REGALWISE SHEPHERDS
HEALTH LINKS
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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