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Digestive System of a Pig

Learning objectives:
After you have studied this chapter, you should:
Get a fundamental understanding of the porcine digestive tract
Describe the essential digestive processes
Understand the role of the digestive organs in digestion and absorption
1. Introduction (HNL/MSH) 2. Anatomy of the digestive system (HNL) The anatomy the porcine digestive tract has been described and illustrated in detail by others (e.g. Sisson, 1975, Moran, 1982)[1] and will only be briefly described in the current chapter.
The digestive system of the pig is fundamentally similar to all other monogastric mammals, but the evolutionary development in size and digestive capacity reflects greatly the habitual diet. Pigs are true omnivores but with a large fraction of the diet coming from plant material. As such they have a great capacity to digest enzyme degradable carbohydrates in the upper part of the gastrointestinal tract, and a well-developed ecosystem in the large intestine to partly ferment and utilize fibrous material.
2.1 Mouth and salivary glands
The pig is born with 8 deciduous teeth increasing to 32 with age. The complete set of permanent teeth consists of 44 teeth with 3 pairs of incisors, 1 pair of canines, 4 pair of premolars, and 3 pair of molars, which are usually not fully acquired until 18 months of age[2]. The oral cavity is lined with a simple stratified squamous epithelium, and saliva is mainly secreted from 3 large glands; the parotid glands, the mandibular glands, and the sublingual glands. Major ducts from the parotid and mandibular glands transport saliva to the oral cavity, while the sublingual glands have multiple openings beneath the tongue. In addition, a number of small glands with a number of excretory ducts are present in the mouth.[3] After leaving the mouth, food enters the pharynx and oesophagus. The pharynx is long and narrow. The esophagus is short and covered with stratified squamous epithelium. Beneath the epithelium, a number of submucosal glands are located. Their function is to secrete mucin and bicarbonate, to neutralize luminal acid and protect the epithelium[4].
2.2 The stomach
The stomach of the pigs consists of a simple compartment that is divided into 4 functionally and structurally different regions. The pars oesophagea is a non-glandular extension of the esophagus into the proper stomach. Ulceration – ulcerous autodigestion of the cutaneous mucosa – of the pars esophagea is a common phenomenon in swine production and develops from a complex interaction of dietary particle size, gastric fluidity, dietary carbohydrate content, presence of gastric organisms, and environmental stress factors.
Next to the pars oesophagea is the glandular cardia, which in contrast to most other species is very large and occupies approximately one third of the stomach luminal surface. The fundic, or proper gastric, region is located between the cardiac and pyloric region. All three contain secretory glands located in so-called ‘gastric pits’. Structurally, they are similar, but they contain different cell types. The major surface of the stomach and lining of the pits are covered with surface mucous cells, that produce thick, tenacious mucus to protect the epithelium against injure from acid and grinding activity.
The gastric pits of the fundic mucosa contain HCl-producing parietal cells that are clustered in the neck of the gland. Distributed between these cells are mucous neck cells that produce thin mucus and proteases. As the only cells of the stomach lining, mucous neck cells divide and migrate either down into the gland or up into the pits and differentiate into any of the mature cell types. Pepsinogen-producing chief cells are located at the base of the fundic glands. In addition, the fundic mucosa also contain endocrine/paracrine somatostatin producing D cells, seretonin producing EC cells, and histamine producing histamine-immunoreactive cells and mast cells (lamina propria)
The cardiac glands have mucous cells that produce mucus, proteases and gastric lipase. The pyloric glands contain gastrin producing G-cells and somatostatin producing D-cells, but the dominating cells are the mucous cells. They do contain mucous neck cells that produce mucus and proteases and zymogen producing chief cells but have no parietal cells. [5]
2.2.1 Size and capacity of the stomach
In suckling pigs the pars esophagea, cardic, fundic and pyloric regions represents about 6, 30, 44 and 20 % of the total mucosal area, respectively, while on weight basis the cardia represents only 20 % but the fundic region 56 % of total mucosa weight.
The weight of the stomach represents 0.5-0.8 % of body weight in suckling pigs and between 1-1.3 % in growing pigs. In adult pigs the stomach accounts for approximately 0.6 % of total body weight. The capacity range from 0.03 l in the new born to approximately 3.5 l in slaughter pigs, and 5 l in adults, while under pressure the capacity under increases to 8 and 12 l for slaughter and adult pigs, respectively. A number of studies have shown that the bulk of the diet can influence the subsequent capacity of the stomach. [6]
2.3 The pancreas[7]
The pancreas is located in proximal duodenum. The body of the pancreas separates in the two lobes with the center surrounding the portal vein. A single pancreatic duct leaves the right lobe and enters the duodenum on a minor palpilla 12-20 cm distal to and separate from the bile duct entry, 20-25 cm from the pylorus.[8]
The pancreas is a mixed endocrine and exocrine organ. The exocrine pancreas consists of the acinar cells and the duct system, representing more than 95 % of the pancreas fresh weight. The acinar cells produce and store pancreatic enzymes and inactive zymogens, and when stimulated release them into the duct system for transport to the duodenum. Water, bicarbonate and other electrolytes of pancreatic juice are produced in centroacinar cells and cells of the intercalary and intralobular ducts.
The endocrine part of the pancreas is restricted to the islets of Langerhans. The islet are distributed throughout the acinar exocrine tissue and contain glucagon producing, alpha cells (15-20% of total islet cells), insulin and amylin producing beta cells (65-80%) , somatostatin producing delta cells(3-10%), pancreatic polypeptide producing PP cells (3-5%), and possibly also ghrelin producing epsilon cells (<1%)[9]
2.4 The liver and gallbladder
The porcine liver is divided into 4 principal lobes along with a small quadrate lobe and a caudate process. The lobes, which are the functional units, are surrounded by fine connective tissue. The lobules consist of plates of hepatocytes interdigitated with hepatic sinoids, arranged radially around a central vein. Kupffer cells, which are specialized macrophages, along with endothelial cell line portions of the hepatic sinoids form part of the reticuloendothelial system. Located in the peripheral interlobular connective tissue is the portal triad; the hepatic portal vein, a hepatic artery and an interlobular bile duct, but additionally also lymphatic vessels[10]. Afferent blood from the portal vein and hepatic artery flows centrally in the hepatic siniods. Bile produced by the hepatocytes drains into bile canaliculi formed by hepatocytes and then through ducts of Hering to the interlobular bile ducts in the portal triad. The interlobular bile ducts merge into larger intrahepatic ducts, which become the extrahepatic biliary system. This includes the hepatic bile duct, which divides into a cystic duct connected to the gallbladder, and a common bile duct connecting to the duodenum. The bile duct enters the duodenum on a major palpilla located 2-5 cm from the stomach pylorus.
2.5 The small intestine
The small intestine comprise of the duodenum (4-4.5%), jejunum (88-91 %) and ileum (4-5 %). The proportion of duodenum in the neonate is similar to that of the adult, whereas differentiation between jejunum and ileum is not clear. Although there are distinctive morphological feature, the duodenum, jejunum and ileum share a lot of common features.
The small intestine consist of 4 major layers; The serosa, the muscularis, the submucosa and the mucosa. The serosa is the outermost layer of the intestinal wall. It has a squamous epithelium forming the mesentery that contains connective tissue, large blood vessels and nerves. The muscular layer contains two types of muscle fibres; an outer layer of longitudal muscles and an inner layer of circular muscles, that are involved in gastrointestinal motility. The submucosa is a layer of connective tissue holding together the large blood and lymphatic vessels and neural complexes. The mucosa consists of 3 sublayers; the muscularis mucosa, the lamina propria and the epithelium. The muscularis mucosa consists of a longitudinal inner muscle and an outer muscle encircling the intestine and produce transient intestinal folds. The lamina propria consists of blood vessels, free lymphocytes and lymph nodes called Peyers patches, and neurons held together by connective tissue. It supports the structure and nourishes the epithelial layer. The epithelial layer consists of a single layer of epithelial cells. They cover the whole luminal surface of the intestine, which is severely folded by the formation of fingerlike projections called villi, and at the base of these Crypts of Lieberkuhn, that are moat-like invaginations.
There are 3 types of epithelial cells on the villus surface: absorptive cells, goblet cells and enteroendocrine cells[11]. They all originate from stem cells located near the base of the crypts. The entocytes migrate from the base to the tip of the villi and during migration, the enterocytes maturate. The digestive function (enzyme activity) begins as the enterocytes migrates over the basal third of the villi. The absorptive function starts to develop as they reach the upper to midlevel and continues to increase until they reach the top of the villi, where they are shed into the lumen. Hence, enterocytes at the surface of the villi are continuously renewed. Goblet cells are secreting viscous mucus, and are interspersed among the enterocytes. Goblet cells increase in number from the proximal jejunum to the distal ileum.
The formation of villi increases the mucosal surface by 10-14 fold compared to a flat surface of equal size. Furthermore, the cell-surface of the enterocytes facing the lumen has an apical membrane forming microvilli (brush-border) that further enhances absorptive surface 14-40 fold. The microvilli have important digestive enzymes and other proteins attached. They extent into a jelly-like layer of glycoprotein known as the glycocalyx that covers the apical membrane. The remaining part of the enterocyte plasma membrane is called the basolateral membrane, referring to the base and side of the cell.
The length of villi increases from the duodenum to the mid-jejunum and then decreases again towards the terminal ileum. This reflects the various functions of the different segments of the small intestine.
Crypts also vary in size and composition along the intestine. They are deepest in the proximal small intestine (duodenum and jejunum) and shorter distally in the ileum. Paneth cells are located at adjacent to stem cells at the base of the crypts[12]. Their exact function is unknown but due to the presence of lysozymes and defensins they most likely contribute to maintenance of the gastrointestinal barrier.
While the duodenum is the site where digesta leaving the stomach is mixed with secretions from the intestine, liver and pancreas, the jejunum is the main site of absorption. Brunner glands, which are located in the submucosa on the part above the sphincter of Oddi[13], produce bicarbonate containing alkaline secretion, which protect the duodenum from the acidic content of chyme, provide an alkaline condition for the intestinal enzymes and lubricate the intestinal walls.
2.5.1 Size and capacity of the small intestine
At birth the small intestine is about 2 m long and has a capacity of 72 ml. At weaning it has more than tripled its length (6.6 m) and has a 9-fold as high capacity (660 ml). The small intestine of fully grown pigs is 16-21 m, weighs 2-2.5 kg and has a capacity of about 20 l. While the small intestine accounts for approximately 4-5 % during the suckling period, it decreases to 1.5 % when reaching slaughter weight.
2.6 The large intestine
The pig has a relatively short caecum and a long colon, consisting of an ascending, transverse and descending colon.[14] The caecum is a cylindrical blind sac located at the proximal end of the colon. The cecum, the ascending and transverse colon and the proximal portion of the descending colon are arranged in a series of centrifugal and centripetal coils known as the spiral colon. The caecum and proximal part of the spiral colon has longitudinal muscular bands resulting in a series pouches (haustra)[15]. The rectum is embedded in fat and is dilated to form ampulla recti just before ending at the anus.
The mucosa of the large intestine has no villi, but columnar epithelial cells with microvilli formed into straight tubular crypts. Numerous goblet cells secreting sulphated carbohydrate-protein complex intersperse the columnar cells to lubricate the colon. The rectum has a simple structure with columnar cells and only few goblet cells.
2.6.1 Size and capacity of the large intestine
During the suckling period the large intestine is small; From a weight of 10 g and a length of 0.8 m and with a capacity of 40 ml at birth to 36 g, 1.2 m and a capacity of 100 ml at 20 d of age. This corresponds approximately to 1.2 % of body weight. After weaning and during the growing period it grows dramatically (2-2.5 % of body weight) and increases its weight to 1.3 kg and length to 5 m at 100 kg with a capacity of approximately 10 l. Adult pigs have a large intestine weighing about 2.8 kg, a length of 7.5 m and a capacity of 25 l.
3. Function of the digestive organs 3.1 Salivary secretion (HNL) Saliva contains a mixture of water (99 %), inorganic salts, mucins, a-amylase. In addition, to serve some protection against diseases, it also contains lysozyme, which breaks down the polysaccharide walls of many kinds of bacteria and immunoglobulin A, which play a critical role in mucosal immunity. Saliva moistens the food, lubricates the esophagus, and initiates the digestion of starch. However, the activity of salivary a-amylase is low, and although secreted in the oral cavity, starch digestion is not believed to be of quantitative importance here, as the time spent in the mouth is too short. Some digestion may on the other hand take place in the proximal part of the stomach prior to acidification with gastric juice. [16] The volume and duration of salivary secretion varies in response to external cognitive or sensory stimuli (cephalic stimulation) and physical and/or chemical stimulation in the mouth. Volume and total activity increases with increased feeding level. However as the ratio of total salivary amylase to total pancreatic amylase is only about 1:250,000 in the postprandial phase[17] (0-5 h after feeding), salivary a-amylase may be considered insignificant from a quantitative point of view.
3.2 Gastric secretion (MSH)
Gastric juice is a clear and slightly viscous fluid. The major constituents in gastric juice are shown in Table 1.

Triglyceride digestion
HCl is secreted by the parietal cells. However, HCl is not produced within the parietal cell because it would destroy the cell. Both H and Cl- are independently transported from the parietal cell into the stomach lumen. Hydrogen ions are generated from the dissociation of carbonic acid that is produced by the enzyme carbonic anhydrase acting upon CO2 and H2O. H is then transported to the stomach lumen though a proton pump (H /K -ATPase). As hydrogen ions are secreted bicarbonate anions accumulate in the cell. To counterbalance this accumulation HCO3- is exchanged for Cl- at the basolateral membrane. The K cations that accumulate within the cells are released back into the lumen in combination with Cl- anions.
HCl plays two important roles in gastric juice. Firstly, it facilitates the protein digestion. HCl denaturates dietary protein, which results in exposure of peptide bonds to proteolytic enzymes. In addition, HCl activates pepsinogen to pepsin and provides a medium of low pH that ensures the optimal activity of the enzyme. Secondly, the low pH provides a non-specific defence mechanism because it inhibits microorganisms from proliferating in the gastric lumen and cause damage to the gastrointestinal tract.
Four types of proteases have been found in the gastric juice of pigs (Table 1). They are all secreted as inactive zymogens (proenzymes that are activated in the lumen) to avoid self-digestion of the cells. The zymogens are activated in the lumen at an acidic pH below 5 or by active pepsin A. Pepsin A is the predominant gastric protease in adult pigs followed by gastricsin. They have strong proteolytic activity at pH 2-3. Pepsin digests approximately 10-15% of dietary protein before it is inactivated in the small intestine[18]. In suckling piglets, chymosin is the predominant protease. It has potent milk clotting activity at pH around 6. Milk clotting is important in suckling animals: it prolongs the passage time of milk along the gastrointestinal tract and enables the thorough digestion and absorption of milk nutrients.
Apart from pepsinogen, the chief cells of the cardiac region of the pig stomach also secrete minor amounts of gastric lipase. This enzyme hydrolyses medium- and long-chain triglycerides and plays a role in the hydrolysis of triglycerides in the stomach of the young pig.
A layer of protecting mucus covers the mucosal surface of the stomach. This layer protects the stomach epithelium from the acid conditions and grinding activity present in the lumen. Mucin secreted by the mucous neck cells of the gastric glands constitutes a major component of the viscous mucus layer.
3.2.1 Regulation of gastric secretion
Gastric acid secretion is regulated by gastrin, histamine, and acetylcholine that stimulates while somatostatin inhibits acid secretion.
Gastrin is produced by G cells in the antral mucosa. The production and release of gastrin is stimulated by food compounds mainly small peptides and amino acids and by nervous reflexes activated by gastric distension when food enters the stomach. Gastrin is secreted into the blood stream and acts on the parietal cells via a G receptor. Histamine is an amplifying substance in acid secretion. Histamine is produced by local mast cells and enterochromaffin-like cells and acts on parietal cells in a paracrine fashion. Acetylcholine is a neural transmitter produced by cholinergic neuraon. Acetylcholine is released as response to activation of stretch receptors[19]. The secretion of hydrochloric acid is most efficient when all three regulators are present. Gastric acid secretion is controlled by a feed back mechanism. When pH is 3 or below[20] acid secretion diminishes and gastrin release is blocked. The acidity prevents amines from diffusing into G cells and activate hormone secretion. Furthermore, acid in the lumen causes D cells to release somatostatin. Somatostatin inhibits the parietal cells from secreting acid and G cells from releasing gastrin.
The regulatory mechanisms that control pepsinogen secretion are much less researched but it is generally believed that the pepsinogen secretion is under same regulatory influences as acid secretion.
The gastric secretory activity can be divided into three phases: cephalic, gastric, and intestinal. The anticipation of food stimulates gastric acid secretion. This is controlled by the central nervous system and is called the cephalic phase. The cephalic phase lasts for minutes and prepares the stomach for the entry of food. The gastric phase begins when food enters the stomach. It lasts for hours and accounts for two thirds of the gastric secretions. During the gastric phase acid and pepsinogen secretion is increased. When digesta enters the duodenum the intestinal phase initiates. This phase functions to decrease gastric motility and to reduce the secretion of gastric acid and pepsinogen. The intestinal phase lasts for hours.
3.3 Pancreatic exocrine secretion (MSH)
The primary function of the exocrine pancreas is 1) to provide digestive enzymes for the digestion of the major nutrients and 2) to neutralize the acidic chyme entering the duodenum from the stomach to allow the pancreatic enzymes to function. The pancreatic juice is a clear, colourless liquid that contains salts, bicarbonate, and enzymes. The acini, the functional part of the exocrine pancreas, are composed of acinar cells, that synthesize and secrete the digestive enzymes and ductal cells where fluids and electrolytes originate from.
The main regulatory pathways that control exocrine pancreatic secretion are the hormones secretin and cholesystokinin (CCK) and nervous stimulation.
Acinar, centroacinar, and duct cells have receptors for secretin, CCK, and acetylcholine. When these binding sites are occupied the cells are stimulated to secrete, however, maximal secretion is observed when all receptors are occupied. Secretin is secreted by the endocrine S cells in the mucosa of the proximal small intestine. Secretin is released in response to acid or fatty acids in the duodenal lumen and it stimulates release of bicarbonate by pancreatic duct cells. CCK is released into the blood stream in response to the presence of animo acids, peptides, and fatty acids in the duodenal lumen. CCK is secreted by I cells in the proximal small intestine and it stimulates the secretion of digestive enzymes by the acinar cells. Acetylcholine, released by nerve endings near the pancreatic cells, stimulates secretion. The neurons are stimulated to release acetylcholine by impulses from the enteric nerve system or through the vagus nerve. The sight and smell of food induces vagal responses leading to pancreatic secretion[21]. This is the cephalic phase of pancreatic secretion analogous to the cephalic phase of gastric secretion described previously. Distension of the stomach also causes a vagovagal reflex stimulating pancreatic secretion, which is the gastric phase of pancreatic secretion. When digesta enters the duodenum it evokes a large increase in the rate of pancreatic secretion and the intestinal phase involves both endocrine as well as neuronal stimuli. The distention of the duodenum produces enteric nerve impulses that lead to the release of acetylcholine. The endocrine (hormonal) part of the intestinal phase occurs in response to the chemical stimulation, digestion products of protein and fat stimulates the release of CCK and the low pH of the digesta stimulates the release of secretin.
The exocrine pancreatic secretion is controlled by a feed back mechanism. Diversion of pancreatic juice from the duodenum increases pancreatic secretion. It has been suggested that trypsin is the main component in this feed back regulation as reintroduction of pancreatic juice or infusion of trypsin but not amylase into the duodenum markedly decreased pancreatic secretion. Furthermore ingestion of raw soybeans containing trypsin inhibitor increases pancreatic secretion. There is strong evidence that this feed back regulation is linked with the release of CCK. Enterostatin, a pentapeptide released from procolipase when it is activated by trypsin in the duodenal lumen, may play a role in the feed back mechanism as well. Intraduodenal infusion of enterostatin hs been shown to inhibit pancreatic enzyme secretion.
3.3.1 a-amylase
Pancreatic α-amylase hydrolyses starch (from plant sources) and glycogen (from animal sources). Starch is composed of amylose, a linear polymer of glucose that is linked by α-1,4 glycosidic bonds and amylopectin, a branched polymer of glucose, that contains both α-1,4 glycosidic bonds and α-1,6 glycosidic bonds. α-amylase cleaves the interior α-1,4 glycosidic bonds of starch. During the lifetime of the enzyme-substrate complex amylase hydrolyzes starch by multiple attacks through cleavage of several bonds. The major products of starch hydrolysis are maltose, isomaltose, maltotriose, sugars composed of two or three glucose units, and α-limit dextrins, polysaccharides of 5 to 10 glucose residues containing both α-1,4 and α-1,6 glycosidic bonds.
3.3.2 Lipases
Pancreatic juice contains three lipolytic enzymes: lipase, phospholipase A2, and carboxyl ester hydrolase, and a protein cofactor, colipase. Lipase is secreted as a fully active enzyme and is the most important enzyme in the digestion of fat. Lipase hydrolyses triglycerides the most abundant lipid in the diet and the products are free fatty acids and monoglycerides. Lipase is strongly inhibited by bile salts in the duodenum and the protein cofactor colipase is the only agent known to counteract this inhibition. Colipase is secreted as a zymogen, procolipase, which requires cleavage by trypsin to become active. Phospholipase A2 splits fatty acids from phospholipids. It is secreted as an inactive zymogen that requires activation by trypsin. Carboxyl ester hydrolase, also known as carboxyl ester lipase and cholesterol ester hydrolase, has an unusually broad substrate specificity, it hydrolyses mono-, di-, and triglycerides, cholesterol and retinol esters and lysophosphatidylglycerols. However, the main physiological function probably is to hydrolyse retinol and cholesterol esters.
3.3.3 proteases
The major proteolytic enzymes secreted by the exocrine pancreas are listed in Table 1. All proteolytic enzymes are secreted as inactive zymogens to protect the gland from autodigestion.

The activation of the proteolytic enzymes is initiated by the activation of trypsin by enterokinase, an intestinal brush-border enzyme. Trypsin then activates all other zymogens as well as trypsinogen. Trypsin is an endopeptidase meaning that it breaks proteins at internal points along the amino acid chain, it specifically cleaves peptide bonds on the carboxyl side of basic amino acids (lysine and arginine). The catalytic activity of chymotrypsin is directed towards peptide bonds involving the carboxyl groups of tyrosine, tryptophan, phenylalanine and leucine. Elastase cleaves on the carboxyl side of aliphatic amino acids (alanine, leucine, isoleucine, valine, and glycine). The carboxypeptidases are zinc-containing metalloenzymes. They are exopeptidases meaning that they remove a single amino acid from the carboxyl-terminal end of proteins and peptides.
3.3.4 Pancreatic secretion and dietary composition
The enzymatic composition of the pancreatic juice has been shown to be dependent on the dietary composition.
3.4 Bile secretion (HNL)
The bile has pH of 7.4-7.9 and contains bile salts, phospholipids, cholesterol (summing up to a total lipid content of 0.6-0.7 %), sodium, potassium, chloride, bicarbonate, mucus and bile pigments, of which the latter are endogenous waste products. Bilirubin is a major end product of red blood cell turnover produced by Kupffer cells and transported to hepatocytes for conjugation. The conjugated bilirubin is secreted in the bile responsible for its green/yellow colour. In the intestine conjugated bilirubin is converted by the microflora to urobilinogen, then to urobilin and stercobilin[22] and finally excreted by defaecation, giving faeces its characteristic brown colour. Some urobilinogen is reabsorbed and excreted by the kidney as urobilin, which is responsible for the yellow colour of urine.
Both bile acids and phospholipids play an important role in digestive function, and the molar ratio of total phospholipid to total bile salts is 1:10.1[23]. Bile salts are conjugated bile acids, and their function is to aid emulsification and absorption of lipids. The bile acids in porcine bile are mainly conjugated with glycine but also some taurine (6.5 %). Chenodeoxycholic acid (CDCA), found in the form of 31.3 molar % glyco-CDCA and 3% taurine-CDCA is de novo synthesized from cholesterol by the hepatocytes. Hyocholic acid (HCA) in the form of 12.6 % glyco-HCA is produced by hydroxylation of CDCA. Reduction of HCA by the microflora of the intestine leads to formation of hyodeoxycholic acid (HDCA), which in bile is found as 48.2 % glyco-HDCA and 3.5 % tauro-HDCA . In contrast to humans, pig bile contains very little cholic acid(CA), found as glyco-CA (1.3 %). When excreted to the intestine conjugated bile acids are deconjugated and converted by the microflora in the distal small intestine. A majority of the bile acids are reabsorbed in the distal small intestine and transported to the liver via the portal vein. Along with de novo synthesized bile acids they are reconjugated and again excreted in bile. This phenomenon is termed entero-hepatic circulation, and is a mechanism to cope with the demand of bile acids, which by far exceeds the capacity for production. The phospholipids of porcine bile is entirely in the form of phosphatidyl choline, dominated by the 16:0-18:2 diacyl forms (59.6 %), followed by 16:0-18:1 (18.4 %) and 18:0-18:2 (15.9 %). [24]
The bile secretion from the hepatocytes is constant, but bile is only released to the intestine, when needed for lipid digestion. Hence, when little or no food is present in the duodenum, the Sphincter of Oddi is closed and bile is diverted from the bile duct to the gall bladder, where the bile is concentrated. When food, particularly fat-rich food, enters the duodenum, the Spincter of Oddi is relaxed and the gall bladder contracts by a combination of neural and hormonal factors. Gut endocrine cells are stimulated to release CCK, while neurale receptors located at the Spincter of Oddi in conjuction with the intramural plexus coordinates the bile duct and bladder peristalsis.
In bile duct cannulated pigs, where the Sphincter of Oddi is not controlling bile flow, the total bile flow over 24 hours has previously been measured to be 38 and 46 ml/kg in 60 and 45 kg pigs, respectively. Using re-entrant cannulation of the bile duct, which allow gallbladder storage of bile and regulation of flow by the Sphincter of Oddi, it was found that a traditional European pig diet induced a bile 24-h bile flow of 48 ml/kg, while a semi-synthetic diet based on starch, sucrose, casein, maize oil and cellulose led to a flow of 30 ml/kg. Measurement of bile flow by cannulation of the common bile duct and re-entrant cannulation of the proximal duodenum to reintroduce bile at the same rate of excretion resulted in flows of 35 ml/kg for 43 kg pigs fed a wheat-fish meal-casein diet and 59 ml/kg when a similar diet was supplemented with 40 % wheat bran. Hence, the bile flow is influence by the diet. Increasing fat content of the diet from 2 to 10 % induce a dramatic increase in bile acid secretion along with a moderate increase in phospholipid and cholesterol output. A further increase in fat content to 20 % of the diet does not lead to further increase in bile acid flow, while phospholipid and cholesterol output continue to increase. Lipid composition also influences the bile output. While degree of saturation does not appear to influence the rate of bile acid and phospholipid secretion, the secretion of cholesterol is increased.[25]
3.5 Small intestinal digestion and absorption (MSH)
3.5.1 Digestion of carbohydrates
The luminal phase of carbohydrate digestion applies only to starches and the enzyme involved is α-amylase secreted from the pancreas. Starch hydrolysis products (maltose, isomaltose, maltotriose, and α-limit dextrins) and dietary disaccharides (sucrose and lactose) are digested in the membranous phase by digestive enzymes that are a structural part of the intestinal surface membrane.
Four different oligo

Secretors and Non-secretors Disease Susceptibility

Human population can be categorized into secretors and non-secretors based on A, B and H antigen on basis of presence or absence of these blood group antigens in the body fluids and secretions, such as saliva, sweat, tears, semen, serum, mucus present in the digestive tract or respiratory cavities etc. Secretors are individuals that secrete blood group antigens in their body fluids while non-secretors are the individuals that do not secrete them in their body fluids and secretions.
It is a known fact that ABO blood type is controlled by blood type coding genes present on the chromosome 9q34 but the secretor status of an individual is decided by interaction of a separate gene (called secreting gene) with these blood type genes. The presence of the secreting gene in a person’s genome makes him a secretor and absence makes him a non secretor. The gene is designated as (Se) for Secretors and (se) for Non-secretors and it is entirely independent of the blood type A, B, AB or O. The individuals secreting antigens in the body fluid are designated as ‘ABH secretors’ in blood banks. Individuals having O blood group secrete antigen H, A blood group secrete A and H antigens, B blood group secrete B and H antigens in the fluids.
A secretor gene helps a person to gain a degree of protection against different environmental conditions especially the micro flora of a particular environment and also the lectins present in them. It helps them in promoting the growth of friendly, stable blood type intestinal bacterial ecosystem which depends on the blood type antigens present in the mucus of an individual. Secretor status does modify carbohydrates in the fluids present in the body and their secretions and it also affects and influences the attachment and persistence of the micro flora present in the body. Secretors are at a higher advantage than non-secretors. Non-secretors have a potential health disadvantage. They possess many metabolic traits such as carbohydrate intolerance, immune susceptibilities. Different tests are available for determining an individual’s secretor status. Most common test uses saliva or other body fluids of an individual for testing the secretor status. These tests are based on the principle of Agglutination Inhibition where the antigens are neutralized by the corresponding antibodies so that these antibodies will not be further be available to neutralize or agglutinate the same antigens residing on the red blood cells. ELISA could also be used for determining the presence of the secreted Lewis antigens in the saliva or other body fluids.
The alleles Se and se differ in the frequency and have an anthropological value. They occur in different frequency in different populations. They have a high frequency in the American Indiana and a low frequency in the southern Indians. In US 20% of the population is secretors whereas 80% of the population consist of non-secretors. The fusion allele of the FUT2 (secretor type alpha(1,2)-fucosyltransferase) gene at a high frequency and a new se385 allele in a Korean population
SECRETOR AND NON-SECRETOR A person secreting blood group antigens into the body fluids and other secretions like saliva, semen, tear, mucous in the digestive tract and respiratory cavities are named as secretors. In similar terms they put their blood type antigens in the body fluids. They secrete antigens according to their blood type, A secrete antigen A and H, B secret antigen B and H, O secrete antigen O and AB secrete A, B and H antigen. Secretors expresses Lewis b (Leb) antigens on the RBC where as non-secretor expresses Lewis a (Le a) on their RBC.These antigens in the body fluids give additional protection to the individual against the various microorganisms and the lectins present all around us.
15- 20% of the population consists of non-secretor. These individual fail to secrete the blood group antigens in their body fluids hence they become susceptible to bacterial and superficial yeast infections. A large no of them sometimes also suffer from the autoimmune disorder. This could also be correlated with the secretor and non-secretor phenotype. The body secretions of secretors and non-secretors differ quantitatively and also qualitatively. The type and quantity of the antigens present in it differ among different individuals. In some cases the non-secretors may contain the A and B antigens in the saliva but the quantity is less and even quality is very low hence they have similar functional problem.
There are certain properties which are specific for secretors and differ in non-secretors. Some are listed below:
Intestinal alkaline phosphatase activity ABH secretor correlates the activity of alkaline phosphatase and serum alkaline phosphatase present in the intestine. Non-secretors have low activity of alkaline phosphatase and serum alkaline phosphatase which is responsible for the breakdown of fat and assimilate calcium. Low molecular weight alkaline is present in both secretors and non-secretors and high molecular weight alkaline phosphatase is present only is secretors.
Bacterial flora The ABH blood types influence the population of bacteria residing in the local vicinity of the gut mucin glycoproteins. Bacteria produce enzymes that have the capability to degrade the end sugar of A, B, and H blood antigens and which are consumed as food by them. The B antigen degrading bacteria produce enzyme to remove the end alpha-D-galactose and A antigen degrading bacteria produce enzyme to detach N-acetylgalactosamine which are used as a source of food by them.
Blood clotting The secretor and the ABO genetics influence each other and effect upto 60% of the vWf concentration variation in plasma. Raised levels of factor VIII and vWf may cause thrombotic and heart disease in future. Secretors have the slowest clotting time, thinnest blood, least tendency of platelet aggregation, low amount of factor VIII and von Willebrand factor (vWf). The non-secretors have highest clotting time, thick blood, high amount of factor VIII and von Willebrand factor (vWf) and low bleeding time. The blood viscosity is also influenced by the secretor status of that individual.
Phenotype – Lewis Characteristics of Clotting
Le (a- b-) maximum action of factor VIII and vWf
Very Low bleeding times (seen in A, B and AB)
Le (a b-) intermediary action
Low bleeding times (seen in O)
Le (a- b ) minimum action of factor VIII and vWf
Very Long bleeding times (seen in O)
Blood Type – Lewis and Factors effect Blood Clotting Immunoglobulin Variations
ABH non-secretors express low concentration of IgG immunoglobulin. The secretion of varying concentration of diverse constituents of the blood group is controlled by the secretor gene and it also affects the phagocytic activity of the leucocytes which provides an added advantage to the non-secretors. The leucocytes of the non-secretors possess a greater ingestion power when compared to the secretors. The O and B blood group non-secretors have the highest phagocytic activity.
The presence of different concentration of anti-I in the an individuals serum is affected by the ABO group, secretor status and sex of the individual. The secretors females have a high level of anti-I in the serum as compared to the males. The non-secretor have low levels of IgA and IgG antibodies and hence have frequent problems with the heart valve.
Genetics and Biochemical pathways
The secretion of the blood group antigens in the body fluids and other secretions are genetically influenced by certain allelomorphic genes. Secretor gene contains two alleles (Se) and (se). The dominant gene Se is present in the homozygous or heterozygous condition in the secretors which lead to the secretion of antigens into the body fluids. se is recessive allele and is present in non-secretors in the homozygous condition. SeSe and seSe produces a dominant secretor phenotype and sese produces a recessive non-secretor phenotype.
Basically three genes are responsible for the formation of the A and B antigens. They are namely ABO, Hh, and Sese genes encoding glycosyltransferases which produces the A and B antigens. H antigen present in the individual with O blood group is the precursor for the formation of A and B antigens. H antigen act as a backbone for A and B antigens. The O gene is considered as amorphic. The allele Hh and Sese reside on each locus and are closely linked together. It is also suggested that one of the allele has arisen by the gene duplication of the other. The second allele on the same locus is really rare. The product related to this allele hasn’t been discovered yet and hence it is considered as amorph.
The oligosaccharide responsible for the formation of the A and B antigen can exist in a simple linear fashion or a complex branched fashion. Infants A, B and H antigens contain high amount of linear chained oligosaccharide whereas oligosaccharides present in an adult contain high amount of branched chained oligosaccharides
The A and B antigen is synthesized from a common intermediate known as substance H. The conversion is carried out by the addition of a sugar molecule to the non reducing end of the H oligosaccharide chains. This addition affects the reactivity of H antigen.
The ABH substances are secreted in the Urinary respiratory tract, gastrointestinal tract by mucous glands residing there. The secretor gene regulates the synthesis of blood group antigens in the glands of small intestinal mucosa. The secretors and non-secretors produce A and B substances which are basically glycoproteins in pylorus and Brunner’s glands and produce A and B substances those are soluble in alcohol and glycosphingolipids in nature.
The secretors also produce ABH substances in the prostate and lactating mammary glands. The secretion of breast is rich in H substance but poor in substance A and virtually absent in substance B. The synthesis of these constituents in the pancreas and secretory cells of sweat gland is not controlled by the secretor gene. The blood groups substances were also found in the calyxes and collecting tubules of the secretors (Se) but it could not be concluded that whether they are produced by the kidneys or are generally excreted. These secretions were noticed in the eight to nine weeks old salivary glands and stomach and later it appears throughout the gastrointestinal tract.
Glycosphingolipids carrying the A or B oligosaccharides are present on the membranes of RBC’s, epithelial and endothelial cells and are also present in the plasma in the soluble form. The glycoproteins carrying the similar A and B oligosaccharides are responsible for their activity in the body fluids. In the body fluids they are present in the secreted form. The A and B oligosaccharides which do not contain the carrier proteins are present in the milk and urine.
The chromosome 19 containsFUT 1 and FUT 2 genes which code for fucosyltransferase. FUT genes numbered from 1-7 and form clusters which are responsible for the production of enzymes called as fucosyltranferases. The cluster is located on chromosome 19q13.3. Fucosyltranferase helps in the formation of fucose moiety which is added to the H antigen and further gylcosylate the A or/and B antigens.
H antigen is a basic blood group antigen present in each and every human being but the content varies in different individuals of the same ABO group. A general pattern indicates that its strength varies as O>A2>A2B>B>A1>A1B. Water soluble H antigen has been demonstrated in the saliva and the body fluids of the individuals.H antigens are fucose containing glycan units which are present on the glycolipids or glycoproteins residing on the erythrocyte’s membrane or in the secretions. The fucosylatedglycans are the substrate for the enzyme glycosytransferases that are responsible for the formation of the Lewis and A, B blood group antigen epitopes.
Secretors contain both the alleles whereas non secretor contains the “null allele” for FUT2 gene. The FUT 2 gene codes for fucosyltranferaseenzyme in the exocrine tissues which lead to formation of antigens in the body secretions and body fluids.
The A and B genes produce glycosyltranferase that add sugar to oligosaccharide chains that is converted to H antigen. The H antigen are constructed on the oligosaccharide chain. The oligosaccharide chains could be of two type : Type 1 and type 2. The glycosphingolipids present in the plasma and on the membranes of glandular and parenchymal cells and glycoproteins present on the cell surfaces or body fluids carry either the type 1 or type 2 chains. The glycolipids antigens present on the RBC contain type 2 chains.
A gene encodes N-acetyl-galactosaminyl-transferase and B gene-encodes galactosaminyl-transferase and add GalNAc and Gal in alpha (1-3) linkages which is acts on the H gene transferase. The H gene produces fucosyltransferase that add fucose to the terminal Galactose molecule of type 2 chain. It forms an alpha (1-2) linkage. A and B antigens are constructed when the A and B transferases attach respective sugars to the type 1 or type 2 chain substituted with Fucose.
The secretor gene FUT2 located at 19q13.3 and codes for the activity of the glycosyltransferasesin concert with the FUT1 gene coding for H antigen, needed to assemble both the ABO and Lewis blood group and are active in mucous gland and goblet cells which interact with each other and lead to secretions of antigens in the fluids.
The expression patterns of both the genes are different. The FUT1 (H) gene is dominantly expressed in the erythroid tissues which lead to the formation of the H enzyme whereas the FUT2 (secretor) gene is expressed in the secretory tissues and lead to the formation of secretor enzyme. The product of the H enzyme or H gene resides on the erythrocytes and product of secretor gene resides on mucins in secretions.
If an individual lack these alleles, he/she will not be able to express the above active enzymes therefore they would be deficient of the substrates which are required by the A or B glycosyltransferases. Therefore they would not express the A and B epitopes.
Correlation between Lewis Phenotype and ABH Secretor status The Lewis typing also helps in finding the ABH secretor status. The production of Lewis antigens is genetically controlled. Individuals possessing the Lewis (Le) gene would produce the Lewis antigens which are carried in the plasma by different substances and are absorbed onto the Red blood Cells present in one’s blood.
The ABO determinants and H/h blood groups factors seem to show structurally corelation to Lewis blood determinants. FUT1 provide the glycans for glycosyltransferases which convert Lewis antigen to ABH antigens. FUT2 allele is expressed in the secretor and is responsible for the expression of type1 H determinant.
The secretors convert their Lewis a antigen to Lewis b therefore they are (a-b ) and the non-secretor are (a b-) as they lack the FUT2 responsible for glycosyltransferase which could convert Lewis a antigen to Lewis b antigen.
Lewis (Le) gene and Secreting (Se) gene interact with each other. Initially Lewisais formed and if Se gene is absent in an individual the Lewisa substance is absorbed on the RBC and the individual is typed as Lewisa but in secretors the Se gene controls the activation of the H gene which causes addition of an additional sugar to Lewisa which convert it to Lewisb. Secretors contain both Lewisa and Lewisb in their plasma but absorb Lewisb preferentially on the red blood cells and the individual is typed as Lewisb.
Hence we could interpret that presence of Lewis gene would type an individual as Lewisa positive or Lewisb negative or vice versa. An individual could not be positive for both. A person containing both Lewis gene and Secreting gene are typed as Lewisa negative and Lewisb positive whereas a person having the Lewis gene but not the secretor gene is typed as Lewisa positive and Lewisb negative. Individual who does not have Lewis gene regardless of secretor gene is typed as Lewisa negative and Lewisb negative.
Note: Lewis Double Negative (LDN) is a sub type of non secretors but Lewis typing cannot be used for them to determine the ABH secretor status.
Detection methods The presence and absence of the antigens in the body fluids could be detected by Agglutination Inhibition and Lewis typing.
Agglutination Inhibition test could be divided into two parts:-
Part I – Antibody Neutralization:
To determining one’s secretor status, the saliva of the individual is mixed by the antiserum (Anti-A, Anti-B or Anti-H) available commercially. In secretors the soluble substances i.e. blood group antigens will react with the antibodies present in the antiserum and will get neutralized.
Part II – Agglutination Inhibition:
The bed blood cells obtained commercially are added to the test mixture. In secretors agglutination of the RBC do not take place as no free antibodies are available to agglutinate them. All the antibodies have reacted with the soluble antigens present in the saliva whereas in non-secretors agglutination would occur upon addition of the RBC as no blood group antigens are present in the saliva so antibodies present in the antiserum are not neutralized and hence would be free to react with the test RBC cells which are added to the test mixture. Hence agglutination is a negative test for secretor status and positive test for the non-secretor status.
Note: Anti-H lectin containing phytohaemagglutinin virtually specific for human RBC. Thirteen Cucurbitaceaespecies have been investigated for the anti-H activity present in their seed lectins. Lectins has been extracted and purified from Ulexeuropaeus seeds. It could be used to demonstrate the H secretor status of blood group O individual and also for subgrouping the blood group A individuals.
Lewis typing:
Individuals carrying the Lewis gene produce Lewis antigens that are carried by the plasma and are also adsorbed on the red blood cells. Lewis antigens do not reside only on the red blood cells. Initially the gene gives rise to Lewisa. If Se gene is present it activates H gene which interact with the Lewisa and add a sugar to Lewisa and hence get converted it to Lewisb. Both Lewisa and Lewisb in present in the plasma of the secretors. If the Se gene is not present then the Lewisa substance is adsorbed on the red cells and individuals are typed as Lewisa.
The secretor status of an individual could be determined with help of Lewisa and Lewisb antibodies mixed with an individual’s saliva and observing the agglutination macroscopically.
Disease Susceptibility among Secretors and Non-secretors Digestive system
Non-secretors are more prone to the diseases caused by the oral bacteria in the digestive system of an individual. It includes ulcers, celiac diseases gastric carcinoma pernicious anemia etc. It could lead to dysplasia or increase in the number of cavities present in the digestive tract. Non-secretors are less resistant to the infection caused by Helicobacter pylori which could lead to the formation of peptic and duodenal ulcers. It could easily colonize and cause inflammation in the non-secretors. The non-secretors lack the blood group antigens in the mucus secretions therefore H.pylori attach to the walls of the digestive tract and cause infection. The secretors have a tendency to secrete free ABH antigens in their intestinal secretions which effect the bacterial and lectins adherence to the microvilli present in the gut. The secretors produce these antigens and prevent H.pylori attachment. These antigens act as a decoy in the secretors which prevent them from attaching with the host tissues. The non-secretors also show a lower IgG immune response to the H.pylori. They have extreme rate of bleeding and stomach ulcers but correlation between these complications and the secretor status have not been documented yet. The non-secretors are not able to turn off the digestive enzymes and hence they produce large amount of enzyme pepsin and hence are more prone to duodenal ulcers. 50% of the duodenal ulcers are present in non-secretors. 30-40% of group O individuals are affected by the duodenal ulcers and 15- 20 % are affected by the gastric ulcers. They show a high risk factor along with the gene coding for hyperpepsinogenemia I which impact in the risk of duodenal ulcers. Group A individuals have a higher tendency of having gastric cancer and pernicious anemia. Statistics shows that 20% of the group A individuals are affected by gastric cancers and 25% are affected by the pernicious anemia.
Oral pathology
The non-secretors are more prone to oral diseases like mouth and esophagus cancer, epithelial dysplasia etc. They have more cavities than secretors.
Diabetes
The ABH non-secretors and Lewis negative (Le a-b-) individuals have a high risk of developing insulin dependent diabetes or complications arising from diabetes. Secretors with juvenile diabetes have a low chance of developing retinopathy. The ABH non secretors which are affected by insulin dependent diabetes mellitus, they show mean levels of C3c and C4 is lower as compared to ABH secretors.
Metabolic Syndrome X
The Lewis negative men are predisposing to syndrome X and prothrombic metabolism. They have high levels of BMI, SBP, triglycerides and low levels of insulin in serum and plasma glucose while fasting. This relationship is not true for women and is only applicable for the men.
Respiratory System
Secretors have an added protection against the harmful environmental assaults directed towards our lungs and as usual non-secretors have a health disadvantage. They are over represented among the people suffering from influenza viruses A and B, rhinoviruses, respiratory synsytial virus and echinoviruses. The secretors who are miners or smokers do receive a protection against the disastrous effects of the cigarette smoking. Asthma is very common among the individuals working in the coal mines. Upon research it was concluded that asthma among them is also related to the non-secretor phenotype present in them. The non-secretor has a tendency to snore and are more prone to COPD (Chronic Obstructive Pulmonary Disease).
Heart disease
The ABH non-secretor phenotype have a high risk of developing myocardial infarction and Lewis negative individuals have a high risk of developing chronic heart disease (CHD) and also ischemic heart disease (IHD). They contain high levels of triglycerides. Alcoholism has a positive interaction with the Lewis negative individuals. Alcohol consumption is protective in these individuals.
Autoimmune Disease
Autoimmune disorders such as Sjogren’s syndrome, spondylitis, sclerosis, arthropathy, arthritis, and Grave’s disease are more prone in non-secretors. The ABH non-secretors affected with grave’s disease produces high levels of antitubulin antibodies as compared to secretors and are unable to produce the water soluble glycoproteins in the saliva.
Fetal Loss and Infertility
ABO antigens are also found on the sperm of the secretors. These are obtained from the seminal secretions present in them. ABO incompatibility could exist between the wife and husband if could affect the fertility of an individual. This issue has not been properly studied and is therefore under research.
Rheumatic Fever
The secretors and group O individuals are resistant to Rheumatic fever and more number of cases have been recorded in the non-secretors. Secretor status could also determine whether the rheumatic fever would be followed by streptococcal pharyngitis or not.
Neisseria species
The non-secretors who do not produce water soluble antigens in the saliva are at the risk of getting infected by Neisseria meningcococcal disease. The immune capabilities of the secretor provide a relative protection in the secretors. The ABH non-secretors produce low level of anti-meningococcal salivary IgM antibodies which provide protection to the secretors against the microorganism.
Candida species
Non-secretors are barriers of candida species and therefore are frequently affected by the candida infections. The glycocompounds secreted by secretors in the body fluids inhibit adhesins present on the yeast which are responsible for their adhesion with the body tissues. This leads to the development of the chronic hyperplastic Candidiasis. Statistics shows that 68% on the non-secretors are affected by chronic hyperplastic candidiasis. Non-secretor women are affected by recurrent idiopathic vulvovaginal Candidiasis. An individual with a combination of non-secretors and absence of Lewis gene are at relative risk of developing recurrent idiopathic vulvovaginal Candidiasis.
Tumor Markers
The individuals with homozygous active Le alleles (Le/Le) and inactive (se/se) alleles shows a highest mean value of CA19-9 tumor marker. The Lewis negative individuals irrespective of Se genotype have negative values for CA19-9. The Lewis negative individuals have higher mean value for DU PAN-2 as compared to Le-positive individuals. We can conclude that CA 19-9 marker is not an appropriate tumor marker for Le-negative individuals but DU-PAN-9 is an appropriate tumor marker.
UTI
Non-secretors show a higher risk of getting recurrent urinary tract infection (UTI) and renal scars as compared to secretors. This susceptibility is higher among negative Lewis subset. Statistics of a study done on women affected with recurrent urinary tract infection stated that 29% of the non-secretor women were affected by UTI and 26% of Lewis (a-b-) women were affected by the UTI. The non-secretor phenotype and blood group B and AB phenotype work together to increase the risk of UTI among women. Women and children suffering from renal scarring with and without the antibiotic treatment for UTI are prone to UTI and pyelonephritis. 55-60% of non-secretors develop renal scars and 16% on secretors develop renal scars. C-reactive protein levels, erythrocyte sedimentation rate and body temperature are higher in the non-secretors that in secretors with recurrent UTI.
Conclusion It concludes that there exist a statistical association between the individual’s blood-group secretor phenotype and the diseases they are susceptible to. So knowing your secretor status is advantageous as we can use the nutritional supplements more intelligently and effectively. It also makes us aware of the diseases, illness and metabolic dysfunction we are prone to, difference in the levels of intestinal alkaline phosphatase activity, propensities towards blood clotting, tumor markers and different ingredients of breast milk so that we can manage them before hand and would be prepared for them in the near future.

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