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Strategies for managing pancreatitis in small animals

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Herbal medicines and low-fat meat and vegetable diets can prevent pancreatitis in dogs and cats, and can also be used to resolve acute and chronic stages of the disease. 

Pancreatitis is commonly diagnosed and treated in small animal veterinary medicine. However, its causes and pathophysiology remain poorly understood, except to say that it is usually a sterile condition. The acute end of the disease spectrum is associated with high mortality, although there is good potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either dogs or cats can cause refractory pain and progressive exocrine and endocrine functional impairment.1

Despite the importance of pancreatitis as a clinical syndrome, almost no trials of diets or drugs exist for its treatment and prevention, except for the critically ill patient. The prescription of low-fat kibble and canned foods, although common, is largely untested. Thus, any attempt to formulate an evidence-based approach to pancreatitis, whether using drugs, diet or natural therapies, must begin with a review of the current understanding of the disease’s pathophysiology.

There is confusion in the veterinary literature about the definitions of acute and chronic pancreatitis, and there are very few studies on the pathophysiology of naturally-occurring pancreatitis in dogs and cats. But enough laboratory evidence has accumulated to formulate a likely model of pathogenesis.

Pathophysiology of pancreatitis

Part of the confusion surrounding pancreatitis may stem from the fact that the conditions that incite it vanish once the organ has become inflamed. Nitric oxide (NO) and its impact on micro-circulation appear to play a pivotal role in the pathogenesis of the condition.2,3 The onset of pancreatitis is marked by a lack of NO, whereas the acutely inflamed state is marked by an abundance of NO. Preventing and treating pancreatitis thus require almost opposite approaches. The role of the gut is also being explored as a source of oxidative stress which aggravates existing pancreatic inflammation.

Role of nitric oxide and endothelial dysfunction

There are two types of NO germane to the pathogenesis of pancreatitis:4

  • Inducible nitric oxide – of importance in the progression of pancreatitis
  • Endothelial – of relevance in the initiation of pancreatitis

Inducible NO is found in the pancreas parenchyma, where it regulates normal pancreatic exocrine secretion,5 both by boosting pancreatic microvascular blood flow and by directly regulating enzyme secretion. Normally, its presence is key to a properly functioning pancreas. When pancreatitis is in full swing, however, inducible NO levels are high. The pancreas becomes engorged with blood and edematous, enzymes are disgorged, and the pancreas becomes congested. Meanwhile, the strong free radical activity of NO further heightens inflammation, making NO an important target for future pharmaceuticals in the treatment of acute pancreatitis.

The heightened levels of NO and blood flow during pancreatitis are in opposition to the state of reduced micro-circulation and NO levels that trigger pancreatitis to begin with.6 Before acute pancreatitis develops, there is:

  • Impairment of pancreatic micro-circulation in the early phase
  • Reduced blood flow
  • Increased platelet adhesion and clot formation.

These events are caused by a reduction of endothelial NO in the vasculature of the pancreas; this is known as endothelial dysfunction (ED). ED promotes the initiation of inflammation because of its associated:

  • Increased vascular permeability
  • Increased leukocyte-endothelial cell adhesion and leukocyte egress.

Experimental evidence supports the notion that a lack of endothelial NO, causing associated ED, is what triggers pancreatitis. Endothelial NO synthase reduces the severity of the initial phase of experimental acute pancreatitis.4 NO synthase inhibition by pharmaceuticals has been shown to trigger acute pancreatitis.7

In short, then, to support endothelial NO levels is to prevent ED; and to prevent ED is to prevent pancreatic inflammation. To resolve chronic pancreatitis, and to prevent its incidence in the first place, clinicians need to focus on the cause of ED. For the most part, ED in small animals is caused by diet.

Diabetes, insulin resistance, and endothelial dysfunction

Veterinarians are used to thinking of pancreatitis as a cause of diabetes mellitus (DM), through the destruction of beta-islet cells. Diabetes mellitus is also an important precursor to pancreatitis, however, and not just a sequela.8

Diabetes often precedes pancreatitis because it is linked to ED. In Type 1 diabetes, ED is consistently found in advanced stages of the disease. For Type II diabetes, ED may even precede it.9 Both types of diabetes are the by-product of insulin resistance.

Insulin resistance alters gene expression for a number of pathways known to culminate in ED, including:

  • Increased secretion of pro-inflammatory cytokines
  • Decreased secretion of adiponectin from adipose tissue
  • Increased circulating levels of free fatty acids
  • Post-prandial hyperglycemia.

At the same time, insulin resistance promotes diabetes. Once diabetes is present, increased intracellular concentrations of glucose metabolites in endothelial cells heighten their dysfunction by:

  • Impairing mitochondria function
  • Increasing oxidative stress
  • Activating protein kinase C, causing a halt in endothelial nitric oxide production.

The upshot of chronic insulin resistance is that:

  • Endothelin levels increase
  • Endothelial NO levels drop
  • Vessels constrict
  • White blood cells adhere to and move across blood vessels into the pancreatic interstitium
  • Platelets adhere to endothelial cells to form clots, aggravating any tendencies to hypoxia.

Subclinical pancreatitis can now begin and the animal is also more prone to severe acute episodes. Insulin resistance and subsequent ED are important targets for intervention in resolving chronic pancreatic inflammation, and preventing future episodes. While several herbal formulas can target these self-same pathways, instituting an appropriate diet will help guarantee lasting success in managing these cases.

Preventing pancreatitis with diet

Typically, veterinarians think to limit only fat intake in the animal’s food, but insulin resistance, obesity and a heightened predisposition to pancreatitis are not caused by high fat intake alone. Processed starch-based canned and kibble diets are arguably the most common cause of insulin resistance in veterinary medicine. Pancreatitis becomes a rare event when these diets are avoided. Commercial canned and kibble diets are rapidly absorbed and frequently carbohydrate-based, provoking a surge in post-prandial glucose that leads to chronically high insulin levels and eventually insulin resistance, with its attendant sequelae, including a systemic tendency to inflammation, including in the pancreas. Insulin resistance does not just result in diabetes mellitus, and can be presumed to be present in all overweight animals.

In the author’s experience, a minimally processed (raw or homemade) balanced diet of meat and vegetables is of the most benefit in preventing pancreatitis in carnivores. Pancreatitis seldom occurs in animals fed these diets. Once acute pancreatitis is present, however, the familiar recommendation of nothing-per-os (NPO) applies.

Chinese herbs for pancreatic ailments

Targeting insulin resistance – Damp Heat formulas

Three Seeds Combination (San Ren Tang)

Three Seeds Combination has a clinical reputation for reversing insulin resistance and Type II diabetes mellitus, particularly in the feline. Coix markedly increases insulin sensitivity and has been shown to reduce adipose tissue weight, leptin and insulin levels.10 The formula is anti-inflammatory, but also reduces predisposition to ED, thus helping to both resolve chronic pancreatitis and reduce the risk of future episodes.

Animals needing this formula often have a wet, swollen and lavender tongue, although it can also be a mild red color. The pulse is usually deep and toned.

Four Marvels Combination (Si Miao San)

This formula is used to manage acute pancreatitis, whether mild or severe. It increases insulin sensitivity and studies have verified its benefits in pancreatitis through its antioxidant effects.11

The patient that benefits from Si Miao San has a tendency towards acute inflammation, oxidation and associated insulin resistance, usually manifesting as inflammation at multiple epithelial surfaces (especially the ears, skin, colon, biliary tree and bladder). Signs of Cushing’s can also occur. The tendency to acute inflammation is marked by a superficial and toneless pulse. The tongue is often red or purple-red.

Targeting endothelial dysfunction

Minor Bupleurum

Minor Bupleurum interferes with the production of cytokines that promote ED.12 It is most helpful in resolving sub-acute to chronic pancreatitis, especially when due to systemic infection or immune dysregulation. These cases will often have inflammation manifesting in other organs, especially the liver and kidneys (as glomerulonephritis), but also including the eyes (glaucoma, uveitis), lungs (pneumonia, pneumonitis), nervous system (disc disease, vestibular disease), and even the skin. Occasionally, the animals have a prior history of cancer.

Animals benefiting from Minor Bupleurum almost invariably have deep, toned strong pulses. One or more vagal symptoms are common, including chronic cough, vomiting, bloating and constipation.

Glehnia and Rehmannia

Glehnia and Rehmannia Combination, known also as Yi Guan Jian, contains two plants, Angelica and Rehmannia, that counter ED to restore normal micro-circulation and actively resolve chronic inflammation in a number of tissues.12 The formula is contraindicated in acute active pancreatitis, since the organ is now severely congested and edematous. It can resolve mild low-grade pancreatitis, and prevent recurrences.

Animals that benefit from this formula have reduced circulation to epithelial surfaces, creating dryness, mild gastric inflammation, and irritable bowel syndrome. Animals often display mild to moderate liver enzyme elevations; older animals may have mild to moderate azotemia. Anemia and chronic weight loss may be present, as well as a tendency to timidity or anxiety. The pulse is often thin and the tongue pale, perhaps with a lavender center.

Targeting bacterial causes

Agastache Combination (Huo Xiang Zheng Qi San)

Patients often have Damp Heat tendencies, yet do not respond to San Ren Tang and Si Miao San. Huo Xiang Zheng Qi San should be considered next, in case bacteria are inciting the inflammation. Agastache is a strong antimicrobial formula with a broad spectrum of effect against many species of viruses, nematodes, fungi and bacteria.13,14,15

Agastache also interferes with cell adhesion,16 thereby reducing white blood cell ingress into the interstitium, and subsequent inflammation.

Consider this formula for chronic pancreatitis in young animals, especially if the disease is, or has been, associated with chronic refractory small bowel diarrhea or suspected small intestinal bacterial overgrowth.

Using herbs — administration via enema

While injectable forms of herbal medicine are not yet available for the NPO patient, quantities of the appropriate formula can be delivered to an acutely ill dog via

enema. A patient’s response to an herbal formula delivered by enema is often rapid and dramatic, with enzyme elevations subsiding significantly and the patient stabilizing within a couple of days. Compounds in the formulas are absorbed across the large intestine mucosa into the portal circulation, and from there move rapidly to the systemic circulation, bypassing any gastroparesis.

Method

  • Use two to three times the normal dose for the patient (see chart on page xx), and give TID to QID.
  • Suspend each dose in a maximum of 10 ml to 15 ml of warm water.
  • Instill into the transverse colon using a small rubber French feeding tube.
  • Use only granular extracts or crushed tablets, never liquid extracts, for administration via enema.

All the formulas in this article can be obtained in various formats from nphc.ca.

Much more detail on veterinary clinical uses of these and other products can be obtained from the College of Integrative Veterinary Therapies, and from the Essential Guide to Chinese Herbal Formulas: Bridging Science and Tradition (S Marsden, 2014, published by CIVT).

Oral dosing

Weight (kg) Weight (lbs) BID dose (mls) BID dose

(550 mg tabs)

BID dose

(tsp granular extracts)

4 10 0.30 1.00 0.25
8 20 0.45 1.50 0.50
12 25 0.60 2.00 0.75
23 50 0.90 3.00 1.00
32 70 1.20 4.00 1.50
/5 150 1.80 6.00 2.00
120 250 2.40 8.00 3.00

Case example: Falco Teefy

Falco is a nine-year-old male neutered Border Collie cross who presented with a chief complaint of pancreatitis. Recent history included removal of an infiltrative lipoma from the caudal thorax, and episodes of a nocturnal hacking cough ending in the vomiting of foamy material.

The pancreatitis seemed to gear up over a long period, with nausea, vomiting and pica occurring since the summer of 2016; it did not respond to antacids or anti-emetics. A protocol was eventually settled on, consisting of 0.2 mg/kg prednisone, a round of metronidazole and milk thistle. Two herbal formulas, Yi Guan Jian and San Ren Tang, were also initiated.

Falco de-stabilized in October of 2016 when herb use became less consistent. Yi Guan Jian alone was resumed along with metronidazole and continued prednisone use. Although Falco seemed at first to improve again, he had to be hospitalized in November for pancreatitis.

Clinical signs at that time included lethargy, fever, diarrhea and abdominal pain. ALP was increased to several times the normal value, and an enlarged liver was seen on ultrasound. A snap test showed a strong positive result for CPL and pancreatitis.

Physical examination showed strong-toned mid-depth pulses that responded well to acupuncture of prominent Gall Bladder channel points. In addition to acupuncture, Falco was given anti-emetics, fluid therapy, hydromorphone and the typical low-fat bland processed diet. A derivative of Minor Bupleurum was introduced as the new herbal formula.

Response of Falco’s ALP and CPL to Minor Bupleurum

Falco gradually improved over the next two weeks, but had no appetite for a bland diet, so a low-fat processed kangaroo diet was fed instead. Improvements in laboratory data steadily accrued even as improvements in symptoms were more erratic.

Over the long term, prednisone was discontinued, and the combination of Minor Bupleurum and Three Seeds Combination proved sufficient to eradicate all symptoms. This use of herbs continues to date, as does the processed kangaroo diet.

Case discussion

It is common for veterinarians to manage problems in an integrative fashion, using both herbs and drugs together. In Falco’s case, the low doses of prednisone would have favored insulin resistance and ED, but were successfully countered with Yi Guan Jian and San Ren Tang, two formulas for chronic GI inflammation. When first one and then the other of these formulas were discontinued, the negative effects of the prednisone were no longer countered, and the pancreas erupted with inflammation, fueled by a high-fat, albeit raw diet.

Minor Bupleurum was the main intervention that arrested symptoms and disease progression in Falco. Its use was indicated by the characteristic pulse, history of cancer, nausea, and the history of a chronic cough that ended in vomiting. Herb use should be continued as long as processed diets are fed, to counter the latter’s tendencies to promote inflammation and ED.

The author acknowledges the contributions to this case study of Jana Teefy, AHT, RLAT, and Jennifer Marshall, BSc, DVM, both of Edmonton Holistic Veterinary Clinic.

Conclusion

Pancreatitis can be prevented in carnivores by using herbal medicines and low-fat meat and vegetable diets. Once these therapies are instituted, episodes of pancreatitis consistently cease.

Herbal formulas may also be used to resolve acute and chronic stages of the disease, and work along with diet to eliminate the inciting factor of recurrent and chronic pancreatitis — reduced endothelial nitric oxide.

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Dr. Steve Marsden is co-founder of Edmonton Holistic Veterinary Clinic, and is arguably the foremost holistic veterinary practitioner in the world. As such, he spends three months a year teaching veterinarians on five continents. In 2009, the Canadian Veterinary Medical Association honoured Dr. Steve as “Small Animal Veterinarian of the Year”, and in 2010, the American Holistic Veterinary Medical Association named him “teacher of the year”. In addition to his veterinary work, he spends half his time treating people, thanks to his credentials as a naturopathic physician and his training as a Chinese medical practitioner.