Normal Development, Structure, and Function

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Chapter 320 Normal Development, Structure, and Function

Chris A. Liacouras

Development

The primitive gut is recognizable by the 4th wk of gestation and is composed of the foregut, midgut, and hindgut. The foregut gives rise to the upper gastrointestinal (GI) tract including the esophagus, stomach, and duodenum to the level of the insertion of the common bile duct. The midgut gives rise to the rest of the small bowel and the large bowel to the level of the mid-transverse colon. The hindgut forms the remainder of the colon and upper anal canal. The rapid growth of the midgut causes it to protrude out of the abdominal cavity through the umbilical ring during fetal development. The midgut subsequently returns to the peritoneal cavity and rotates counterclockwise until the cecum lies in the right lower quadrant. The process is normally complete by the 8th wk of gestation.

The liver derives from the hepatic diverticulum that evolves into parenchymal cells, bile ducts, vascular structures, and hematopoietic and Kupffer cells. The extrahepatic bile ducts and gallbladder develop 1st as solid cords that canalize by the 3rd mo of gestation. The dorsal and ventral pancreatic buds grow from the foregut by the 4th wk of gestation. The two buds fuse by the 6th wk. Exocrine secretory capacity is present by the 5th mo.

Cis-regulatory genomic sequences govern gene expression during development. Modules of cis sequences are linked and allow a cascade of gene regulation that controls functional development. Extrinsic factors have the capacity to influence gene expression. In the gut, several growth factors, including growth factor-β, insulin-like growth factor, and growth factors found in human colostrum (human growth factor and epidermal growth factor), influence gene expression.

Propulsion of food down the GI tract relies on the coordinated action of muscles in the bowel wall. The contractions are regulated by the enteric nervous system under the influence of a variety of peptides and hormones. The enteric nervous system is derived from neural crest cells that migrate in a cranial to caudal fashion. Migration of the neural crest tissue is complete by the 24th wk of gestation. Interruption of the migration results in Hirschsprung disease. Newborn bowel motor patterns are different from adults. Normal fasting upper GI motility is characterized by a triphasic pattern known as the migrating motor complex. Migrating motor complexes occur less often in neonates and they have more nonmigrating phasic activity. This leads to ineffective propulsion, particularly in premature infants. Motility in the fed state consists of a series of ring contractions that spread caudad over variable distances.

Digestion and Absorption

The wall of the stomach, small bowel, and colon consists of four layers: the mucosa, submucosa, muscularis, and serosa. Eighty-five percent of the gastric mucosa is lined by oxyntic glands containing cells that secrete hydrochloric acid, pepsinogen, and intrinsic factor, and mucous and endocrine cells that secrete peptides having paracrine and endocrine effects. Pepsinogen is a precursor of the proteolytic enzyme pepsin, and intrinsic factor is required for the absorption of vitamin B₁₂. Pyloric glands are located in the antrum and contain gastrin-secreting cells. Acid production and gastrin levels are inversely related to each other except in pathologic secretory states. Acid secretion is low at birth but increases dramatically by 24 hr. Acid and pepsin secretion peak in the 1st 10 days and decrease from 10 to 30 days after birth. Intrinsic factor secretion rises slowly in the 1st 2 wk of life.

The small bowel is ∼270 cm long at birth in a term neonate and grows to an adult length of 450-550 cm by 4 yr of age. The mucosa of the small intestine is composed of villi, which are finger-like projections of the mucosa into the bowel lumen that significantly expand the absorptive surface area. The mucosal surface is further expanded by a brush border containing digestive enzymes and transport mechanisms for monosaccharides, amino acids, dipeptides and tripeptides, and fats. The cells of the villi originate in adjacent crypts and become functional as they migrate from the crypt up the villus. The small bowel mucosa is completely renewed in 4-5 days, providing a mechanism for rapid repair after injury, but in young infants or malnourished children, the process may be delayed. Crypt cells also secrete fluid and electrolytes. The villi are present by 8 wk of gestation in the duodenum and by 11 wk in the ileum.

Disaccharidase activities are measurable at 12 wk, but lactase activity does not reach maximal levels until 36 wk. Even premature infants usually tolerate lactose-containing formulas because of carbohydrate salvage by colonic bacteria. In children of African and Asian ethnicity, lactase levels may begin to fall at 4 yr of age, leading to intolerance to mammalian milk. Mechanisms to digest and absorb protein, including pancreatic enzymes and mucosal mechanisms to transport amino acids, dipeptides, and tripeptides, are in place by the 20th wk of gestation.

Carbohydrates, protein, and fat are normally absorbed by the upper half of the small intestine; the distal segments represent a vast reserve of absorptive capacity. Most of the sodium, potassium, chloride, and water are absorbed in the small bowel. Bile salts and vitamin B₁₂ are selectively absorbed in the distal ileum, and iron is absorbed in the duodenum and proximal jejunum. Intraluminal digestion depends on the exocrine pancreas. Secretin and cholecystokinin stimulate synthesis and secretion of bicarbonate and digestive enzymes, which are released by the upper intestinal mucosa in response to various intraluminal stimuli, among them components of the diet.

Carbohydrate digestion is normally an efficient process that is completed in the distal duodenum. Starches are broken down to glucose, oligosaccharides, and disaccharides by pancreatic amylase. Residual glucose polymers are broken down at the mucosal level by glucoamylase. Lactose is broken down at the brush border by lactase, forming glucose and galactose; sucrose is broken down by sucrase-isomaltase to fructose and glucose. Galactose and glucose are primarily transported into the cell by a sodium- and energy-dependent process, whereas fructose is transported by facilitated diffusion.

Proteins are hydrolyzed by pancreatic enzymes, including trypsin, chymotrypsin, elastase, and carboxypeptidases, into individual amino acids and oligopeptides. The pancreatic enzymes are secreted as proenzymes, which are activated by release of the mucosal enzyme enterokinase. Oligopeptides are further broken down at the brush border by peptidases into dipeptides, tripeptides, and amino acids. Protein can enter the cell by separate noncompetitive carriers that can transport individual amino acids or dipeptides and tripeptides similar to those in the renal tubule. The human gut is capable of absorbing antigenic intact proteins in the 1st few weeks of life because of “leaky” junctions between enterocytes. Entry of potential protein antigens through the mucosal barrier might have a role in later food- and microbe-induced symptoms.

Fat absorption occurs in 2 phases. Dietary triglycerides are broken down into monoglycerides and free fatty acids by pancreatic lipase and colipase. The free fatty acids are subsequently emulsified by bile acids, forming micelles with phospholipids and other fat-soluble substances, and are transported to the cell membrane, where they are absorbed. The fats are re-esterified in the enterocyte, forming chylomicrons that are transported through the intestinal lymphatics to the thoracic duct. Medium-chain fats are absorbed more efficiently and can directly enter the cell. They are subsequently transported to the liver via the portal system. Fat absorption can be affected at any stage of the digestion and absorption process. Decreased pancreatic enzymes occur in cystic fibrosis, cholestatic liver disease leads to poor bile salt production and micelle formation, celiac disease affects mucosal surface area, abnormal chylomicron formation occurs in abetalipoproteinemia, and intestinal lymphangiectasia affects transport of the chylomicrons.

Fat absorption is less efficient in the neonate compared with adults. Premature infants can lose ≤20% of their fat calories compared with ≤6% in the adult. Decreased synthesis of bile acids and pancreatic lipase and decreased efficiency of ileal absorption are contributing factors. Fat digestion in the neonate is facilitated by lingual and gastric lipases. Bile salt–stimulated lipase in human milk augments the action of pancreatic lipase. Infants with malabsorption of fat are usually fed with formulas that have a greater percentage of medium-chain triglycerides, which are absorbed independently of bile salts.

The colon is a 75-100 cm sacculated tube formed by 3 strips of longitudinal muscle called taenia coli that traverse its length and fold the mucosa into haustra. Haustra and taenia appear by the 12th wk of gestation. The most common motor activity in the colon is nonpropulsive rhythmic segmentation that acts to mix the chyme and expose the contents to the colonic mucosa. Mass movement within the colon typically occurs after a meal. The colon extracts additional water and electrolytes from the luminal contents to render the stools partially or completely solid. The colon also acts to scavenge by-products of bacterial degradation of carbohydrates. Stool is stored in the rectum until distention triggers a defecation reflex that, when assisted by voluntary relaxation of the external sphincter, permits evacuation.

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Chapter 320 Normal Development, Structure, and Function

Chris A. Liacouras

Development

The primitive gut is recognizable by the 4th wk of gestation and is composed of the foregut, midgut, and hindgut. The foregut gives rise to the upper gastrointestinal (GI) tract including the esophagus, stomach, and duodenum to the level of the insertion of the common bile duct. The midgut gives rise to the rest of the small bowel and the large bowel to the level of the mid-transverse colon. The hindgut forms the remainder of the colon and upper anal canal. The rapid growth of the midgut causes it to protrude out of the abdominal cavity through the umbilical ring during fetal development. The midgut subsequently returns to the peritoneal cavity and rotates counterclockwise until the cecum lies in the right lower quadrant. The process is normally complete by the 8th wk of gestation.

The liver derives from the hepatic diverticulum that evolves into parenchymal cells, bile ducts, vascular structures, and hematopoietic and Kupffer cells. The extrahepatic bile ducts and gallbladder develop 1st as solid cords that canalize by the 3rd mo of gestation. The dorsal and ventral pancreatic buds grow from the foregut by the 4th wk of gestation. The two buds fuse by the 6th wk. Exocrine secretory capacity is present by the 5th mo.

Cis-regulatory genomic sequences govern gene expression during development. Modules of cis sequences are linked and allow a cascade of gene regulation that controls functional development. Extrinsic factors have the capacity to influence gene expression. In the gut, several growth factors, including growth factor-β, insulin-like growth factor, and growth factors found in human colostrum (human growth factor and epidermal growth factor), influence gene expression.

Propulsion of food down the GI tract relies on the coordinated action of muscles in the bowel wall. The contractions are regulated by the enteric nervous system under the influence of a variety of peptides and hormones. The enteric nervous system is derived from neural crest cells that migrate in a cranial to caudal fashion. Migration of the neural crest tissue is complete by the 24th wk of gestation. Interruption of the migration results in Hirschsprung disease. Newborn bowel motor patterns are different from adults. Normal fasting upper GI motility is characterized by a triphasic pattern known as the migrating motor complex. Migrating motor complexes occur less often in neonates and they have more nonmigrating phasic activity. This leads to ineffective propulsion, particularly in premature infants. Motility in the fed state consists of a series of ring contractions that spread caudad over variable distances.

Digestion and Absorption

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