocked

, or prior infection. In dogs, EPI is most common in young German Shepherds, and in Finland

Rough Collie The Rough Collie (also known as the Long-Haired Collie) is a long-coated dog breed of medium to large size that, in its original form, was a type of collie used and bred for herding sheep in Scotland. More recent breeding has focused on the Co ...

s, and is inherited. In German Shepherds, the method of inheritance is through an autosomal recessive gene. In these two breeds, at least, the cause appears to be immune-mediated as a sequela to

lymphocytic A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adapt ...

pancreatitis. The German Shepherd makes up about two-thirds of cases seen with EPI. Other breeds reported to be predisposed to EPI include

terrier Terrier (from Latin ''terra'', 'earth') is a type of dog originally bred to hunt vermin. A terrier is a dog of any one of many breeds or landraces of the terrier type, which are typically small, wiry, game, and fearless. Terrier breeds vary ...

breeds,

Cavalier King Charles Spaniel The Cavalier King Charles Spaniel is a British breed of toy dog of spaniel type. Four colours are recognised: Blenheim (chestnut and white), tricolour (black/white/tan), black and tan, and ruby; the coat is smooth and silky. The lifespan is u ...

Chow Chow The Chow Chow is a spitz-type of dog breed originally from northern China. The Chow Chow is a sturdily built dog, square in profile, with a broad skull and small, triangular, erect ears with rounded tips. The breed is known for a very dense ...

s, and Picardy Shepherds.

Symptoms

In animals, signs of EPI are not present until 85 to 90 percent of the pancreas is unable to secrete its enzymes. In dogs, symptoms include weight loss, poor hair coat,

flatulence Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed enviro ...

, increased appetite,

coprophagia Coprophagia () or coprophagy () is the consumption of feces. The word is derived from the grc, κόπρος , "feces" and , "to eat". Coprophagy refers to many kinds of feces-eating, including eating feces of other species (heterospecifics), of ...

, and diarrhea. Feces are often yellow-gray in color with an oily texture. There are many concurrent diseases that mimic EPI, and severe pancreatitis is one that if allowed to continue unabated can lead to EPI.

Diagnosis and treatment

The most reliable test for EPI in dogs and cats is serum trypsin-like immunoreactivity (TLI); a low value indicates EPI. Fecal elastase levels may also be used for diagnosis in dogs. In dogs, the best treatment is to supplement the animals' food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used. (Pork pancreas should not be used because of the rare transmission of pseudorabies). Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is

oral ulcer A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying caus ...

ation and bleeding. Because of malabsorption, serum levels of cyanocobalamin (vitamin B12) and

tocopherol Tocopherols (; TCP) are a class of organic chemical compounds (more precisely, various methylated phenols), many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rat ...

(vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical

cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...

, dogs that have serious cobalamin issues should instead be treated with

hydroxocobalamin Hydroxocobalamin, also known as vitamin B12a and hydroxycobalamin, is a vitamin found in food and used as a dietary supplement. As a supplement it is used to treat vitamin B12 deficiency including pernicious anemia. Other uses include treatment ...

or methylcobalamin. Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency. Cats may suffer from

deficiencies. If there is

bacterial overgrowth Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is ...

in the intestine, antibiotics should be used, especially if treatment is not working. In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease. However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis. One possible

sequela A sequela (, ; usually used in the plural, sequelae ) is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word, meaning “sequel”, it is used in the medical field to mean a complication ...

, volvulus (mesenteric torsion), is a rare consequence of EPI in dogs.

References

External links

{{Gastroenterology Dog diseases Pancreas disorders Steatorrhea-related diseases