EPI * Exocrine Pancreatic Insufficiency

The convenient method of treatment for EPI is with replacement enzymes. These enzymes are needed to break down all foods that a dog ingests. Although raw  pancreas is considered an excellent treatment, this is not always obtainable, hence the preference for pancreatic replacement enzymes.

If you live outside the USA, please check with your vet if any of the following enzyme products are available to treat your EPI dog with:

Enzyme potency in the USA is measured in USP units (this is a different measurement than elsewhere in the world).
The necessary 3 ingredients (enzymes) with "powdered" "prescription enzyme replacement supplements range from:

Most often, the initial recommended dose is 2.8 grams or 1 teaspoon of enzymes with each meal (approximately 1 cup of food) . But talk to your vet- -they need to determine what the proper dose is for your individual dog. Over-the-counter enzyme replacement products do not supply enough of the proper amount of enzymes needed for an EPI dog.

 If you would like to try using raw pancreas;  beef, lamb or pork pancreas may be used. One to three or four ounces of raw pancreas can replace one teaspoon of pancreatic extract. Raw pancreas may be frozen in cubes for future use and thawed naturally, but never heat on the stove or in the microwave.

Powdered enzymes may be kept in tightly sealed double plastic bags and then in a sealed contained in the refrigerator to lengthen the longevity of the stored enzyme, however, it is very important to be kept dry since moisture ruins the enzymes.

 Once an EPI dog is stable, the goal is to reduce the amount of enzymes given to the smallest dose possible without causing a flare-up.

The following is a list of various replacement enzymes used in the treatment of EPI.  The most widely used enzymes for EPI are as follows:
PANCREZYME is an enzymatic concentrate derived from the porcine pancreas gland, available in powder form.

VIOKASE an enzymatic concentrate derived from the porcine pancreas gland, available in powder or tablet form. Currently has been said to be discontinued... but still available on various websites.

PANCREATIN an enzymatic concentrate derived from the porcine pancreas gland, available in powder.

PANAKARE PLUS TABLETS enzymatic concentrate derived from the porcine pancreas gland with serum concentrations of fat soluble vitamins A, E &D.  Made by Neogen Vet.

GENERIC PANCREATIN If you have a positively VETERINARY diagnosed dog with EPI and are interested in ordering bulk-priced supplemental pork-based enzymes, they can be directly purchased from http://www.enzymediane.com/

• PANCREATIN 6x10
• PANCREATIN 8x10
  
  

LYPEX is an enzymatic concentrate derived from the porcine pancreas gland, available in capsules, must be opened and sprinkled on food. Do not incubate on the food. The purified and concentrated pancreatic enzymes are made into micro-pellets and each pallet is enteric-coated. This gives 100% protection to the enzymes from the damaging degradative acids present in the stomach.
Within ten minutes of the pellets passing the stomach to the alkaline environment of the small intestine the protective enteric coating dissolves and releases the protected enzymes to maximize digestion.(available in England and Europe)

Some lesser known enzymes are:
PANCRECARB

CREON (these are enteric coated granules in capsules, do not break open and incubate on food as instructed for all other enzymes)
CREON is commonly used in many places outside the U.S.  The CREON enzyme capsule products comes in 5, 10, 20 strengths.  The one that seems most suited to treating EPI dogs is CREON 10 which has 10,000 USP of Lipase, 37,500 USP of Protease, 33,200 USP of Amylase.

If you are interested in purchasing CREON on-line..... one of our EPI FORUM members, Frank, put together a fabulous database on CREON including the brand name, website address, the cost of the CREON, shipping costs, and breakdown of price per capsule. This PDF is a wealth of information. Please feel free to check it out. Click on: CREON pricing-2.pdf

ULTRASE

PANCREASE

TOTAL-ENZYMES
In some cases, a dog may have pork-based allergies, or meat protein allergies. If so, you may want to try an alternative plant-based enzyme. Although not as potent as pork-based enzymes a possible consideration would be Total-Zymes. This plant-based enzyme product has been used with success by some EPI owners whose dogs cannot tolerate porcine-based enzymes.  If you click on this PetEnzymes icon it will take you directly to their site:

FROM:  Encyclopedia of Canine Clinical Nutrition, Pibot P., Biourge V. and Elliott D.A. (Eds.). International Veterinary Information Service, Ithaca NY - Last updated: 8-Jan-2008; (www.ivis.org), A4203.0108

Gastrointestinal problems are a major concern for small-animal practitioners. Specifically chronic disorders of the digestive tract can be difficult to manage because of the limitations of the diagnostic procedures and the multiplicity of possible causes. The current chapter summarizes the basic facts on gastrointestinal physiology of dogs including the intestinal microflora and the immune system. The most frequent digestive disorders are presented in a problem orientated manner including diagnostic aspects and medical and dietary treatment. The role of dietetics is considered specifically for each of the different types of disease considered.    

1. Digestive Tract Physiology

The small intestine (SI) is the principal site for digestion and absorption of nutrients, and is key to electrolyte and fluid absorption. The villi and microvilli contribute to the huge surface area, which facilitates absorption and assimilation of nutrients. Enterocytes are highly specialized cells involved in absorption processes. A brush border (or microvillus membrane; MVM) is present on the luminal surface of the enterocytes, and contains enzymes necessary for digestion of nutrients. Carrier proteins assist in the transport of amino acids, monosaccharides and electrolytes. The turnover of both enterocytes and microvillar proteins is influenced by luminal factors such as pancreatic enzymes, bile salts and bacteria.

Digestion and Absorption of Food

Proteins

Protein digestion is initiated in the stomach by the enzyme pepsin. It is inactivated once it has passed into the duodenum. Protein digestion in the small intestine is carried out by pancreatic and MVM enzymes. Peptides and free amino acids are produced by the digestive processes and small peptides and amino acids are absorbed by specific carriers in the MVM  

Lipids

Dietary fats are emulsified by their interaction with bile acids in the small intestine, and subsequently digested by the pancreatic enzymes lipase, phospholipase and cholesterol esterase. Triglycerides are digested to monoglycerides and free fatty acids. In combination with bile acids, micelles are formed enabling absorption as monoglycerides and free fatty acids .Bile acids are reabsorbed by a specific carrier mechanism in the ileum, and then recycled by the liver. After absorption, long-chain fatty acids are re-esterified to triglycerides, incorporated into chylomicrons and then enter the lymphatics. Medium and short chain fatty acids were originally thought to be absorbed directly into the portal circulation, but recent work has questioned this theory (Sigalet et al., 1997).  

Carbohydrates

Starch is the major digestible polysaccharide in common food and is degraded by pancreatic amylase to maltose. Maltose and other dietary disaccharides (lactose and sucrose) are digested by MVM enzymes to constituent monosaccharides, which are then absorbed by specific transporters or by facilitated transport. Monosaccharides are then transported across the basolateral membrane into the portal circulation  

Minerals

Macrominerals and trace elements are mainly absorbed from the small intestine, but the large intestine may also take part in the absorption processes. Active calcium absorption is subjected to regulatory mechanisms that are mediated by vitamin D, parathyroid hormone and calcitonin. These homeostatic mechanisms allow the organism to adapt to the different dietary intakes within certain limits. However, in dogs a fraction of dietary calcium is absorbed by passive processes. Phosphorus is less well studied and seems to be regulated by similar mechanisms. Magnesium is absorbed without homeostatic regulation so that the blood magnesium levels have a higher variation. Sodium, potassium and chloride are mainly absorbed in the small intestine and the absorption rates normally exceed 90 per cent. The trace elements are mainly absorbed from the small intestine, but the colon may also contribute to the absorption of trace elements. The absorption rates of zinc, iron and manganese are subjected to regulatory mechanisms. Active transport systems have been demonstrated for manganese and copper. Other elements are absorbed by passive diffusion.

Vitamins

Lipid-soluble vitamins (A, D, E and K) are dissolved in mixed micelles, and passively absorbed across the MVM.

Water-soluble vitamins, most notably B vitamins, are absorbed by passive diffusion, facilitated transport or active transport. The absorptive mechanisms for folic acid and vitamin B12 are more complicated, summarized here: Assimilation of folate. Dietary folate is present in the diet as a conjugated form (with glutamate residues). This conjugate is digested by folate deconjugase, an enzyme on the microvillar membrane, which removes all but one residue, before uptake via specific carriers situated in the mid-small intestine.

Assimilation of cobalamin. Following ingestion, cobalamin is released from dietary protein in the stomach. It then binds to non-specific binding proteins (e.g. "R-proteins"). In the small intestine cobalamin transfers onto intrinsic factor (IF), which is synthesized by the pancreas. Cobalamin-IF complexes pass along the intestine until the distal small intestine, where cobalamin is transported across the mucosa and into the portal circulation.

Intestinal Microflora

The resident bacterial flora is an integral part of the healthy intestinal tract and influences development of microanatomy, aids in digestive processes, stimulates the development of the enteric immune system, and can protect against pathogen invasion. Healthy individuals are immunologically tolerant of this stable flora, and loss of tolerance may contribute to the pathogenesis of chronic enteropathies e.g., inflammatory bowel disease (IBD).

The populations of bacterial flora quantitatively increase from the duodenum to colon, and are regulated endogenously and by a number of factors, including intestinal motility, substrate availability, various bacteriostatic and bacteriocidic secretions (e.g., gastric acid, bile and pancreatic secretions). A functional ileocolic valve is the anatomical barrier between the colonic and small intestinal microflora. Abnormalities or dysfunction in any of these factors may lead to bacterial flora abnormalities, which may be quantitative or qualitative.

The normal SI flora is a diverse mixture of aerobic, anaerobic and facultative anaerobic bacteria. The total upper small intestinal bacterial counts reported in humans is less than 10^3-5 CFU*/mL. (* CFU: Colony Forming Unit)

There is currently no consensus as to what constitutes a "normal" SI population in healthy dogs; some studies suggest that healthy dogs can harbor up to 10⁹ CFU/mL aerobic and anaerobic bacteria in the proximal SI. Therefore, the "cut-off" for normal flora in dogs cannot be extrapolated from humans, and descriptions of small intestinal bacterial overgrowth (SIBO) in dogs using a cut-off value of 10⁵ may be spurious. The intestinal microflora is subjected to endogenous and exogenous regulatory influences. Diet composition will impact the concentrations of bacteria in the gut. High protein diets favor the growth of proteolytic bacteria, especially clostridia, while certain fermentable fibers stimulate the saccharolytic bacteria, for instance bifidobacteria and lactobacilli.

Role of the Mucosal Immune System

The SI mucosa has a general barrier function, but must also generate a protective immune response against pathogens, whilst remaining "tolerant" of harmless environmental antigens such as commensal bacteria and food. Yet despite recent advances in our understanding of the structure of and interactions in the immune system, it is still unclear as to how it decides to respond to or become tolerant of a particular antigen.

The gastrointestinal tract harbors the largest number of immune cells in the body. The gut-associated lymphoid tissue (GALT) consists of inductive and effector sites. Inductive sites comprise Peyer's patches, isolated lymphoid follicles, and the mesenteric lymph nodes, whilst effector sites comprise the intestinal lamina propria and epithelium.

Such a distinction, however, is not absolute, and there is overlap between the functions of these different sites. The population of immune cells is diverse and includes T and B lymphocytes, plasma cells, dendritic cells, macrophages, eosinophils and mast cells. Protective immune responses are critical for guarding against pathogen invasion, and both cell-mediated (synthesis of cytotoxic cells) and humoral (immunoglobulin production) responses can be produced. However, of equal if not greater importance is maintenance of mucosal tolerance. This is not surprising, given that the majority of luminal antigens are derived from innocent dietary components or endogenous microflora. Generation of active immune responses to such ubiquitous molecules is both wasteful and potentially harmful, since it could lead to uncontrolled inflammation. Indeed, a break down in immunological tolerance to commensal bacteria is thought to be a critical step in the pathogenesis of inflammatory bowel disease.

Whilst the mechanisms by which mucosal tolerance actually occurs have been well characterized, the fundamental question of how the GALT decides when to and when not to become tolerant remains unresolved. Nevertheless, the critical cell in generating tolerance is the CD4⁺ T-cell, either by down-regulatory cytokine synthesis (e.g., TGF-β, or IL-10) or via cell-cell interactions (e.g., through CD25⁺, the IL-2 receptor). Interestingly, the cytokines that mediate tolerance (namely TGF-β, and IL-10) also facilitate IgA production, the most important mucosal immunoglobulin. Therefore, generation of mucosal tolerance could potentially occur in parallel to specific IgA responses. Interestingly, IgA "coats" the mucosal surface and protects by immune exclusion (i.e. preventing antigens from crossing the mucosal barrier). Given that immune exclusion limits the amount of antigen to which the mucosal immune system is exposed, its effect is also "tolerance-generating" because it minimizes immune responsiveness.