Stomach
Peptic ulcer
Most disorders of gastric function are best assessed initially using radiological investigations and endoscopy. Most peptic ulcers are associated with Helicobacter pylori infection which weakens the protective mucous coating of the stomach and duodenum. The organism is present in the mucosa and is protected from stomach acidity by the creation of a more neutral microenvironment through the secretion of large amounts of urease and the subsequent conversion of urea to ammonia and carbon dioxide. This reaction forms the basis of the urea breath test to detect H. pylori infection. In the few patients who present with atypical or recurrent peptic ulceration that is resistant to treatment with H2 antagonists, proton pump inhibitors and antibiotics to eradicate H. pylori, biochemical tests to quantify plasma [gastrin] may be of value.
Tests for H. pylori infection
Urea breath test
This non-invasive test relies on the urease activity of H. pylori to detect active infection. The patient ingests either 13C- or 14C-labelled urea, and urease, if present, hydrolyses urea into ammonia and isotopically labelled carbon dioxide. Carbon dioxide is absorbed from the gut and subsequently expired in the breath where it can be trapped and quantified. This breath test is used both for the identification of patients with active infection and for establishing the effectiveness of treatment.
Serological tests
Patients infected with H. pylori develop antibodies to the organism that can be detected by serological testing. While serological tests are used to identify patients who have been infected with the organism, they are less helpful in confirming its eradication because of the slow reduction in antibody titres.
Table 14.1 The principal examples of biochemical tests described in this chapter for the investigation of GI tract disease
| Condition to be investigated | Biochemical investigations |
| Peptic ulcer Helicobacter pylori | 13C urea breath test Antibodies to H. pylori |
| Zollinger–Ellison syndrome | Plasma [gastrin] |
| Acute pancreatitis | Serum amylase activity |
| Chronic pancreatic insufficiency | Faecal elastase |
| Intestinal malabsorption Coeliac disease | Anti–tissue transglutaminase IgA |
| Bacterial colonisation | Glucose hydrogen breath test |
| Bile acid malabsorption | Serum 7α-hydroxy-4- cholesten-3-one |
| Inflammation (any cause) | Faecal calprotectin |
| Verner–Morrison syndrome | Plasma [VIP] |
| Carcinoid syndrome | Urinary 5–hydroxyindoleacetic acid |
| Laxative abuse | Urine laxative screen |
Faecal antigen testing
Enzyme immunoassays can be used to detect the presence of H. pylori in stool specimens.
Gastrin
Gastrin is a polypeptide released by the G cells in the gastric antrum and duodenum and is a potent stimulator of gastric acid production. Its release is normally inhibited if the gastric pH is low, but circulating levels are increased in patients with chronic hypochlorhydria. Thus, plasma [gastrin] may be elevated as a physiological response to achlorhydria or hypochlorhydria due to gastritis, treatment with H2 antagonists, proton pump inhibitors, pernicious anaemia or previous vagotomy. Increased plasma [gastrin] may also be found in patients with hypercalcaemia or following gastric surgery, as a result of which the antral mucosa may have become isolated from gastric contents. The most important clinical application for the measurement of gastrin is in the investigation of patients with gastric acid hypersecretion thought to be caused by a gastrinoma (Zollinger–Ellison syndrome).
Zollinger-Ellison syndrome
This syndrome is due to a gastrinoma, that is, neoplasia of either pancreatic gastrin-producing cells or gastric gastrin-producing cells, the former being the more common site. Approximately 60% of gastrinomas are malignant and 30% occur as part of the MEN syndrome (type I) (Table 16.8; p. 251). Increased gastrin production leads to chronic hypersecretion of gastric acid, which in turn causes peptic ulceration and sometimes diarrhoea and fat malabsorption leading to steatorrhoea. The steat-orrhoea is thought to be due to high [H+] in the intestinal lumen; this inhibits the action of pancreatic lipase. In some patients, an isolated simple duodenal ulcer or diarrhoea may be the presenting feature.
The diagnosis of gastrinoma is based on the detection of an unequivocally elevated fasting plasma [gastrin] in the presence of gastric acid hypersecretion. Patients should not be receiving proton pump inhibitors or H2 receptor blockers at the time of measurement. Provocative testing may be necessary in about 15% of patients where the basal plasma [gastrin] concentration is normal or only slightly increased and gastrinoma is suspected. The preferred test involves the IV injection of secretin which usually produces a 2-fold increase in plasma [gastrin] in patients with gastrinoma, while no change occurs in patients with G-cell hyperplasia.
The pancreas
The pancreas is a complex gland with important endocrine and exocrine functions. Its principal endocrine role relates to the regulation of glucose metabolism through the secretion of insulin and glucagon from the islets of Langerhans, and is discussed elsewhere in this volume (Chapter 6). Pancreatic juice is produced by the exocrine tissue and released into the duodenum where it is mixed with partially digested food. It is an alkaline fluid that contains a mixture of enzymes essential for protein, carbohydrate and lipid digestion. Secretion is induced in response to nervous stimuli, but mainly by the hormones secretin and cholecystokinin-pancreozymin (CCK-PZ). These are secreted by the small intestine in response to the entry of food.
Acute pancreatitis
Acute pancreatitis is commonly associated with gallstones or alcoholism; vascular and infective causes have also been recognised. Confirmation of the clinical diagnosis mainly depends on serum amylase activity measurements. Serum [calcium] may fall considerably in severe cases of acute pancreatitis, but sometimes not for a few days; it probably falls as a result of the formation of insoluble calcium salts of fatty acids in areas of fat necrosis.
Serum amylase
Amylase in serum arises mainly from the pancreas (P-isoamylase) and the salivary glands (S-isoamylase). Serum P-isoamylase activity is a more sensitive and more specific test than total amylase for the detection of acute pancreatitis, but total serum amylase activity is most often measured and is usually, but not always, greatly increased in acute pancreatitis.
Serum amylase activities greater than 10 times the normal value are virtually diagnostic of acute pancreatitis. Maximum values of more than five times the upper reference limit are found in about 50% of cases, but are not pathognomonic of acute pancreatitis, since similarly high values sometimes occur in the afferent loop syndrome, mesenteric infarction and acute biliary tract disease, as well as in acute parotitis.
Smaller and more transient increases may occur in almost any acute abdominal condition (e.g. perforated peptic ulcer), or after injection of morphine and other drugs that cause spasm of the sphincter of Oddi. Moderate increases have also been reported in patients with DKA. In patients with acute pancreatitis, serum amylase activity usually returns to normal within 3–5 days.
Macro-amylasaemia
In this rare disorder, part of the serum amylase activity circulates as a high molecular weight form which, unlike normal amylase, is not cleared by the kidney. The diagnosis may be made when the increased serum amylase activity is found to be persistent and accompanied by a normal urinary amylase activity.
Chronic pancreatitis
Impaired secretion of pancreatic enzymes may not be evident until the disease is advanced, but may then give rise to malabsorption, especially steatorrhoea. Tests involving the analysis of bicarbonate and enzyme activity in duodenal aspirate were previously regarded as the gold standard for assessing exocrine pancreatic function. However, they require a high degree of technical expertise and are time consuming, expensive and uncomfortable for the patient, and have now been replaced by pancreatic imaging techniques. The direct measurement of pancreatic elastase in faeces is now regarded as the most useful biochemical test of exocrine pancreatic secretion.
Faecal elastase
Elastase is a pancreas-specific enzyme that is not degraded during intestinal transport. Concentrations in faeces are 5–6 times higher than those of duodenal fluid, and low levels are associated with pancreatic insufficiency. Although patients with modest degrees of pancreatic insufficiency cannot be reliably identified, its diagnostic sensitivity in patients with severe disease is high. False-positive results may be observed in some patients with watery diarrhoea.
Faecal elastase is not affected by pancreatic enzyme replacement therapy and is a convenient test to perform since only a single stool sample is required. It is recommended as the test of first choice in the investigation of patients presenting with diarrhoea thought to be of pancreatic origin.
Small intestine and colon
Tests of absorptive function
Carbohydrate absorption
With the widespread availability of small bowel histology, previously established non-invasive tests for investigating the absorptive capacity for carbohydrates have been discontinued in many centres. For example, the xylose absorption test, which was used to investigate the ability of the intestine to absorb monosaccharides, is now available only in a minority of laboratories. Similarly, the measurement of intestinal permeability by quantifying the absorption and urinary excretion of an oral mixture of disaccharide (lactulose) and monosaccharide (rhamnose) is now rarely performed in routine clinical practice. Other than demonstrating that an abnormality may exist, these tests are non-specific and non-diagnostic and will not be considered further
Disaccharidase deficiency
Disaccharidase deficiency may be exhibited as intolerance to one or more of the disaccharides – lactose, maltose or fructose. The defect may be congenital or acquired. The most reliable way of specifically diagnosing disaccharidase deficiency is to measure enzyme activity in small intestinal biopsy specimens. Many gastroenterologists advocate monitoring the symptomatic response to a low dairy diet as the most reliable test for lactase deficiency, which is the most common of the disaccharidase deficiencies.
Fat absorption
The faecal fat test, which involves 3- or 5-day collections of stools for the measurement of unabsorbed fat, has traditionally been used to assess fat absorption. However, due to difficulties relating to the inherently unpleasant nature of the test, inadequate sample collection, lack of analytical quality control and standardisation, and the limited diagnostic information provided by a positive result, many laboratories are abandoning the use of this test and it can no longer be recommended.
Triglyceride (triolein) breath test
This test avoids the difficulties and unpleasantness of collecting faeces over several days. Following digestion and absorption of an oral dose of [14C] triolein (the marker is in the fatty acid component), part of the fatty acid is metabolised to 14CO2, which is then excreted in expired air. A high 14CO2 excretion is associated with normal fat absorption, whereas 14CO2 excretion is low in patients with fat malabsorption. Despite the simplicity of this test, it is rarely requested and is not widely available. Breath tests have a low sensitivity for mild or moderate malabsorption.
Amino acid absorption
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