Bailliere's clinical gastroenterology最新文献

There is international agreement that dyspepsia refers to pain or discomfort centred in the upper abdomen. However, the term ‘discomfort’ has been variably defined. While other symptoms may often be simultaneously present, gastro-oesophageal reflux disease can usually be clearly distinguished by the presence of predominant heartburn. Dyspepsia is a frequent reason for consultation in primary care and in gastrointestinal practice. With the widespread availability and utilization of endoscopy, it has become evident that a structural (or organic) explanation is found in only a minority of patients presenting with dyspepsia. Operationally, functional dyspepsia is defined as persistent or recurrent dyspepsia for 3 or more months in the absence of a clinically identifiable structural disease causing the symptoms. It has been proposed, based on symptoms, that functional dyspepsia be subdivided into symptom subgroups to promote patient homogeneity. The initially proposed ‘clustering’ of symptoms into ulcer-like and dysmotility-like functional dyspepsia has proved a dismal failure because of the considerable overlap observed, the lack of stability over time and the failure to identify robust pathophysiological abnormalities or responses to therapy. A subcategorization based upon the most bothersome symptom is theoretically more attractive but needs to be prospectively and rigorously tested.

Gastrointestinal motor abnormalities are frequent findings in patients with functional dyspepsia. However, these abnormalities are rather non-specific and seem to be restricted to a proportion of patients. Furthermore, they are not necessarily time-linked to symptom perception. The relationship of digestive motor derangements and symptoms in functional dyspepsia remains, therefore, unsettled. A variety of methodological and conceptual shortcomings characterize many of the studies investigating the relationship between gastrointestinal motility disorders and dyspeptic symptoms, and this obviously contributes to a higher level of uncertainty in the field. Recent reports suggest that gastrointestinal dysmotility is associated with perception of some dyspeptic symptoms, at least in a subset of patients. Well-conducted studies using appropriate methodology are needed to verify whether gastrointestinal motor disorders play a causal role in functional dyspepsia and whether this is of clinical relevance.

Symptoms of functional dyspepsia, such as epigastric pain, bloating or early satiety and nausea, are non-specific and are likely to arise from different mechanisms. Current evidence suggests the presence of at least two subgroups: patients who respond to a prolonged course of acid suppression and patients who show a significant overlap of symptoms with other functional gastrointestinal disorders such as irritable bowel syndrome. An enhanced sensitivity of visceral afferent pathways with or without associated autonomic dysregulation appears to play an important role in the aetiology of symptoms in the second group. In the absence of visceral hypersensitivity, neither the slowing of gastric emptying nor the presence of chronic gastritis appears to be sufficient to cause symptoms of functional dyspepsia. The mechanisms and aetiology of visceral hypersensitivity are incompletely understood. An alteration in the interplay between vagal and spinal afferents, and the inadequate activation of antinociceptive systems in response to tissue irritation, may play a role in symptom generation.

To determine whether functional dyspepsia and irritable bowel syndrome are different entities, epidemiological data, factor analysis studies, physiological data and associated psychological symptoms were reviewed. Between 30% and 60% of patients with either diagnosis also meet the criteria for the other diagnosis, a level greater than expected to occur by chance but not sufficient to infer an identity. Most factor analysis studies identify independent clusters of symptoms corresponding to functional dyspepsia and irritable bowel syndrome. Visceral hypersensitivity is seen throughout the gastrointestinal tract in both disorders, but the motility patterns seen in association with functional dyspepsia (principally antral hypomotility and delayed gastric emptying) differ from the motility patterns seen in irritable bowel syndrome. Psychological symptoms are similar in these two disorders but are not believed to be aetiological for either of them. Thus, based on a factor analysis of gastrointestinal symptoms and differences in intestinal motility, functional dyspepsia and irritable bowel syndrome appear to be different entities.

Functional dyspepsia is a chronic disorder of unknown aetiology. The lack of endoscopic abnormalities in patients with this disorder has led many physicians to believe that gastrooesophageal reflux disease may be responsible for most symptoms. Our group has addressed this issue, by pathophysiological studies in a large cohort of Dundee patients with persistent dyspeptic symptoms. Peptic ulcer and gallstones were excluded in all patients by appropriate tests. Ambulatory pH monitoring showed oesophageal acid reflux that lay above the conventional diagnostic threshold in approximately 20% of patients. This subset was diagnosed as having gastro-oesophageal reflux disease.

In the remainder, moderate or severe reflux-like symptoms were reported by approximately 44% patients, who were categorized as reflux-like functional dyspepsia. Reflux symptoms were mild or absent in 36% patients, who were categorized as non-reflux-like dyspepsia. While oesophageal pH profiles lay within the conventional normal range in both of these functional dyspepsia subgroups, patients with reflux-like functional dyspepsia had significantly greater acid exposure values, including total oesophageal acid exposure time, percentage time at a pH of less than 4.0, DeMeester scores and pain reflux event correlation. Hence patients with reflux-like functional dyspepsia have oesophageal acid exposure that lies below the diagnostic threshold for gastro-oesophageal reflux disease but exceeds that of patients with non-reflux dyspepsia. The high pain/reflux event correlation in reflux-like functional dyspepsia suggests that subthreshold oesophageal acid exposure may be associated with troublesome reflux symptoms.

Primary, hereditary or genetic haemochromatosis is one of the most common inherited disorders in a Caucasian populations with a disease frequency of 1:300–400 and a carrier frequency of approximately 10%. The basic genetic defect remains unknown, although the haemochromatosis gene has now been cloned and is known to be a member of the MHC non-classical class I family. Many factors—environmental, genetic and non-genetic in nature—influence the degree of iron loading in affected individuals. In particular, pathological and physiological blood loss influence iron stores in haemochromatosis. The iron concentration in the liver is an important determinant of survival because a hepatic iron concentration in excess of 400 μmol/g dry weight is usually associated with cirrhosis. Patients with cirrhosis secondary to haemochromatosis are at risk of hepatocellular carcinoma. The combination of improved awareness of the disease and the appropriate use of genetic testing for the common C282Y mutation should lead to earlier diagnosis and therapy.

Wilson disease is a recessively inherited disorder of copper transport. Clinical features are highly variable, with any combination of neurological, hepatic or psychiatric illness. The age of onset varies from 3 to 50 years of age. Diagnosis is challenging because no specific combination of clinical or biochemical features is necessarily definitive. The genetic defect is due to a variety of abnormalities in a copper-transporting membrane ATPase. Most of the more than 80 mutations are present at a low frequency, and mutations differ between ethnic groups. At least two mutations are sufficiently common to aid in rapid diagnosis, in European and Asian populations respectively. Molecular analysis can provide a definitive diagnosis for asymptomatic sibs. Treatment, using chelating agents or zinc, is most effective when started before permanent tissue damage occurs.

The presence of jaundice in the neonate, infant or young child presents a broad differential diagnosis. The ‘disease’ may be benign, as in breast-milk jaundice, or potentially fatal, as in hereditary fructose intolerance. The cause of the jaundice may be a primary hepatic disorder, such as extrahepatic biliary atresia, or secondary to a non-hepatic cause, such as haemolysis or sepsis. There may be significant hepatic injury and dysfunction, as in fulminant viral hepatitis, or simply elevation of plasma bilirubin, as in Gilbert's syndrome. p] In this chapter we will discuss the familial hyperbilirubinaemia syndromes. This diverse group of disorders is characterized by hepatic dysfunction in the absence of hepatocellular injury. The first section of the chapter will discuss the unconjugated hyperbilirubinaemias: Crigler-Najjar syndrome I, Crigler-Najjar syndrome II and Gilbert's syndrome. The discovery of the gene for bilirubin uridine diphosphate glucuronosyltransferase has increased our understanding of the genetic heterogeneity and clinical presentation of the Crigler-Najjar syndromes. The remainder of the chapter will discuss the conjugated hyperbilirubinaemias: Rotor syndrome and Dubin-Johnson syndrome. These rare diseases share many clinical features; however, they can be readily distinguished by biochemical markers in the urine and bile.

α₁-Antitrypsin deficiency (PiZ) is frequent in Caucasian populations. The predominant clinical correlates of this inborn error, i.e. chronic liver disease, emphysema, and vasculitic syndromes including their pathogenetic background are discussed in the present review.