Diseases of the gastrointestinal tract are a major cause of morbidity and mortality. Approximately 10% of all general practitioner consultations in the United Kingdom are for indigestion, and 1 in 14 is for diarrhoea. Infective diarrhoea and malabsorption are responsible for much ill health and many deaths in the developing world. The gastrointestinal tract is the most common site for cancer development. Colorectal cancer is the second most common cancer in men, and population-based screening programmes exist in many countries. Functional bowel disorders affect up to 10–15% of the population and consume considerable health-care resources. The inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, together affect 1 in 250 people in the Western world, with substantial associated morbidity. • digestion (mechanical, enzymatic and peristaltic) • absorption – the products of digestion, water, electrolytes and vitamins • protection against ingested toxins • 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). 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. • parasympathetic pathways (vagal and sacral efferent), which are cholinergic, and increase smooth muscle tone and promote sphincter relaxation • sympathetic pathways, which release noradrenaline (norepinephrine), reduce smooth muscle tone and stimulate sphincter contraction. 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. 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. 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. A barium swallow can give useful information about oesophageal motility. Videofluoroscopy, with joint assessment by a speech and language therapist and a radiologist, may be necessary in difficult cases. Oesophageal manometry (see Fig. 22.1, p. 840), often in conjunction with 24-hour pH measurements, is of value in diagnosing cases of refractory gastro-oesophageal reflux, achalasia and non-cardiac chest pain. Oesophageal impedance testing is useful for detecting non-acid or gas reflux events, especially in patients with atypical symptoms or those who respond poorly to acid suppression. Dyspepsia describes symptoms such as discomfort, bloating and nausea, which are thought to originate from the upper gastrointestinal tract. There are many causes (Box 22.14), including some arising outside the digestive system. Heartburn and other ‘reflux’ symptoms are separate entities and are considered elsewhere. Although symptoms often correlate poorly with the underlying diagnosis, a careful history is important to detect ‘alarm’ features requiring urgent investigation (Box 22.15) and to detect atypical symptoms which might be due to problems outside the gastrointestinal tract.
Alimentary tract and pancreatic disease
Clinical examination of the gastrointestinal tract
Functional anatomy and physiology
Oesophagus, stomach and duodenum
Gastric secretion
Gastrin released from antral G cells in response to food (protein) binds to cholecystokinin receptors (CCK-2R) on the surface of enterochromaffin-like (ECL) cells, which in turn release histamine. The histamine binds to H2 receptors on parietal cells and this leads to secretion of hydrogen ions, in exchange for potassium ions at the apical membrane. Parietal cells also express CCK-2R and it is thought that activation of these receptors by gastrin is involved in regulatory proliferation of parietal cells. Cholinergic (vagal) activity and gastric distension also stimulate acid secretion; somatostatin, vasoactive intestinal polypeptide (VIP) and gastric inhibitory polypeptide (GIP) may inhibit it. (ACh-R = acetylcholine receptor; ATPase = adenosine triphosphatase)
Small intestine
Epithelial cells are formed in crypts and differentiate as they migrate to the tip of the villi to form enterocytes (absorptive cells) and goblet cells.
Digestion and absorption
Fat
Step 1: Luminal phase. Fatty acids stimulate cholecystokinin (CCK) release from the duodenum and upper jejunum. The CCK stimulates release of amylase, lipase, colipase and proteases from the pancreas, causes gallbladder contraction and relaxes the sphincter of Oddi, leading bile to flow into the intestine. Step 2: Fat solubilisation. Bile acids and salts combine with dietary fat to form mixed micelles, which also contain cholesterol and fat-soluble vitamins. Step 3: Digestion. Pancreatic lipase, in the presence of its co-factor, colipase, cleaves long-chain triglycerides, yielding fatty acids and monoglycerides. Step 4: Absorption. Mixed micelles diffuse to the brush border of the enterocytes. Within the brush border, long-chain fatty acids bind to proteins, which transport the fatty acids into the cell, whereas cholesterol, short-chain fatty acids, phospholipids and fat-soluble vitamins enter the cell directly. The bile salts remain in the small intestinal lumen and are actively transported from the terminal ileum into the portal circulation and returned to the liver (the enterohepatic circulation). Step 5: Re-esterification. Within the enterocyte, fatty acids are re-esterified to form triglycerides. Triglycerides combine with cholesterol ester, fat-soluble vitamins, phospholipids and apoproteins to form chylomicrons. Step 6: Transport. Chylomicrons leave the enterocytes by exocytosis, enter mesenteric lymphatics, pass into the thoracic duct, and eventually reach the systemic circulation.
Water and electrolytes
Pancreas
Ductular cells secrete alkaline fluid in response to secretin. Acinar cells secrete digestive enzymes from zymogen granules in response to a range of secretagogues. The photograph shows a normal pancreatic duct (PD) and side branches, as defined at magnetic resonance cholangiopancreatography (MRCP). Note the incidental calculi in the gallbladder and common bile duct (arrow). (CCK = cholecystokinin; VIP = vasoactive intestinal polypeptide)
Control of gastrointestinal function
The nervous system and gastrointestinal function
Investigation of gastrointestinal disease
Imaging
Contrast studies
Ultrasound, computed tomography and magnetic resonance imaging
Endoscopy
Capsule endoscopy
Tests of function
Oesophageal motility
Presenting problems in gastrointestinal disease
Dysphagia
Dyspepsia
Alimentary tract and pancreatic disease
WordPress theme by UFO themes