Chapter 42: Alterations of Digestive Function in Children

• These are study notes regarding alterations of digestive function in children

Meconium Ileus

• Intestinal obstruction in newborns caused by abnormally sticky meconium formed in utero
• Meconium fills the entire intestine before birth and is passed rectally within the first 12-72 hours after birth
• Most common form of intestinal obstruction in newborns

Meconium Ileus: Types

• Simple: Thickened meconium obstructs the ileum, causing proximal dilatation, bowel wall thickening, and congestion
• Complex: Associated with bowel atresia, volvulus, necrosis, or perforation, requiring surgical intervention

Meconium Ileus: Etiology

• Occurs in up to 20% of infants with cystic fibrosis (CF) due to abnormal mucus production or impaired pancreatic enzymes
• Can also occur without CF, possibly due to non-CFTR gene mutations

Meconium Ileus: Pathophysiology

• Terminal ileum is plugged with thick, viscous meconium due to insoluble calcium-glycoprotein in abnormal mucus
• Proximal ileum distends with liquid, walls hypertrophy and segment distal collapses
• Obstructed meconium is thick, which causes inadequate peristalsis resulting in impaction

Meconium Ileus: Complications

• Volvulus (twisting of the intestine)
• Atresia (absence or abnormal narrowing of an opening or passage in the body)
• Perforation

Meconium Ileus: Physical Exam

• Abdominal distention develops in the first few days after birth
• No meconium passage, vomiting begins within hours or days
• Infants with CF may show tachypnea, intercostal retractions, and grunting respirations
• Distended abdomen shows dilated intestinal loops containing firm, movable masses
• Empty rectal ampulla

Meconium Ileus: Prevention

• Preconception and prenatal CF carrier screening for all women of reproductive age
• Prenatal diagnosis via ultrasound or MRI

Meconium Ileus: Treatment

• Hyperosmolar enema (meglumine diatrizoate) under fluoroscopy for uncomplicated cases
• Warm saline enema with 4% N-acetylcysteine to aid evacuation
• Surgical management for complex cases: tube enterostomy, open enterostomy, or meconium mass resection

Meconium Ileus: Prognosis

• Improving survival rates, approaching 100%
• Mortality increases if peritonitis occurs

Cystic Fibrosis (GI Effects)

• Autosomal recessive disease affecting exocrine glands, impacting multiple organ systems (primarily GI and respiratory)

Cystic Fibrosis: Pathophysiology

• GI presentation: dysfunction of the CF transmembrane regulator (CFTR) protein which is located on epithelial membranes and regulates chloride and sodium ion channels
• CFTR protein dysfunction leads to altered sodium, chloride, and potassium resorption, resulting in reduced clearance from tubular structures
• Mucus obstructs pancreatic ducts, blocking pancreatic enzyme flow, causing intestinal malabsorption and pancreatic changes
• Diabetes mellitus develops due to CFTR protein mutation dysregulating beta-cell insulin secretion
• Hallmark pathophysiologic triad of CF includes obstruction, infection, and inflammation evident throughout the GI tract and within the airways
• Also called mucoviscidosis or fibrocystic disease of the pancreas

Cystic Fibrosis: Organ Involvement

• Sweat Glands: Elevated sodium and chloride leads to hyponatremia, hypochloremia, heat prostration and shock
• Esophagus: Can cause gastroesophageal reflux and risk for aspiration
• Intestine (Newborn): Viscid meconium leads to meconium ileus with intestinal obstruction and meconium peritonitis
• Intestine (Older Child/Adult): Inspissated mucofecal masses leads to partial intestinal obstruction with severe cramping pains, gastroesophageal reflux volvulus (obstruction), intussusception (prolapse), and Distal intestinal obstruction syndrome
• Pancreas (Enzyme Deficiency): Inspissation of secretions obstructing ducts leads to malabsorption, fatty stools, malnutrition which can then lead to Hypoproteinemia, iron deficiency anemia, recurrent pancreatitis, pancreatic cysts decreased vitamins A, D, E, and K absorption, Growth failure, Vitamins A, D, E, and K deficiency, rectal prolapse, Decreased bone density and risk of fractures in adolescents and adults, Insulin deficiency Glucose intolerance and Diabetes mellitus
• Liver: Inspissation of bile in biliary system can lead to focal biliary cirrhosis and shrunken liver which further leads to portal hypertension, hepatic steatosis and Steatorrhea from lack of bile salts
• Salivary Glands: Inspissation of secretions can lead to mild patchy fibrosis of salivary glands
• Paranasal Structures: Viscid mucus can lead to retention of mucus and clouding seen on sinus roentgenograms which can lead to Mucopyoceles with nasal deformity or orbital cavity extension
• Nose: Nasal polyps leads to obstruction of nasal airflow
• Lungs: Viscid mucus in bronchioles and bronchi leads to obstruction causing bronchiolectasis, bronchiectasis, and chronic lung infection which can lead to hemoptysis, pneumothorax, cor pulmonale, atelectasis, chronic bacterial infection and respiratory failure
• Reproductive Tract (Male): Viscid genital tract secretions leads to the developmental failure of normal vas deferens which leads to delayed puberty and Sterility
• Reproductive Tract (Female) Distention of endocervical epithelial cells with cytoplasmic mucin leads to delayed puberty and decreased fertility which can cause Polypoid cervicitis while taking oral contraceptives

Cystic Fibrosis: Clinical Manifestations

• Gastrointestinal symptoms often precede pulmonary issues
• Approximately 85% of those with CF present early in life with pancreatic insufficiency, which causes nutrient malabsorption and failure to thrive (FTT)
• Steatorrhea and abdominal distention → common symptoms with potential sequelae: distal intestinal obstruction syndrome (DIOS), fibrotic colonopathy, intussusception, and focal biliary cirrhosis
• Children who are pancreatic sufficient → greater risk of developing pancreatitis, gastrointestinal cancers and hepatobiliary abnormalities which can cause pancreatic transplant or death

Cystic Fibrosis: Diagnosis

• All U.S. states screen newborns for CF via blood test to detect immunoreactive trypsinogen
• Genetic screening and sweat test are required for diagnosis
• To determine the extent of pancreatic function, 72-hour fecal fat measurements are used

Cystic Fibrosis: Treatment

• Goal of treatment with PI: reduce malabsorption of nutrients and improve growth
• Most children require pancreatic enzyme replacement therapy (PERT) for life administered before or with every meal, snack, or enteral feeding supplementation
• High-caloric, high-protein diets with frequent snacks and vitamin supplements for malnutrition, with enteral supplements as needed
• Nutritional status and growth should be carefully monitored, and growth hormone may be included with nutritional supplements

Cystic Fibrosis: Prognosis

• Determined by the degree of pulmonary involvement
• Death is caused by a combination of respiratory failure and cor pulmonale

Celiac Sprue

• Autoimmune disease that damages the small intestinal villous epithelium due to gluten (gliadin) ingestion (found in wheat, rye, barley, and oats)
• The diseases damages the small intestinal villous epithelium when there is ingestion of gluten
• Also called celiac disease or gluten-sensitive enteropathy

Celiac Sprue: Etiology

• Multiorgan disease with a strong genetic predisposition with human leukocyte antigen DQ2 (HLA- DQ2)and HLA-DQ8
• Presents more frequently in children with type 1 diabetes mellitus, autoimmune thyroid or liver disease, Down syndrome, Turner syndrome, Williams syndrome, selective immunoglobulin A (IgA) deficiency, Addison disease, and first-degree relatives with celiac disease
• Increased risk for non-Hodgkin's lymphoma and rarely, small intestinal adenocarcinoma
• Nonceliac gluten sensitivity (GS) is similar but without autoantibodies or villous atrophy
• IgE-mediated wheat allergy causes gastrointestinal symptoms and dermatitis/wheezing

Celiac Sprue: Pathogenesis

• Complex involving genetic, cellular, and humoral immunologic factors
• Environmental factors include early infections, gut microbiota in infants, feeding patterns, and gluten timing and amount

Celiac Sprue: Pathophysiology

• HLA-DQ2- or HLA- DQ8-induced CD4+ T-cell– mediated autoimmune injury to small intestinal epithelial cells
• Increased intraepithelial lymphocytes, villi atrophy, crypt hyperplasia in the upper small intestine cause malabsorption of nutrients
• High levels of transglutaminase 2 IgA (TG2) and endomysial IgA autoantibodies correlate with the acute phase of the disease
• Atrophy leads to accelerated shedding of epithelial cells from the villi which leads to the increase in epithelial cell production resulting in hypertrophy of the crypts of Lieberkühn that compensate for loss of epithelial cells from villi
• Result of the above process leaves patches of bald mucosa causing loss of mucosal surface area and brush-border enzymes that causes severe malabsorption
• Damage to the mucosa of the duodenum and jejunum exacerbates malabsorption
• Secretion of intestinal hormones (secretin, cholecystokinin) may be reduced, decreasing pancreatic enzyme and bile secretion
• Potassium loss causes muscle weakness
• Magnesium and calcium malabsorption causes seizures or tetany
• Unabsorbed fatty acids combine with calcium which increases phosphorus excretion that leads to bone reabsorption and calcium unavailable to bind oxalate in the intestine leading to hyperoxaluria
• Fat malabsorption in the jejunum is a major cause of steatorrhea
• Vitamin K malabsorption causes hypoprothrombinemia
• Iron and folic acid malabsorption causes cheilosis, anemia, and a smooth, red tongue
• Vitamin B12 absorption is impaired with extensive ileal disease
• Folate and iron deficiencies

Celiac Sprue: Clinical Manifestations

• Onset depends on the age of the infant when gluten is added to the diet (usually by 18 months)
• Severity of symptoms varies
• Children older than 3 years may have mild to severe gastrointestinal symptoms or no symptoms
• In infants, early signs include failure to thrive, anemia, abdominal pain, distention, and diarrhea. Stools are pale, bulky, greasy, foul-smelling, and may contain oil droplets with three to five such movements occur daily with vomiting and abdominal pain being prominent in infants but unusual in older children
• Classic physical manifestations of organic failure to thrive: abdominal protuberance, wasted buttocks and limbs, and hypotonia
• Manifestations in 3-4 month olds: growth failure, anorexia, and constipation
• Extraintestinal manifestations of malabsorption: rickets, tetany, frank or occult bleeding, or anemia
• Other symptoms: constipation; anorexia; urinating more at night; a smooth and red tongue; bruising and bleeding easily and hypomagnesemia and hypocalcemia leading to irritability, tremor, convulsions, tetany, bone pain, osteomalacia, and dental abnormalities
• Prolonged vitamin D deficiency is prolonged - rickets and clubbing of terminal phalanges are likely
• Cutaneous manifestation: dermatitis herpetiformis is manifested by blister formation with a symmetrical distribution on the extensor surfaces of the elbows (90%), knees (30%), shoulders, midline of the back, or buttocks, sacral region, scalp, nuchal area, face, and groin

Celiac Sprue: Clinical Manifestations in Older Children

• 86% will fingerprint changes (ridge atrophy)
• Delayed puberty and infertility indicate subtle gluten-sensitive enteropathy

Celiac Sprue: Diagnosis

• Clinical findings confirmation with serologic measurements of antiendomysial and antitransglutaminase IgA antibodies and HLA-DQ2 or HLA-DQ8
• Duodenal biopsy which detects classic mucosal changes
• Initial biopsy may be followed by a second intestinal biopsy to demonstrate regeneration of intestinal villi after treatment with a gluten-free diet
• Later age diagnosis is associated with younger age gluten avoidance
• Many children with celiac disease remain undiagnosed

Celiac Sprue: Treatment & Prognosis

• Lifelong adherence to a gluten-free diet (GFD) is required involving elimination of wheat, rye, barley, and malt
• Elimination of Lactose (milk sugar) due to possible lactose intolerance
• Infants: fat-soluble vitamins, iron, and folic acid supplements to treat deficiencies
• Breast-feeding at the time of gluten introduction delays the appearance of celiac disease
• Prognosis: most children have complete remission of symptoms with clearing of serologic markers who also have an excellent prognosis
• Refractory CD resists treatment with a gluten-free diet that is rare requiring Steroids or immunosuppressants for treatment

Celiac Sprue: Complications

• Increased incidence of malignant disease (T-cell lymphoma) in refractory celiac disease (failure to heal after 6 to 12 months of a strict gluten-free diet

Cirrhosis in Children

• Fibrotic scarring of the liver in response to inflammation and tissue damage
• Most forms of chronic liver diseases in children can progress to cirrhosis
• Causes include cystic fibrosis, biliary atresia, infectious hepatitis, and Wilson disease
• Nonalcoholic fatty liver disease (Steatohepatitis) is increasing in children due to correlation with increase in childhood obesity which can also progress to cirrhosis and liver cancer
• Complications can be portal HTN, the opening of collateral vessels between the portal and systemic veins, and varices
• Symptoms: experience growth failure (nutritional deficits) and developmental delay (gross motor function due to ascites and weakness)
• Prognosis: The cause of cirrhosis may influence its severity and course with some types of cirrhosis that can be stabilized if the cause is identified and treated early

GERD in Children

• Gastroesophageal reflux (GER); passage of gastric contents into the esophagus independent of swallowing
• In infants; normal and nonpathologic, may be asymptomatic
• In newborns; gastroesophageal reflux or regurgitation is normal (physiologic reflux) because neuromuscular control of the gastroesophageal sphincter is not fully developed
• In premature infants; frequency of reflux is highest decreasing during the first 6 to 12 months of life
• Children usually outgrow their reflux

GERD: Pathophysiology

• Influenced by genetic, environmental, anatomic, hormonal, and neurogenic factors
• Transient lower esophageal sphincter relaxations (TLESRs) are the most common cause
• Inadequate adaptation of sphincter tone to changes in abdominal pressure also may be implicated
• Factors that maintain lower esophageal sphincter integrity: location of the gastroesophageal junction in a high pressure zone within the abdomen, mucosal gathering within the sphincter, and angle the esophagus is inserted into the stomach
• Reflux persists if any one of these pressure-maintaining factors is altered
• Other mediators of GER: esophageal peristalsis or clearance, mucosal resistance (mediates the noxiousness of the refluxate), and delayed gastric emptying
• Reflux of acidic gastric contents can result in inflammation of the esophageal epithelium (esophagitis) and stimulation of the vomiting reflex

GERD: Treatment and Complications

• Mild GER resolves without treatment usually within 12 months
• Significant complications include esophagitis, hemorrhage, stricture, Barrett esophagus and, rarely, adenocarcinoma
• Gastroesophageal reflux disease (GERD): occurs when it is the cause of troublesome symptoms or complications described as esophageal or extraesophageal in nature
• Greatest risk for complicated GERD: prematurity, neurologic impairment, esophageal atresia, obesity, hiatal hernia, achalasia, chronic lung diseases, and certain genetic disorders (cystic fibrosis)
• Clinical manifestations of GERD: excessive regurgitation or vomiting; food refusal/anorexia; unexplained crying, choking, or gagging; sleep disturbance; dysphagia; and abdominal or epigastric pain

GERD: Diagnosis and Management

• Clinical manifestations often confirm a diagnosis of GERD
• Symptoms such as irritability, crying, feeding refusal, and regurgitation can be common and not specific to GERD
• Esophageal pH monitoring with impedance using a 24-hour pH probe and endoscopy with biopsy are used when there are unusual symptoms or treatment failure
• Management of infant reflux: small, frequent feedings; prolonged feeding duration and slower flow rate; frequent burping and position changes; and thickened feedings
• Lifestyle changes for older children: weight loss, smoking cessation, sleeping position changes, and avoidance of caffeine, chocolate, alcohol, and spicy foods
• Medications include gastric acid suppression therapy with proton pump inhibitors (esomeprazole) and prokinetic agents (bethanechol) for erosive esophagitis only
• Routine use of medications requires caution due to adverse side effects
• If there is no improvement the use of medications or if the child has life threatening events with reflux then an antireflux surgical procedure (gastropexy and fundoplication) is performed
• Fundoplication: re-creates a valve by wrapping the fundus of the stomach around the lower esophagus and can be completed using laparoscopic techniques
• Complications: mucosal erosion, bleeding, dysphagia, failure to thrive, reactive airway disease, and aspiration pneumonia develops in 1/3 of infants with GERD

Portal Hypertension in Children

• Increased pressure in the portal venous system
• A major cause of morbidity and mortality in children with liver disease
• Basic causes include increased resistance to blood flow within the portal system and increased volume of portal blood flow
• Resistance to flow can occur anywhere in the portal circulatory system
• Associated with cirrhosis, intraabdominal infections, portal vein thrombosis, congenital anomalies of the portal vein, and congenital hepatic fibrosis

Portal Hypertension: Extrahepatic vs Intrahepatic

• Extrahepatic (prehepatic): Obstruction of portal vein; usually caused by thrombosis due to abdominal trauma, pancreatitis, abdominal infections, and some systemic disorders; No specific cause can be found in approximately two thirds of these children where umbilical infection is usually to blame. Treatment includes mesoportal bypass which restores normal physiologic portal flow to the liver and corrects portal hypertension and reduces life-threatening bleeding and coagulation disorders
• Intrahepatic: Primary cause is liver fibrosis that can lead to cirrhosis with increased resistance to portal blood flow by constricting and reducing the compliance of hepatic sinusoids. Causes of liver fibrosis include chronic hepatitis, biliary atresia, nonalcoholic fatty liver disease, and congenital hepatic fibrosis
• Clinical Manifestations: splenomegaly, upper gastrointestinal tract bleeding, ascites, hepatopulmonary syndrome, hepatorenal syndrome, and hepatic encephalopathy

Portal Hypertension: Diagnosis & Prognosis

• Diagnosis objectives are to locate the site of the venous block and identify the disease responsible for the portal hypertension using a thorough physical examination; laboratory evaluation of liver function, WBC, and platelet count; ultrasonographic imaging (sonoelastography); endoscopic evaluation; and biopsy
• Treatment is the same as that in adults
• Prognosis depends almost entirely on its cause, with extrahepatic cases typically resulting in recovery with little morbidity and intrahepatic prognoses depending on their underlying cause

Pyloric Stenosis

• Infantile hypertrophic pyloric stenosis (IHPS) is the most common cause of intestinal obstruction in infancy
• Defined as acquired narrowing & distal obstruction of the pylorus, and a common cause of postprandial vomiting
• Usually occurs in the first few weeks or months of life
• Whites have a higher incidence than blacks or Asians, and full-term infants are more susceptible than premature infants
• Related to environmental, hereditary factors, a deficiency of nitric oxide synthase containing neurons, an abnormal innervation of the myenteric plexus and infantile hypergastrinemia
• Cause in Infant: unknown; increased gastrin secretion by the mother in the last trimester of pregnancy raises the likelihood of pyloric stenosis as well stress-related factors in the mother may be a factor
• Exogenous prostaglandin E administration and a family history of pyloric stenosis also increase the risk (genetic predisposition)

Complications of Diarrhea in Children

• Pathophysiologic mechanisms of diarrhea: osmotic, secretory, intestinal dysmotility, or inflammatory
• Prolonged diarrhea is more dangerous in infants and children due to their smaller fluid reserves and more rapid peristalsis and metabolism
• In children, dehydration can develop rapidly if any disturbance increases fluid secretion into the GI lumen (secretory diarrhea), draws fluid into the lumen by osmosis (osmotic diarrhea), reduces intestinal transit time with luminal fluid retention (intestinal dysmotility) or causes inflammation that results in malabsorption and an increased luminal osmotic load from nutrients, fluid, and blood, which may increase gut motility (inflammatory diarrhea)