Diseases of the Small Intestine

By | July 3, 2015

Macroscopic anatomy

The intestinal tract can be divided into the small intestine and the large intestine. The main function of the small intestine is the digestion and absorption of food, while the large intestine is responsible for the absorption of water, electrolytes and some vitamins. The small intestine commences at the pylorus and terminates at the ileocaecocolic junction. It is divided into three parts; the duodenum, jejunum and ileum ().

The pylorus marks the start of the duodenum lying on the right side of the abdomen at the level of the ninth rib. The descending limb moves caudally in contact with the right flank. It terminates just before the pelvic inlet forming a U-bend where the ascending limb moves craniomedially to the level of the sixth lumbar vertebra, close to the root of the mesentery and the left kidney. The duodenum now curves ventromedially forming the start of the jejunum. The two pancreatic ducts and the bile duct open 5 to 8 cm from the pylorus.

The jejunum and ileum form the main part of the small intestine commencing at the ventromedial flexure of the duodenum and terminating at the ileocaecocolic junction. The jejunum and ileum are loosely suspended on a long mesentery which allows the intestine to form loops or coils. There is no clear demarcation between jejunum and ileum.

The small intestine is supplied with blood from branches of the coeliac and cranial mesenteric arteries. Venous drainage is via the gastric and cranial mesenteric veins, into the portal vein and on to the liver. Lymphatic drainage of the duodenum is to the hepatic lymph nodes and from the jejunum and ileum via the mesenteric lymph nodes to the cysterna chyli and the thoracic duct.

Preganglionic parasympathetic and postganglionic sympathetic nerves supply the small intestine. In addition there is an intrinsic autonomic nerve supply between the muscle layers called the myenteric plexus or Auerbach’s plexus. Another such intrinsic system lies in the submucosa called Meissner’s plexus.

Microscopic anatomy

The wall of the small intestine is similar throughout its length and is composed of outer serosal, muscular, submucosal and mucosal layers.

The serosa is a thin sheet of epithelial cells which is continuous with the parietal peritoneum. The muscular layer is composed of smooth muscle fibres arranged in two distinct layers; an outer longitudinal layer and a thicker inner circular layer. The latter layer forms the ileocaecocolic sphincter. Between the layers lies Auerbach’s plexus. The submucosa is mainly composed of elastic fibres and collagen. It is richly supplied with blood vessels, lymphatics and neurones. Large lymphatic nodules called Peyers patches, are found throughout the antimesenteric border of the small intestine; they are most prominent in the distal ileum.

The mucosa is the innermost layer which consists of an epithelial lining, intestinal glands, lamina propria and muscularis mucosae. The epithelial cells are also known as enterocytes. The lining is thrown into large folds called villi which effectively increase the surface area by 10 times. The cells on these villi have small finger-like projections called microvilli which increase the surface area a further 20 times (). Between the villi there are large numbers of tubuloalveolar glands secreting into the crypts of Lieberkiihn. They produce mucus and protect the duodenal lining from gastric acid.

The enterocyte layer is only one cell thick and lies on a basement membrane. It is columnar in shape and interspersed with goblet cells and enteroendocrine cells (). Cells originate from the crypts of Lieberkiihn, which lie at the base of the villi as pore-like openings onto the surface, and slowly migrate up the villi towards the tip, becoming functionally mature on the way. The cells already on the tips slough off and are lost in the faeces (). This process is called epithelial renewal and occurs every 4 days (). The goblet cells are found in the crypts and on villi and take their name from their shape and the fact that they secrete mucus. Enteroendocrine cells, or argentaffin cells, are wedge-shaped cells lying on the basement membrane between the enterocytes. Many types are now recognized. They are part of a family of cells called the amine precursor uptake and decarboxylation (APUD) cells. They secrete a series of hormones including cholecystokinin, secretin and gastrin ().

The lamina propria forms a layer immediately below the base of each villus and extends into the villus itself. This layer is composed of loose collagen, elastic fibres and reticulin. Blind-ending lacteals or lymphatic ducts lie in the centre of each villus. Submucosal capillaries infiltrate the villus forming a dense network and smooth muscle fibres from the muscularis mucosae enter the villus to assist in contraction of the lymph vessels (). Small numbers of mast cells, lymphocytes, fibroblasts and leucocytes, and plasma cells are found in the lamina propria.

Physiology

The function of the small intestine is to complete the digestion of nutrients and ensure their subsequent absorption into the general circulation. This is achieved in three phases;

1 Intraluminal digestion involving enzymes produced by the stomach and exocrine pancreas together with bile.

2 Mucosal digestion involving enzymes associated with the microvilli which further hydrolyse the products of intraluminal digestion.

3 The absorption of end products into the enterocytes and then into the capillaries or lacteals.

To aid the digestive process a large volume of water is secreted into the duodenum which ensures the intestinal contents remain isotonic. This is only possible because there are pores present between the enterocytes in the duodenum making it very permeable. The permeability of the small intestine decreases in the more distal segments and is minimal in the large intestine.

Control of the digestive process is under the influence of neural reflexes and hormones. The former are mediated from the central nervous system, through the vagus nerve and are associated with the sight, smell and taste of food. This stimulates release of gastrin in the stomach with production of pepsin and acid. The same vagal reflex stimulates release of exocrine pancreatic secretion. Hormonal control of digestion is mediated through cholecystokinin, secretin and gastrin inhibitory peptide. When acid chime reaches the duodenum it stimulates gastrin inhibitory peptide (GIP) which reduces further gastrin secretion. Cholecystokinin is produced by the enteroendocrine cells of the duodenum in response to the presence of fat and amino acids stimulating the release of exocrine pancreatic secretion rich in enzymes. It also inhibits gastrin secretion and contracts the gall bladder which results in bile entering the duodenum. Secretin is also produced from the duodenal enteroendocrine cells in the presence of acid and stimulates the production of exocrine pancreatic secretion low in enzyme and rich in bicarbonate ().

Protein digestion

The majority of protein is hydrolysed in the proximal small intestine although the process starts in the stomach (). Pepsin in the stomach is a non-specific endopeptidase which splits proteins into smaller peptides. Proenzymes in the pancreatic secretion are activated by duodenal enterokinase when they enter the intestine and trypsin then continues to activate more of itself and other enzymes (). Trypsin and chymotrypsin split proteins into smaller peptides while carboxypeptidase A and B cleave terminal amino acids from these peptides. The end result of this intraluminal digestion is some free amino acids but mainly small peptides (). Elastase is also present and splits internal bonds of proteins. Nucleic acids are also split by other specific enzymes such as ribonuclease and deoxyribonuclease ().

Free amino acids can now be absorbed across the small intestine while the larger peptides undergo further digestion by brush border enzymes known as peptidases (). While larger peptides are split at the brush border, dipeptides are absorbed into the enterocyte and split by peptidase within the cell. Seven different peptidase enzymes have been recognized to date (). The absorption of amino acids is an energy-dependent active process closely linked to sodium transport, in turn it is thought closely linked to adenosine triphosphatase (ATPase) mechanisms creating a transenterocyte gradient. Different carriers are used for different classes of amino acids. From the enterocyte, amino acids leave the small intestine via the portal circulation. Some may be used by the enterocytes for repair and as an energy source ().

Carbohydrate digestion

Most dietary carbohydrate is composed of starch although smaller amounts of dissacharides such as lactose and sucrose may be present. Other carbohydrate in the diet cannot be digested because the enzymes required are not present in the dog and cat. They include hemicellulose, cellulose and lignin, termed dietary fibre ().

Little digestion of carbohydrate occurs until it reaches the small intestine. Starch is composed of amylose linked together by alpha 1—4 bonds and amylopectin linked by alpha 1—6 bonds. Alpha amylase present in pancreatic secretion splits starch into smaller saccharide units by cleaving the alpha 1—4 bonds while being unable to split the alpha 1—6 bonds in starch (). The products of this digestion are maltose, maltotriose and limited dextrins with a small amount of free glucose ().

Before absorption can occur the products of alpha-amylase digestion must undergo further digestion by the brush border enzymes, the disaccharidases (). These enzymes lie on the microvilli surface together with carrier proteins for absorption of their products. Enzymes include lactase, sucrase, maltase (glucoamylase) and alpha dextrinase (isomaltase). These enzymes are most active in the jejunum and the end products glucose, galactose and fructose, are absorbed into the enterocytes. There are specific carriers present which actively absorb the monosaccharides into the enterocyte. In this way absorption can occur even against a concentration gradient during a large meal (). Sucrose and lactose do not undergo intraluminal digestion but are digested on the brush border by specific disaccharide enzymes and absorbed into the enterocytes.

Fat digestion

Triglyceride forms the bulk of dietary fat which is digested and absorbed with great efficiency. Other ingested fats like cholesterol and phospholipid are less efficiently digested. Triglyceride is classified according to the fatty acid chain length into those with only eight carbon atoms termed short-chain triglycerides (SCT), those with between eight and 12 carbon atoms termed the medium-chain triglycerides (MCT) and those with more than 12 carbon atoms, the long-chain triglycerides (LCT). The difference in chain length is important when considering the method of digestion and absorption ().

Intraluminal digestion of LCT requires the presence of lipase and bile salts. The former splits the triglyceride into free fatty acids and monoglyceride while the latter acts as a detergent, providing a water/lipid interface for lipase to digest the fat. An emulsion or micelle is formed by the segmental intestine contractions mixing the fat, lipase and bile salts, forming an emulsion or micelle. The micelle results in the production of very small particles of lipid which create a large surface area for digestion and absorption. Once digestion has occurred the micelle transports the free fatty acids to the brush border for absorption into the enterocyte (). Other fat-soluble products such as fat-soluble vitamins are also absorbed in this process. Fatty acids diffuse into the enterocytes passively because of the lipid membrane. To maintain the concentration gradient for this process, fatty acids in the enterocytes are rapidly converted to triglycerides, which are less osmotically active. Triglycerides attach to carrier proteins (lipoproteins), to form chylomicrons, which then leave the enterocytes and enter the lacteals. The formation of chylomicrons improves the solubility of the fat which allows the triglyceride to enter the general circulation, where it is carried to the liver or tissues.

Short- and medium-chain triglyceride are more water soluble than LCT and the process of lipase digestion is thus more efficient. Micelle formation is not essential, and the fatty acids can be absorbed into the enterocyte directly. Once in the cell they reform into triglyceride and are absorbed directly into the portal blood rather than the lacteal. In addition SCT and MCT can be absorbed intact into enterocytes and then into the portal blood without intraluminal digestion ().

Bile salts are in short supply during a large meal and are therefore conserved by the animal. Once the fat has been absorbed they are re-absorbed into the ileal enterocytes and travel via the portal blood to the liver to be immediately reused. This process is very efficient in the normal dog and is called the enterophepatic circulation of bile salts ().

Pathophysiology of diarrhoea

A definition of diarrhoea might be given as faeces which are unformed as a result of increased bulk or fluid content. This may occur as a consequence of several mechanisms:

  • Osmotic changes
  • Active secretion
  • Increased permeability
  • Altered motility

Most cases of diarrhoea are induced by one of these factors and some cases may involve more than one mechanism at the same time ().

  1. Osmotic diarrhoea is most frequently associated with retention of nutrients in the intestinal lumen, e.g. exocrine pancreatic insufficiency, brush border enzyme deficiency or from malabsorption syndromes. In all cases non-absorbed products create an osmotic gradient between the intestine and the plasma, with the movement of fluid from the plasma into the intestine. Carbohydrate exerts the greatest osmotic gradient because bacterial degradation yields organic acids, amines and ammonia which increase the osmotic effect. An important feature of osmotic diarrhoea is that usually it is easily resolved by fasting the animal.
  2. In secretory diarrhoea there is active fluid secretion into the lumen of the intestine which is independent of any of the other mechanisms described. Most secretion normally originates from the crypt area while most absorption occurs at the tips of the villi. When secretion becomes greater than absorption, diarrhoea develops. The fluid is normally isotonic and there is a major loss of bicarbonate which causes metabolic acidosis to develop. Active secretion of fluid is mediated through cyclic adenosine monophosphate (cAMP) which is itself driven by hormonal stimulation. Various bacterial toxins will also stimulate this mechanism including those produced by Escherichia coli, Salmonella spp. and cholera. In addition, bacterial degradation of fat yields hydroxy fatty acids which also stimulate intestinal secretion, as will unabsorbed bile acids, prostaglandins and serotonin. Various intestinal and pancreatic tumours, thyroid carcinoma and conditions causing hypergastrinaemia also induce hypersecretion.
  3. Normally there are small pores between the crypt cells which allow fluid movement into the intestinal lumen. This is a passive process and when it becomes greater than the absorptive capacity of the intestine, diarrhoea develops. Changes in pore size, with a consequent increase in’permeability, may occur because: (1) there is increased hydraulic pressure as in cardiac disease or lymphatic obstruction; and (2) inflammation of the intestinal mucosa resulting in physical damage to the mucosa. Most frequently only simple sugars and amino acids are lost but if the damage is severe then large molecular plasma proteins may also be lost giving rise to a protein-losing enteropathy.
  4. Many clinicians believe diarrhoea is caused by increased intestinal motility. This is frequently not the case. There are basically two types of intestinal motility: (1) segmentation; and (2) peristalsis. The former is thought to be the primary intestinal motility which mixes chyme and allows efficient absorption of nutrients, whilst peristalsis moves the contents of the intestine towards the rectum. When diarrhoea occurs it is often due to failure of segmentation and thus of mixing and absorption. The peristalsis which occurs is reflexly stimulated by increased volumes of chyme which are moved towards the rectum and voided as diarrhoea.

Introduction to enteritis

Diseases of the small intestine may be conveniently divided into those which are acute and sudden in onset such as canine parvovirus and those which are chronic in nature, such as malabsorption syndromes. As with all classifications there will always be some degree of overlap of conditions. For example, canine parvovirus may start as an acute gastroenteritis but following physical damage to the small intestine chronic enteritis associated with malabsorption may develop.

Acute enteritis may be described as being sudden in onset in a previously healthy animal. It is usually self-limiting with recovery following several days of acute symptoms. Chronic enteritis on the other hand occurs where a dog or cat has persistent or intermittent diarrhoea over a period of weeks or months. The animal is often bright and may lose weight in spite of a good appetite.

Table Differential diagnosis of acute enteritis

Dietary
Sudden diet changes
Incorrect diet
Scavenging
Overfeeding
Reduced fibre
Dietary allergy
Lactase deficiency
Viral
Canine parvovirus
Distemper
Infectious canine hepatitis
Feline enteritis
Rotavirus infection
Coronavirus infection
Bacterial
Salmonellosis
Campylobacteriosis
Tyzzer’s disease
Miscellaneous bacterial infections
Other
Haemorrhagic gastroenteritis
Intestinal obstruction
Intussusception

In this chapter conditions associated with acute enteritis are discussed (Table Differential diagnosis of acute enteritis) followed by some of those conditions which are often described as chronic in nature (Table Differential diagnosis of chronic enteritis).

Table Differential diagnosis of chronic enteritis

Parasitic
Roundworm infection
Giardiosis
Cryptosporidium spp.
Maldigestion
Exocrine pancreatic insufficiency
Bile acid deficiency
Brush border enzyme deficiency
Malabsorption
Lymphocytic – plasmacytic enteritis
Gluten sensitivity
Eosinophilic enteritis
Lymphangiectasia
Regional enteritis
Neoplasia (lymphosarcoma)
Bacterial overgrowth
Endocrine disorders
Feline hyperthyroidism
Addison’s disease
Toxaemic states
Renal disease
Chronic liver disease
Other
Cardiac disease

Acute enteritis

Chronic small intestinal diseases

 

Selections from the book: “Digestive Disease in the Dog and Cat” (1991)