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Exocrine Pancreatic Insufficiency (EPI)

Wednesday, May 25, 2016

 

Introduction

Exocrine Pancreatic  Insufficiency (EPI) is a syndrome that is caused by the insufficient production of digestive enzymes by the pancreas. It can be congenital, inherited or acquired leading to loss of weight, polyphagia (excessive hunger or increased appetite), bulky faeces or diarrhoea and occasional vomiting. These signs are attributable to maldigestion and malabsorption of nutrients after approximately 90% of the secretory capacity of the exocrine pancreas has been lost. The ages that are predisposed to this condition range between 1-4 years for congenital cases and between 4-8 years for acquired cases. The breeds that are commonly affected with this syndrome are German Shepherd Dogs (42%), Rough-coated Collies, Eurasians and English Setters for inherited cases while any medium to large breed of dog can acquire the disease. No sex predilection has been observed.

 

 

Anatomy of the Pancreas

 

The pancreas consists of endocrine cells localized within structures named the Islets of Langerhans, which contain multiple endocrine cell types including the β cells that secrete insulin, and the exocrine pancreas, which is composed of acinar cells and ductal structures. Pancreatic acinar cells form a basic structure called an acinus that surrounds a central lumen open to the duct system. Pancreatic acinar cells produce, store and secrete enzymes necessary for the digestion and absorption of food in the small intestine. Digestive enzymes are secreted through the apical membrane of the acinar cell into small intercalated ducts that are directly connected to increasingly larger intralobular ducts that join the main pancreatic duct. The main pancreatic duct joins the common bile duct just prior to the ampulla of Vater, where both pancreatic and liver products enter the small intestine. Blockage of the passage of materials through the ampulla of Vater, for example by the lodging of a bile stone or by the growth of a tumor, leads to increased pressure in the duct system and gives rise to acute pancreatitis.

 

Etiology and Pathophysiology of Exocrine Pancreatic Insuff

Exocrine Pancreatic  Insufficiency (EPI) is caused by idiopathic pancreatic acinar-tissue atrophy (PAA) in majority of cases (~ 50%, age of onset usually <1-2 years), though there is a suggestion of an autosomal-recessive trait for PAA in German shepherds. Recent studies have however shown that this condition is not caused by a simple autosomal-recessive trait. This condition can also be a consequence of chronic pancreatitis in older dogs (>4 years of age). In very rare instances, this condition can be associated with diabetes mellitus in congenital pancreatic hypoplasia.

 

Progressive pancreatic acinar atrophy leads to lack of pancreatic digestive enzymes in the small intestinal lumen causing impaired nutrient absorption and transport resulting in polyphagia, profound weight loss and loose voluminous stools. Atrophy of the acinar cells is preceded by accumulation of lymphocytes, and acinar apoptosis (in GSD). Gastrointestinal mucosal trophic factors, regulatory peptides and intrinsic factors are also deficient in pancreatic secretions in this syndrome, leading to changes in small intestinal mucosal function and microanatomy.  No evidence of specific anti-pancreatic antibodies in circulation have been observed. in some instances, there is destruction of pancreatic enzymes in the intestines e.g. in gastric hypersecretion. There is also possible small intestinal bacterial overgrowth due to undigested luminal food stuff that may alter the intestinal microbiota causing dysbiosis.  Other causes include malabsorption of vitamin B12, vitamin E, and rarely vitamin K. Generalized malnutrition might further affect the GI mucosa while loss of islet cells has been reported to cause diabetes mellitus in patients with EPI secondary to chronic pancreatitis but does not occur in patients with PAA.

 

Client history

The client presents a dog with a history of weight loss despite a normal or increased appetite (polyphagia). There is also foul-smelling, loose, bulky faeces (stools). The increased faecal volume has a cow patty–like consistency. The number of defecations is also Increased (usually >3/day).

Coprophagia or even pica, flatulence, and borborygmus is also reported with a previous history of acute vomiting (rare), abdominal pain, diarrhea associated with acquired disease - pancreatitis. Polydipsia or polyuria in patients with concurrent diabetes mellitus is also noted including instances of nervousness and aggression (rare).

 
Clinical signs

Physical examination shows a poor body condition, muscle wasting, poor hair quality (hair coat), polyphagia, bulky faeces and or diarrhea. Coprophagia is common and helps to differentiate it from IBD [Inflammatory bowel disease]. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Diagnosis

  1. History

  2. Clinical signs 

  3. Biochemistry

    • Canine trypsin-like immunoreactivity (cTLI) This species-specific test is used to quantify trypsinogen and trypsin in serum. A cTLI concentration < 2.5 mcg/L after withholding food for > 8 hours is considered confirmatory. A serum cTLI concentration between 2.5 and 5.7 mcg/L may be associated with occult EPI. Serum cTLI should be retested in 1 to 2 months. Decreased cTLI concentration is highly sensitive and specific for EPI and is not affected by enzyme supplementation. Low serum - trypsin like immunoreactivity . Rule out acute pancreatitis (raised ALT, reduced cholesterol).

    • Low serum cobalamin [Blood biochemistry: vitamin B12] +/- high folate.

    • Non-specific alterations suggestive of malnutrition:

      • Hypoproteinemia - very rare.

    • Faecal elastase concentration This enzyme-linked immunosorbent assay has high sensitivity but low specificity. Faecal elastase concentration is a new test validated in dogs. Low fecal elastase is indicative of EPI. However there is a high false positive rate (23%). Diagnosis should always be confirmed by cTLI.  A value > 20 mcg/g helps to eliminate EPI. Values < 10 mcg/g will require confirmation with cTLI. Faecal analysis for proteolytic activity commonly used to diagnose exocrine pancreatic insufficiency is EXTREMELY misleading with false positive and false negative results - with highly sensitive and specific TLI assay available no reason to do fecal analysis.

  4. Gross autopsy findings
    • Pancreatic atrophy.

  5. Histopathology findings
    • Pancreatic acinar atrophy.

    • Fibrotic change associated with chronic inflammation.

 
Differential diagnosis

Weight loss and diarrhea

  • Inflammatory bowel disease .

  • Intestinal neoplasia .

  • Renal failure [Kidney: chronic kidney disease (CKD)].

  • Neoplasia of other systems.

  • Parasites of gastrointestinal tract, eg Giardia.

  • Metabolic/endocrine disease.

  • Toxaemia/sepsis [Shock: septic].

  • Poor diet.

  • Hepatic failure [Liver: acute disease].

  • Lymphocytic plasmacytic enteritis .

  • Eosinophilic enteritis .

  • Lymphangiectasia [Protein-losing enteropathy].

  • Small intestinal bacterial overgrowth [Antibiotic-responsive diarrhea] , stagnant loop syndrome/antibiotic responsive enteropathy.

  • Drug therapy.

  • Gluten sensitive enteropathy .

  • Primary or secondary causes of chronic small-bowel diarrhea

  • Disorders associated with weight loss (eg, systemic conditions, diabetes mellitus, hepatic failure, malignancies, and many others)

Polyphagia

  • Diabetes mellitus .

  • Hyperadrenocorticism [Hypoadrenocorticism].

  • Hyperthyroidism due to functional neoplasm.

 

Treatment

Standard treatment
  • Pancreatic enzyme replacement .

  • Highly digestible, +/- fat restricted ;15% Diabetes Mellitus diet .

  • Medium chain triglyceride [Fat] supplementation may be given with care.

  • Cobalamin/vitamin B12 supplementation (1mg SQ, q1month) (parenteral NOT oral).

  • Vitamin E/vitamin K supplements if needed.

 
Monitoring

 

Improvements will be noticed in the following order:

  • Normal faeces passed (48-72 h).

  • Weight gain (over weeks).

  • Polyphagia reduces (reduces once weight restored).

Subsequent management
  • If basic treatment regime failing, course of antibiotic (oxytetracycline 28d PO) indicated for bacterial overgrowth /antibiotic responsive enteropathy.

  • Further evaluation for concurrent small intestinal disease.

  • If poor response try H-2 antagonists prior to feeding to protect enzyme replacer against gastric acid [Cimetidine].

Patient Monitoring
 
 
  • Regular weight checks. 
  • Rapid weight gain is expected, but body weight may fail to normalize despite remission of clinical signs.
  • Diarrhea resolves in 2 to 7 days in uncomplicated cases. 

 

                                                          EPI Patient before treatment