ALIMENTARY CANAL.2.0 LITERATURE REVIEW2.1 GASTROINTESTINAL TRACTThe alimentary tract also known as the gastrointestinal (GI) tract can serve multiple functions such as digestion, osmoregulation and protection by detoxification or immune function. The GI tract provides continuous water, electrolytes and nutrients to the body. To do this, food is moved through the digestive tract, digestive juices are secreted for food digestion, water, electrolytes and digestive products are absorbed. The absorbed substances are circulated to the gastrointestinal organs through the blood. All these are regulated by the local, nervous and hormonal systems (‘Guyton and Hall Physiology Review’).
The GI can be defined also as a specialized system that functions to ingest particulate or liquid nutrients by reducing them to an absorbable size for easy transportation across the cell membranes of the mucosal lining (Davis, 2000). As studied by (Seely et al., 2004), the GI theoretically refers to the stomach and small intestine but is often used as a synonym for the digestive tract. The GI tract is an important interface of exchange between ingested food and the body (Audren Fournell et al., 2016). The gastrointestinal tube example the oral cavity, the small intestine, pancreas and the portal veins are referred to as glucosensors because they detect variations in glucose levels (Audren Fournell et al.
, 2016). The GI can be divided into the upper gastrointestinal tract made up of the esophagus, stomach and the duodenum and the lower gastrointestinal tract consisting of the small and large intestine. The deep organs that make up the GI tract are the mouth, esophagus, stomach, small intestine, large intestine (including the rectum and anus).
Food enters the mouth and passes to the anus through the deep organs of the GI tract (NIH, 2013). The GI tract’s accessory organs include the liver, pancreas and the gall bladder (Scanlon, 2011).DIAGRAM OF THE DIGESTIVE SYSTEM2.2 WALLS OF THE GASTROINTESTINAL TRACTFour layers making up the GI tract are the Mucus Layer, the Submucus Layer, the Muscular Layer and the Serous or fibrous Layer.
2.21 Mucus Layer This is also known as the mucosa and it’s the deepest part of the gastrointestinal wall layer. The mucosa interacts with the stomach contents and facades the GI cavity. The mucosa is the absorptive and secretory layer. There are specialized goblet cells that secrete mucus throughout the GI tract found within the mucosa. The mucosa is made up of three layers; muscularis mucosae, lamina propria, the inner mucous epithelium (Seely et al., 2004).
Muscularis mucosae: This is the superficial thin smooth muscle layer (Seely et al., 2004). It is absent in the mouth and pharynx.
It divides the mucus layer from the submucus layer lying beneath it (Anders, 2011). This layer supports in the contraction and relaxation of the sphincter muscle in the GI tract (Kim et al., 2011).Lamina propria: This is made up of a loose connective tissue (Seely et al., 2004). It is made up of the immune cells which provides defense for the GI tract, blood vessels, nerves and fibroblasts (Anders, 2011).Mucous epithelium: The epithelial cells here vary across the tract.
It is a damp stratified squamous epithelium in the mouth, oropharynx, esophagus, and anal canal and simple columnar epithelium in the remainder of the GI tract (Seely et al., 2004). The epithelium aids in protection and is made up of mucus secreting cells, enterocytes, entero-endocrine cells, M cells and the paneth cells (found only in the small intestine).2.2.2.
Submucus LayerThis layer is also known as the submucosa layer. It is a thick connective tissue layer containing nerves, blood vessels and small glands that lies underneath the mucosa (Seely et al., 2004). The submucosa also contains the Brunner’s gland in the duodenum.
The submucus layer serves the mucosa layer. The absorbed elements that pass through the mucosa are picked up from the blood vessels of the submucosa. The plexus of nerve cells in this layer forms the submucosa plexus otherwise known as the Meissner’s plexus.
It is a parasympathetic ganglionic plexus consisting of axons and many scattered cell bodies (Seely et al., 2004).2.
2.3. Muscular LayerThe muscular layer is also called the muscularis externa. It consists of an inner layer of circular smooth muscle and an outer layer of longitudinal smooth muscle. The two exceptions to this are the upper esophagus, which has striated muscle, and the stomach, which has three layers of smooth muscle (Seely et al.
, 2004). The stomach has the inner oblique layer and in addition to the inner circular layer is the Auer Bach’s plexus which is responsible for the innervation of peristalsis and mixing movement in the GI tract. These muscles cause food to move and churn with digestive enzymes down the tract. 2.2.4. Serous or fibrous LayerThis is the outermost layer of the GI tract wall.
Portions of the gastrointestinal tract that project into the peritoneal cavity have a serosa as the outmost layer. This serosa is called the visceral peritoneum. It consists of a thin layer of connective tissue and a simple squamous epithelium that aids in absorption. When the outer layer of the digestive tract is derived from a nearby connective tissue, the tunic is called the adventitia or a fibrous layer and is made up of a connective tissue covering that blends with the surrounding connective tissue (Seely et al., 2004). It is composed of avascular connective tissue and a simple squamous epithelium which increases area of absorption.
2.3. STOMACHThis is a J-shaped, sack like organ that hangs beneath the diaphragm in the upper left portion of the abdominal cavity and has a capacity of about 1 liter or more (David et al., 2012) and maximally 2-3 liters of food but reduces to near empty volume of about 45-74 milliliters in an adult human.
The stomach has the most distensible property in the gastrointestinal tract. Superior to the stomach is the esophagus and it continuous inferiorly with the duodenum of the small intestine. Borders of the stomach are; superiorly, the stomach is surrounded by the diaphragm, esophagus and the left lobe of the liver. The transverse colon and the duodenum surrounds it inferiorly, anteriorly it surrounded by the left lobe of the liver and the anterior abdominal wall, while posteriorly the stomach is surrounded by the abdominal aorta, pancreas, spleen, left kidney and the adrenal gland (Wilson and Waugh, 1996).The stomach plays a critical role in the storage of food, instigating digestion of proteins, eliminating bacteria with the help of the strong acidic gastric juice and to move the churned food into the small intestine as chyme (Stuart, 2011).
It secretes mucus bicarbonate at the mucosa surface, which protect against corrosive properties of gastric juice (Jonathan and Colby, 2009). Parietal cells present here in the gastric glands of the pyloric region secretes intrinsic factor and a concentrated solution of hydrochloric acid. Intrinsic factor is a glycoprotein that binds to vitamin B12 thereby making the vitamin more absorbable in the ileum. Vitamin B12 is an important element in the synthesis of deoxyribonucleic acid (DNA) (Seely et al., 2004).2.3.1.
Anatomical division of the StomachThe stomach is divided into four segments each of which has diverse cells and functions (Hines and Joe, 2010). These segments are the fundus, corpus (body), cardia and pylorus.Cardia: Is the region of the stomach that the contents from the esophagus is emptied into first. It continues from the esophagus to the esophageal or cardia opening. Also surrounding the cardia opening is the cardiac sphincter or the lower esophageal sphincter. The cardiac sphincter is known as a physiological constrictor and not anatomically seen.
Fundus: It is a dome shaped structure formed by part of the greater curvature of the stomach. It is superior to the cardiac opening and sited to the left cardiac region.Corpus: Is known as the body of the stomach and the largest segment of the stomach.
Food stored here undergoes digestion and churning. Mixing of food occurs majorly in the body of the stomach.Pylorus: The opening between the stomach and the small intestine is known as the pyloric opening, surrounded by a relatively thick ring of smooth muscle called the pyloric sphincter (Seely et al., 2004). It is also known as the atrium. Two curvatures found in the stomach are the lesser and greater curvatures on the left and right side of the stomach respectively.DIAGRAM OF THE STOMACH2.3.
2. Walls of the stomachThe stomach has four layers which differ somewhat from those of the gastrointestinal tract. These layers are:Serous layer: This is the outmost layer of the stomach. It is formed by the peritoneum, a thin layer of connective tissue covered with mesothelium (Daniels and Allum, 2005). It is also known as the protective layer of the wall.Muscular layer: This is made up of an outer longitudinal layer, a middle circular layer and an inner oblique layer (Seely et al., 2004). In some part of the stomach, these three layers are merged such as the fundus.
Mucus and Submucosa layer: The inner most part of the muscular wall are the submucosa and the mucosa, which are thrown into large folds of rugae when the stomach is empty. This disappears once the stomach is filled with food (Seely et al., 2004).
The submucosa is rich in mast cells, macrophages, lymphocytes, eosinophilic leukocytes and plasma cells. Vessels and nerves here are the arteries, veins, lymphatics and Meissner’s plexus (Daniels and Allum, 2005).2.3.3.
Glands of the stomachTwo major glands found here which opens in to the gastric pits of the stomach are: The Oxyntic gland and the Pyloric gland. The Oxyntic gland are found at the fundus of the stomach. It is made up of three cells; the mucus producing cells called the mucous neck cells, the parietal (oxyntic) cells which produce hydrochloric acid and intrinsic factor, zymogenic (chief) cells which produce pepsinogen the inactive form of pepsin (Seely et al., 2004). The pyloric gland found here are made up of the G cells that produces gastrin, mucus cells, enterochromaffin cells, and enterochromaffin like cells.
Structurally, the pyloric gland is similar to the oxyntic cells but contains little peptic cells and almost no parietal cell.2.4. THE INTESTINES (SMALL/LARGE)2.4.
1. SMALL INTESTINEThis part of the GI tract is found in between the pyloric sphincter and the ileocecal valve opening into the large intestine. The small intestine is designed for digestion and absorption of ingested products (Treuting and Dintzis, 2012) and as in other animals, it is subdivided into; Duodenum, Jejunum, Ileum. Each part contains four layers: mucosa (barrier epithelium layer, lamina propria and muscularis mucosae), submucosa, muscularis propria and serosa.
The muscle layer here has the typical circular and longitudinal smooth muscle layers that mix the chyme with digestive secretions and propel the chyme toward the colon. Stimulatory impulses to the enteric nerves of these muscle layers are carried by the vagus nerves.2.4.2. Parts of the small intestineThe small intestine is divided into;Duodenum: This is the uppermost part of the small intestine. It is a short structure (20-25cm) with a C-like shape (Drake et al.
, 2005). It surrounds the head of the pancreas and receives gastric chyme from the stomach, together with digestive juices from the pancreas (digestive enzymes) and the liver (bile). the duodenum contains Brunner’s glands which produces a mucus-rich alkaline secretion containing bicarbonate that neutralizes gastric acid in the chyme. At the origin, peritoneum covers the duodenum about an inch (2.5cm) thereby making it a retroperitoneal organ (Gourevitch, 2005). Nutrients are highly absorbed here.Jejunum: This is the midsection of the small intestine. It is about 2.
5cm long and connects the duodenum to the ileum. The jejunum contains the plicae circulares and villi that increase its surface area. The suspensory muscle of the duodenum marks the division between the jejunum and the duodenum. Products of digestion (glucose, amino acids, fatty acids) are absorbed into the bloodstream here. Hence, the jejunum is the major site for nutrient absorption.Ileum: This is the final section of the small intestine. It is about 3cm long, contains villi structurally similar to the jejunum.
It absorbs mainly vitamin B12 and bile acids,as well as other remaining nutrients. The ileum joins to the cecum of the large intestine at the ileocecal junction (Drake et al., 2015). Lymph nodules called Peyer’s patch are numerous in the mucosa and submucosa of the ileum.2.
4.3. Functions of the small intestineThe small intestine is crucial for delivering dietary glucose, as well as substrate molecules for liver gluconeogenesis, into our bloodstream (Cherrington and AD.Banting, 1997); thus, it impacts blood glucose homeostasis on two fronts. Most chemical digestion and absorption takes place in the small intestine.
Also, Peyer’s patches, a site for antigens from potentially harmful microorganism in the GI tract are sampled and presented to the immune system is located in the ileum of the GI system. Gastrointestinal hormones released by the small intestine such as secretin, cholecystokinin regulate the movement of the gastrointestinal tract and secretory activities of the small intestine and pancreas.2.5. LARGE INTESTINEThe large intestine also recognized as the colon ranges from the ileocecal valve to the anus, thus bordering the small intestine on three sides (Stuart, 2011). The colon is only about 6 feet (1.
8m) in length (Bradford, 2015). However, the colon is much wider than the small intestine, but shorter. 2.
5.1. Divisions of the Large IntestineThe colon is divided into four parts: the ascending colon, the transverse colon, the descending colon and the sigmoid colon. Each part signifies a location in the broken rectangle shape that the colon forms in the body. The ascending colon is the right arm of the broken rectangle. The beginning of the ascending colon is called the cecum which is connected to the small intestine and the appendix.
The transverse colon is the top arm that extents from the left side to the right side like a bridge. The left arm is called the descending colon. The sigmoid is the “broken” part of the rectangle that formed an S-shape hanging off the descending colon. This part drains into the rectum (Bradford, 2015). Retroperitoneally, is the ascending colon, descending colon and the rectum while the cecum, appendix, transverse colon and the sigmoid colon are intraperitoneal (U.
S National library, 2011). The mucosa lining here is the simple columnar epithelium. This epithelium is not formed into folds or villi like that of the small intestine but has numerous straight tubular glands called crypts.
The crypts are slightly similar to those of the small intestinal glands, and are made up of three cell types that include absorptive, goblet, and granular cells. The major difference between these cell types and that of the small intestine is that the goblet cells dominates and the other two cells reduces in number (Seely et al., 2004). 2.
5.2. Function of the ColonThe major function of the large intestine is to reabsorb fluids and salts that passes through it and then excrete the unwanted solid waste products by creating stool. The large intestine also functions in mechanical digestion through processes such as austral churning, peristalsis, gastro colic and gastrointestinal reflexes. It features also in chemical digestion that ferment carbohydrate and protein or amino acid breakdown (D.U.H.S, 2014).
Synthesis of vitamin K by colonic bacteria provides a cherished supplement to dietary sources and makes clinical vitamin K deficiency rare (El-Yassin, 2012). Among its roles of preserving intestinal homeostasis, the colon is also essential to water and electrolyte transport (Szmulowiez and Hull, 2011).2.6.
INTESTINAL ABSORPTION OF GLUCOSE Intestinal Absorption can be defined as the transfer of compounds or substances from the gut lumen across the gut wall to the tissues of the body, including the lymph or blood of vertebrates and hemolymph of arthropods. One of the systems involved in delivering glucose to the systemic circulation through the absorption of carbohydrate-digested products is the small intestine. The small intestine is crucial for delivering dietary glucose, as well as substrate molecules for liver gluconeogenesis, into our bloodstream (Cherrington and AD. Banting, 1997) thus, it impacts blood glucose homeostasis. Studies from some investigators (Alada and Oyebola, 1996, Alada and Oyebola, 1997), have provided evidence that the intestine plays a demanding role in glucose homeostasis. Intestinal function is undoubtedly controlled by both neural and hormonal mechanisms (Bird et al., 1996). Most studies dealing with the regulatory effects of hormones and peptides on intestinal absorption are conducted in vitro or involve the use of exogenously administered compounds during in vivo investigations.
Recent studies indicate that a number of gastrointestinal peptides may be involved in the regulation of intestinal glucose absorption.Complex carbohydrates reaching the small intestine must be hydrolyzed to monosaccharides such as glucose or galactose in order to be transported across the intestinal mucosa. Absorption of glucose entails transport from the intestinal lumen, across the epithelium and into the blood. Efflux of glucose from the enterocytes into the blood is believed to be mediated by GLUT2 as a facilitative uniporter with a low affinity but high transport capacity (Mueckler M et al., 1994). Glucose is transported across the brush-border membrane of enterocytes either by energy-dependent sodium-dependent glucose cotransporter 1 (SGLT1) when its absorption does not exceed 30–50 mm, or by diffusion at a higher concentration (Fullerton & Parsons, 1956; Debnam & Levin, 1975; Lostao et al. 1991).
SGLTI is a membrane protein that couples two molecules of Na+ together with one molecule of glucose. The passive transport out of the basolateral surface of enterocytes contains a facilitated-diffusion glucose transporter (GLUT2) which allows glucose to transport from the small intestinal epithelial cells into the extracellular medium near the blood capillaries (Röder et al., 2014).
Translocation of GLUT2 from cytoplasmic vesicles into the apical membrane significantly increases the capacity of glucose uptake by the enterocyte (Affleck et al., 2003, Zheng et al., 2012, Grefner et al., 2015). Thus, any factor that influences the activities of SGLT1 and GLUT2 will also alter the absorption and metabolism of glucose.
Human GLUT5 is known to be replicated from small intestinal cDNA, and was proposed as a second hexose transport system in the brush border (apical) membrane of intestinal epithelial cells along with SGLT1 (Kayano., et al 1990). Another theory is that apical GLUT2 provides a shunt, moving glucose back out into the lumen and providing an osmotic control during the absorptive process (Greenlee et al., 2003). The sodium-independent, facilitated-diffusion glucose/hexose transporters (GLUTs) are a family of fundamental membrane proteins that mediate the transport of hexoses across plasma membranes (Shepherd et al., 1999).
The members of the GLUT family are distinguished by differential affinities for their substrates and tissue-specific expression and regulation (Joost et al., 2002). Five isoforms of the GLUT family have been designated to; GLUT1 majors in glucose transport to the erythrocytes, GLUT2 transports glucose to the liver and small intestine, GLUT3 transports glucose to the brain, GLUT4 transports glucose to the muscles and fat and GLUT5 also together with the energy-dependent Sodium-dependent Glucose Cotransporter 1 (SGLT1) transports fructose and to some extent glucose to the small intestine. It is worth mentioning that The small intestine and kidney express the isoforms GLUT1, GLUT2, GLUT3, GLUT5 and the Na+-dependent glucose transporter. However, GLUT2 is the primary isoform responsible for transport across the basolateral membrane of intestinal epithelial cells (Thorens et al., 1990) while GLUT5 mediates fructose and to some degree glucose uptake from the intestinal lumen and efflux from the intestinal epithelia (Blakemore et al., 1995).
However, the amount of the facilitative hexose transporter GLUT5 protein was believed to have decreased during fasting and increased during refeeding. This is in accordance with previous studies showing that food ingestion involves de novo synthesis of GLUT5 mRNA and protein (Ferraris, 2001). In refed rats, GLUT2 was recruited from the basolateral enterocyte membrane to the apical brush-border membrane. Recruitment of this GLUT2 to the apical membrane has been reported in previous studies and is partly controlled by the SGLT1-dependent activation of a protein kinase C (Kellett & Helliwell, 2000b; Helliwell et al.
, 2000a). Also, during dietary restriction, the affinity of the carriers for sugars increases (Debnam & Levin, 1975) and a 72 h fast causes an overall increase in glucose absorption in rats (Das et al., 2001).
Moreover, an increase in intestinal absorptivity which allows paracellular movement of macromolecules has been observed during fasting and malnutrition (Worthington et al., 1974; Welsh et al., 1998; Boza et al., 1999).DIAGRAM OF GLUCOSE TRANSPORTERSFurthermore, Intestinal absorption of glucose is related in some manner to absorption of sodium ion. In the small intestine epithelial cells, K+ channels provide the driving force required for Na+-dependent uptake of glucose into small intestinal epithelial cells. The glucose uptake is however driven by the Na+ transmembrane gradient and membrane potential.
Hence, there are different opinions as to how K+ channels play a role in regulating blood glucose concentration. The obstruction of K+ channels in peripheral tissues is primarily due to increasing peripheral insulin sensitivity, enhancing insulin release from pancreatic islets and increasing it in basal metabolic rate (Upadhyay et al., 2013; Tucker et al 2012; Müssig et al., 2009). However, K+ channels that regulate glucose absorption in the small intestine have long been ignored.
The presented model of the absorption of glucose provides an understanding into how intestinal epithelial cells maintain intracellular ion homeostasis (DIAGRAM OF PROVE). The driving force for this transport protein is the Na+ electrochemical gradient that is generated by the basolateral Na+/K+ ATPase (Gal-Garber et al., 2003). Na+/K+ ATPase is an integral transmembrane protein in the basolateral membrane of mammalian small intestinal cells which extracts three Na+ and takes in two K+. This mechanism aids in maintaining the negative membrane potential of small intestinal epithelial cells to facilitate Na+ entry across the luminal membrane, which initiates the apical absorption of glucose in SGLT1 (Thorsen et al., 2014; Palanikuma et al., 2015). Na+/Ca2+ exchangers (NCX) and sodium hydrogen exchangers (NHE) are found to express in the small intestinal epithelium (Wu, P et al.
, 2015). NHE is a major non-nutritive Na+ absorptive pathway of the intestine. Plasma membrane NHE considered to date in animal cells utilizes the inward Na+ gradient created by the activity of Na+/K+-ATPase to extrude H+ against its electrochemical gradient in an electroneutral fashion. It is therefore not surprising that NHE3 can regulate the activity of SGLT1 and then intestinal glucose absorption (Palanikuma et al., 2015). However, at present, studies on the regulatory mechanisms of intestinal glucose absorption are very limited and mainly concentrate on SGLT1 (Ikum et al., 2008).REFERENCE