Gastroenterology and Nutrition
Development of the Gastrointestinal System
Folding occurs along the embryo in a cephalocaudal progression that leads to the incorporation of some of the endodermal-lined yolk sac into the embryo, which in turn results in the creation of the primitive gut. The primitive gut is composed of the foregut, midgut, and hindgut. The foregut is most cephalic and will become the esophagus and stomach. The midgut becomes the small intestines, and the hindgut becomes the colon ( Fig. 10-1).
Figure 10-1 The foregut, midgut, and hindgut of the primitive gut tube are formed by the combined action of differential growth and lateral and cephalocaudal folding. The foregut and hindgut are blind-ending tubes that terminate at the buccopharyngeal and cloacal membranes, respectively. The midgut is at first completely open to the cavity of the yolk sac. (From Larsen WJ, Sherman LS, Potter SS, Scott WJ, editors. Human embryology. 3rd ed. New York: Churchill Livingstone; 2001. p. 237.)
The liver forms at about the third week of gestation as an outgrowth, known as the hepatic diverticulum or liver bud, of the endodermal epithelium of the foregut. This connection grows and narrows to form the bile duct to connect the developing liver to the foregut. A small ventral outgrowth forms that will develop into the gallbladder and connecting cystic duct. The intrauterine failure to develop a complete biliary tree can lead to extrahepatic biliary atresia of embryonic or fetal form, which occurs in 10% to 35% of all cases. 1
The pancreas develops in two separate locations as a bud from the endodermal-lined foregut. The dorsal pancreas develops from a bud on the dorsal surface opposite the developing biliary tree. The dorsal pancreatic bud is located within the dorsal mesentery and grows with a central dorsal pancreatic duct draining to the foregut through the minor papilla. The ventral pancreatic bud develops close to the developing bile duct. When the duodenum rotates to become C-shaped, the bud is rotated onto the dorsal surface along the dorsal pancreas in a position immediately below and behind it. The two developing pancreas parts grow together, and the dorsal pancreatic duct fuses with the ventral pancreas to form the main pancreatic duct (of Wirsung) draining through the major papilla into the duodenum ( Fig. 10-2).
Figure 10-2 Development of the primordial pancreas from the ventral aspect. A, Fifth week of development. B, Sixth week of development. C, Seventh week of development. D, The late fetus, showing fusion of the dorsal and ventral pancreatic ducts and regression of the distal portion of the dorsal duct. (From Carlson BM. Human embryology and developmental biology. 2nd ed. St Louis: Mosby; 1999. p. 338.)
During the sixth week of gestation the small intestines and the colon herniate into the umbilical cord as a result of the rapid growth of the liver. The intestine then rotates around a central axis formed by the superior mesenteric artery. This counterclockwise rotation is completed, and the intestine migrates back into the abdominal cavity to be fixed in position. This rotation results in the colon being located anterior to the small intestines, with the cecum being located in the right lower quadrant. An interruption during this physiologic herniation and rotation will result in abnormalities. When the gut fails to return to the abdominal cavity, an omphalocele is formed. This abnormality occurs in approximately 2.5 in 10,000 births. There is a high rate of associated developmental defects, such as cardiac abnormalities, spinal defects, and chromosomal abnormalities. Malrotation is another abnormality that occurs when the midgut fails to rotate completely. Malrotation can cause the inappropriately positioned small bowel to twist on the superior mesenteric artery and lead to vascular insufficiency and volvulus. The gold standard for diagnosis of malrotation remains the upper gastrointestinal tract series that shows the duodenal C-loop crossing to the left of midline at a level equal to or greater than the pylorus. 2
The hindgut forms the most distal part of the primitive gut. It develops into the distal third of the transverse colon and the upper part of the rectal canal. Initially the urogenital system and the hindgut join together in the cloaca. The two systems separate from each other, and the rectal canal fuses with the surface to form an open pathway that will form the anus and rectum. Any abnormalities with this development can result in a continued connection, or urorectal fistula, between the urologic and gastrointestinal tracts. When the anorectal canal fails to fuse with the surface, a rectoanal atresia occurs with resulting imperforate anus. Imperforate anus occurs in 1 in 50,000 live births and has a high incidence of other associated birth defects. 3
The ENS is the nervous system that regulates intestinal smooth muscle to control gastrointestinal motility. The ENS is composed of a complex network of ganglia that function independently from the central nervous system. Although independent, the ENS can be influenced by vagal and pelvic nerves of the parasympathetic nervous system and spinal nerves. Within the ENS the interstitial cells of Cajal are the pacemaker cells and are responsible for the coordinated smooth muscle contractions within the gut.
KEY POINTS: GASTROINTESTINAL DEVELOPMENT
1. The most common form of transesophageal fistula is proximal esophageal atresia with a distal tracheoesophageal fistula.
2. Although most cases of biliary atresia are caused by a destructive, perinatal inflammatory process, a subset appears to be caused by a prenatal developmental abnormality of the extrahepatic biliary tree that is associated with other congenital anomalies, such as polysplenia.
3. Rotational abnormalities of pancreas development can be observed either as an annular pancreas presenting with obstruction or as ductal abnormalities presenting with pancreatitis later in childhood.
4. Delayed passage of meconium should raise consideration of both anatomic abnormalities (e.g., variants of imperforate anus) and motility disorders (e.g., Hirschsprung disease).
Meconium
When meconium is not passed by 48 hours of life, the possibility of an anatomic or neuromuscular abnormality must be considered, such as Hirschsprung disease. 4
Fetal Growth and Assessment
13. What do the terms low birth weight (LBW), very low birth weight (VLBW), and extremely low birth weight (ELBW) indicate?
Medical Problems of the Growth-Restricted Infant
17. What are the long-term risks of IUGR?
Development: Because this group is heterogeneous, the outcome depends on perinatal events, the etiology of growth retardation, and the postnatal socioeconomic environment. In general, the asymmetric growth-retarded baby does not show significant differences in intelligence or neurologic sequelae but does demonstrate differences in school performance related to abnormalities in behavior and learning.
Caloric Requirements
Energy, being neither created nor destroyed, conforms to classic balance relationships. Energy balance is a state of equilibrium when energy intake equals expenditure plus losses. If energy intake exceeds expenditure plus losses, the infant is in positive balance, and excess calories are stored. If energy intake is less than expenditure plus losses, the infant is in negative balance, and calories are mobilized from existing body stores. Maintenance, or basal, energy requirements are the energy needs required to cover basal metabolic rate or resting energy expenditure; total energy expenditure in infants is the sum of the energy required for basal metabolic rate, activity, thermoregulation, diet-induced thermogenesis, and growth. The energy balance equation may be stated as follows:
LBW infants require at least 120 cal/kg/day, partitioned to approximately 75 cal/kg/day for resting expenditure and the remainder for specific dynamic action (10 cal/kg/day), replacement of inevitable stool losses (10 cal/kg/day), and growth (25 cal/kg/day) ( Table 10-1).
TABLE 10-1
CALORIC REQUIREMENTS OF LOW-BIRTH-WEIGHT INFANTS
| REQUIREMENTS (kcal/kg/day) | |
| Resting ∗ | 50 to 75 |
| Specific dynamic action | 5% to 8% of total intake |
| Stool losses | 10% of total intake |
| Growth | 25 to 45 |
| Total † | 85 to 142 |
∗Estimate includes caloric expenditure for maintenance of basal metabolism plus activity and response to cold stress.
†Includes sum of resting and growth requirements for specific dynamic action and replacement of stool losses plus an increment of 15% to 18%.
The RQ is the ratio of the volume of carbon dioxide (CO2) produced to the volume of oxygen (O2) consumed per unit of time (Vco2/VO2). This ratio varies with the type of nutrient oxidized. In addition, the energy produced varies with the type of substrate burned. Thus various substrates have different RQs, and varying proportions of different nutrients result in different energy production per liter of O2 consumption or CO2 production. The RQs and caloric equivalents of O2 and CO2 for carbohydrate, fat, and protein are shown in Table 10-2.
The energy cost of growth includes the energy used for synthesis of new tissues (e.g., absorption, metabolism, and assimilation of fat and protein) and the energy stored in these new tissues. The energy cost of growth varies with the type of tissue added during growth. The precise caloric requirements for growth are unknown. A wide range of values for energy cost of growth in neonates has been determined (1.2 to 6 kcal/g of weight gain). Separate evaluations of energy expenditure requirement for fat and protein deposition in premature newborns estimate that 1 g of protein deposition requires 7.8 kcal, and 1 g of fat requires 1.6 kcal.
Carbohydrate Requirements
23. The rate of endogenous glucose production in neonates has been estimated to range from 4 to 6 mg/kg/min. Do these values represent the ideal carbohydrate intake in neonates?
Excessive intake of carbohydrate in infant feedings may lead to delayed gastric emptying, emesis, diarrhea, and abdominal distention caused by excessive gas formation as colonic bacteria digest the extra carbohydrates. The excessive administration of intravenous glucose, at rates exceeding 13.8 mg/kg/min, may be associated with metabolic complications such as hyperglycemia, glycosuria, and osmotic diuresis. In addition, the excessive glucose metabolized is stored mainly as fat. Early overfeeding may be an important factor in later childhood and adult obesity, though more recent work suggests that genetic factors may be as important. 5
25. Why do infant formulas contain comparable amounts of lactose and glucose polymers?
The malabsorbed lactose is fermented in the colon, forming various gases such as CO2, methane, and hydrogen and short-chain fatty acids such as acetate, propionate, and butyrate. These short-chain fatty acids are absorbed in the colon, reducing energy losses in the stools and maintaining the nutrition and function of the colon. Despite these putative benefits of lactose fermentation, metabolic concerns that result from the reduced digestion and absorption of lactose in the small intestine include the following:
Protein Requirements
The amino acids that cannot be synthesized in the body are regarded as essential amino acids:
The whey-to-casein ratio of cow’s milk protein is 18:82 and that of human milk protein is 60:40. In total, most formulas contain up to 1.5 times more protein than human milk in order to approximate the protein quality of human milk. 6
32. What are the non-nutritive roles of protein in human milk?
Whey proteins are known to be involved in the immune response (immunoglobulins), lactose synthesis (alpha-lactalbumin), and other host defenses (lactoferrin).
Casein phosphopeptides are believed to enhance the absorption of minerals.
Casein fragments are thought to increase intestinal motility.
Glycoproteins may promote the growth of certain beneficial bacteria.
33. Name the methods used for determining protein requirements.
Factorial method (based on reference data of infant body composition)
Balance method (protein intake = protein retention − inevitable protein losses)
Indices of protein nutritional status (e.g., plasma albumin and transthyretin concentrations; protein intake required to maintain these indices within an acceptable range)
Milk-based formulas (e.g., Similac Advance, Enfamil LIPIL, Good Start Supreme): 2.1 to 2.8 g/100 kcal or about 1.5 to 1.8 g/100 mL
Preterm formulas (e.g., Similac Special Care, Enfamil Premature LIPIL):
Follow-up formulas for LBW weight infants (e.g., Similac NeoSure Advance, EnfaCare LIPIL):
Lipid Requirements
42. What are the beneficial effects of lipid emulsions in a premature infant?
43. What is the percentage of calories provided by fat in human milk?
The percentage of fat calories in human milk is between 40% and 55%.
45. What structural features of fatty acids improve enteral absorption?
Shorter-chain-length to medium-chain triglycerides are absorbed more efficiently than long-chain triglycerides.
Fatty acids with double bonds are absorbed more efficiently.
46. What are the energy contents of long-and medium-chain triglycerides?
47. What is the energy cost of synthesizing fat from carbohydrate?
50. What are the side effects of LCPUFA depletion?
51. What is the advantage of supplying calories as lipid rather than carbohydrate in infants with chronic lung disease?
The RQ of lipids is lower than that of carbohydrate. Therefore the use of lipid infusions should theoretically decrease CO2 production in infants with bronchopulmonary dysplasia, one of the cardinal problems of infants with chronic lung disease in the neonatal period.
52. What is the advantage of using a 20% lipid emulsion versus a 10% lipid emulsion in newborn infants?
Total Parenteral Nutrition: Monitoring and Complications
54. What is the usual distribution of nutrients in total parenteral nutrition (TPN) solutions used for neonates?
55. What are the metabolic advantages of using different regimens containing high carbohydrate (67%) and low fat (5%) or low carbohydrate (34%) and high fat (58%)?
There are none. The administration of TPN solutions containing a moderate carbohydrate (60%) to fat (32%) ratio has been shown to result in a higher nitrogen retention rate than that of the unbalanced regimens. 7
56. Hyperglycemia is a common complication observed in ELBW infants receiving parenteral nutrition. Should insulin infusions be provided routinely to these infants?
In most infants hyperglycemia is a transient problem and resolves when the rate of glucose or lipid administration is reduced. Insulin infusions have been used for infants weighing less than 1000 g who develop hyperglycemia (serum glucose level in excess of 150 mg/dL) and glycosuria during the course of parenteral nutrition, providing low glucose infusion rates (<12 mg/kg/min). In these infants insulin infusions at rates of 0.04 to 0.1 U/kg/h have been shown to improve glucose tolerance and promote weight gain, compared with infants in a control group. 89
57. The clearance of intravenous fat emulsions in neonates is improved by all the following measures except for which of the following? (A) Increasing the period of infusion from 8 to 24 hours; (B) adding a low dose of heparin to the TPN solutions (1 U/mL); (C) exposing the fat emulsions to ambient light or to phototherapy lights; (D) using 20% instead of 10% lipid emulsions.
The answer is (C). Exposure of lipid emulsions to ambient or phototherapy lights increases the formation of triglyceride hydroperoxide radicals but does not enhance lipid clearance. Lipid clearance in neonates is improved by prolonging the infusion period; by adding heparin to TPN solutions (which releases lipoprotein lipase from capillary endothelial cells); and by using 20% lipid emulsions, which contain a lower phospholipid content than 10% lipid emulsions.
58. Why do premature infants who receive prolonged courses of parenteral nutrition develop osteopenia resulting in pathologic bone fractures?
59. Which of the trace elements in TPN solutions can be potentially toxic for patients with cholestatic liver disease?
Enteral Nutrition
Lactose is the major source of carbohydrate in human milk and in formulas for term infants. The preterm formulas contain a mixture of lactose and glucose polymers to compensate for the developmental lag and lower concentration of lactase in the intestinal mucosa. Lactose, however, remains important both in calcium absorption and as a prebiotic. Glycosidase enzymes involved in the digestion of glucose polymers are active in preterm infants.
Soy formulas are recommended for the following:
69. Why are early minimal enteral feedings recommended for preterm infants receiving parenteral nutrition?
Gastrointestinal hormones such as gastrin, enteroglucagon, and pancreatic polypeptide may have a trophic effect on the gut. Postnatal surges of these hormones occur in preterm infants receiving minimal enteral feedings. Minimal enteral feeding has also been reported to produce more mature small intestinal motor activity patterns in preterm infants. Thus early minimal enteral feedings given along with parenteral nutrition may improve subsequent enteral feeding tolerance and may shorten the time to achieve full enteral intake. Furthermore, enteral feedings stimulate the enterohepatic circulation and are known to lessen parenteral nutrition–associated liver disease. The most recent Cochrane Review, however, suggests that the evidence for this effect is unclear, at best. 10
70. What are the reported advantages of feeding human milk to preterm infants over the commercially available infant formulas?
71. Does human milk completely meet the nutritional requirements of VLBW preterm infants (birth weight below 1500 g)?
Breastfeeding
In studies of AGA gavage-fed infants, there was significantly lower energy expenditure in the infants fed human milk compared with those fed formula. 11
76. A mother has breastfed her 5-week-old infant exclusively. She now calls with the concern that she has recently noticed a burning pain in her nipple during breastfeeding. You examine the mother and note some erythema of her areola. You diagnose a fissure and advise her to use dry heat and a few drops of milk on her areola after breastfeeding. She calls back in a few days to report that the pain is increasing. What other diagnosis should you consider?
77. A mother calls you and explains that she is worried because her 4-day-old baby is not receiving enough breast milk. How do you assess whether a newborn is receiving sufficient amounts of breast milk during the first week after birth?
78. You see a 5-day-old male infant in the office for a routine check after early hospital discharge. The mother reports no particular problems; he is much easier to manage than she thought a newborn would be. She is breastfeeding every 3 hours but lets him sleep at night (last night he slept for 6 hours). About once a day she notes that he has dark yellow urine in his diaper. He had a dark-green, tarry stool yesterday. The mother thinks her milk has “come in,” but she acknowledges no signs of engorgement. You examine the infant and note jaundice to the level of the umbilicus and dry skin but moist mucous membranes. He is responsive and alert. You examine the mother and note that her breasts are moderately engorged. The infant’s body weight is 11 ounces below his birth weight of 7 pounds, 8 ounces. You check his serum bilirubin concentration, which is 11 mg/dL. There is no blood group incompatibility. How would you manage this case, and what would you advise the mother?
