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Exocrine Pancreatic Insufficiency

by Sher Belonus

Forward:
A disease of many names (EPI, PAA, Malabsorption or Malassimilation), this condition is over represented in the GSD and the White Shepherd descending from the GSD. Hereditary in nature in the White Shepherd, it is determined to be an auto-somal recessive. On this count we can be considered lucky, as it is possible to breed away from this disease and diminish its presence within our breed.

Many vets do not recognize EPI when it is presented. They will run the gamut of tests for worms, IBS, allergies, etc. as they search around for the cause of the problem. This results in enlarged bills for the dog owner and frustration for the vet who searches in vain within the parameters of common ailments. Because of this, this article has been written with two angles in mind. The first is to assist the owner who suspects EPI in their dog, the second to be a printable reference you can take to your vet and get them on the right track.

For my boy, Blitz, and for all his White Shepherd friends and relatives. March 3, 2003

Anatomy:
The pancreas is an elongated, tapered organ, tanish pink in color, which resides in close proximity to the duodenum (the first section of the small intestine). The tapered nature of the organ is often described as a “head” “body” and “tail”. It is covered with a thin connective tissue casing, which extends inward partitioning the gland into lobules. The bulk of the pancreas is made up of pancreatic exocrine cells and their associated ducts. Within the exocrine tissue are millions of small cell clusters called the Islets of Langerhans. These are the endocrine cells of the pancreas. They secrete insulin, glucagon and other hormones. For our purposes, we will discard the endocrine function and merely deal with the exocrine.

Pancreatic exocrine cells are arranged in clusters called acini. The exocrine cells are packed with membrane-bound secretory granules. These granules contain digestive enzymes that are released into the lumen (the cavity inside a hollow organ or vessel) of the acinus. From there these secretions flow into ever-larger intralobular ducts, which eventually collect into the main pancreatic duct and drain directly into the duodenum.



Pathogenesis:
Pancreatic acinar cell tissue located on the exocrine portion of the pancreas is responsible for the creation and release of pancreatic digestive enzymes. These enzymes are vitally important to proper food digestion and assimilation of nutrients. The three primary enzyme group types are protease, lipase and amylase. Protease enzymes are necessary for proper protein breakdown and digestion. The two major pancreatic proteases are trypsin and chymotrypsin. These are created and kept in secretory vesicles (a closed membranous shell) as the inactive proenzymes trypsinogen and chymotrypsinogen. Lipases are created and released for digesting fats, and amylases for carbohydrates. PAA (pancreatic acinar atrophy) is the culprit responsible for the vast majority of cases of canine EPI. The nutrients ingested by EPI affected dogs are not broken down into proper absorbable forms due to the lack of intraluminal enzyme activities.

Some dogs may also develop secondary changes to the intestinal mucosa. If secondary changes occur, it is going to have an impact on the genesis of malassimilation. The changes to the intestinal mucosa can include villous (villi – tiny hair-like structures in the intestinal wall responsible for absorbing nutrients) atrophy, inflammatory cells and changes within the mucosal enzyme activities. SIBO (small intestine bacterial overgrowth) is a common side problem of EPI and can be responsible for many mucosal changes. It is speculated by some that the lack of pancreatic secretions containing possible antibiotic properties is the cause of EPI related SIBO.

Clinical Features:
It was once believed that a solitary severe case of acute pancreatitis or repeated bouts of mild, chronic pancreatitis could result in a progressive loss of pancreatic acinar tissue. Recent studies now conclude that this form of EPI is uncommon and that the bulk of EPI cases presented are heritable (GSD) or of an adult onset nature (idiopathic, non-breed specific). Dogs affected by the heritable form are usually young when symptoms manifest (around age 2 or below typically). Dogs affected by the idiopathic form are typically mature or into their geriatric phase of life and may or may not have exhibited a history of chronic pancreatitis. When the disease reaches its peak and 90% or more of the pancreatic acinar ability is lost; the dog will present with the clinical signs of nutrient malassimilation. Up until that time, the dog will appear normal. 

Owners typically present undiagnosed dogs with EPI to a veterinarian for a chronic weight loss history though the dog may be a ravenous eater with a large appetite. No matter how much the dog eats it continues to drop weight. Quite literally, the dog could eat copious amounts morning, noon and night and yet starve to death. The dog may also exhibit an increase in thirst. 

The character of the fecal excretions can be normal, soft and of a cow-patty nature, or watery. The EPI affected dog will often go off a normal bowel movement schedule having bowel movements frequently throughout the day and night. 

Gastric distress such as stomach gurgling, continual flatulence, and burping are typical and may also manifest.

Some owners describe their dogs experiencing pica (eating of inedible things such as dirt, wood, etc.) and coprophagia (stool eating). EPI affected dogs exhibiting pica and coprophagia are not doing so for behavioral reasons. The dog is merely desperate to ingest nutrients from any source.

Poor skin and coat conditions are common with the coat being brittle, dry and lack luster. Staining of the perineal region may occur while the dog is experiencing steatorrhea (fecal matter that is frothy, foul smelling and floats because of a high fat content).

Extended bleeding upon venipuncture in affected dogs may result due to a lack of fat-soluble vitamin K in the dogs system.

Diagnosis:
The result of standard laboratory testing is normal (chemistry profiles, urinalysis, CBC, etc.). Dogs may exhibit a higher than normal serum ALT (a liver enzyme that plays a role in protein metabolism) activity due to disrupted small intestinal barriers and the resulting hepatic (liver) inflammation. Many will also have hypocholesterolaemia (the presence of abnormally small amounts of cholesterol in the circulating blood).

Standard diagnostic testing, history examination, and physical examination will not be able to differentiate between small bowel disease and malassimilation from EPI at this point. Further screening must be done.
The triglyceride challenge test and fecal analysis measuring the level of trypsin activity and the presence of undigested food particles can be performed in the vets office and a tentative, presumptive diagnosis made.

The triglyceride challenge test presumes that the affected canine may have a lower than normal fat absorption. The triglyceride challenge test is conducted as follows:
A. Upon completion of a 12 hour fast, a serum sample is obtained. The dog is then given 3 to 4 ml of corn oil per kilogram of body weight by oral administration.
B. Measurement of the serum triglyceride concentration is conducted at 0, 2, and 3 hours after the corn oil has been administered.
1. Normal: two to three times increase in triglyceride above the baseline sample level in post corn oil samples. 
2. Abnormal: no value changes in triglyceride between baseline sample and post corn oil samples.
C. Upon the finding of an abnormal response, the test should be repeated at a later date and 2 tsp. of pancreatic enzyme powder should be added to the corn oil dose.
1. Pancreatic enzyme positive response: two to three times increase in serum triglyceride concentrations above the baseline sample level.
2. Pancreatic enzyme negative response: no value changes between the baseline sample and the post corn oil samples. Primary small intestinal disease should be investigated if a negative response is received.

A qualitative assessment of the fecal matter for trypsin activity will seek out intact muscle fibers (if feeding raw or BARF), starch granules and undigested fat particles. 

In recent years a test called the TLI (trypsin-like immunoreactivity test) has been developed and is now considered a standard in diagnosis. The testing entails obtaining a serum sample from the canine after a 12 to 18 hour fast and submitting the sample to a qualified lab for analysis. The analysis searches for the presence of the pancreatic enzyme trypsin. Dogs with EPI have extremely low, abnormal concentrations of this enzyme in their serum.

Currently the availability of qualified labs is limited. Texas A&M has a lab able to process a TLI test. Contact info for the lab at Texas A&M is as follows:

TLI: 
GI LAB, TAMU: Send .5 ml fasting (12-18 hrs.) serum. Sample is stable at ambient temperatures. COST: $33.75 
DR. WILLIAMS - GI LAB
TAMU CVM
COLLEGE STATION, TX 77845-4474
(409) 862-2861
E-MAIL: gilab@cvm.tamu.edu
TLI/ COBALAMIN/ FOLATE: 
GI LAB, TAMU: Send 1.5 ml non-hemolyzed, fasting (12-18 hrs.) serum. COST: $58.50
DR. WILLIAMS - GI LAB
TAMU CVM
COLLEGE STATION, TX 77845-4474
(409) 862-2861
E-MAIL: gilab@cvm.tamu.edu


Treatment:
The treatment for EPI is the administration of enzyme replacements given with each meal. If the diagnosis of EPI is accurate, and if sufficient enzyme supplementation is provided, diarrhea and other symptoms will begin to resolve in a matter of days, followed by gradual weight gain. It is important to confirm the diagnosis of EPI before starting pancreatic enzyme replacement. Enzyme replacement prices can be expensive, and usually must be given for life. Medicating on supposition is never a good idea and can cause unnecessary harm to the animal and the owner’s wallet!

Once an appropriate dose of enzyme replacement is found that controls the symptoms, the enzyme dose can be reduced until the lowest dose that maintains control is found. Powder form enzyme is generally more effective than tablets, although you may find the tablets easier to administer. 

Two common brands of enzyme replacement are Viokase and Pancrezyme. Both are effective in controlling EPI symptoms. These products are made of freeze-dried and then powdered porcine pancreas. You will need a veterinary prescription for either of these products. The replacement enzyme doses are determined by the weight of the animal being treated and response to the amount given. 

Raw bovine or porcine pancreas is another treatment method. Though sometimes hard to obtain, a source of fresh, raw pancreas is an excellent option in controlling the symptoms of EPI and costs much less than the veterinary formulas Viokase or Pancrezyme. Make sure the stock the fresh pancreas comes from is certified disease free and is of a caliber for human consumption. Most dogs really enjoy the fresh pancreas option of treatment as a taste treat. It also has the bonus of adding additional protein and iron from a raw natural food source. 

Raw pancreas should be chopped into small bite-size bits and stored in a ziplock type of bag in the freezer. It is easiest to store the pancreas measured out per bag in the amount needed for one feeding. Before feeding remove a bag from the freezer and thaw at room temperature. NEVER defrost raw frozen pancreas in the microwave. The heat from microwave defrosting kills the active enzyme contained within the pancreas and renders the pancreas useless to your dog. When the pancreas is thawed, mix with a high protein, low fat/low fiber kibble.

The amount of raw pancreas to administer is based on weight of the dog. The formula to calculate how much your dog will need is approximately 3 to 4 ounces of raw pancreas per 20 kg of the dog’s weight. You will probably need to experiment a bit with the amount to find what works best for your dog as individual needs may vary.

The last treatment option is human grade Pancreatin. This can be obtained in most health food/herbal supplement type stores or off the Internet without a prescription and is manufactured by many companies (Now, Country Life, and VitaLine to name a few). Pancreatin, like Viokase and Pancrezyme, is freeze-dried and powdered porcine pancreas. Pancreatin comes in tablet or gel-cap form and is extremely economical when compared to veterinary formulas and sometimes raw pancreas. When purchasing Pancreatin it is extremely important to be able to gauge the USP levels of the enzymes per dose. You need to give your dog a dose equaling USP levels of 57,000 units of lipase, 285,000 units of protease, and 428,000 units of amylase equivalent per teaspoon of a Viokase type product. 

Pancreatin comes in various strengths such as 4x, 5x, and 6x. These numbers mean the contained pancreatic enzyme is concentrated to a strength of 4 times, 5 times, or 6 times that of a nonconcentrated dose. If a Pancreatin product claims 4x-500 mg, this works out to a concentrated dose equivalent to 2000 mg of Pancreatin. In 2000 mg of Pancreatin, a standard USP scale might work out to 50,000 units of Amylase, 50,000 units of Protease, and 9,000 units of Lipase per pill, capsule, or dose. At this scale a dosage of 4 capsules might be sufficient to suppress symptoms of EPI. Four capsules at that strength would together add up to 200,000 units of Amylase, 200,000 units of Protease, and 36,000 units of Lipase. Again, keep in mind that this is an average and your individual dog’s needs may vary. You will need to experiment a bit to fit your dog’s requirements. It is not recommended that you use a Pancreatin product that does not give you a USP breakdown to view. Without the USP levels of the product you cannot approximate an appropriate dosage per feeding.

Pancreatin if in tablet form should be crushed to powder and sprinkled on top of the dog’s kibble. If the Pancreatin is in gel capsule form, break open the gel-caps and sprinkle on top of the dog’s kibble.

Some animals do not respond to enzyme replacement alone. These animals may benefit from medications that enhance/augment enzyme replacement. Certain drugs that block H-2 receptors in the stomach can increase enzyme effectiveness by preventing the breakdown of the enzymes in the stomach. 

In some cases the dog’s diet may need to be modified. Feeding a highly digestible diet substantial in protein and low in fat and fiber may benefit many patients.

Prognosis:
Treatment of exocrine pancreatic insufficiency is typically necessary for life, though there have been cases documented of spontaneous remission. Most dogs with EPI due to pancreatic acinar atrophy respond positively to enzyme replacement, and have a very good long-term prognosis living normal, full lives.



**
Pancreatic Lobule graphic provided by First Principles of Gastroenterology: The Basis of Disease and an Approach to Management used with permission

Other sources of info:

Pancreatic Insufficiency Disorder also called Exocrine Pancreatic Insufficiency. http://www.peteducation.com/cats_dogs/pancr_insuff.htm  

Pancreatic Hypoplasia 
http://www.peteducation.com/puppies/pancrhypoplasia.htm   

Pancreatic Insufficiency
http://www.homevet.com/petcare/expi.html

Pancreatic Insufficiency, short plain language question & answer format
http://www.vetinfo.com/dpaninsf.html

Help for treating Exocrine Pancreatic Insufficiency, Messages from other people with suggestions:

There is an excellent e-mail list for people with dogs with EPI and they also have another list where you can order Enzymes at a more reasonable price, that is where I get mine from. If you print out and really read their welcome page, you will learn a whole lot about how to treat a dog with EPI.
Only very mild cases can be treated without animal enzymes.. but there are ways to help cut the costs.
Once an EPI dog is stabilized, it can lead a very normal life.
Here is the list address: k9-EPIGLOBAL@ yahoogroups. com

For anyone that has a shepherd with EPI .....I belong to a group that does buying in bulk for the enzymes. 6x is the equivalent of the normal enzymes such as Pancreatin and Viocase (I cant remember the rest of the brand names). They also have 8x which is stronger. The cost is $120 for 2.2 lbs. The woman that organizes it charges an extra $20 on the first order only. It has saved me a bundle since Sassy is on 4 tsp of 8x per day. They are the same enzymes you get at the vet for between $90 & $120 for 12 ozs and they keep well in the fridge.

Just wanted to add to this that anyone with an EPI dog should join the yahoogroup k9-EPIGLOBAL, where you will find a ton of helpful people and information, including the details on the enzymes mentioned in this post. I've been purchasing my enzymes through the woman mentioned in this post for 3 years now, have been very happy with her service and saved literally thousands of dollars. I also wanted to mention that the extra $20 charge on the first purchase goes towards GSD rescue, other than that the enzymes are sold at cost including packaging and shipping, the woman does not make a profit in any way.   Jodi

Here's a link to an article about using pig pancreas to provide the digestive enzymes to an EPI affected dog:
http://www.ellsbury.com/cheetahfaqs.htm

 

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