ГоловнаЗворотній зв'язок

Гастроэнтерология (анг,рус)

Short theoretic material

Anatomy

The oesophagus is a muscular tube 25 cm long which extends 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.

Gastro-oesophageal reflux resulting in heartburn affects approximately 30% of the general population. 

Pathophysiology 

Occasional episodes of gastro-oesophageal reflux are common in health. Reflux is followed by oesophageal peristaltic waves which efficiently clear the gullet, alkaline saliva neutralises residual acid, and symptoms do not occur. Gastro-oesophageal reflux disease develops when the oesophageal mucosa is exposed to gastric contents for prolonged periods of time, resulting in symptoms and, in a proportion of cases, oesophagitis.

Etiology

1.      abnormal of the lower oesophageal sphincter:

A.    reduced tone:

-          dietary factors (coffee, tea),

-          smoking,

-          alcohol,

-          pregnancy, obesity (resulting in increased intra-abdominal pressure);

-          preparations (Papaverin, Nitrats, Teophyllin, etc.)

B.     inappropriate relaxation;

-          hiatus hernia;

-          dietary factors (fried, fatty food, macaroni; these food result in delayed gastric emptying, increased intra-gastric acidity)

2.      defective oesophageal clearance;

 

Fig. 1 Factors associated with the development of gastro-oesophageal reflux disease.

Abnormalities of the lower oesophageal sphincter: In health, the lower oesophageal sphincter is tonically contracted, relaxing only during swallowing. Some patients with gastro-oesophageal reflux disease have reduced lower oesophageal sphincter tone, permitting reflux when intra-abdominal pressure rises. In others, basal sphincter tone is normal but reflux occurs in response to frequent episodes of inappropriate sphincter relaxation. 

Hiatus hernia: (see Fig. 2) causes reflux because the pressure gradient between the abdominal and thoracic cavities, which normally pinches the hiatus, is lost. In addition, the oblique angle between the cardia and oesophagus disappears. Many patients who have large hiatus hernias develop reflux symptoms, but the relationship between the presence of a hernia and symptoms is poor. Hiatus hernia is very common in individuals who have no symptoms, and some symptomatic patients have only a very small or no hernia. Nevertheless, almost all patients who develop oesophagitis, Barrett's oesophagus or peptic strictures have a hiatus hernia.  

  Important features of hiatus hernia

1. Occurs in 30% of the population over the age of 50 years;

2. Often asymptomatic;

3. Heartburn and regurgitation can occur;

4. Gastric volvulus may complicate large para-oesophageal hernias.   

 

Fig.2  Types of hiatus hernia.

 

Delayed oesophageal clearance: Defective oesophageal peristaltic activity is commonly found in patients who have oesophagitis. It is a primary abnormality, since it persists after oesophagitis has been healed by acid-suppressing drug therapy. Poor oesophageal clearance leads to increased acid exposure time. 

 

Gastric contents: Gastric acid is the most important oesophageal irritant and there is a close relationship between acid exposure time and symptoms. 

 

Defective gastric emptying: Gastric emptying is delayed in patients with gastro-oesophageal reflux disease.

 

Increased intra-abdominal pressure: Pregnancy and obesity are established predisposing causes. Weight loss may improve symptoms. 

 

Dietary and environmental factors: Dietary fat, chocolate, alcohol and coffee relax the lower oesophageal sphincter and may provoke symptoms. There is little evidence to incriminate smoking or NSAIDs as causes of gastro-oesophageal reflux disease. 

 

Clinical features 

The major symptoms are heartburn and regurgitation, often provoked by bending, straining or lying down. 'Waterbrash', which is salivation due to reflex salivary gland stimulation as acid enters the gullet, is often present. A history of weight gain is common. Some patients are woken at night by choking as refluxed fluid irritates the larynx. Others develop dysphagia. A few present with atypical chest pain which may be severe, can mimic angina and is probably due to reflux-induced oesophageal spasm. 

 

Complications 

1. Oesophagitis 

A range of endoscopic findings, from mild redness to severe, bleeding ulceration with stricture formation, is recognised (see Fig. 3). There is a poor correlation between symptoms and histological and endoscopic findings. A normal endoscopy and normal oesophageal histology are perfectly compatible with significant gastro-oesophageal reflux disease. 

 Fig.3 Reflux oesophagitis. The gullet is inflamed and ulcerated (small arrows) and there is early stricturing (large arrow).

 

2. Barrett's oesophagus 

 

Fig. 4 Barrett's oesophagus. Pink columnar mucosa extends up the gullet. Small islands of squamous mucosa remain (arrow).

Barrett's oesophagus ('columnar lined oesophagus'-CLO) is a pre-malignant glandular metaplasia of the lower oesophagus, in which the normal squamous lining is replaced by columnar mucosa composed of a cellular mosaic containing areas of intestinal metaplasia (see Fig. 4). It occurs as an adaptive response to chronic gastro-oesophageal reflux and is found in 10% of patients undergoing gastroscopy for reflux symptoms. Community-based epidemiological and autopsy studies suggest the true prevalence may be up to 20 times greater as the condition is often asymptomatic until first discovered when the patient presents with oesophageal cancer. CLO principally occurs in Western Caucasian males and is rare in other racial groups. It is the major risk factor for oesophageal adenocarcinoma, with a lifetime cancer risk of around 10%. The epidemiology and aetiology of CLO are poorly understood. The prevalence is increasing, and it is more common in men (especially white) and those over 50 years of age. It is weakly associated with smoking but not alcohol. Recent studies suggest that cancer risk is related to the severity and duration of reflux rather than the presence of CLO per se but this remains to be proven. Recent attention has focused on the importance of duodenogastro-oesophageal reflux, containing bile, pancreatic enzymes and pepsin in addition to acid. The molecular events underlying the progression of CLO from metaplasia to dysplasia to cancer are not well understood but E-cadherin polymorphisms, p53 mutations, transforming growth factor-β (TGF-β), epidermal growth factor (EGF) receptors, COX-2 and tumour necrosis factor-α (TNF-α) may play roles in neoplastic progression. 

Diagnosis requires multiple systematic biopsies to maximise the chance of detecting intestinal metaplasia and/or dysplasia. 

Management. Neither potent acid suppression nor antireflux surgery will stop progression or induce regression of CLO, and treatment is only indicated for symptoms of reflux or complications such as stricture. Endoscopic ablation therapy or photodynamic therapy can induce regression but 'buried islands' of glandular mucosa may persist underneath the squamous epithelium and cancer risk is not eliminated. At present these therapies remain experimental but show promise; they are used in patients with high-grade dysplasia (HGD) or early malignancy that is not suitable for surgery. 

Regular endoscopic surveillance is often performed to detect dysplasia and prevent malignancy or diagnose it at a curable stage. Surveillance can detect tumours at earlier stages and improve 2-year survival but, because most CLO is undetected until cancer develops, surveillance strategies are unlikely to influence the overall mortality rate of oesophageal cancer. Surveillance is expensive and cost-effectiveness studies have been conflicting. Surveillance is currently recommended every 1-2 years for those without dysplasia and 6-12-monthly for those with low-grade dysplasia. Oesophagectomy is widely recommended for those with HGD as the resected specimen harbours cancer in up to 40%. This may be an over-estimate and recent data suggest that HGD often remains stable and may not progress to cancer, at least in the medium term. Close follow-up with biopsies every 3 months is an alternative strategy for those with HGD. Further studies are required to confirm recent evidence suggesting that more selective surveillance at longer intervals may be safe and more cost-effective. 

 

Anaemia 

Iron deficiency anaemia occurs as a consequence of chronic, insidious blood loss from long-standing oesophagitis. Almost all such patients have a large hiatus hernia. Nevertheless, hiatus hernia is very common and other causes of blood loss, particularly colorectal cancer, must be considered in anaemic patients, even when endoscopy reveals oesophagitis and a hiatus hernia. 

 

Benign oesophageal stricture 

Fibrous strictures develop as a consequence of long-standing oesophagitis. Most patients are elderly and have poor oesophageal peristaltic activity. They present with dysphagia which is worse for solids than for liquids. Bolus obstruction following ingestion of meat can lead to absolute dysphagia. A history of heartburn is common but not invariable; many elderly patients presenting with strictures have no preceding heartburn. 

Diagnosis is made by endoscopy, and biopsies of the stricture are taken to exclude malignancy. Endoscopic balloon dilatation or bouginage is undertaken. Subsequently, long-term therapy with a proton pump inhibitor drug at full dose should be started to reduce the risk of recurrent oesophagitis and stricture formation. The patient should be advised to chew food thoroughly, and it is important to ensure adequate dentition. 

 

Investigations 

Young patients who present with typical symptoms of gastro-oesophageal reflux, without worrying features such as dysphagia, weight loss or anaemia, can be treated empirically. 

Investigation is advisable if patients present in middle or late age, if symptoms are atypical or if a complication is suspected. Endoscopy is the investigation of choice. This is performed to exclude other upper gastrointestinal diseases which can mimic gastro-oesophageal reflux, and to identify complications. A normal endoscopy in a patient with compatible symptoms should not preclude treatment for gastro-oesophageal reflux disease. 

When, despite endoscopy, the diagnosis is unclear or if surgical intervention is under consideration, 24-hour pH monitoring is indicated. This involves tethering a slim catheter with a terminal radiotelemetry pH-sensitive probe above the gastro-oesophageal junction. The intraluminal pH is recorded whilst the patient undergoes normal activities, and episodes of pain are noted and related to pH. A pH of less than 4 for more than 6-7% of the study time is diagnostic of reflux disease. 

 

Management 

Lifestyle advice, including weight loss, avoidance of dietary items which the patient finds worsen symptoms, elevation of the bed head in those who experience nocturnal symptoms, avoidance of late meals and giving up smoking are recommended but rarely needed. 

Proprietary antacids and alginates, which are said to produce a protective mucosal 'raft' over the oesophageal mucosa, are taken with considerable symptomatic benefit by most patients. Antacids widely available for self-medication and are used for relief of minor dyspeptic symptoms. The majority are based on combinations of calcium, aluminium and magnesium salts, all of which have individual side-effects. Calcium compounds cause constipation, while magnesium-containing agents cause diarrhoea. Aluminium compounds block absorption of digoxin, tetracycline and dietary phosphates. Most have a high sodium content and can exacerbate congestive heart failure.

-          Magnesium Trisilicate Mixture 10 – 20 ml 3 – 4 times daily before meals;

-          Aluminium Hydroxide 300 mg\5 ml Liquid 300 – 600 mg as needed between meals and at bedtime or as directed by physician.

Histamine H2-receptor antagonist drugs. These are competitive inhibitors of histamine at the H2-receptor on the parietal cell. Dyspeptic symptoms remit promptly, usually within days of starting treatment. They are moderately effective for the management of reflux disease.  H2-receptor antagonist drugs help symptoms without healing oesophagitis. They are well tolerated, and the timing of medication and dosage should be tailored to individual need. 

-          Cimetidine 800 mg at bedtime; treatment should be continued for at least 4 – 8 weeks; maintenance: 400 mg at bedtime;

-          Ranitidine (Zantac) 150 mg twice a day or 300 mg at night for 4 – 8 weeks; maintenance: 150 – 300 mg at night;

H+/K+ ATPase ('proton pump') inhibitors. These are substituted benzimidazole compounds that specifically and irreversibly inhibit the proton pump hydrogen/potassium ATPase in the parietal cell membrane. They are the most powerful inhibitors of gastric secretion yet discovered, with maximal inhibition occurring 3-6 hours after an oral dose. They have an excellent safety profile. Proton pump inhibitors (omeprazole and lansoprazole) are also much more effective than H2-antagonists for healing and maintenance of reflux oesophagitis. Proton pump inhibitors are the treatment of choice for severe symptoms and for complicated reflux disease. Symptoms almost invariably resolve and oesophagitis heals in the majority of patients. Recurrence of symptoms is common when therapy is stopped and some patients require life-long treatment at the lowest acceptable dose.

-          Omeprazole (Losec) 20 – 80 mg once daily or twice daily up to 8 – 12 weeks;

-          Lansoprazole (Prevacid) 30 mg  once daily or twice daily for 4 – 8 weeks;

 

 

Fig. 5 Treatment of gastro-oesophageal reflux disease: a 'step-down' approach.

 

Patients who fail to respond to medical therapy, those who are unwilling to take long-term proton pump inhibitors and those whose major symptom is severe regurgitation should be considered for anti-reflux surgery. This can be undertaken by an open operation but is increasingly being carried out laparoscopically. Although heartburn and regurgitation are alleviated in most patients, a proportion develop complications such as inability to vomit and abdominal bloating ('gas-bloat syndrome').

 

Issues in older people gastro-oesophageal reflux disease

The prevalence of gastro-oesophageal reflux disease is higher in older people and complications are more common.

The severity of symptoms does not correlate with the degree of mucosal inflammation in old age.

Late complications such as peptic strictures or bleeding from oesophagitis are more common in older people.

Aspiration from occult gastro-oesophageal reflux disease should be considered in older patients with recurrent pneumonia.

 

 

 

 

8