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Clinical approach to diarrhoea in dogs and cats

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Category: Schede
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  • Disciplina: Gastroenterologia
  • Specie: Cane e Gatto

Diarrhoea is defined as an increase in the frequency of bowel movements, in the volume or in the liquid content of the faeces. Several mechanisms can lead to diarrhoea:

  • Osmotic diarrhoea
    It occurs when solutes are present within the intestinal lumen, which are able to retain water and produce large volumes of watery stools.
  • Exudative diarrhoea (due to increased permeability)
    It occurs following increased intestinal permeability, with the consequent loss of electrolytes, plasma proteinsand blood into the intestinal lumen.
  • Secretory diarrhoea
    It occurs due to an alteration of intestinal transport mechanisms, making the reabsorption of all the fluids present within the lumen impossible.
  • Impaired motility diarrhoea
    • Hypomotility can lead to intestinal stasis and bacterial proliferation.
    • Hypermotility can cause diarrhoea, as less time is available for the reabsorption of solutes and water.

Diarrhoea can be further classified into acute and chronicand, based on the location involved, in diarrhoea of the small or large bowel.

In the patient with diarrhoea it is important to quickly establish if the condition is acute or chronic, if the patientis in a state of shock, in potentially life-threatening conditions, if the diarrhoea is from the small or large bowelor from both, and if other signs of systemic disease are present. All of these answers can be provided by a good clinical history and by the physical examination of the patient.

Diarrhoea is defined as acute when its duration is of under 3 weeks.The most frequent causes are: the diet (sudden changes, food poisoning, food intollerance, allergies, etc.), chemical intoxications, infectious conditions (bacteria, viruses, fungi, parasites), anatomical alterations (intussusception, foreign bodies, etc.) and metabolic disorders (hypoadrenocorticism, pancreatitis). Patients who are alert, responsive and not dehydrated do not necessarily require an in-depth examination, while subjects in a state of shock, with systemic signs, abdominal pain or with other abnormalities on physical examination (e.g., masses, tissue thickening, organomegaly, etc.) require a more thorough and detailed investigation.

Diarrhoea is defined as chronicwhen it persists for more than 3 weeks.  By definition, this type of diarrhoea is not self-limiting and for the correct treatment of the patientthe underlying cause must be identified.

 

DIAGNOSTIC APPROACH

Goal of the diagnostic approach is to exclude extra-intestinal diseases and to differentiate disorders of the small bowelfrom those of the large bowel.  In these cases, a complete blood count and a biochemical profile may give useful information on the patient’s state of hydration and raise suspicion on the possible presence of infectious diseases or of metabolic disorders (e.g., hypoadrenocorticism, etc.). Urinalysis is always important as it completes the metabolic profile and can give useful information on the renal function status and on urinary tract health. When indicated, other tests should be performed, in order to assess the hormone status of the patient(e.g., T4, ACTH stimulation test, etc.) as well as to carry out diagnostig imaging studies such as X-ray and abdominal ultrasound examinations. Faecal examination is important for the detection of intestinal parasites and should always be performed. The bacteriological examination of the faeces may be indicated especially in cases of chronic diarrhoea, but its validity is often questionable.  In the presence of chronic diarrhoea, pancreatic insufficiency and malabsorption should be excluded before continuing with the inspection of the gastrointestinal tract by endoscopy and the histological evaluation of biopsies of the stomachand intestine.  Other tests that may be useful are rectal citology, which could be indicative of a bacterial problem if a high number of neutrophils are present in the smear, the search for faecal occult blood,6 that might be indicative of gastrointestinal ulcers, and the measurement of the alpha-1 protease inhibitor,7 that may reveal the presence of a protein-losing enteropathy (PLE), even at an early stage. However, care must be taken in the execution of these tests as both the diet and the faecal-sample collection modality may influence the results.

 

THERAPEUTIC APPROACH

Most cases of non-complicated acute diarrhoea are self-limiting and respond very well to symptomatic treatment.

Fluid therapy8,9 is very important in these patients. The fluids chosen should be balanced in order to correct dehydration and electrolyte imbalances. The fluids administered are often supplemented with electrolytes, glutamine, vitamins and, when necessary, glucose. The total volume to be administered should be calculated using the following formulas:

  • Total volume = % dehydration + maintenance
  • Dehydration = estimated % dehydration x body weight x 10
  • Maintenance= 2 ml x kg x 24

In the presence of nausea or vomiting, the patientmay be treated with antiemetic, anti-nausea and prokinetic medications that can help reduce vomitingand hence fluid losses.

Mucosa protectors and adsorbents, such as bismuth subsalicylate, aluminium-based chelating products, magnesium or barium may also be administered.10 They can pick up bacteria and toxins and protect the mucosa from further damage.

Anticholinergic drugs11 and oppioids12 can be used to stop the diarrhoea, but are not recommended in cases of ileus.Should these drugs be used, caution is necessary, especially with drugs such as loperamide, as patients with an MDR-1 mutation may exhibit neurological side effects. The author of this article rarely uses these drugs.

Antibiotics may be indicated in patients with signs of bacterial translocation and sepsis, or in those with a confirmed protozoan infection.In these cases, broad-spectrum medications may be used, such as penicillins (ampicillin, amoxicillin, etc.) that can act against gram-positive and gram-negative bacteria, either alone or in combination (when indicated) with antibiotics against anaerobic bacteria (e.g., metronidazole) and gram-negative bacteria (fluoroquinolones, aminoglycosides). It is not always necessary to combine more than one antibiotic, and one must always remember that some of these drugs have major side effects, while others should not be given before the patientis fully rehydrated. Metronidazole also has an immunomodulatory action and can help reduce intestinal inflammation. Other antibiotics that can be used are tetracyclines and tylosin, which acts especially against anaerobic bacteria (Clostridium); in the presence of colitis, sulfasalazine may also be used. Sulfasalazine contains a sulfamidic fraction (sulfapyridine) that is linked to a fraction of salicylic acid (mesalazine). The bacteria in the large intestinecan break this bond, releasing the two fractions. The salicylic acid component can thus act locally, reducing inflammation, while the sulfonamide fraction may have an antibacterial activity. As always, attention must be paid to the side effects, which may include keratoconjunctivitis sicca and gastrointestinal symptoms with vomiting.

In the presence of diarrhoea caused by colitis, the addition of soluble fibres (psyllium, pumpkin, Metamucil, etc.) in the treatment regimen may have a very positive effect;this because fibres are the energy source of colonocytes and help cell regeneration. In the presence of a prevalently small bowel diarrhoea, glutamine, an energy source of enterocytes which reduces bacterial translocation, should be supplemented.

Probiotics13-15 are living organisms that can have several positive effects.They can have an  antagonistic action against pathogenic intestinalbacteria, modify the local immune response and alter permeability. They are however species-specific and their effect is temporary, lasting only until their presence within the intestine. Prebiotics are selective substrates used by probiotics for their development; they usually consist of non-digestible carbohydrates such as inulin, lactoferrin, lactulose and others.

Whenever parasite sare present, anti-parasite medications should be used, but they should be used also when the tests are apparently negative; this because eggs are not always found in the faeces during the examination and hence a negative result does not entirely rule out the presence of parasites.

The diet16-19 is the most important therapeutical component in the course of diarrhoea. Initially, the diet should be bland and easily digestible. For the first few days the author of this article uses homemade diets (e.g., chicken, fish, rice, cooked vegetables), unless well-documented intolerances/allergies are present, or low fat easily digestible commercial diets. Then, easily digestible and/or hypoallergenic diets may be introduced, depending on the needs of each patient. It is important to remember that cats are not small dogs; being strictly carnivores, they always need very high amounts of proteinin their diet, especially when they are sick.

If vitamin B12 levels are low, or if lesions of the ileum that may inhibt absorption are present, vitamin B12 should be administered parenterally; recent studies20 have in fact shown that in case of vitamin deficiency complete healing is much slower or impossible.

In the presence of chronic diarrhoea caused by inflammation, such as IBD, immunosuppressive medications may be necessary. The decision should be made based on the histopathology of gastrointestinalbiopsies and on the patient's response to the treatments carried out up to that time (response to diet, etc.). Different drugs can be used, such as local or systemic steroids, alone or in combination with other immunosuppressive agents; the choice depends on the preferences of the physician and on the patient's response (for further information refer to the articles on the treatment of enteropathyand IBD).

The approach to the patientwith diarrhoea is largely dependent on the clinical signs present, on their duration and on the existing underlying causes.Therapy should be focused on treating the symptoms and, when possible, on eliminating or treating the underlying causes.

 

INTESTINE ANATOMY AND PATHOPHYSIOLOGY

Small intestine
The small intestine consists of the duodenum, jejunum and ileum; each segment is composed of several layers, which, in cross section and from the outside towards the lumen, are: the serosa, muscularis, submucosa and mucosa (Fig. 1). The inner part of the mucosa is extremely important, as it is responsible for the secretion, digestion and absorption of the various substances reaching the intestine. The function of the small intestine is to complete digestion (which started in the mouth and stomach) and to absorb digested products. The mucosal surface is coated with villi interspaced with crypts. The villi contain lymphatic and blood capillaries, as well as smooth muscle fibres (Fig. 2). The functional unit of the small intestineconsists of villi and crypts.

The villi have an absorptive function and the longer they are, the greater the available surface area for absorption. Crypts have a secretory function and may continuously produce enterocytes; the undifferentiated cells at the base of the crypts migrate to the villi and become mature enterocytes, the apical surface of which extends into the microvilli that are necessary for the digestion and absorption of nutrients. At their extremities are digestive enzymes and the proteins necessary for the digestion and transport of nutrients, such as enterokinase, oligosaccharides, enzymes for carbohydrates, for nucleic proteins, etc. The microvilli can increase the absorptive surface of the small intestineby about 600 times.

The main source of energy for enterocytes is glutamine. In cases of glutamine deficiency the villi lose their structure; this compromises epithelial integrity and the immune function. For these reasons, enteral nutritionand the use of glutamine are very important.

The absorption of simple sugars, of amino acids and of some fatty acids occurs through active transporters or by passive diffusion. Folic acid is absorbed in the proximal segment of the small intestineand vitamin B12 in the ileum.

In the small intestine,motility is exercised through segmental and peristaltic contractions.The segmental contractions slow down the passage of food material through the gut and provide a “mixing action”, improving contact with digestive enzymes and the intestinal mucosa, favoring the absorption of nutrients and water. During fasting, segmental contractions are infrequent. Peristaltic contractions move the material along the gastrointestinaltract; they can occur during both fasting and feeding. During fasting, these contractions can be divided into three phases: a first quiescent phase, then a weak contractile activity phase and finally a phase with migrating myoelectric complexes (MMC). This last phase is triggered by motilin and may be stimulated by erythromycin. The duration of postprandial motility depends on the type of diet: the presence of fibres and lipids may prolong postprandial motility.

Gut-associated lymphoid tissue (GALT). The lymphoid tissue of the intestineis that part of the immune system which is present within the digestive tract. This system is responsible for protecting the mucosa from attacks by pathogens. It consists of inductive and effector sites, and is constituted by the Peyer's patches, the immune system cells of the lamina propria and the T-lymphocytes in intraepithelial spaces. The Peyer's patches are collections of lymphoid cells present in the mucosa of the small intestine; their function is to assess the antigens presented by the M cells, which are located above the patches themselves. B-lymphocytes and plasma cells are scattered throughout the lamina propria. IgAs are the most important immunoglobulins for mucosal defense and are produced and secreted in response to luminal antigens. Some B-cells produce IgEs or IgMs. IgAs may also have antiviral properties. T-lymphocytes are the third defense mechanism of the mucosa. These cells are located in intraepithelial areas and are protected from direct exposure to antigens through tight junctions along the apical surface of epithelial cells. It is believed that these suppressor and cytotoxic T-cells have a role in the development of inflammatory bowel disease (IBD).

Large intestine
The large intestine starts from the ileocolic valve and is divided into: caecum, colon, rectum and anus. The caecum is not well developed in carnivores. Cats have a short colon and this limits their ability to use poorly digestible starches and fibres. The colon is functionally divided into a proximal and a distal segment.

Histologically, the large intestine is characterized, starting from the lumen outwards, by: the mucosa, submucosa, muscularis and serosa.The mucosa of the large intestineis smooth and villi are absent. Glandular structures are present which extend deep into the mucosa and are lined with epithelial cells that secrete mucus.

The intestinal content is mixed in the proximal colon and water is reabsorbed.This happens through rhythmic contractions (RPCs) and retrograde giant contractions (RGC). In the distal colon the RGCs and the migrating contractions propel the material into the rectum, from where it is finally expelled. Differences in motility are present in the various segments of the colon, however tonic contractions are present in all segments and may last from several minutes to some hours.

The functions of the colon are the absorption of sodium, chlorine, water and the production and storage of faeces.The absorption of Na and Cl occurs in the proximal colon through active pumps and the action of aldosterone and corticosteroids; water is instead absorbed through a passive movement across epithelial cells. In case of irritation and inflammation of the mucous membrane, the water-absorption capacity is greatly reduced, resulting in episodes of diarrhoea. Mucus is produced and secreted in response to luminal stimuli, it acts as a lubricant for the passage of stools and protects the colonic mucosa from any insults. An increased production of mucus can be seen secondary to irritation or damage of the mucosa.

The colonic microflora. The bacteria of the colon make up the largest intestinal bacterial population; their function is varied and concerns the immune system and the production of energy, amino acids and lipids.  Bacterial colonization begins shortly after birth and undergoes continuous changes until the local immune system does not reach full maturity. Each subject has a unique bacterial flora and its composition depends on the age, breed, diet, living environment and on the eventual presence of inflammatory conditions.1-4 Anaerobic bacteria are abundant (Bacteroides spp. and clostridia, etc.), as are aerobes, such as E. coli and other enterobacteriaceae, Streptococcus spp. and lactobacilli. The by-products of bacteria are responsible for the colour and odour of faeces, and excessive production of gas leads to flatulence. Bacteria produce some beneficial substances, such as folic acid, vitamin K and B-complex vitamins, as well as some potentially toxic ones, among which ammonia. The relationship between bacteria and the host depends on the colonic motility present, on the presence of mucus and on an adequate mucosal defense.

Short chain fatty acids. The colonic microflora can metabolize carbohydrates, proteins, lipids and fibres with the formation of short chain fatty acids (SCFA), CO2, water, methane and hydrogen. SCFAs include acetate, butyrate and propionate. Their beneficial effect consists in the acidification of the intestinal environment, thus maintaining potentially toxic compounds (e.g., ammonia) in a non-ionized and therefore less harmful state. In addition, SCFAs are precursors for the synthesis of lipids and of hepatic gluconeogenesis. They help to maintain the normal fluid and electrolyte balance in the colon as well as a healthy luminal bacterial flora, preventing the invasion of pathogens. The microflora can protect against pathogenic bacteria and seems to have a role also in the development of IBD.

Butyrate is metabolized by colonocytes and is an important energy source;it can also induce the production of anti-inflammatory cytokines such as IL-10 that have a role in the mutual recognition of the microflora and the host.5 The most important source of butyrate are fibres, which are soluble and highly fermentable.

 

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