A 56 year old man has a twenty year history of occasional heartburn but is otherwise healthy and taking no medication except for over-the -counter antacid tablets . He attends his GP surgery complaining of worsening heartburn for the past twelve months. The pain is burning, retrosternal and usually occurs after eating or when lying down or bending over. He frequently awakes with a bitter taste in his mouth.
Gastro-oesophageal reflux disease (GORD) is a common condition seen in every stage of population, especially in obese and pregnant people. In order to gain an understanding in this disease, and generate a successful treatment, having a knowledge of anatomy and microanatomy of gastro-oesophageal junction, understanding the causes, symptoms and complications of this disease, being aware of the protection mechanisms of body and knowing diagnosis and management techniques is crucially important.
Oesophagus is a 25cm long muscular tube which provides a passage to the food. It is situated between oropharynx and stomach, and is lined by stratified squamous epithelium cells. The peristalsis is achieved by aid of circular muscles inside and longitudinal muscles outside which both continues into stomach. Its superior â…“ is made up of skeletal muscles and is controlled voluntarily whereas its inferior â…” is made up of smooth muscles. There are two muscular sphincters at each end of oesophagus, upper oesophageal sphincter and lower oesophageal sphincter. Lower oesophageal sphincter (LOS), just below the diaphragm, is the place where stratified squamous epithelium cells change into glandular simple cuboidal epithelium cells and acts as a physiological sphincter in prevention of reflux. LOS is normally closed and opens by stimulation of stretch receptors in oesophagus by food. Stomach is situated in the left upper quadrant of the abdomen and is the organ of chemical and mechanical digestion. It has four anatomical parts: cardia, fundus, body and pylorus. All these parts have mucous neck cells which secrete mucus. Additionally fundus and body has parietal cells secreting HCl (Hydrochloric acid) and intrinsic factors, some endocrine cells secreting hormones, chief cells secreting pepsin and pylorus contains G-cells secreting Gastrin. Parietal cells have Histamine Hâ‚‚, Acetylcholine and Gastrin receptors so presenting these substances to parietal cells can cause Adenylate cyclase (on Histamine Hâ‚‚ binding) and Calcium ion (on Acetylcholine and Gastrin binding) to stimulate Protein Kinases which further stimulates Kâº/Hâº ATPase (proton pump) for acid secretion . HCl converts pepsinogen into pepsin which breaks down proteins into polypeptides.
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Repetitive upflow of acid in stomach into oesophagus is known as the Gastro-oesophageal Reflux Disease(GORD). In stomach, on top of epithelial cells, there is a layer of mucous which acts as a barrier and also HCOâ‚ƒâ»(base) is present to increase the pH and minimise the effects of acid. Prostoglandins increase blood flow and improve production of HCOâ‚ƒâ»and mucous. But, oesophagus doesn't have a protection mechanism such as stomach so, due to recurrence of reflux, oesophagitis which is the inflammation of oesophagus, and heartburn which is pain in the retrosternal (behind the sternum) area occur. Non-Steroid Anti Inflammatory Drugs such as aspirin prevent Prostogandin formation hence inhibit its effects and in case of reflux, can trigger the symptoms of GORD due to increased acid present."The main cause of gastro-osephageal reflux is the failure of lower oesophageal sphincter tone and of secondary peristalsis in oesophageal body. Various other factors may predispose to reflux. Pregnancy is commonly associated with reflux, owing partly to sex hormones lowering the gastro-oesophageal sphincter pressure, and partly to pressure from intra-abdominal mass which is also an effect of obesity on reflux. Smoking, eating fat and chocolate, drinking coffee, tea and alcohol, and certain drugs (e.g. calcium antagonists and B2 antagonists) act by reducing lower oesophageal sphincter pressure." (Souhami and Moxham, Textbook of Medicine, 4th Edition, Page 765, Churchill Livingstone)Also, delay in gastric emptying, infections, swallowing of corrosives, defects in clearing oesophagus and Hiatus Hernia causes GORD. "Hiatus Hernia 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."(Boon et al, Davidson's Principles and Practice of Medicine, 20th edition, Page 878, Churchill Livingstone.) Hiatal hernia is extension of stomach to the thoracic cavity due to the loss of abdominal and thoracic pressure difference. In sliding Hiatus Hernia, gastro-oesophageal junction part extends over diaphragm. In rolling/para-oesophageal Hiatus hernia, some part of fundus of stomach extends over diaphragm where LOS stays below the diaphragm.
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There are mechanisms in human body to prevent gastric reflux. The stomach is inferior to oesophagus so, due to gravity, the flow of contents is headed for the stomach. This is supported by peristalsis which is successive contractions in inferior direction. Besides, the stomach joins to oesophagus at an angle which prevents direct backflow of stomach content in reflux. The most important protection is the presence of Lower Oesophageal Sphincter in which pressure is proportional to intra-gastric and intra-abdominal pressures and acts as a barrier for upflow of stomach contents. Saliva produced in salivary glands in oral cavity has a basic structure (contain bicarbonate) which neutralise any acid present after swallowing. Moreover, swallowing is an action of pushing the contents in oral cavity and oesophagus downwards so it pushes anything in oesophagus back into stomach. "Other ant reflux mechanisms involve the intra-abdominal segment of the oesophagus which acts as a flap valve. In addition, the mucosal rosette formed by folds of the gastric mucosa and the contraction of the crural diaphragm acting like a pinchcock, prevent ant reflux mechanism." (Kumar and Clark,Clinical Medicine, 7th edition, Page 250, Saunders)
Oesophageal Mucosal defence Mechanisms
(Kumar and Clark,Clinical Medicine, 7th edition, Page 250, Saunders)
Mucus and the unstirred water layer trap bicarbonate. This mechanism is a weak buffering mechanism compared to that in the stomach and duodenum.
The apical cell membranes and the junctional complexes between cells act to limit diffusion of proton into the cells. In oesophagitis, the junctional complexes are damaged leading to increased proton diffusion and cellular damage.
Bicarbonate normally buffers acid in the cells and intracellular spaces. Hydrogen ions impair the growth and replication of damaged cells.
Acid stimulates primary sensory neurones in the oesophagus by activating the vanilloid receptor-1. This can initiate inflammation and release of proinflammatory substances from the tissue and produce pain. Pain can also be due to contraction of longitudinal oesophageal muscle.
In absence or defect of any of the protective mechanisms, reflux can take place and repetition of this situation can cause Gastro-oesophageal Reflux Disease.
GORD has several distinctive symptoms which in long term turn into complications. The most important symptom of the GORD is heartburn. Heartburn is a burning sensation behind the sternum area because of the nerve stimulation upon delivering acid to retrosternal area. The burning pain can increase by lying down or changing body posture into a horizontal position. This can lead to sore throat and laryngitis. Regurgitation, i.e. acid taste in mouth is also a characteristic. It can lead to glossitis and dental problems. Nausea can be felt due to the reverse action of peristalsis. Difficult swallowing and dysphagia(inability to swallowing) can develop in these patients. The presence of GORD for a long time can cause complications. Oesophagitis is the inflammation of oesophagus seen as ulceration, bleeding and strictures. It can range from mild to severe. Due to oesophageal bleeding present for a long time, iron deficiency anaemia can develop. The nerve stimulation in oesophagus due to acid being present or acid delivering to throat promote cough which can cause constriction in bronchioles resulting in respiratory problems such as asthma. If the acid passes the larynx and enters to lung, it can cause pulmonary fibrosis or lung infections such as pneumonia. If the acid passes into nasal cavities, it can develop problems associated with ear. Gastric volvulus can occur due to twisting of hiatus hernia and cause gastric obstruction raising a pain. GORD being present for a long time can lead to Barrett's oesophagus." With time the epithelium of the lower oesophagus undergoes metaplasia, i.e. it converts to a columnar mucous secreting form, a reaction that may well be protective. Barrett's oesophagus is the term given to this metaplastic columnar epithelium of the lower oesophagus, which is at high risk of developing dysplasia and invasive adenocarcinoma."(Young et al, Wheather's Functional Histology, 5th Edition, Page 268, Churchill Livingstone)
There is a range of available investigations for diagnosis of GORD. The most preferred and widely used method is endoscopy. Upper gastrointestinal endoscopy provides visual view of oesophagus by means of a camera attached to a tube and can confirm hiatus hernia and oesophagitis. Biopsy can be taken by endoscopy which helps for diagnosis of Barrett's oesophagus. Barium swallow, before endoscopy, was a widely used method for diagnosing GORD. In this method, patients swallow a Barium solution which can provide contrast imaging and X-ray video images are taken. The patient is asked to stand up, bend down, lie down and take several other positions to detect the degree of reflux. However, in absence of oesophagitis, this method can fail to show truthful X-ray images. Only a chest x-ray can be taken to detect any anatomical oesophageal anomalies or hiatus hernia. A full blood count can help to diagnose any blood loss and microcytic anaemia due to ulceration and blood loss. If the muscle action of oesophagus and functioning of sphincter is wanted to be tested, a manometry test is performed. A tube inserted into stomach from the mouth and the pressure exerted on tube is tested which can give information about sphincter contractions. A very important another test is 24 hour oesophageal pH test. A catheter with a pH sensor is placed into oesophagus from nose and it detects the pH change due to reflux. With this method, how many times reflux occurs are detected for 24 hours. This method is preferred if no certain diagnosis can be made by 24 hours endoscopy.
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Treatment of GORD involves several factors requiring some lifestyle changes at first, followed by pharmacological drug treatment and if required, surgery. "The modification of lifestyle is an integral part of initially managing GORD. These changes are such as to elevate the head of the bed, stop smoking, stop excessive ethanol consumption, reduce dietary fat, reduce meal size, avoid bedtime snacks, reduce weight in overweight people, avoid specific foods such as chocolate, carminatives(e.g. spearmint, peppermint), coffee, tea, cola beverages, tomato juice and citrus fruit juices, avoid specific medications such as anticholinergics, theophyine, benzodiazepines, opiates, Calcium channel antagonists, Î² adrenergic antagonists, progesterone and Î± adrenergic antagonists."(Yamada et al, Handbook of Gastroenterology, Page 209, Lippincott Williams and Wilkins) Drug treatment can be achieved by Antacids, Histamine Hâ‚‚ receptor antagonists and proton pump inhibitors. The main aim in the drug treatment is to decrease amount of acid in stomach to minimize the pain. Antacids such as Aluminium Hydroxide, Gaviscon, Magnesium salts inhibit the pepsin, and act on raising pH by neutralising acid. It only gives symptomatic relief since it is not absorbed into bloodstream and is not effective after leaving the stomach. Acid (Hâº) is secreted by parietal cells in stomach and secretion is triggered by Histamine Hâ‚‚, Acetylcholine and Gastrin, however, Histamine Hâ‚‚ produced from mast cells is the strongest stimulus since it also affects Acetylcholine and Gastrin action. Histamine Hâ‚‚ receptor antagonists such as Ranitidine and Cimetidine, therefore, can decrease acid production by blocking Histamine Hâ‚‚ receptors. However, some acid is still secreted by Acetylcholine and Gastrin. Proton pump inhibitors such as Omeprazole blocks the H+/K+ ATPase and inhibits all three Histamine, Acetylcholine and Gastrin receptors so no acid is produced at all. Also, Pro-Kinetic Metoclopramide which is a dopamine antagonist prokinetic agent, can help by increasing contraction of sphincters and minimise reflux. Beside the lifestyle changes and drug treatment the less preferred ways such as endoscopic therapy and surgical treatments, for instance Laparoscopic Nissen fundoplication can also be used. "Current surgical techniques return the oesophagus junction to the abdominal cavity, mobilise the gastric fundus, close the diaphragmatic cura snugly and involve a short tension free fundoplication."(Kumar and Clark,Clinical Medicine,7th Edition, Page 252, Saunders) If the patient is not willing to continue drug treatment for a long time or is intolerant for the drugs used in treatment, surgery may be preferred.