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Latest health and behavior news and advice from the veterinarians at Tufts University.

Features January 2014 Issue

Exocrine Pancreatic Insufficiency In Dogs

A dog with this condition can starve to death no matter how much she eats — unless the disease is diagnosed and managed correctly.

“Three years ago, Maya started having an ‘iffy’ stomach,” says Paula Gatens of Waynesville, North Carolina. But it didn’t appear to be anything serious. “She would eat something and get diarrhea, but then it would go away,” Ms. Gatens relates. “Like other German shepherds, she had a sensitive stomach, but she was a normal dog.”

About three weeks before Maya’s fourth birthday, however, she began to experience diarrhea that wouldn’t go away. “We put her on a high-fiber diet, and that seemed to help a bit,” Ms. Gatens says. “But then all of a sudden she lost about 15 pounds in two to three weeks. Her stools were enormous — and soft.”

Paula Gatens with Maya, who is fine now that she has been properly treated for exocrine pancreatic insufficiency. She was literally starving when the disease was first diagnosed.

Ironically, Maya was one of the lucky ones. The clinical signs of the disease that was ravaging her body were so clear that she was easy to diagnose. Her condition is called exocrine pancreatic insufficiency, or EPI. In a nutshell, it’s an inability to digest food. The dog is ravenous and eats copious amounts, but the food and the calories it contains go right through her system without being broken down and absorbed, so she starves because her body can’t use the nutrients she takes in. “Maya was eating acorns, grass, six cups of food a day,” Ms. Gatens says, but she couldn’t relieve her hunger or keep on weight.

Other symptoms, besides wasting away despite a voracious appetite:

  • Eliminating more frequently, sometimes every hour or two.
  • Greasy, voluminous, unformed stools, often yellowish but sometimes grayish.
  • Eating substances a dog wouldn’t normally eat.
  • Increased rumbling sounds from the stomach.
  • Flatulence.
  • Personality changes, veering either toward fearfulness or sudden crankiness/aggression.

The disease can strike any dog from a young puppy to an elderly “dowager,” but German shepherds have a predisposition. That, along with Maya’s symptoms, helped her veterinarian pinpoint her disease relatively easily.

It’s not always a slam dunk. Some dogs don’t display symptoms, or don’t have all of them, or display them only to a certain degree. “There are variable degrees of expression of this disease trait, from a mild form to the most severe form, where patients are ravenous, losing weight, and passing large volumes of stool that are essentially undigested food,” says Tufts veterinarian Mary Labato, DVM, DACVIM, a specialist in small animal internal medicine. If the disease is mild, and if the dog is not a German shepherd, it can be harder for a vet to do quick sleuthing.

The cause of the illness

Exocrine pancreatic insufficiency develops when the exocrine pancreas fails to produce and secrete the enzymes required for digesting food. In the main, the pancreas is an endocrine organ, meaning it secretes substances — often hormones —directly into the bloodstream (such as the hormone insulin, which is necessary for metabolizing the blood sugar glucose). But it does have some exocrine functions, which is to say that is it secretes certain substances to a “far-away” environment via ducts.

Among those substances: enzymes essential for food digestion, which normally get sent from the pancreas to the intestine to help break down food for absorption by the body. These enzymes include amylase, which is involved in the digestion of carbohydrates found in grains, fruits, and vegetables; lipase, essential for the digestion of fat; and trypsin and proteases, needed to digest protein. (Carbs, fat, and protein are the three calorie-containing nutrients.)

In dogs with exocrine pancreatic insufficiency, the enzymes are neither manufactured nor secreted. The pancreas, literally, becomes insufficient in that regard. Its exocrine cells are atrophied. Unfortunately, symptoms do not appear until some 80 to 95 percent of the cells at issue are destroyed; it is detected late in the game.

While in German shepherds the condition is usually hereditary, in other breeds, it often is the result of some other problem. For instance, says Dr. Labato, it can be “an acquired problem after severe pancreatitis [inflammation of the pancreas].”

In fact, Dr. Labato says, these days, with breeders aware of the disease and screening for the trait in German shepherds, veterinarians are more likely to see the condition as a complication of some other disease in a dog of any breed than in a German shepherd genetically primed to develop the problem. And since the hereditary form that afflicts some German shepherds produces the most pronounced symptoms, like the kind Maya had, more often veterinarians will see dogs with milder symptoms that are less obviously suggestive of EPI.

A definitive diagnosis

If a dog is suspected of having exocrine pancreatic insufficiency, the only way to confirm the diagnosis is to administer a trypsin-like immunoreactivity (cTLI) test. As we said above, trypsin is one of the enzymes needed to digest food — protein, specifically. And trypsinogen is a prohormone that is also produced by the exocrine pancreas, and needed to create trypsin. The test, a blood test before which the dog must have been fasted for at least 12 hours, checks how much of that substance is in the bloodstream. The normal range is along the lines of 5 to 35 micrograms per liter of blood. A level lower than that is generally definitive for a diagnosis.

Often, a blood test for the presence of vitamin B12, known as cobalamin, will be administered as well. A cobalamin deficiency occurs in four out of five dogs with exocrine pancreatic insufficiency, and some research suggests it can be at least partly responsible for the personality changes seen in dogs with the condition, making them perhaps more fearful and timid or more aggressive with, say, other dogs — or at least somewhat confused or disoriented, impairing cognitive function. Paula Gatens’s dog, Maya, was found not to have very low levels when she was first diagnosed with the disease, so Ms. Gatens didn’t think any personality changes would come into play.

Treatment

Managing exocrine pancreatic insufficiency involves a five-pronged approach that includes supplementation with digestive enzymes missing from the dog’s pancreas, feeding the dog 150 percent of her usual rations, treatment for bacterial overgrowth in the gut that results from the disease, cobalamin supplementation, and a low-fiber diet.

Supplementation of digestive enzymes: Enzymes to take the place of those not produced by the pancreas are needed at every single meal. Ideally, there are no between-meal treats, but if there are, the dog must be supplied with enzymes at those eating occasions also. The enzymes of choice are porcine (pig) enzymes that have been ground to a powder or are given as tablets, granules, or other formulations. “The amino acid sequence of the enzymes are a closer match between pigs and dogs than between, say, cows and dogs,” Dr. Labato says. “Also,” she adds, “it is inexpensive for enzyme manufacturers to obtain pig pancreas from a slaughter house.” Furthermore, “with all of the bovine viral disease that people are now concerned about, it is harder to get cow by-products for medical use these days.”

It used to be thought that mixing powdered enzymes in the dog’s food and then pre-soaking it in lukewarm water allowed for some pre-digestion before the dog actually consumed the victuals. But there have now been “a couple of studies to support the notion that this is not necessarily needed,” Dr. Labato comments. Thus, if for whatever reason your dog takes the enzymes more easily in another form that is not powdered, your vet can advise you on whether that form is okay for your pet. For some dogs, softening the food-powder mixture in water helps avoid mouth sores that can possibly occur because of the caustic attributes of the powdered enzymes. Every dog reacts differently.

Note: If the food and enzymes have been heated to too high a temperature prior to serving, the enzymes will be destroyed. If it’s too chilled, they’ll be inactivated. At room temperature or very close to that is best.

150 percent of usual rations: Dogs who have experienced significant wasting because of the disease need to catch up. Until a dog’s body is back to itself, 150 percent of the amount of food she’s supposed to get should be given daily in small meals, at least 2 hours apart.

Low-fiber diet: Most, but not all, dogs with exocrine pancreatic insufficiency fare better on a diet that is very low in fiber, less than 4 percent. Fiber interferes with the function of the replacement enzymes, and it can inhibit absorption of certain nutrients, to boot.

That said, different dogs do better on different kinds of diets. For some, a very high-protein, grain-free food is the right choice, while other dogs with exocrine pancreatic insufficiency actually need some grain, with its attendant fiber. Complicating the issue further is that there are two kinds of dietary fiber, soluble and insoluble. Soluble fiber slows digestion (a good thing if you want to absorb the most nutrients), while insoluble fiber tends to speed the transit time of food through the digestive system. And very often, both kinds of fiber are contained in a single food. A veterinarian, particularly a board-certified veterinary nutritionist, can help you experiment safely until you come up with the fiber level and the fiber quality that is right for your dog. You’ll know because her stool volume, color, and quantity will be normal, or at least close to normal.

Treatment for SIBO: SIBO stands for “small intestinal bacterial overgrowth,” meaning that lack of ability to properly digest food in the small intestine (where the lion’s share of digestion takes place once food leaves the stomach) creates an environment that allows “bad” bacteria to overtake “good” bacteria, worsening the gastrointestinal signs of the disease. Today, veterinarians are starting to replace the term SIBO with SID, which is short for small intestinal dysbiosis. It’s a little more precise because “dysbiosis” refers to a bacterial imbalance rather than a bacterial overgrowth per se.

Whichever term your vet’s office uses, the doctor will often not lose time after diagnosis of exocrine pancreatic insufficiency taking a cell culture and growing it in the lab to see whether bad bacteria are present. She will go straight to prescribing an antibiotic to kill any offending bacteria that may be lurking — not an unreasonable approach since virtually all dogs diagnosed with exocrine pancreatic sufficiency also have SIBO. That was the approach with Maya. In fact, with the porcine enzymes her “soft stools went away right away,” says Ms. Gatens. “But they [still] gave her antibiotics.”

Some vets wait a week or two after starting the dog on porcine enzyme supplementation to see if that corrects the bacterial imbalance. If the dog’s stools continue to have yellowish coloring or remain loose and “ploppy” even with the administration of porcine enzymes, then antibiotic treatment will begin. The antibiotics most commonly used are metronidazole (Flagyl), amoxicillin/clavulanic acid (Clavamox), and tylosin (Tylan). Sometimes enrofloxacin (Baytril) will be prescribed if it is suspected — or learned upon further examination — that the offending bacteria are of the E. coli variety. Usually the dog receives a two- to four-week course of antibiotics, although “some patients require more long-term administration,” says Dr. Labato. If SIBO, or SID, is indeed present, a positive response should be observed in about a week to 10 days. (Don’t stop giving the antibiotic after just a few days if you don’t see any improvement right away in the dog’s stools.) If a positive response is not seen in that time period, the vet will often change the antibiotic. For instance, that’s when she might switch from, say, metronidazole to enrofloxacin on the suspicion that a different type of bacteria has taken hold.

B12 supplementation: Since more than four out of five dogs with exocrine pancreatic insufficiency are estimated to have insufficient levels of vitamin B12, it’s a good idea for the vet to test blood levels of that nutrient at the same time she orders a trypsin-like immunoreactivity blood test. It will save money because only one blood draw is needed, and the price is lower when it’s packaged with the TLI test. And it’s critical. If B12 levels are low and not corrected, the dog will not bounce back sufficiently.

Maya’s B12 levels were tested right up front and found to be in the 600s (meaning 600+ nanograms of B12 per liter of blood). Too low is generally considered to be less than 300, so B12 supplementation was not ordered. But, says Ms. Gatens, she did have SIBO, which “just ate away at her B12 stores.” It’s a vicious cycle. Inadequate B12 levels will set the stage for SIBO, and then the presence of SIBO can keep the B12 stores even lower.

Within 3 months, Maya’s B12 levels had fallen from the 600s to the 100s. “That made her dog reactive,” Ms. Gatens says. “Some dogs get really lethargic, but some can get nasty,” she adds. Maya became harder to have around others of her species — enough so that Ms. Gatens even took her to a behaviorist, who regretfully announced, finally, that she couldn’t work with Maya. It was because the problem was medical rather than truly behavioral. Once she was put on B12 supplementation, the problem largely cleared up. The supplement of choice is a schedule of B12 injections rather than pills that contain the nutrient. With most pills, the B12 never makes it to the bloodstream. The vet will look for B12 levels to be in the normal-to-upper range once B12 supplementation has begun. Levels in the normal range are usually not sufficient.

“Maya is much better now that she’s on B12,” Ms. Gatens remarks — “still a bit reactive” but in general not impossible to keep calm when other dogs are around.

In fact, says Ms. Gatens, today — three years after her diagnosis and the start of treatment — Maya is “great. She’s a good dog. Still intense. She was intense even before this started, so I think she will always be.” But the two are great pals, and Ms. Gatens is thrilled that her companion is “thriving now” when she was once so sick. 

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