Oesophagus, stomach and duodenum

This muscular tube extends 25 cm from the cricoid cartilage to the cardiac orifice of the stomach. It has an upper and a lower sphincter. A peristaltic swallowing wave propels the food bolus into the stomach (Fig. 22.1).

The stomach acts as a ‘hopper’, retaining and grinding food, then actively propelling it into the upper small bowel (Fig. 22.2).

Gastric secretion

Gastrin, histamine and acetylcholine are the key stimulants of acid secretion. Hydrogen and chloride ions are secreted from the apical membrane of gastric parietal cells into the lumen of the stomach by a hydrogen–potassium adenosine triphosphatase (ATPase) (‘proton pump’) (Fig. 22.3). The hydrochloric acid sterilises the upper gastrointestinal tract and converts pepsinogen – which is secreted by chief cells – to pepsin. The glycoprotein intrinsic factor, secreted in parallel with acid, is necessary for vitamin B₁₂ absorption.

Small intestine

The small bowel extends from the ligament of Treitz to the ileocaecal valve (Fig. 22.4). During fasting, a wave of peristaltic activity passes down the small bowel every 1–2 hours. Entry of food into the gastrointestinal tract stimulates small bowel peristaltic activity. Functions of the small intestine are:

Digestion and absorption

Fat

Dietary lipids comprise long-chain triglycerides, cholesterol esters and lecithin. Lipids are insoluble in water and undergo lipolysis and incorporation into mixed micelles before they can be absorbed into enterocytes along with the fat-soluble vitamins A, D, K and E. The lipids are processed within enterocytes and pass via lymphatics into the systemic circulation. Fat absorption and digestion can be considered as a stepwise process, as outlined in Figure 22.5.

Carbohydrates

Starch is hydrolysed by salivary and pancreatic amylases to alpha-limit dextrins containing 4–8 glucose molecules; to the disaccharide, maltose; and to the trisaccharide, maltotriose.

Disaccharides are digested by enzymes fixed to the microvillous membrane to form the monosaccharides, glucose, galactose and fructose. Glucose and galactose enter the cell by an energy-requiring process involving a carrier protein, and fructose enters by simple diffusion.

Protein

The steps involved in protein digestion are shown in Figure 22.6. Intragastric digestion by pepsin is quantitatively modest but important because the resulting polypeptides and amino acids stimulate CCK release from the mucosa of the proximal jejunum, which in turn stimulates release of pancreatic proteases, including trypsinogen, chymotrypsinogen, pro-elastases and procarboxypeptidases, from the pancreas. On exposure to brush border enterokinase, inert trypsinogen is converted to the active proteolytic enzyme trypsin, which activates the other pancreatic proenzymes. Trypsin digests proteins to produce oligopeptides, peptides and amino acids. Oligopeptides are further hydrolysed by brush border enzymes to yield dipeptides, tripeptides and amino acids. These small peptides and the amino acids are actively transported into the enterocytes, where intracellular peptidases further digest peptides to amino acids. Amino acids are then actively transported across the basal cell membrane of the enterocyte into the portal circulation and the liver.

Water and electrolytes

Absorption and secretion of electrolytes and water occur throughout the intestine. Electrolytes and water are transported by two pathways:

• the paracellular route, in which passive flow through tight junctions between cells is a consequence of osmotic, electrical or hydrostatic gradients

• the transcellular route across apical and basolateral membranes by energy-requiring specific active transport carriers (pumps).

In healthy individuals, fluid balance is tightly controlled, such that only 100 mL of the 8 litres of fluid entering the gastrointestinal tract daily is excreted in stools (Fig. 22.7).

Vitamins and trace elements

Water-soluble vitamins are absorbed throughout the intestine. The absorption of folic acid, vitamin B₁₂, calcium and iron is described on page 1024.

Protective function of the small intestine

Physical defence mechanisms

There are several levels of defence in the small bowel (Fig. 22.8). Firstly, the gut lumen contains host bacteria, mucins and secreted antibacterial products, including defensins and immunoglobulins which help combat pathogenic infections. Secondly, epithelial cells have relatively impermeable brush border membranes, and passage between cells is prevented by tight and adherens junctions. These cells can react to foreign peptides (‘innate immunity’) using pattern recognition receptors found on cell surfaces (Toll receptors) or intracellularly. Lastly, in the subepithelial layer, immune responses occur under control of the adaptive immune system in response to pathogenic compounds.

Immunological defence mechanisms

Gastrointestinal mucosa-associated lymphoid tissue (MALT) constitutes 25% of the total lymphatic tissue of the body and is at the heart of adaptive immunity. Within Peyer’s patches, B lymphocytes differentiate to plasma cells following exposure to antigens, and these migrate to mesenteric lymph nodes, to enter the blood stream via the thoracic duct. The plasma cells return to the lamina propria of the gut through the circulation and release immunoglobulin A (IgA), which is transported into the lumen of the intestine. Intestinal T lymphocytes help localise plasma cells to the site of antigen exposure, as well as producing inflammatory mediators. Macrophages in the gut phagocytose foreign materials and secrete a range of cytokines, which mediate inflammation. Similarly, activation of mast-cell surface IgE receptors leads to degranulation and release of other molecules involved in inflammation.

Pancreas

The exocrine pancreas (Box 22.1) is necessary for the digestion of fat, protein and carbohydrate. Proenzymes are secreted from pancreatic acinar cells in response to circulating gastrointestinal hormones (Fig. 22.9) and are activated by trypsin. Bicarbonate-rich fluid is secreted from ductular cells to produce an optimum alkaline pH for enzyme activity.

Colon

The colon (Fig. 22.10) absorbs water and electrolytes. It also acts as a storage organ and has contractile activity. Two types of contraction occur. The first of these is segmentation (ring contraction), which leads to mixing but not propulsion; this promotes absorption of water and electrolytes. Propulsive (peristaltic contraction) waves occur several times a day and propel faeces to the rectum. All activity is stimulated after meals, probably in response to release of motilin and CCK. Faecal continence depends upon maintenance of the anorectal angle and tonic contraction of the external anal sphincters. On defecation, there is relaxation of the anorectal muscles, increased intra-abdominal pressure from the Valsalva manœuvre and contraction of abdominal muscles, and relaxation of the anal sphincters.

The nervous system and gastrointestinal function

The central nervous system (CNS), the autonomic system (ANS) and the enteric nervous system (ENS) interact to regulate gut function. The ANS comprises:

Imaging

Contrast studies

X-rays with contrast medium are usually performed to assess not only anatomical abnormalities but also motility. Barium sulphate provides good mucosal coating and excellent opacification but can precipitate impaction proximal to an obstructive lesion. Water-soluble contrast is used to opacify bowel prior to abdominal computed tomography and in cases of suspected perforation. The double contrast technique improves mucosal visualisation by using gas to distend the barium-coated intestinal surface. Contrast studies are useful for detecting filling defects, such as tumours, strictures, ulcers and motility disorders, but are inferior to endoscopic procedures and more sophisticated cross-sectional imaging techniques, such as computed tomography and magnetic resonance imaging. The major uses and limitations of various contrast studies are shown in Box 22.3 and Figure 22.11.

22.3   Contrast radiology in the investigation of gastrointestinal disease

	Barium swallow/meal	Barium follow-through	Barium enema
Indications and major uses	Motility disorders (achalasia and gastroparesis) Perforation or fistula (non-ionic contrast)	Diarrhoea and abdominal pain of small bowel origin Possible obstruction by strictures Suspected malabsorption Crohn’s disease assessment	Altered bowel habit Evaluation of strictures or diverticular disease Megacolon Chronic constipation
Limitations	Risk of aspiration Poor mucosal detail Low sensitivity for early cancer Inability to biopsy	Time-consuming Radiation exposure Relative insensitivity	Difficult in frail or incontinent patients Sigmoidoscopy needed to see rectum Low sensitivity for lesions < 1 cm

Ultrasound, computed tomography and magnetic resonance imaging

Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) are key tests in the evaluation of intra-abdominal disease. They are non-invasive and offer detailed images of the abdominal contents. Their main applications are summarised in Box 22.4 and Figure 22.12.

22.4   Imaging in gastroenterology

	Ultrasound	CT	MRI	CT-PET
Indications and major uses	Abdominal masses Organomegaly Ascites Biliary tract dilatation Gallstones Guided biopsy of lesions Small bowel imaging	Assess pancreatic disease Hepatic tumour deposits CT colonography (‘virtual colonoscopy’) Tumour staging Assess lesion vascularity Abscesses and collections	Hepatic tumour staging MRCP Pelvic/perianal disease Crohn’s fistulae Small bowel visualisation	Detection of metastases not seen on ultrasound or CT Images can be fused with CT to form composite image
Limitations	Low sensitivity for small lesions Little functional information Operator-dependent Gas and obesity may obscure view	Cost Radiation dose	Claustrophobic patients Contraindicated in presence of metallic prostheses, cardiac pacemaker, cochlear implants	Signal detection depends on metabolic activity within tumour – not all are metabolically active

Endoscopy

Videoendoscopes provide high-definition imaging and accessories can be passed down the endoscope to allow both diagnostic and therapeutic procedures, some of which are illustrated in Figure 22.13. Endoscopes with magnifying lenses allow almost microscopic detail to be observed, and imaging modalities, such as confocal endomicroscopy, autofluorescence and ‘narrow band imaging’, are increasingly used to detect subtle abnormalities not visible by standard ‘white light’ endoscopy.

Upper gastrointestinal endoscopy

This is performed under light intravenous benzodiazepine sedation, or using only local anaesthetic throat spray after the patient has fasted for at least 4 hours. With the patient in the left lateral position, the entire oesophagus (excluding pharynx), stomach and first two parts of duodenum can be seen. Indications, contraindications and complications are given in Box 22.5.

22.5   Upper gastrointestinal endoscopy

Indications

• Dyspepsia over 55 yrs of age or with alarm symptoms

• Atypical chest pain

• Dysphagia

• Vomiting

• Weight loss

• Acute or chronic gastrointestinal bleeding

• Screening for oesophageal varices in patients with chronic liver disease

• Abnormal CT scan or barium meal

• Duodenal biopsies in the investigation of malabsorption and to confirm a diagnosis of coeliac disease prior to commencement of gluten-free diet

• Therapeutic, including treatment of bleeding lesions, banding/injection of varices, dilatation of strictures, insertion of stents, placement of percutaneous gastrostomies

Contraindications
• Severe shock • Recent myocardial infarction, unstable angina, cardiac arrhythmia*	• Severe respiratory disease* • Atlantoaxial subluxation* • Possible visceral perforation
Complications
• Cardiorespiratory depression due to sedation	• Aspiration pneumonia • Perforation

^*These are ‘relative’ contraindications; in experienced hands, endoscopy can be safely performed.

Capsule endoscopy

Capsule endoscopy (Fig. 22.14) uses a capsule containing an imaging device, battery, transmitter and antenna; as it traverses the small intestine, it transmits images to a battery-powered recorder worn on a belt round the patient’s waist. After approximately 8 hours, the capsule is excreted. Images from the capsule are analysed as a video sequence and it is usually possible to localise the segment of small bowel in which lesions are seen. Abnormalities detected usually require enteroscopy for confirmation and therapy. Indications, contraindications and complications are listed in Box 22.6.

22.6   Wireless capsule endoscopy

Indications

• Obscure gastrointestinal bleeding

• Small bowel Crohn’s disease

• Assessment of coeliac disease and its complications

• Screening and surveillance in familial polyposis syndromes

Contraindications

• Known or suspected small bowel stricture (risk of capsule retention)

• Caution in people with pacemakers or implantable defibrillators

Complications

• Capsule retention (< 1%)

Double balloon enteroscopy

While endoscopy can reach the proximal small intestine in most patients, a newer technique called double balloon enteroscopy is also available, which uses a long endoscope with a flexible overtube. Sequential and repeated inflation and deflation of balloons on the tip of the overtube and enteroscope allow the operator to push and pull along the entire length of the small intestine to the terminal ileum, in order to diagnose or treat small bowel lesions detected by capsule endoscopy or other imaging modalities. Indications, contraindications and complications are listed in Box 22.7.

22.7   Double balloon enteroscopy

Indications

Diagnostic

• Obscure gastrointestinal bleeding • Malabsorption or unexplained diarrhoea • Suspicious radiological findings • Suspected small bowel tumour • Surveillance of polyposis syndromes

Therapeutic

• Coagulation/diathermy of bleeding lesions • Jejunostomy placement

Contraindications

• As for upper gastrointestinal endoscopy

Complications

• As for upper gastrointestinal endoscopy

• Post-procedure abdominal pain (≤20%)

• Pancreatitis (1–3%)

• Perforation (especially after resection of large polyps)

Sigmoidoscopy and colonoscopy

Sigmoidoscopy can be carried out either in the outpatient clinic using a 20 cm rigid plastic sigmoidoscope or in the endoscopy suite using a 60 cm flexible colonoscope following bowel preparation. When sigmoidoscopy is combined with proctoscopy, accurate detection of haemorrhoids, ulcerative colitis and distal colorectal neoplasia is possible. After full bowel cleansing, it is possible to examine the entire colon and the terminal ileum using a longer colonoscope. Indications, contraindications and complications of colonoscopy are listed in Box 22.8.

22.8   Colonoscopy

Indications*

• Suspected inflammatory bowel disease

• Chronic diarrhoea

• Altered bowel habit

• Rectal bleeding or iron deficiency anaemia

• Assessment of abnormal CT colonogram or barium enema

• Colorectal cancer screening

• Colorectal adenoma and carcinoma follow-up

• Therapeutic procedures, including endoscopic resection, dilatation of strictures, laser, stent insertion and argon plasma coagulation

Contraindications

• Acute severe ulcerative colitis (prefer unprepared flexible sigmoidoscopy)

• As for upper gastrointestinal endoscopy

Complications

• Cardiorespiratory depression due to sedation

• Perforation

• Bleeding following polypectomy

---

^*Colonoscopy is not useful in the investigation of constipation.

Magnetic resonance cholangiopancreatography

Magnetic resonance cholangiopancreatography (MRCP) has largely replaced endoscopic retrograde cholangiopancreatography (ERCP) in the evaluation of obstructive jaundice since it provides comparable images of the biliary tree and pancreas, providing information that complements that obtained from CT and endoscopic ultrasound examination (EUS).

Endoscopic retrograde cholangiopancreatography

Using a side-viewing duodenoscope, it is possible to cannulate the main pancreatic duct and common bile duct. Nowadays, ERCP is mainly used in the treatment of a range of biliary and pancreatic diseases that have been identified by other imaging techniques such as MRCP, EUS and CT. Indications for and risks of ERCP are listed in Box 22.9.

22.9   Endoscopic retrograde cholangiopancreatography (ERCP)

Indications

Diagnostic ERCP

• Biliary or pancreatic disease where other imaging is equivocal or is contraindicated

• Ampullary biopsy or biliary cytology

Therapeutic ERCP

• Biliary disease

Removal of common bile duct calculi*

Palliation of malignant biliary obstruction

Management of biliary leaks/damage complicating surgery

Dilatation of benign strictures

Primary sclerosing cholangitis

• Pancreatic disease

Drainage of pancreatic pseudocysts and fistulae

Removal of pancreatic calculi (selected cases)

Contraindications

• Severe cardiopulmonary comorbidity

• Coagulopathy

Complications

• Occur in 5–10% with a 30-day mortality of 0.5–1%

General

• As for upper endoscopy

Specific

• Biliary disease

Bleeding following sphincterotomy

Cholangitis (if biliary obstruction is not relieved by ERCP)

Gallstone impaction

• Pancreatic disease

Acute pancreatitis

Infection of pseudocyst

---

^*Laparoscopic surgery is preferred in fit individuals who also require cholecystectomy.

22.10   Endoscopy in old age

• Tolerance: endoscopic procedures are generally well tolerated, even in very old people.

• Side-effects from sedation: older people are more sensitive, and respiratory depression, hypotension and prolonged recovery times are more common.

• Bowel preparation for colonoscopy: can be difficult in frail, immobile people. Sodium phosphate-based preparations can cause dehydration or hypotension and should be avoided in those with underlying cardiac or renal failure. Minimal preparation CT colonograms provide an excellent alternative in these individuals.

• Antiperistaltic agents: hyoscine should be avoided in those with glaucoma and can also cause tachyarrhythmias. Glucagon is preferred if an antiperistaltic agent is needed.

Tests of infection

Tests of function

A number of dynamic tests can be used to investigate aspects of gut function, including digestion, absorption, inflammation and epithelial permeability. Some of the more commonly used ones are listed in Box 22.12. In the assessment of suspected malabsorption, blood tests (full blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), folate, vitamin B₁₂, iron status, albumin, calcium and phosphate) are essential, and endoscopy is undertaken to obtain mucosal biopsies. Faecal calprotectin is very sensitive at detecting mucosal inflammation.

Radioisotope tests

Many different radioisotope tests are used (see Box 22.13). In some, structural information is obtained, such as the localisation of a Meckel’s diverticulum. Others provide functional information, such as the rate of gastric emptying or ability to reabsorb bile acids. Yet others are tests of infection and rely on the presence of bacteria to hydrolyse a radio-labelled test substance followed by detection of the radioisotope in expired air, such as the urea breath test for H. pylori.

Investigations

Dysphagia should always be investigated urgently. Endoscopy is the investigation of choice because it allows biopsy and dilatation of strictures. If no abnormality is found, then barium swallow with videofluoroscopic swallowing assessment is indicated to detect major motility disorders. In some cases, oesophageal manometry is required. High-resolution manometry allows accurate classification of abnormalities. Figure 22.15 summarises a diagnostic approach to dysphagia and lists the major causes.