PART 20 - Mike South



Part 20

DISORDERS OF THE GASTROINTESTINAL TRACT AND HEPATIC DISORDERS

20.1

Abdominal pain and vomiting in children

S. W. Beasley

Acute abdominal pain and vomiting are common symptoms in children and a frequent reason for children to be taken to the doctor. Their causes are many and diverse; those that require surgery must be distinguished from those with a medical origin. While there is considerable overlap of age in many disorders (e.g. gastro-oesophageal reflux), other conditions only occur within a specific age range; for example, pyloric stenosis is not seen after the age of 3 months.

Abdominal pain in the first 3 months of life

Abdominal pain without other symptoms is unusual in early infancy. Severe pain may be accompanied by vomiting, abdominal distension, constipation or other features, in which situation it is more likely to have a surgical cause, e.g. malrotation with volvulus.

Infantile colic is an extremely common condition that usually commences in the first few weeks of life. The cause is poorly understood. The term ‘colic’ is used because of the common assumption that this pattern of behaviour is due to colicky abdominal pain but this explanation is controversial, and there are other hypotheses including an irritable temperament (Ch. 4.1).

The infant:

• has attacks of screaming

• draws up the legs

• is unable to be comforted.

Vomiting is absent, bowel actions are passed normally and the infant is otherwise thriving well. There is no evidence of a strangulated inguinal hernia. The colic almost invariably disappears by the fourth month of age; until then, treatment is supportive. In some infants, apparent colic may be due to oesophagitis from gastro-oesophageal reflux or to hunger in inadequately breastfed babies. Crying babies may cause stress in the family, which in turn may increase the child’s irritability. In a vulnerable or unstable family situation this may place the infant at risk of abuse.

Abdominal pain later in the first year

The main surgical cause of abdominal pain between 3 and 12 months of age is intussusception. Vomiting is a frequent accompanying feature, such that, when the colicky abdominal pain is not pronounced, intussusception must be distinguished from other causes of vomiting in this age group (see below).

Intussusception

In intussusception, the distal ileum (the intussusceptum) telescopes into adjoining distal bowel (the intussuscipiens), resulting in intestinal obstruction. It can occur at any age but is most likely in the infant between 3 and 18 months who suddenly develops screaming attacks of pain with vomiting. During each episode of pain the infant becomes pale and may draw up the legs.

The spasms of pain tend to last 2–3 minutes and occur at intervals of about 10–20 minutes, although after a while the pain becomes more persistent. Vomiting is an early symptom. The passage of a few loose stools early on represents evacuation of the bowel distal to the obstruction. The small volume and limited duration of loose stools in intussusception helps differentiate it from acute gastroenteritis. Congestion of the intussusceptum may lead to the passage of bloodstained or ‘redcurrant’ stools. Many infants with intussusception present with little more than pallor, lethargy and vomiting and may have little evidence of abdominal pain. Should these symptoms be ignored, the infant may progress to develop signs of septicaemia or shock.

The infant with intussusception looks pale, lethargic, anxious and unwell. A vague mass may be felt in the right or left upper quadrants of the abdomen but, once abdominal distension has developed, the mass becomes obscure and difficult to palpate. The apex of the intussusceptum may be palpable on rectal examination in a few, and the examining glove may be bloodstained. A plain X-ray of the abdomen will often be normal but may show an unusual bowel gas distribution or features of bowel obstruction. Ultrasound examination may be helpful in making the diagnosis. Where intussusception is suspected clinically or confirmed on ultrasonography, a gas or barium enema must be performed unless the child has peritonitis. The enema will demonstrate the position of the apex of the intussusception.

Treatment

Intussusception can be reduced non-operatively by gas enema or by hydrostatic reduction under ultrasonographic control; these techniques are successful in 80–90% of patients (Fig. 20.1.1). If gas enema facilities are not available, a barium enema under continuous fluoroscopic control is a less effective but satisfactory alternative. Peritonitis and septicaemia, which suggest the presence of dead bowel, are the only contraindications to attempted enema reduction. A dehydrated child should have intravenous fluid resuscitation and be wrapped in warm blankets before commencing an enema reduction. The success of enema reduction is recognized when there is sudden or rapid flow of gas or barium into the ileum. If partial reduction is achieved, and the child remains in good clinical condition, a further enema should be attempted after several hours (so called ‘delayed repeat enema’), and in about half of these patients it will be successful. Recurrence of intussusception occurs in about 9% of children after enema reduction, usually within days. Surgery is reserved for:

• those in whom enema reduction has failed

• those who have clinical evidence of necrotic bowel, such as peritonitis and septicaemia

• those in whom there is evidence of pathological lesions at the lead point.

Differential diagnosis

Gastroenteritis is often confused with intussusception but becomes obvious on clinical grounds by the volume and persistence of the fluid stools. The plain radiological appearance of the abdomen may be similar in both conditions. Where doubt persists, ultrasonography or a gas or barium enema is indicated. Other causes of intestinal obstruction include volvulus secondary to malrotation, a band from a Meckel diverticulum, a duplication cyst or a strangulated inguinal hernia. Examination of the groin will detect the irreducible tender lump of a strangulated hernia.

Acute abdominal pain in older children

Children often present with abdominal pain and in most no specific cause is found. Constipation and mesenteric adenitis are probably the most common non-surgical identifiable causes.

Acute appendicitis

Appendicitis may occur at any age, although it is rare under 5 years of age. Early diagnosis is difficult in the young child (under 5 years) and in the mentally retarded child; the majority of these children have established peritonitis or an appendix abscess at presentation. Delays in the diagnosis of acute appendicitis in childhood is related in part to its variable symptomatology. For example, there may be relatively little abdominal pain, vomiting may be absent and diarrhoea may be a misleading feature.

Nevertheless, the most important and consistent feature is localized abdominal pain. The pain may be intermittent and colicky initially, or situated in the epigastrium or periumbilical region, but soon shifts to the right iliac fossa. Constant pain that is worse with movement is the result of peritoneal irritation (‘peritonism’). Vomiting occurs in the majority of children, and some may pass a loose stool. The temperature is usually normal or slightly elevated but occasionally may be in excess of 38°C.

Physical examination of the abdomen should be directed at showing that movement of adjacent peritoneal surfaces exacerbates the pain. The child’s cooperation makes assessment easier, and repeated examination of the abdomen may be required to make the diagnosis. A child with appendicitis usually will exhibit tenderness and guarding localized to the right iliac fossa. Gentle palpation and percus-sion tenderness, performed while observing the child’s face, will provide the most reliable evidence of abdominal tenderness and involuntary guarding. Rebound tenderness is an unreliable sign in children, and attempts to elicit the sign may cause unnecessary pain and destroy the child’s confidence in the doctor. Rectal examination is required rarely and is primarily indicated if a pelvic appendix or pelvic collection is suspected. It should not be performed if examination of the ventral abdominal wall has already enabled a confident diagnosis of acute appendicitis to be made. Bowel sounds may be normal or reduced and contribute little to the diagnosis.

Peritonitis should be suspected when the child is acutely ill with abdominal pain and fever and is reluctant to move. On examination, there will be generalized abdominal tenderness and guarding.

Laboratory studies and radiology are rarely helpful in making the diagnosis. However, the urine should be checked routinely.

Clinical example

Mark, a 10-year-old boy, had 36 hours of constant lower abdominal pain, which steadily became more severe. He vomited once initially, and was ‘off his food’. Movement made the pain worse. On examination, he was afebrile but appeared flushed. He was tender to gentle palpation in the right iliac fossa and had percussion tenderness in the same region. The urine contained a few white and red cells but no bacteria. No other investigation was performed. At laparoscopy an acutely inflamed appendix was removed.

Differential diagnosis

Mesenteric adenitis is the most difficult disorder to distinguish from acute appendicitis. In general, localization of pain and tenderness is variable and less specific, and the temperature may be higher. Guarding is rarely present in mesenteric lymphadenitis.

Other conditions that may mimic acute appendicitis are relatively uncommon. Meckel diverticulitis has symptoms identical to those of appendicitis, such that differentiation is possible only at laparoscopy or laparotomy. Pain in the right iliac fossa may represent radiation from torsion of the right testis or a strangulated inguinal hernia, and highlights the importance of examination of the genitalia in all boys with lower abdominal symptoms (Ch. 9.1). Acute abdominal pain may occur with renal colic, pyelonephritis and, at times, acute glomerulonephritis. Pain and tenderness is usually referred to the loin. Urine analysis and radiology will confirm the diagnosis. In Henoch–Schönlein purpura, the abdominal pain is often severe and colicky, and may be accompanied by vomiting. The characteristic skin lesions over the buttock and legs may be inconspicuous or absent when the child is first examined.

In the appropriate ethnic group, sickle cell anaemia is a prominent cause of acute abdominal pain and should be considered in a pale child with splenomegaly.

Children with cystic fibrosis frequently experience episodes of abdominal pain from faecal impaction (called ‘meconium ileus equivalent’), a well known manifestation of this disease. The symptoms resolve following a bowel washout.

It is unusual for constipation in an otherwise normal child to produce sufficient abdominal pain to suggest a surgical emergency. A plain X-ray of the abdomen will demonstrate the extent of faecal accumulation (Fig. 20.1.2). It should be remembered, however, that the diagnosis of constipation is usually made on clinical grounds and that X-ray examination should be reserved for other indications or more complex cases.

Less common causes of abdominal pain include urinary tract infection, haemolytic–uraemic syndrome and diabetes. Acute hepatitis, cholecystitis and pancreatitis, although all rare in childhood, may also cause abdominal pain. In pancreatitis, vomiting is prominent and epigastric tenderness with guarding may be marked. These children often look ill and obtunded. Pancreatitis may follow a blunt injury to the abdomen, e.g. a handlebar injury, and several weeks later may produce a pancreatic pseudocyst. The diagnosis is suggested by estimation of the plasma or urinary amylase or plasma lipase, and is confirmed with computed tomography (CT) or magnetic resonance imaging (MRI). The management of acute pancreatitis involves correction of shock, intravenous fluid administration, nasogastric suction to keep the stomach empty, and analgesia.

Right lower lobe pneumonia may masquerade as appendicitis. The child is usually febrile, with an increased respiratory rate, and has a cough. Signs of pneumonia may be difficult to elicit clinically, so that a chest X-ray will be required.

A general summary of disorders associated with abdominal pain is listed in Table 20.1.1.

Peptic ulceration

The abdominal pain of peptic ulceration is epigastric and usually is unrelated to meals. Nausea and vomiting may occur. Haematemesis and melaena suggest the diagnosis; alternatively it may be made following investigation of iron deficiency anaemia.

Acute gastritis and acute duodenitis produce abdominal pain with epigastric tenderness. A positive hydrogen breath test is suggestive of Helicobacter pylori infection. Culture of biopsy specimens taken during endoscopic examination of the upper gastrointestinal tract will confirm H. pylori (Ch. 20.4). Treatment with ampicillin, metronidazole or tripotassium dicitratobismuthate (De-Nol) is usually successful but relapses are common.

Reflux oesophagitis

Gastro-oesophageal reflux is common in infancy but usually resolves with growth. Sometimes it may persist into later childhood, with symptoms of belching, acid eructation and intermittent vomiting. Substernal and epigastric pain (‘heartburn’) suggests reflux oesophagitis. Oesophageal pH monitoring measures lower oesophageal pH over a period of 24 hours and can establish the relationship of reflux to symptoms (Ch. 20.4). Oesophagoscopy and biopsy may confirm oesophagitis. Initial management may involve the administration of H2-receptor antagonists but, where non-operative measures fail or if an oesophageal stricture is present, surgical correction of the reflux by laparoscopic fundoplication may be indicated.

Recurrent abdominal pain in children

Recurrent bouts of abdominal pain is a fairly common paediatric presentation and one that may cause great anxiety to parents. The clinical example is illustrative of this syndrome.

Clinical example

Thomas, aged 7 years, was brought in by his mother, who stated that for the last 4 months he had had severe bouts of abdominal pain. The attacks occurred at any time, but were more frequent at breakfast time. He was never awakened at night by them. Vomiting was not a feature, and his bowels had been regular. The pain usually was localized to the periumbilical region and usually lasted less than 1 hour. His parents felt that Thomas was pale and had a poor appetite. He was of normal height and weight. Physical examination was unremarkable. The urine was clear. Further questioning elicited the fact that the bouts of abdominal pain had occurred periodically since the age of 3 years.

Doctors will be impressed by the concern exhibited by parents of these children, who vividly describe the severe pain the child experiences; but there is a disparity between the parents’ description and the physical findings on examination of the abdomen. Investigation almost invariably produces negative results. Enquiry into the personality of the child and into the home situation may reveal that the child is anxious or stressed, but often the pain occurs for no apparent reason. Sometimes the episodes of pain appear to be related to stress within the family. A diagnosis of non-organic recurrent abdominal pain can be made only after careful appraisal of the child in relation to the environment, and when the physical examination is normal. Most children need no investigations apart from urine culture. Further investigation is required if the abdominal pain is associated with abdominal tenderness or distension, bile stained vomiting, persistent diarrhoea, fever, weight loss or urinary symptoms. This may include full blood examination, erythrocyte sedimentation ratio (ESR), C reactive protein (CRP), radiological and endoscopic studies of the gastrointestinal tract, and specific investigations for malabsorption and inflammatory bowel disease. The urine should be examined. If the vomitus is bile-stained, malrotation with volvulus should be excluded by an urgent barium meal.

The general status of the patient must be assessed. Retardation of height and growth may occur in chronic inflammatory bowel disease, malabsorption syndromes and tuberculosis. Pallor may be associated with anaemia or conditions such as lead poisoning, sickle cell anaemia and other haemolytic diseases.

Management

Parents will find it helpful to realize that the problem has been taken seriously by the doctor, and the doctor must understand the parents’ perception of the abdominal pain. With this knowledge and the negative physical findings, reassurance can be given more positively. Once parents are convinced that there is no significant organic basis to the recurrent abdominal pain they are usually much relieved. The child should be encouraged in all activities and self-esteem improved. Recurrent pain tends to disappear by the age of 12 years but in females may recur at the time of menarche. However, some children with recurrent pain in childhood present in adult life with symptoms of irritable bowel syndrome. In some, as time goes by the child’s abdominal pain may become associated with and eventually replaced by migraine headaches.

Vomiting in the neonatal period

Neonates frequently vomit small amounts of mucus and blood swallowed during labour. This vomiting usually clears spontaneously within 24 hours. If not, gastric lavage with normal saline will usually relieve it. In the early weeks of life, many normal newborn babies regurgitate after feeds. The cause of this ‘spitting up’ or ‘possetting’ is not clear but is presumably related to gastro-oesophageal reflux.

Systemic infection

Vomiting is one of the many non-specific signs of infection in the neonate. Thus, unexplained vomiting should be an indication to culture the blood, urine and cerebrospinal fluid. Urine will usually be obtained by suprapubic aspiration in this age group.

Bowel obstruction

In duodenal obstruction, vomiting appears early and is bile-stained because the site of the obstruction is almost always at the second part of the duodenum, just distal to the ampulla of Vater. In duodenal atresia, there may be other abnormalities such as Down syndrome and imperforate anus. The bile-stained vomiting commences from birth. The diagnosis is made on plain X-ray of the abdomen (Ch. 11.5). Where there is bowel obstruction beyond the duodenum (e.g. small bowel atresia, Hirschsprung disease and meconium ileus), vomiting commences slightly later and is associated with increasing abdominal distension (Ch. 11.5). A strangulated inguinal hernia may cause a bowel obstruction when a loop of ileum becomes trapped within the hernial sac at the external inguinal ring. The diagnosis becomes evident when a tender irreducible lump is observed in the groin (Ch. 9.1).

Malrotation with volvulus

Volvulus in a neonate or infant with malrotation causes a high bowel obstruction and produces bile-stained vomiting. The volvulus may cut off the blood supply to the midgut and lead to small bowel infarction, septicaemia and death if not treated promptly. Any infant with bile-stained vomiting, otherwise unexplained, should be assumed to have malrotation with volvulus until proven otherwise. A barium meal will confirm the diagnosis. An urgent laparotomy is required to untwist the bowel (Fig. 20.1.3) and to perform a Ladd procedure to broaden the mesentery of the small bowel: this will prevent subsequent volvulus.

Cerebral hypoxia

There is often a history of fetal distress during labour and asphyxia at birth requiring resuscitation. Following this, some infants remain lethargic and feed poorly, while others may be abnormally wide awake, excessively irritable and cry frequently. The cry may be high-pitched and associated with intermittent twitching and hypertonia; there is head retraction and the thumbs are adducted across the palms with flexion of the fingers. The Moro reflex may be exaggerated but in severe cerebral anoxia it may be lost. The fontanelle tension is not increased initially, unless there has been cerebral haemorrhage, but within 24 hours cerebral oedema occurs and causes a rise in the fontanelle tension. In cerebral anoxia the vomiting occurs before or after feeding, and may be forceful.

Treatment

Cerebral haemorrhage is shown on ultrasonography, which may also demonstrate cerebral oedema. Treatment is symptomatic: sedation with diazepam 0.1–0.3  mg/kg i.v. or phenobarbital 2  mg/kg i.m. may be required. The pulse, temperature, state of consciousness and degree of dehydration should be monitored. Aspiration of vomitus is potentially dangerous. Oral fluids are given in small volume and are offered frequently. An intravenous infusion may be necessary but fluid requirements on the first day of life are only 60  ml/kg. This amount increases gradually each day until the end of the first week, when they reach 150  ml/kg. Frequent blood glucose estimations will detect hypoglycaemia early, before it exacerbates the cerebral disturbance and accentuates the vomiting.

Subdural haematoma

With the current high standard of obstetrics, a subdural haematoma is now rare in the neonatal period. In about 50% of infants, vomiting is the only symptom. In others, vomiting is accompanied by developmental delay, convulsions, an expanding head and retinal haemorrhages. The diagnosis is confirmed on ultrasonography and CT. A subdural haematoma later in childhood must alert the clinician to the possibility of child abuse.

Hypoglycaemia

Vomiting may be the only symptom of hypoglycaemia in the neonatal period. It is more common in ‘small for dates’ babies and in infants of diabetic mothers but may be seen in any stressful situation in the neonatal period, including low birth weight, neonatal meningitis, septicaemia and severe Rhesus isoimmunization. Symptomatic hypoglycaemia does not usually occur with a blood glucose in excess of 2  mmol/l.

Renal disease

In the neonatal period, urinary infection and renal insufficiency may present with vomiting and poor weight gain, reflecting an underlying urinary tract abnormality. Initial urological investigation will include urine culture, renal ultrasonography, micturating cystourethrography and estimation of electrolytes, urea and creatinine. Renal tubular lesions occasionally present in the neonatal period with vomiting.

Adrenal insufficiency

Congenital adrenal hyperplasia, in which there is deficiency of the enzyme 21-hydroxylase (Ch. 19.3), presents with ambiguous genitalia in the female. If this is not recognized (as in the male), it may lead to unexplained vomiting, dehydration and collapse early in the second week of life. If the adrenal insufficiency is of the salt-losing type, the diagnosis is further suspected by finding low levels of sodium and elevated levels of potassium in the serum, and is confirmed by appropriate hormonal studies.

Inborn metabolic errors

Although individually rare, there are a number of inborn errors involving, separately, amino acid, carbohydrate and organic acid metabolism. Most are inherited recessively, and a number can now be treated. Frequently, the presentation is with unexplained vomiting, lethargy, collapse, seizures and coma (Ch. 10.5).

Vomiting in infancy

Vomiting is a common non-specific symptom in infancy, and disease of almost every system may present with vomiting.

Infection

Vomiting is frequently caused by infections such as tonsillitis, otitis media, pneumonia, meningitis and urinary tract infection. Physical examination will exclude many of these but early signs may be minimal in meningitis and pneumonia, such that a lumbar puncture and chest X-ray will be required if these are suspected. In infants with urinary tract infection, dysuria, frequency of passing urine and loin pain cannot be relied upon for diagnosis, and the urine must always be examined. When infection is controlled, the urinary tract should be imaged to exclude underlying structural abnormalities.

Lesions of the gastrointestinal tract

Conditions that produce vomiting in infancy are different from those seen in the neonatal period, except for duodenal obstruction from volvulus complicating malrotation, and gastro-oesophageal reflux. Failure to recognize malrotation with volvulus may result in infarction of the entire midgut (Ch. 11.5). Bowel trapped in a strangulated inguinal hernia in an infant will also produce vomiting. The diagnosis can be made easily if the inguinal orifices are examined (Ch. 9.1).

Gastro-oesophageal reflux

See Chapter 20.4.

Pyloric stenosis

This is one of the most dramatic causes of vomiting in infancy. Typically, the onset is dramatic, commencing between the second and sixth week of life. Males are affected five times more often than females and there is a definite familial incidence. Before the onset of vomiting, these infants fed well and were thriving. The vomiting is forceful and rapidly becomes projectile. The infant loses weight and becomes dehydrated. Despite vomiting, these infants remain hungry and are keen to feed even immediately after vomiting. The vomitus is not bile-stained but may contain altered blood. The diagnosis is made clinically by feeling the thickened pylorus (‘pyloric tumour’) in the midline in the epigastrium between the rectus abdominis muscles or in the angle between the right rectus and the liver edge. The pyloric tumour is palpable as a hard mobile mass about the size of a small pebble or olive. Peristaltic waves passing from the left costal margin to the right hypochondrium (‘golf ball waves’) may be visible long after the last feed. Palpation of the tumour is sufficient to establish the diagnosis. Pyloric stenosis can also be shown on ultrasonography (which reveals a thickened pylorus) and barium meal (which shows delayed gastric emptying and a narrow pyloric canal). These infants develop a hypokalaemic, hypochloraemic metabolic alkalosis which, together with dehydration, must be corrected before surgery. Pyloromyotomy is curative (Fig. 20.1.4).

Gastroenteritis

Vomiting in association with fluid stools is suggestive of gastroenteritis, particularly if the stools contain mucus or blood. However, these features may be seen in a variety of other medical and surgical disorders, which include intussusception and appendicitis. The diagnosis and management of gastroenteritis is discussed in Chapter 20.2.

Malabsorption

In the majority of malabsorption syndromes vomiting is not a feature. At times, in the more severe cases of coeliac disease (gluten enteropathy, Ch. 20.3) vomiting may be prominent. A gluten-free diet rapidly reverses the clinical features of this disorder.

Intussusception

Vomiting commences early in intussusception and is the most consistent symptom. The general features, diagnosis and treatment are discussed in more detail on pages 709–710.

Clinical example

Tim, a previously well 22-month-old infant, suddenly became unwell with onset of vomiting and a temperature of 38.5°C. Within 12 hours he started passing frequent, loose motions. Associated with this he appeared to have bouts of abdominal pain. On the second day the vomiting stopped but the diarrhoea persisted at a rate of more than eight stools per day. On presentation to the emergency department, Tim’s weight was 13.6  kg compared with 14.5  kg 3 weeks previously. He was clinically assessed to be 5–8% dehydrated and was treated with an oral rehydration solution via a nasogastric tube. A provisional diagnosis of acute gastroenteritis was made. His temperature gradually settled over 24 hours days and oral feeds were introduced once rehydration was complete. His stools returned to their normal pattern after 5 days. Rapid stool testing for rotavirus antigen was positive.

Strangulated inguinal hernia

Strangulation of an inguinal hernia is common in infants and young children. All irreducible inguinal hernias should be assumed to be strangulated. In practice, the vast majority of so-called irreducible hernias can be reduced manually by skilled hands (Ch. 9.1).

Vomiting in older children

Vomiting in older children is usually associated with infection, particularly viral or bacterial infection of the respiratory and gastrointestinal tracts. Nevertheless, there are some other less frequent but important causes of vomiting.

The possibility of an intracranial neoplasm should always be considered in a child with unexplained vomiting. There may be signs of increased intracranial pressure with midline cerebellar tumours, tumours involving the fourth ventricle and tumours involving the pons or medulla. Initially, vomiting tends to occur in the morning before breakfast. There may be remissions for several days but the vomiting invariably returns.

Migraine

In the older child, the association of severe paroxysmal frontal headache with pallor and vomiting is suggestive of migraine (Ch. 17.5). A positive family history is common. Transient loss of vision, transient hemiparesis, cerebellar ataxia or ophthalmoplegia may be evident. In some children migraine is precipitated by minor trauma. In the younger child, attacks of pallor or vomiting may be the only symptom. The diagnosis of migraine is made on clinical history but, where it is difficult to exclude an intracranial space-occupying lesion clinically, cerebral CT may be required.

Acute appendicitis and peritonitis

In acute appendicitis in childhood, vomiting is a frequent early symptom but is usually preceded by pain. The general features of appendicitis are described on pages 710–712. In the young child (under 5 years), vomiting with or without diarrhoea may be the only obvious symptom. Physical examination in this age group can be difficult and unreliable; the child will prefer to lie still, as movement worsens the pain. This pain and the fear of its exacerbation by palpation may make the child appear uncooperative. It is only by repeated examination of the abdomen and an ongoing high index of suspicion that the diagnosis will be made before widespread peritonitis has developed.

Poisoning

Vomiting and respiratory and circulatory collapse in a previously well child should raise the possibility of poisoning (Ch. 5.3). Non-accidental poisoning is becoming more frequent, and the age incidence of children attempting suicide is decreasing. A history of family discord and emotional problems in the child is not always volunteered.

Psychological causes of vomiting

Psychogenic vomiting may occur in any age group. It can be associated with attempts to force-feed a toddler or a schoolchild, after punishment, and as an attempt to avoid situations perceived as threatening, such as going to preschool or school. Almost any stressful situation may precipitate vomiting in a tense or anxious child. The absence of abnormal physical signs will be a feature.

Cyclical vomiting

Cyclical vomiting is a syndrome of persistent periodic vomiting of childhood. The severity varies, but ketosis and metabolic acidosis may develop rapidly. The aetiology is unknown and attacks usually cease spontaneously. Children with cyclical vomiting are often tense and anxious and may develop migraine or psychosomatic disease later in life. Recurring episodes of volvulus from malrotation, and metabolic disease, should be excluded before labelling these children as having cyclical vomiting.

20.2

The child with diarrhoea

G. Alex, M. Oliver

Diarrhoea is defined as a measured stool volume greater than 10  ml/kg per day. Both the consistency of the stool (loose or watery) and frequency (usually at least three stools in a 24-hour period) are important defining features of diarrhoea. Acute diarrhoea lasts less than 10 days and has a major impact on both fluid and electrolyte status, while chronic diarrhoea suggests that the symptom is present for more than 2–3 weeks and can have a significant effect on the nutritional state of a child. The basic pathological mechanisms causing diarrhoea include osmotic, secretory and inflammatory processes (Table 20.2.1). Often more than one mechanism may operate simultaneously to cause diarrhoea. The commonest cause of acute diarrhoea in children is an enteric infection (acute gastroenteritis).

Acute gastroenteritis

Aetiology

Rotavirus infection (Fig. 20.2.1) is the most common cause of acute gastroenteritis in children under 5 years of age in developed countries, causing 40–50% of cases where hospital admission is required. It accounts for more severe episodes in infants in developing countries than any other single pathogen; it is more likely to cause dehydration, and is associated with a higher mortality than most other agents. The mucosal damage it causes (Fig. 20.2.2), and hence the need for structural repair, has considerable nutritional implications for malnourished children. Asymptomatic reinfection can occur several times and helps maintain immunity.

Enteric adenoviruses (types 40 and 41) cause 5–15% of cases requiring admission to hospital, and several other virus pathogens have been recognized, such as calicivirus, astrovirus and other small viruses, which accounts for a further 15%.

Bacteria cause fewer episodes than viruses in developed countries. Campylobacter jejuni is responsible for 5–10% of cases. Salmonella spp., Shigella spp. and various types of Escherichia coli each account for a small percentage. In developing countries, E. coli (enterotoxigenic, enteropathogenic and enteroinvasive) and Shigella spp. are especially important: E. coli because of the huge number of episodes it causes, and Shigella because it causes prolonged debilitating illness and antibiotic-resistant strains are emerging.

Giardia lamblia rarely causes acute dehydrating diarrhoea but another parasite, Cryptosporidium, is now known to cause 1–4% of cases of acute diarrhoea in infants admitted to hospital.

Clinical features

Symptoms of acute gastroenteritis include vomiting, fever and watery diarrhoea (up to 10–20 stools daily).

Blood, mucus and the passage of small frequent bowel actions accompanied by abdominal pain suggests a diagnosis of bacterial gastroenteritis.

Acute gastroenteritis is a diagnosis of exclusion. A few loose stools and vomiting does not necessarily equate with the diagnosis. There are several systemic disorders and surgical emergencies that can mimic infective gastroenteritis (Table 20.2.2).

Management

Once the diagnosis of acute gastroenteritis is made on thorough clinical history and physical examination, the next step is to assess the degree of dehydration and institute an appropriate plan for rehydration. This should be combined with nutritional support that aids the patient during the recovery phase.

Dehydration

This risk is related to the child’s age, with young infants being at greatest risk. This is because infants less than 1 year of age have a high surface area:body volume ratio, resulting in increased insensible fluid loss. They also have a tendency to more severe vomiting and diarrhoea compared with older children and adults.

Fluid loss is usually assessed on the basis of percentage body weight loss. Physical signs of dehydration are not usually apparent until 4% of body weight is lost.

The signs of dehydration traditionally described are outlined in Table 20.2.3. However, three signs discriminate adequately between dehydration and adequate hydration: deep breathing, decreased skin turgor and poor peripheral perfusion.

Electrolyte loss

This is usually isotonic (water and electrolytes being lost in equal amounts). Hypertonic hypernatraemic dehydration (fluid loss  >  electrolyte loss) occurs in 5–10% of cases of acute gastroenteritis, and hypotonic hyponatraemic dehydration (electrolyte loss  >  fluid loss) can occur if the colon (a major site of sodium reabsorption) is out of circuit, e.g. short gut syndrome.

If corrected too rapidly, hypernatraemic dehydration will result in convulsions due to rapid shifts of water into cells. Hyponatraemic dehydration can also cause significant neurological morbidity and mortality and, in contrast to the hypernatraemic state, requires vigorous replacement of sodium.

Rehydration guidelines

See also Chapter 6.1

No dehydration

• Nutritional intake and fluids should not be modified but should be offered ad libitum to keep up with ongoing losses

Mild to moderate dehydration

• Oral rehydration solution (ORS) is the cornerstone of successful rehydration and is recommended globally for the management of acute diarrhoea

• The success of ORS is based on the basic observation that intestinal sodium transport is enhanced by glucose transport in the small intestine and that this sodium-coupled mechanism for glucose transport remains intact during acute gastroenteritis

• To facilitate optimal absorption of sodium, glucose and water, the sodium and glucose must be in the range recommended (Table 20.2.4)

• Rehydration should take place over 4–6 hours and can be given orally or, if either vomiting or fluid refusal is a problem, a nasogastric tube may be used to achieve a steady infusion of fluid

• Volume required for rehydration  ’  estimated deficit and maintenance; maintenance for:

 • 1–3 months of age  ’  120  ml/kg/24  h

 • 3–12 months of age  ’  100  ml/kg/24  h

 • 12 months onwards  ’  80  ml/kg/24  h

 (see Tables 20.2.5 and 20.2.6)

Severe dehydration (10% plus)

• Circulatory insufficiency is present and intravenous therapy is required. The usual requirement is to fill the vascular compartment quickly to restore circulation. This will require rapid rehydration, often using boluses of normal saline by intravenous or intraosseous infusion

• Once dehydration is corrected and normal organ perfusion is restored, ORS can be used in conjunction with intravenous fluids. The latter is rarely required for longer than 24 hours

• Clinical observations must be highlighted: this allows the physician to reassess the patient’s state of hydration and also helps confirm the diagnosis of acute gastroenteritis

• All patients with dehydration require regular checks on pulse, temperature and respiration, and strict fluid balance charts must be kept. The child should be weighed on admission and, in severe cases, after 6 hours and 24 hours, with an increase in weight being a reliable sign of rehydration. However, in some patients weight may not fall even in the presence of severe dehydration, especially if the child has an ileus, so other signs of dehydration must be sought.

Recommendations on nutritional management

Breastfeeding should continue through rehydration and maintenance phases of treatment, and formula feeds need to be restarted after rehydration. Use of special formulas or diluted formulas is unjustified.

Pharmacotherapy

• Infants and children with acute gastroenteritis should not be treated with antidiarrhoeal agents

• Antibiotic treatment may be indicated in Salmonella spp. gastroenteritis in the very young (100  mosmol/l), this indicates an osmotic diarrhoea.

Malabsorption with chronic diarrhoea

Diarrhoea is the most common presentation of malabsorption. Diarrhoea can be defined as increased frequency, fluidity and volume of stool. The following discussion will provide a systematic approach to the child with malabsorption and diarrhoea based on the type of stool, i.e.:

• fatty

• watery or

• bloody.

Some illustrative cases will be provided.

Fatty diarrhoea (steatorrhoea)

The differential diagnosis of fat malabsorption is quite wide ranging (Table 20.3.2); however, if one understands the normal physiology of fat digestion and absorption, the differential diagnosis is much less daunting. Conditions that cause steatorrhoea can also be associated with protein maldigestion and/or malabsorption, although symptoms most commonly relate to the malabsorption of fat. The presence of fat in the stool is also more readily observed than protein.

Clinical example

Mary was 9 months old. She presented with poor weight gain, chronic diarrhoea and a history of recurrent respiratory illnesses, including one admission at age 3 months with ‘bronchiolitis’. Loose stools were found each time her nappy was changed. On occasion mother had noted oil drops in the stool. Despite the poor weight gain, Mary had an excellent appetite and was described as a voracious eater. She consumed a mixed diet, including infant formula, appropriate for age. Cereal was introduced at age 6 months. Mother also commented that she tasted salty when she kissed Mary.

On examination, Mary was found to be a thin wasted girl. Her height was on the 50th percentile and her weight was less than the 3rd percentile. She had mild finger clubbing, peripheral oedema, pallor of the tongue and palmar creases but no signs of chronic liver disease. There was no abdominal distension of note, although she had a fine scaling rash over her trunk. Respiratory examination was normal. No other abnormal physical signs were present.

Results of investigations included Hb 85  g/l (normal range, 110–140) with a normocytic normochromic film, normal white cell count and differential; albumin 24  g/l (normal range, 34–44) and normal liver function tests. Stool microscopy revealed copious fat droplets. 3-day faecal fat excretion estimation demonstrated an output of 35% of ingested fat (normal 60  mmol/l is diagnostic of cystic fibrosis). Genetic testing indicated that she was homozygous ΔF508 (the commonest mutation), consistent with her relatively severe symptoms. Introduction of pancreatic exocrine replacement therapy, a high fat diet and vitamin supplements alleviated her diarrhoea and eventually corrected her failure to thrive, anaemia and skin rash.

Fat and protein digestion and absorption

Ingested fat in the form of triglycerides, cholesterol and phospholipids is, to a large extent, digested in the lumen of the small intestine and absorbed in the jejunum. This requires bile salts, which form micelles and solubilize the fat; pancreatic enzymes, such as lipase and colipase, which digest the fat; and an intact intestinal mucosa, which is required for absorption of the products of digestion. Following digestion in the micelles, breakdown products diffuse across the enterocyte apical membrane and are reconstituted in the cell into chylomicrons. These are small packets of triglyceride, phospholipid and cholesterol which associate with carrier proteins, such as beta lipoprotein, essential for cellular trafficking of the chylomicrons. After the chylomicrons are reconstituted they exit the mucosa into the lymphatic system and subsequently pass into the systemic circulation. Some small chain triglycerides can bypass this system and enter the portal venous system directly.

Protein digestion begins in the stomach by the action of pepsin and acid. However, most protein hydrolysis occurs in the lumen of the jejunum by action of pancreatic proteases. These are secreted as inactive precursors. Chymotrypsin is converted to trypsin by the action of the small intestinal enzyme enterokinase. Activated trypsin further activates chymotrypsin and other proteases, such as carboxypeptidase. The products of protein hydrolysis are amino acids and oligopeptides. The latter are further hydrolysed to mono-, di- and tripeptides by brush border hydrolyases and are absorbed by specific membrane transporters. Di- and tripeptides undergo hydrolysis to amino acids in the cytoplasm of the enterocyte. Isolated protein maldigestion/malabsorption is extremely rare. It usually occurs in association with malabsorption of other macronutrients.

Fat malabsorption

Diseases of the pancreas and the small intestine are the usual causes of steatorrhoea in children. Chronic liver disease may cause steatorrhoea but this is in the setting of severe and obvious liver disease (such as the patient who is cirrhotic and jaundiced) and is not usually a diagnostic problem.

Steatorrhoea causes bulky stools and can lead to other nutritional deficits. Fat is responsible for approximately 40% of caloric intake in the Western diet. Thus, fat malabsorption can lead to failure to thrive due to an energy-deficient diet. Some vitamins are fat-soluble and require normal fat digestion for their absorption. These include A, D, E and K. Thus patients with steatorrhoea may also develop signs of fat-soluble vitamin deficiency, as described above. Essential fatty acids such as arachidonic acid are also malabsorbed in patients with pancreatic malabsorption. A scaling skin rash is one physical manifestation of essential fatty acid deficiency.

Pancreatic and intestinal diseases associated with fat malabsorption can also result in protein and carbohydrate maldigestion/malabsorption. Thus it is not uncommon to find a mixed picture of malabsorption. Protein maldigestion/malabsorption results in hypoproteinaemia. The main physical manifestations are growth failure, peripheral oedema and ascites.

Pancreatic disease

Cystic fibrosis

See also Chapter 14.6.

Cystic fibrosis:

• is the commonest cause of pancreatic malabsorption in the Caucasian population

• has an incidence in the population of approximately 1 per 2000

• is an inborn error in epithelial chloride secretion (cystic fibrosis transmembrane conductance regulator (CFTR)).

Organs affected include:

• gastrointestinal tract and liver

• sinopulmonary tract

• pancreas

• exocrine portion of the sweat glands

• vas deferens

• sweat duct (CFTR absorbs rather than secretes chloride in this organ).

Because of the fluid and salt transport defects, patients with cystic fibrosis produce more viscous secretions in lung, gut, pancreas and vas deferens, leading to:

• chronic suppurative lung disease

• nasal polyps

• pancreatic insufficiency

• intussusception

• meconium ileus and distal intestinal obstruction syndrome

• infertility

• elevated sweat sodium and chloride, which can lead to heat prostration in warmer climates.

Chronic liver disease will develop in 10–15% of children with cystic fibrosis.

Malabsorption in cystic fibrosis frequently results in malnutrition and there may be symptoms and signs of specific nutrient deficits such as hypoalbuminaemic oedema, night blindness due to vitamin A deficiency or skin rash due to essential fatty acid deficiency. Median life expectancy is 30 years, with death usually from respiratory failure or haemorrhage from portal hypertension and oesophageal varices.

Many mutations have been identified in the CFTR. Depending on what part of the channel the mutation affects, the phenotype can vary from mild to severe disease. Individuals with milder mutations have milder lung disease and do not usually have malabsorption, as pancreatic function is normal.

Newborn screening:

• can detect cystic fibrosis in the neonatal period

• involves measurement of immunoreactive trypsinogen and/or CFTR mutations

• is the commonest mode of presentation when it is performed.

In children with the severe phenotype who are missed by screening, or in countries where screening is not performed, presentation is usually in the first year with chronic diarrhoea and failure to thrive, with or without respiratory symptoms. In milder phenotypes, patients may not present until adult life with respiratory disease or infertility.

Diagnostic investigations for cystic fibrosis are:

• elevated sweat sodium and chloride (‘sweat test’) – simplest and cheapest

• CFTR mutation analysis.

Treatment is usually undertaken in a tertiary referral multidisciplinary clinic and involves:

• physiotherapy, inhalation therapy and antibiotics for chest disease

• pancreatic enzyme supplements and nutritional support

• specific therapy may be required for the other intestinal/liver complications.

Shwachman syndrome

The features of Shwachman syndrome are:

• agenesis of the pancreatic acinus

• short stature

• dysplasia of the metaphysis of the long bones

• cyclical neutropenia.

There is no specific diagnostic test; treatment includes pancreatic exocrine replacement and treatment of infections.

Chronic pancreatitis

Causes of chronic pancreatitis include:

• protein energy malnutrition

• hereditary pancreatitis (rare)

• idiopathic fibrosing pancreatitis (rare).

Small bowel disease

Coeliac disease (gluten enteropathy)

Coeliac disease is a disorder characterized by intestinal injury induced by the cereal protein gluten. Gluten is a glycoprotein found in wheat, barley and rye and, to a lesser extent, oats. In susceptible individuals, the ingestion of gluten induces a cell-mediated injury of the intestinal mucosa resulting in severe villous atrophy, crypt hyperplasia and infiltration of the epithelium with lymphocytes (intraepithelial lymphocytes). In Western countries, the incidence of coeliac disease in the general population may be as high as 1 in 70, although not all affected individuals develop the classical manifestations of coeliac disease.

Modes of presentation include:

• ‘Classical’ coeliac disease (Fig. 20.3.2)

• between 9 and 18 months of age

• 

anorexia, weight loss, abdominal distension and wasting

• chronic diarrhoea with or without:

• iron deficiency anaemia

• hypoproteinaemic oedema

• fat-soluble vitamin deficiency

• The older child with:

• growth failure

• chronic diarrhoea

• iron deficiency

• Positive antibody screening (now the commonest form of assessment leading to diagnosis).

Examples of antibodies used to screen when there is suspicion of coeliac disease include:

• antigliadin

• anti endomysial

• antitissue transglutaminase antibodies.

Antiendomysial and antitissue transglutaminase antibodies have sensitivity and specificity of greater than 95%. However, it is important to note that these are screening tests only.

The following are important points in the approach to the diagnosis of coeliac disease in childhood:

• small bowel biopsy is mandatory for the diagnosis (Fig. 20.3.3)

• small bowel biopsy should be performed while the patient is on an unrestricted diet

• there is no place for an empirical trial of a gluten-free diet

• definitive diagnosis is important, as treatment is a lifelong gluten-free diet.

A second biopsy can be undertaken to establish that the intestine has returned to normal on a restricted diet. If there is doubt about the diagnosis, a subsequent gluten challenge with repeat biopsy can be undertaken.

Enterocyte defect

Abetalipoproteinaemia is a recessively inherited defect in chylomicron assembly. Patients develop steatorrhoea early in life with:

• fat-soluble vitamin deficiencies

• low serum cholesterol and triglycerides.

Small bowel biopsy reveals fat laden enterocytes.

Impaired lymphatic drainage

Obstructed lymphatic drainage prevents chylomicrons from migrating from the gut to the systemic circulation. The main cause is intestinal lymphangiectasia. This can lead to:

• fat malabsorption

• low serum cholesterol and triglycerides

• hypoproteinaemia and lymphopenia (loss of lymph into gut lumen)

• abnormal mucosal biopsy.

Other causes of reduced mucosal surface and reduced contact time

Miscellaneous inflammatory and surgical conditions can lead to loss of absorptive surface or reduced contact between chyme and the mucosa. Such conditions include:

• milk protein intolerance (severe)

• infections such as rotavirus infection

• severe immunodeficiency disorders

• autoimmune enteropathy

• short gut syndrome (surgical removal)

• motility disorders causing very rapid intestinal transit.

Clinical example

George was 9 years old. He presented with a 6-month history of intermittent bloating, abdominal pain and diarrhoea up to 6–7 times per day. He had lost 1  kg in weight in the past 2 months. He reported that dairy products such as milk and ice-cream made his symptoms worse. He had no past history of significant illness. George was the oldest son of Greek migrants. His mother reported that she could not drink milk, as it made her feel sick.

On examination he was well looking. His weight was on the 50th percentile and his height was on the 10th percentile. There was no abdominal distension, organomegaly, signs of chronic liver disease or evidence of nutritional deficiency such as anaemia or peripheral oedema. Examination of his anus did not reveal any evidence of perianal disease.

Investigations included a normal full blood count, differential white cell count and ESR. C reactive protein was less than 1  g/l. Lactose breath hydrogen measurement following oral ingestion of 50  g of lactose increased 100 parts per million above baseline levels within 60 minutes of ingestion of lactose (normal rise 20 parts per million), indicating lactose intolerance.

George was diagnosed as having lactose intolerance. His history suggested ontogenic lactase deficiency. This was confirmed by small bowel biopsy, which demonstrated normal morphology, and disaccharidase measurement, which revealed very low lactase activity but normal sucrase and maltase activities. Treatment is a low-lactose diet.

Watery diarrhoea

Carbohydrate digestion and absorption

Dietary carbohydrates are primarily starch (polysaccharides, amylose and amylopectin), disaccharides (sucrose, in table sugar; lactose, in milk) and some monosaccharides such as fructose.

Starch polymers are large molecules composed of long chains of glucose. These chains are broken down by the action of salivary and pancreatic amylase, which release a disaccharide (amylose), trisaccharide (maltotriose) and a series of branched oligosaccharides (alpha limit dextrins). These molecules are further digested by the brush border enzymes, sucrase–isomaltase and glucoamylase, to the monosaccharide glucose.

The disaccharides sucrose and lactose are metabolized by disaccharidases on the intestinal brush border. Sucrase breaks sucrose down to glucose and fructose and lactase breaks down lactose into glucose and galactose. Glucose and galactose are absorbed by the enterocyte sodium–glucose cotransporter (SGLT), which absorbs the monosaccharides in an energy dependent fashion. Fructose is absorbed by facilitated diffusion (non-energy-dependent) by the transporter termed GLUT-5.

Carbohydrate malabsorption

The presence of non-absorbed osmotically active nutrients in the gut lumen results in osmotic retardation of water absorption, leading to watery diarrhoea. This is referred to as osmotic diarrhoea. Osmotically active compounds are usually low-molecular-weight compounds such as monosaccharides and disaccharides. Osmotic diarrhoea is usually due to maldigestion and/or malabsorption of carbohydrates but can be caused by the ingestion of laxatives such as sorbitol or MgCl2. Unabsorbed carbohydrate present in the lumen of the large bowel is fermented to short chain fatty acids such as butyrate. This results in a highly acidic stool, which can cause perianal excoriation. The colon can absorb the anionic forms of these acids in exchange for bicarbonate, causing a mild hyperchloraemic acidosis.

While stating the obvious, it is important to appreciate that one cannot malabsorb a nutrient that has not been ingested. Thus it is useful to obtain a dietary history in patients suspected of osmotic diarrhoea. One needs to ascertain the nature of the carbohydrates being ingested, and in some instances the age of introduction of the carbohydrate, which can then be compared with the age of onset of symptoms. For example, the onset of osmotic diarrhoea commensurate with the introduction of fruit into the diet suggests the diagnosis of congenital sucrase–isomaltase deficiency.

Disaccharidase deficiencies and monosaccharide malabsorption

Congenital

Ontogenic lactase deficiency:

• occurs in most of the non-Caucasian population of the world

• is dominantly inherited

• is physiological (due to the disappearance of lactase)

• presents in late childhood.

Ingesting lactose causes diarrhoea, bloating, excessive flatus and weight loss. Treatment is a low-lactose diet.

Congenital sucrase–isomaltase deficiency is caused by inactivating mutations in the sucrase–isomaltase gene. These mutations:

• are recessively inherited

• lead to similar symptoms as for lactase deficiency with the ingestion of sucrose

• cause onset of symptoms at the time of weaning when fruit is introduced to the diet.

Treatment is a low-sucrose diet.

Congenital monosaccharide malabsorption refers to defective glucose/galactose malabsorption. Features are:

• mutations in SGLT1

• recessively inherited

• present in the neonatal period.

Treatment is substitution of fructose for glucose–galactose.

Acquired

Except for ontogenic lactase deficiency, acquired disorders are much more common than inherited deficiencies. Lactase is more susceptible to injury than sucrase.

Causes of disaccharidase deficiencies include:

• viral gastroenteritis

• coeliac disease

• chronic giardiasis

• milk protein enteropathy

• small bowel bacterial overgrowth syndrome

• immunodeficiency disorders

• autoimmune enteropathy.

Monosaccharide transporters are less susceptible to injury because, unlike disaccharidase enzymes, they are deeply embedded in the brush border membrane. However, severe enteropathies can occasionally result in monosaccharide malabsorption. Examples include:

• congential villous atrophy (which presents in newborns)

• severe postinfectious enteritis

• milk protein intolerance

• autoimmune enteropathy.

Monosaccharide malabsorption is life-threatening and requires a level of care found only in tertiary paediatric centres. The treatment is to remove the offending carbohydrate from the diet and substitute an alternative. In acquired disorders, treatment may also be required for the primary mucosal disease.

Disorders of fluid and electrolyte transport

In the normal child approximately 5 litres (depending on size!) of fluid and electrolytes enters the upper gastrointestinal tract per day. One litre is ingested and the remaining volume is from normal secretions into the lumen. The majority of this fluid is absorbed before reaching the colon. Stool weights range from 75 to 150  g per day, of which approximately 75% is water. Small increases in stool water, as little as 30–40  ml/d are enough to produce diarrhoea.

Water is absorbed by osmosis through paracellular pathways in the mucosa. Electrolytes are absorbed by a variety of active transport or passive transport processes. Anions such as chloride and bicarbonate can be absorbed or actively secreted. This varies according to the region of small or large intestine. Regulation of gastrointestinal fluid and electrolyte transport is closely integrated by humoral and neural factors involved in fluid and electrolyte homeostasis. Abnormal fluid and electrolyte transport can be due to inherited defects in specific electrolyte transporters, but more commonly it is due to mucosal damage or inflammation.

Congenital

Congenital sodium diarrhoea and congenital chloride diarrhoea are rare inherited disorders of Na/H exchange and Cl/HCO exchange, respectively. They cause:

• diarrhoea in utero which results in polyhydramnios

• profuse diarrhoea, obvious from birth

• systemic electrolyte disturbances.

Acquired

Isolated water and salt malabsorption is very rare in childhood in the developed world. However, defective salt and water transport can contribute to diarrhoea in:

• disorders which damage or inflame the mucosa of small or large intestine

• bile salt malabsorption (bile acids irritate the colonic mucosa and act as potent stimulants of secretion).

Excessive salt and water loss in the stool may lead to dehydration and electrolyte disturbances. Treatment may require salt and water replacement in addition to treatment of the underlying disease.

Bloody diarrhoea

Chronic bloody diarrhoea is usually caused by inflammatory disorders of the colon such as:

• milk colitis in infants

• infections such as bacteria or parasites

• inflammatory bowel disease in older children. The two major forms are:

• ulcerative colitis

• Crohn disease.

Blood is not always obvious in the stool. However, the presence of leukocytes on stool microscopy (Fig. 20.3.4) indicates the presence of colitis. Malabsorption of fluid and electrolytes by the inflamed colonic mucosa is a major factor contributing to diarrhoea. Malabsorption of nutrients is uncommon in milk colitis and inflammatory bowel disease. In contrast, excessive blood and protein loss from the inflamed intestinal mucosa can cause iron deficiency anaemia and hypoproteinaemic oedema. This is called protein-losing enteropathy.

Nutrient malabsorption with little or no diarrhoea

Children present with symptoms and signs of nutrient deficiency with little or no accompanying diarrhoea. This is often due to dietary insufficiency, e.g. inadequate iron intake, but sometimes it can be due to malabsorption of the specific nutrient.

Vitamin B12

Vitamin B12 is ingested in animal protein and is liberated by pepsin in the stomach. In the stomach, the free vitamin B12 binds to a binding protein (R protein) which has greater affinity for the vitamin than intrinsic factor (carrier protein). Intrinsic factor is produced by epithelial cells in the gastric mucosa. The vitamin B12–R protein complex moves to the duodenum where trypsin cleaves the complex, releasing free vitamin B12, which then binds to intrinsic factor. The intrinsic factor–vitamin B12 complex moves to the ileum where it is absorbed into the enterocytes by carrier mediated transport. On entry into the enterocyte, vitamin B12 is separated from intrinsic factor and subsequently exits the enterocyte into the circulation bound to transcobalamin, which carries the vitamin to sites distant from the intestine.

Clinical example

John was 9 months old. He presented with a 6-week history of poor weight gain, irritability and pallor. His mother was also concerned about his development. He was able to sit but could not pull himself to standing. His language had not progressed from babbling, which was in stark contrast to his older sibling, who had several single words at this age. John had a poor appetite but no diarrhoea. He was originally breastfed and his mother ingested a normal diet during pregnancy and lactation.

On examination, John was a pale irritable boy. He had moderate abdominal distension but no organomegaly. He could sit up unsupported but was mildly hypotonic and would not weight bear. There were no focal neurological signs.

Investigation results included: Hb of 65  g/l (normal 120–150) with a megaloblastic blood film, serum B12 50  pmol/l (normal 120–600) and red blood cell folate 350  nmol/l (normal 200–1000). A Shilling test revealed urinary excretion of ingested radioactive vitamin B12 (after parenteral administration of a non-radioactive flushing dose of 1  mg vitamin B12) of 1% (normal 8%), with no enhancement of urinary excretion with the addition of intrinsic factor.

John’s Shilling test suggested a defect in the ileal vitamin B12 transporter, as the test was abnormal and did not recover with the addition of intrinsic factor. His age of presentation and lack of prior intestinal surgery suggest a congenital defect. His symptoms and megaloblastic anaemia corrected with administration of parenteral vitamin B12.

Both congenital and acquired disorders can lead to vitamin B12 malabsorption.

Congenital disorders

Congenital defects in:

• ileal vitamin B12 transporter

• intrinsic factor

• transcobalamin

can lead to vitamin B12 malabsorption and deficiency. This usually presents in the second 6 months of life after the vitamin B12 accumulated during intrauterine life is exhausted.

Symptoms are due to megaloblastic anaemia and the central nervous system effects of deficiency. Babies born to vegan mothers (who ingest no animal product and thus can themselves be vitamin-B12-deficient) and weaned on to a vegan diet can present with a similar picture, although usually in the first 6 months, as they are deficient from birth. Dietary history is important to differentiate between dietary deficiency and malabsorption.

Acquired disorders

Acquired disorders that lead to B12 malabsorption are:

• surgical resection of the ileum

• atrophic gastritis

• gastric surgery

• autoimmune pernicious anaemia (blocking antibodies to intrinsic factor)

• pancreatic insufficiency (failure to hydrolyse vitamin B12–R protein)

• small bowel bacterial overgrowth (competition for vitamin B12 by bacteria).

Iron

Iron absorption occurs in the duodenum and proximal jejunum. An apical enterocyte carrier called the divalent metal cation transporter mediates uptake into the enterocyte. Iron is exported to the circulation via a basolateral process which has not yet been fully defined. In non-breastfed children, only 5–10% of dietary iron is absorbed. The efficiency of iron absorption is greater in breastfed infants because the iron carrier transferrin is present in breast milk. Iron absorption is finely regulated at the level of the enterocyte so that absorption does not exceed requirements. Excessive iron accumulation can lead to multiple organ damage (haemochromatosis).

Iron deficiency is the commonest nutritional deficiency in humans and is usually due to:

• inadequate dietary intake

• excessive gastrointestinal blood loss (bleeding lesions or inflammation).

Inherited defects in iron uptake mechanisms leading to iron deficiency not responsive to oral iron have been described but have not yet been delineated at the molecular or genetic level.

Acquired disorders

Iron deficiency anaemia can occasionally be the primary presenting feature of small intestinal disease such as:

• coeliac disease

• milk protein intolerance

• Crohn disease.

Miscellaneous nutrients

Calcium

Calcium absorption occurs in the duodenum and proximal jejunum and is largely under the regulation of vitamin D:

• hypocalcaemia can be associated with a wide variety of digestive disorders affecting intestinal calcium uptake or the biosynthesis and availability of vitamin D (Ch. 19.5)

• it commonly presents with tetany of the fingers and occasionally seizures.

Zinc

Zinc is absorbed by the small intestine. Zinc deficiency can be due to:

• low breast milk zinc levels in solely breastfed infants

• an inherited defect in zinc absorption (acrodermatitis enteropathica)

• conditions associated with steatorrhoea

• intestinal inflammatory disorders.

Zinc deficiency can cause diarrhoea but the most dramatic manifestation is an erythematous scaly rash on the finger tips and around the perineum and mouth (Fig. 20.3.1).

Magnesium

Magnesium is absorbed in the proximal small intestine. Magnesium malabsorption leading to deficiency can be:

• inherited (primary hypomagnesaemia)

• secondary to other conditions leading to malabsorption.

Hypomagnesaemia causes similar symptoms to calcium deficiency.

Isolated protein malabsorption

Enterokinase deficiency:

• is a very rare disorder

• presents with diarrhoea, growth failure and severe hypoproteinaemia.

Amino acids

Defective amino acid absorption due to mutations in amino acid transporters can occur in:

• Hartnup disease

• cystinuria

• lysinuric protein intolerance.

These defects are rare disorders affecting amino acid transport in gut and kidney and in other organs in the last case. They do not have gastrointestinal symptoms and there are no nutritional consequences because of compensatory absorptive mechanisms for peptide and amino acid absorption.

Summary of the diagnostic approach to suspected malabsorption

Initial clinical assessment and stool examination will suggest the diagnosis in most children. Stool microscopy and measurement of stool-reducing substances can be performed in the clinician’s office and are readily available ‘bedside’ tests. If the diagnosis is not immediately obvious, the clinician will be in a position to investigate a limited differential list with simple and well directed diagnostic tests.

In patients with steatorrhoea the following will be useful but are not necessarily indicated for each patient:

• full blood count and differential white cell count

• serum triglycerides/cholesterol

• sweat test

• small bowel biopsy

• X-ray of long bones.

In patients with carbohydrate maldigestion/malabsorption the following might be indicated:

• breath hydrogen testing: challenge with the carbohydrate of interest (e.g. lactose)

• small bowel biopsy/mucosal disaccharidase activities

• occasionally with monosaccharide malabsorption

• inpatient dietary manipulation with close observation of stool output.

In patients with bloody diarrhoea (if stool cultures negative for pathogens) consider:

• gastroscopy and colonoscopy

• biopsy of small bowel and colon

• sometimes radiology looking for inflammatory bowel disease in jejunum/ileum.

Sometimes highly specialized investigations will be required to establish the diagnosis of some disorders:

• measurement of micronutrients such as iron, zinc and calcium for suspected deficiency

• Schilling test is required for the workup of vitamin B12 deficiency. Abnormally low urinary excretion of the ingested radioactive vitamin B12 indicates vitamin B12 malabsorption

• Schilling test can be used to assess patients with bile salt malabsorption due to ileal resection

• specialized breath tests are used in the workup of bacterial overgrowth syndrome

• immunoglobulins and B- and T-cell subset determination for detection of immunodeficiency disorders.

Practical points

• Diagnosis is not by exclusion

• A thorough history, physical examination and stool examination will suggest the diagnosis in most disorders

• simple well-directed investigations usually confirm the clinical diagnosis

• there is no such thing as a ‘malabsorption workup’

20.4

Gastro-oesophageal reflux and Helicobacter pylori infection

G. Davidson

This chapter discusses gastro-oesophageal reflux (GOR) a very common clinical problem in infants and children, and Helicobacter pylori, an infectious agent that colonizes the stomach in more than 50% of the world’s population. H. pylori infection is acquired in early childhood but its disease manifestations usually do not occur until adulthood. It is also possible that there may be a relationship between the two, and this will be discussed.

Gastro-oesophageal reflux

Gastro-oesophageal reflux can be defined as the spontaneous or involuntary passage of gastric content into the oesophagus. The origin of the gastric content can vary and includes saliva, ingested food and fluid, gastric secretions and pancreatic or biliary secretions that have first been refluxed into the stomach (duodenogastric reflux). The difference between physiological reflux and gastro-oesophageal reflux disease (GORD) is often blurred by the anxiety engendered in parents, particularly first-time parents, by symptoms such as vomiting and irritability. Physiological reflux manifested by spilling, regurgitation and occasional vomiting occurs in more than 60% of healthy infants by 4 months of age, resolves in the majority by 12 months and rarely leads to GORD. Conservative management is important, particularly in an otherwise healthy infant, so as not to label the condition as a disease state when in fact it is not.

The symptoms of GORD in children aged 3–18 years ranges from 1.8–22% and are more refractory and associated with complications such as pain, vomiting, haematemesis, oesophagitis, stricture, growth failure, swallowing difficulties, respiratory symptoms and apnoea.

Pathophysiology (Table 20.4.1)

The main barrier to GOR is the pressure gradient across the lower oesophageal sphincter (LOS) which is formed by the intrinsic LOS (thickened smooth muscle of the lower oesophagus) and the extrinsic striated muscle of the crural diaphragm. Both components work together to generate LOS pressure, which can be measured by intraluminal manometry. The current understanding of LOS function suggests that a LOS pressure of 5–10  mmHg above intragastric pressure is sufficient to maintain an antireflux barrier. Sphincter incompetence as a pathological mechanism for GORD is extremely unlikely. Transient lower oesophageal sphincter relaxation (TLOSR) is the major mechanism responsible for GOR in infants, children and adults. A TLOSR is defined as an abrupt decrease in LOS pressure unrelated to swallowing or oesophageal body peristalsis. TLOSRs are significantly longer in duration than swallow-related sphincter relaxation and also have a lower nadir pressure. It is unclear at present whether GORD in children is characterized by either a higher rate of TLOSR or a greater incidence of GOR episodes during TLOSRs. Both have been noted in adults.

Abdominal straining

Abdominal straining, which occurs frequently in infants, probably exacerbates GOR only when there is simultaneous TLOSR, because both LOS tone and the crural diaphragm are inhibited. The neuroregulation of TLOSR is controlled via a vagovagal reflex. The afferent arm of the reflex is initiated by mechanoreceptors in the wall of the proximal stomach, and the efferent arm via a brain-stem pattern generator. The presynaptic neurotransmitter is acetylcholine and the postsynaptic neurotransmitter is nitric oxide. Feeding is a potent stimulus for TLOSRs, evidenced by the fact that, in children with GORD, TLOSRs increase from four per hour in the fasting state to eight per hour in the fed state.

Oesophageal body peristalsis

Assessment of oesophageal volume clearance is difficult because of the lack of defined motility criteria. Primary oesophageal body peristalsis following a swallow facilitates clearance. Secondary peristalsis is initiated by an abrupt sustained increase in intra-oesophageal pressure that accompanies a reflux episode. The frequency of swallowing and type of pressure wave sequence propagated determine the effectiveness of volume clearance. While severe GORD with reflux oesophagitis is associated with a 30–50% decrease in pressure wave amplitude, this in itself may not impair bolus clearance.

Gastric emptying

The role of gastric emptying in the pathophysiology of GORD is not clear. Delayed gastric emptying could exacerbate GOR by prolonging gastric distension and increasing the frequency of TLOSRs. Studies attempting to correlate a delay in gastric emptying with acid GOR have been inconclusive. While the final answer to this question awaits the development of more sophisticated investigative techniques, there are some children at the severe end of the GORD spectrum in whom delayed gastric emptying may be an issue, especially those with neurological or respiratory disease.

Clinical manifestations

There are many causes of regurgitation and vomiting in infants and children, both within the gastrointestinal tract and external to it. The more common causes are outlined in Table 20.4.2.

Regurgitation can be defined as effortless spilling of gastric content that is usually benign. Vomiting, on the other hand, is a forceful emptying of gastric content that should always be explained. The content of the vomitus is important because of the likely cause, as is the age at onset. Bile staining implies small bowel obstruction and should be examined immediately. Blood staining implies ulceration or gastritis.

Table 20.4.3 highlights the symptoms suggestive of GORD in infants and children. Symptoms do vary according to age. Infants more frequently regurgitate but can also have reflux-related behaviours, which include apparent discomfort, yawning, stretching, stridor or mouthing. Irritability and crying as the sole manifestation of GOR should be assessed with caution as it has been shown recently that in children with proven GORD there was no association and no response to proton pump inhibitors. More serious complications include apnoea, acute life-threatening events and recurrent chest disease secondary to aspiration. Chronic cough without associated lung disease is unlikely to be reflux-related.

Older children, usually over the age of 4 years, can describe common symptoms such as heartburn, chest pain and a sick or sour taste in the mouth, implying refluxate. Some younger children may complain of a hot feeling in the chest, abdomen or throat.

GORD is a common problem in neurologically impaired children and, while regurgitation is the most likely symptom, problems such as recurrent chest disease, feeding difficulties and food refusal, anaemia, weight loss and behavioural changes can all be manifestations of GORD.

There are many potential extra-oesophageal manifestations of GORD and these are highlighted in Table 20.4.4, and need to be considered as they may be the only presenting symptom or sign. Ear nose and throat manifestations such as otitis media, sinusitis and dental erosions are now being recognized

Eosinophilic oesophagitis

This condition has only been recognized in the past decade. GORD is distinguished from eosinophilic oesophagitis by the presence of eosinophils in the oesophageal mucosa. Their presence had previously been thought to be due to acid reflux. The density of eosinophils in the mucosa ( ................
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