BASIC CONSIDERATIONS
Prachi S Karnik, Aditi Dharap, Mukesh Agrawal
Gastrointestinal tract (GIT) disorders are the second commonest cause of morbidity and mortality in Indian children, after respiratory disorders.
Embryologically, GIT is largely derived from primitive endodermal gut tube (Fig. 14.1), except the oral cavity and anus, which develop from ectodermal invaginations on two ends of this tube. In early fetal life, two membranes- buccopharyngeal and cloacal membranes, separate primitive gut tube from oral cavity and anus, respectively.
During 4-5th week, this tube elongates and divides into three segments—foregut, midgut and hindgut. The primitive foregut develops into pharynx, esophagus, stomach and proximal duodenum, while ancillary structures, e.g. liver, gallbladder and pancreas are derived from its ventral and dorsal outpouches, distal to the stomach. Another ventral outpouching of gut, proximal to primitive stomach, develops into respiratory tract and lungs.
The primitive midgut is connected to the yolk sac via vitelline or Omphalomesentric duct till 6-8 weeks, though its proximal part may remain patent in 1-2% population as Meckel's diverticulum. Distal half of duodenum, small intestine, ascending colon and right 2/3rd of transverse colon develop from midgut.
The primitive hindgut develops into left 1 /3rd of transverse colon, descending colon and rectum till the cloacal membrane, to join ectodermal anus. Lower part of this hindgut is vertically divided into two parts-anterior urogenital sinus to form urogenital system and posterior cloacal sinus to form upper part of anal canal. Vascular and muscular layers of gut are derived from mesoderm, while neural elements migrate from the neural crest to differentiate into intrinsic autonomic plexus. GIT also receives extrinsic nerve supply form vagus and splanchnic nerves.
Anatomically, Basic architecture of all parts of GIT is similar, composed of four layers from in-outwards—(a) mucosal layer with its three parts—epithelium, lamina propria and muscularis mucosae, (b) submucosal layer,
(c) muscularis propria with inner circular and outer longitudinal smooth muscles and intervening myenteric plexus, and (d) serosal or adventitious layer. However, variations in mucosal and muscular structure as well as presence of exocrine glands and enzymes, determine specific functions of each part.
Physiologically, apart from the primary function of food assimilation, GIT also acts as physical and immunological barrier between external and internal environment, as well as an endocrinal organ to produce various hormones.
Fig. 14.1: Development of gastrointestinal tract.
PHYSIOLOGY OF DIGESTION___________________________
Digestion and absorption of nutrients is a complex process, involving various digestive enzymes and transporter mechanisms, as follows:
• Carbohydrates, which contribute to ~60-70% of diet, are consumed as polysaccharides (starch, dextrin), disaccharides (sucrose, maltose, lactose) or monosaccharides (glucose, fructose and galactose).
Digestion of carbohydrates involves conversion of all polysaccharides and disaccharides into monosaccharides by salivary and pancreatic amylase, and then by intestinal disaccharidase enzymes, e.g. lactase, sucrase, maltase, isomaltase, etc. Lactose splits into glucose and galactose, sucrose into glucose and fructose and maltose into two molecules of glucose. Disaccharidase enzymes are mainly present on brush borders and easily lost in diarrhea or severe malnutrition to cause carbohydrate intolerance.
Absorption of monosaccharides across the intestinal mucosa is an active, energy-consuming process involving specific carrier substances. Glucose, sodium and certain amino acids share some of these carrier substances (basis for oral rehydration therapy).
• Proteins, constituting ~15-20% of diet, are consumed as complex organic compounds, which need to be split into smaller peptides or constituent amino acids before absorption. However in newborns, even intact protein molecules may be transported across the mucosal cells via pinocytosis, leading to sensitization of immune cells in lamina propria (basis for atopic disorders after early top-feeding).
Digestion of complex proteins into smaller peptides/amino acids requires many enzymes, including (a) pepsin from pyloric and duodenal glands,
(b) trypsin from pancreas, (c) enterokinase from brush borders and (d) peptidase enzymes in intestinal mucosal cells. In addition, gastric acid denatures proteins for easier digestion as well as activates Pepsinogen to Pepsin.
Absorption of amino acids is also an active process, requiring many transport systems. Many amino acids share common transport mechanism, and compete with each other for absorption (basis for Pellagra in maize-eaters, in whom high leucine content of maize interferes with absorption of tryptophan-a niacin precursor).
• Fats, which form ~15-20% of diet, are consumed as visible fats (ghee, oils) or invisible fats (cereals, pulses). Biochemically, fats may be classified as simple fats, e.g. triglycerides (most abundant, ~98%), derived lipids, e.g. cholesterol and compound lipids, e.g. phospholipids.
Digestion of fats requires hydrolysis of triglycerides by pancreatic lipase to convert into diglycerides, then monoglycerides and ultimately, into fatty acids and glycerol. Bile salts from the liver activate lipase and emulsify fats to convert fat-soluble monoglycerides and fatty acids into water-soluble micelles. Lipase, which is also present in salivary and gastric secretion, contributes in pre-pyloric partial fat digestion.
Absorption of fats is a complex process. When micelles come in contact of intestinal epithelium, monoglycerides and fatty acids diffuse into mucosal cells and remaining part of the micelle, i.e. bile acids, move back into lumen for re-utilization. Inside the mucosal cell, monoglycerides are further hydrolyzed by intracellular lipase into fatty acids and glycerol. While water-soluble glycerol quickly enters into portal circulation, long-chain fatty acids are re- esterified into triglycerides. These triglycerides, along with cholesterol and phospholipids form a globular mass, i.e. chylomicrons which are extruded into the intercellular space to pass through lacteals to thoracic duct and finally reach to circulation.
Unlike long-chain fatty acids, medium-chain fatty acids do not require re-esterification and absorbed directly into the portal circulation (basis for the use of medium chain triglycerides as predominant fat in liver diseases).
Physiology of digestion and absorption for micronutrients has been discussed in respective chapters.
14.2