Gastro-intestinal Function Unit (GIFU) at St James’s Hospital
The GIFU at St James’s provides a GI Physiology testing service locally and nationally.
Patients are referred with symptoms of heartburn and/or dysphagia. Research in this area concentrates on patients with benign disease; Barrett’s Oesophagus is an example of mucosal injury due to prolonged exposure to gastric juices and if untreated, one in two hundred patients with this condition will go on to develop a cancer. Other benign diseases include Achalasia and Diffuse Spasm. Tests include oesophageal manometry, 24 hour acid and bile monitoring, gastric motility testing and bowel testing. Studies have shown that ambulatory monitoring of the oesophagus helps to confirm gastroesophageal reflux in patients with persistent symptoms (both typical and atypical) without evidence of mucosal damage, especially when medication is ineffective. It is also often used to monitor the control of reflux in patients with continued symptoms on therapy. Oesophageal manometry is used to diagnose motility problems and may be helpful prior to antireflux surgery.
Research areas within the G.I.F.U at St James’s Hospital
Gastrointestinal physiology is a branch of human physiology addressingthe physical function of the gastrointestinal system.The major processes occurring in the GI System are that of motility, secretion, regulation, digestion and circulation. The function and coordination of each of these actions is vital in maintaining GI health, and thus the digestion of nutrients for the entire body.
Motility The term Motility is used primarily to describe the contraction of the muscles in the gastrointestinal tract. Because the gastrointestinal tract is a circular tube, when these muscles contract, they close off the tube or make the opening inside smaller – they squeeze. These muscles can contract in a synchronized way to move the food in one direction (usually downstream, but occasionally upstream for short distances); this is called peristalsis. Each part of the gastrointestinal tract has a unique function to perform in digestion, and as a result each part has a distinct type of motility and sensation. When motility or sensations are not appropriate for performing this function, they cause symptoms such as bloating, vomiting, constipation, or diarrhea which are associated with subjective sensations such as pain, bloating, fullness, and urgency to have a bowel movement.
The gastrointestinal tract is divided into four distinct parts: the oesophagus, stomach, small intestine, and large intestine (colon). They are separated from each other by special muscles called sphincters which normally stay tightly closed and which regulate and which regulate the movement of food and food residues from one part to another. The gastrointestinal tract generates motility using smooth muscle subunits linked by gap junctions. These subunits fire spontaneously in either a tonic or a phasic fashion. Tonic contractions are those contractions that are maintained from several minutes up to hours at a time. These occur in the sphincters of the tract, as well as in the anterior stomach. The other type of contractions, called phasic contractions, consist of brief periods of both relaxation and contraction, occurring in the posterior stomach and the small intestine, and are carried out by the muscularis externa.
Stimulation The stimulation for these contractions likely originates in modified smooth muscle cells called interstitial cells of Cajal. These cells cause spontaneous cycles of slow wave potentials that can cause action potentials in smooth muscle cells. They are associated with the contractile smooth muscle via gap junctions. These slow wave potentials must reach a threshold level for the action potential to occur, whereupon Ca2+ channels on the smooth muscle open and an action potential occurs. As the contraction is graded based upon how much Ca2+ enters the cell, the longer the duration of slow wave, the more action potentials occur. This in turn results in greater contraction force from the smooth muscle. Both amplitude and duration of the slow waves can be modified based upon the presence of neurotransmitters, hormones or other paracrine signaling. The number of slow wave potentials per minute varies based upon the location in the digestive tract. This number ranges from 3 waves/min in the stomach to 12 waves/min in the intestines.
The patterns of gastrointestinal contraction as a whole can be divided into two distinct patterns, peristalsis and segmentation. Occurring between meals, the migrating motor complex is a series of peristaltic wave’s cycles in distinct phases starting with relaxation followed by an increasing level of activity to a peak level of peristaltic activity lasting for 5-15 minutes. This cycle repeats ever 1.5-2 hours but is interrupted by food ingestion. The role of this process is likely to clean excess bacteria and food from the digestive system.
Peristalsis Peristalsis is the second of the three patterns and is one of the patterns that occur during and shortly after a meal.The contractions occur in wave patterns traveling down short lengths of the GI tract from one section to the next. The contractions occur directly behind the bolus of food that is in the system, forcing it toward the anus into the next relaxed section of smooth muscle. This relaxed section then contracts, generating smooth forward movement of the bolus at between 2-25 cm per second. This contraction pattern depends upon hormones, paracrine signals, and the autonomic nervous system for proper regulation.
Segmentation The third contraction pattern is segmentation, which also occurs during and shortly after a meal within short lengths in segmented or random patterns along the intestine. This process is carried out by longitudinal muscles relaxing while circular muscles contract at alternating sections thereby mixing the food. This mixing allows food and digestive enzymes to maintain a uniform composition, as well as to ensure contact with the epithelium for proper absorption.
Every day, seven litres of fluid are secreted by the digestive system. This fluid is composed of four primary components: ions, digestive enzymes, mucous, and bile. About half of these fluids are secreted by the salivary glands, pancreas, and liver, which compose the accessory organs and glands of the digestive system. The rest of the fluid is secreted by the GI epithelial cells.
Ions The largest component of secreted fluids is ions and water, which are first secreted and then reabsorbed along the tract. The ions secreted primarily consist of H+, K+, Cl-, HCO3- and Na+. Water follows the movement of these ions. The GI tract accomplishes this ion pumping using a system of proteins that are capable of active transport, facilitated diffusion and open channel ion movement.
Digestive Enzymes The second vital secretion of the GI tract is that of digestive enzymes that are secreted in the mouth, stomach and intestines. Some of these enzymes are secreted by accessory digestive organs, while others are secreted by the epithelial cells of the stomach and intestine. While some of these enzymes remain embedded in the wall of the GI tract, others are secreted in an inactive pro enzyme form. When these proenzymes reach the lumen of the tract, a factor specific to a particular proenzyme will activate it. A prime example of this is pepsin, which is secreted in the stomach by chief cells. Pepsin in its secreted form is inactive. However, once it reaches the gastic lumen it becomes activated into pepsinogen by the high H+ concentration, becoming a enzyme vital to digestion. The release of the enzymes is regulated by neural, hormonal, or paracrine signals. However, in general, parasympathtic stimulation increases secretion of all digestive enzmes.
Mucous Mucous is released in the stomach and intestine, and serves to lubricate and protect the inner mucosa of the tract. It is composed of a specific family of glycoproteins termed mucins and is generally very viscous. Mucous is made by two types of specialized cells termed mucus cells in the stomach and goblet cells in the intestines. Signals for increased mucous release include parasympathetic innervations, immune system response and enteric nervous system messengers.
Bile Bile is secreted into the duodenum of the small intestine via the common bile duct. It is produced in liver cells and stored in the gall bladder until release during a meal. Bile is formed of three elements: bile salts, bilirubin and cholesterol. Bilirubin is a waste product of the breakdown of hemoglobin. The cholesterol present is secreted with the faeces. The bile salt component is an active non-enzymatic substance that facilitates fat absorption by helping it to form an emulsion with water due to its amphoteric nature. These salts are formed in the hepatocytes from bile acids combined with an amino acid. Other compounds such as the waste products of drug degradation are also present in the bile.
GI Physiology: Oesophagus
Normal Motility and Function The function of the oesophagusis simply to transport food from the mouth to the stomach, and powerful, synchronized (peristaltic) contractions follow each swallow to accomplish this task. Between swallows, the oesophagus usually does not contract. There is a sphincter muscle separating the oesophagus from the stomach (called the lower esophageal sphincter) which normally stays tightly closed to prevent acid in the stomach from washing up into the oesophagus. However, when we swallow, this sphincter muscle opens up (relaxes) so that the food we swallow can enter the stomach.
Gastroesophageal Reflux Disease The most common symptom that occurs in the oesophagus is heartburn, which is caused when acid washes up into the oesophagus repeatedly (gastroesophageal reflux) and irritates the lining of the oesophagus. This happens when the sphincter separating the stomach from the oesophagus does not work properly; the function of this sphincter is to prevent reflux from occurring when the stomach contracts. This can be due to a weak sphincter muscle, to too-frequent spontaneous relaxation of the sphincter, or to hiatal hernia. Hiatal hernia means that the stomach pulls up into the chest above the sheet of muscle that separates the abdomen from the chest (this muscle sheet is called the diaphragm). A hiatal hernia weakens the sphincter. Gastroesophageal reflux disease may be diagnosed by an ambulatory pH study, which is a recording of the frequency with which acid washes up into the oesophagus. It is done by putting a small, soft tube with one or two acid sensors on it down through your nose into your oesophagus and connecting it to a battery-operated computer for 18-24 hours. You can go about your usual work and social activities during this test.
Dysphagia Dysphagia means ineffective swallowing. Sometimes this occurs because the muscles of the tongue and neck that push the food into the oesophagus are not working properly because of a stroke or a disease affecting the nerves or muscles of the tongue and throat. However, food can also stick because the lower esophageal sphincter does not relax to let the food into the stomach (a disorder called achalasia) or because the oesophagus contracts in an uncoordinated way (a disorder called esophageal spasm). Dysphagia can cause food to back up in the oesophagus and lead to vomiting. There may also be a sensation of something getting stuck or a sensation of pain. Tests for dysphagia include esophageal manometry, which means that a small tube containing pressure sensors is put down through the nose into the oesophagus to measure the contractions of the oesophagus and the relaxation of the lower esophageal sphincter. This test lasts about 30 minutes.
Functional Chest Pain Sometimes patients have pain in their chest that is not like heartburn (no burning quality) and that may be confused with pain from the heart. If you are over 50 years of age, your doctor will always want to first find out if there is anything wrong with your heart, but in many cases the heart turns out to be healthy. In many patients with this kind of pain and no heart disease, the pain comes from spastic contractions of the oesophagus or increased sensitivity of the nerves in the oesophagus or a combination of muscle spasm and increased sensitivity. The test which is used to find out if this is the cause, is esophageal manometry – the same test described above to investigate symptoms of food sticking in the chest. Ambulatory pH studies may also be used to see if gastroesophageal reflux may be the cause of the chest pain.
Normal Motility and Function One function of the stomach is to grind food down to smaller particles and mix it withdigestive juices so that it can be absorbed when it reaches the small intestine. The stomach also empties its contents into the intestine at a controlled rate. The stomach has three types of contractions: (1) There are rhythmic, 3 per minute, synchronized contractions in the lower part of the stomach which create waves of food particles and juice which splash against a closed sphincter muscle (the pyloric sphincter) to grind the food down into small particles. (2) The upper part of the stomach shows slow relaxations lasting a minute or more that follow each swallow and that allow the food to enter the stomach; at other times the upper part of the stomach shows slow contractions which help to empty the stomach. (3) Between meals, after all the digestible food has left the stomach, there are occasional bursts of very strong, synchronized contractions that are accompanied by opening of the pyloric sphincter muscle. These are sometimes called “housekeeper waves” because their function is to sweep any indigestible particles out of the stomach. Another name for them is the migrating motor complex.
Delayed Gastric Emptying (Gastroparesis) The symptoms of delayed gastric emptying include nausea and vomiting. Poor emptying of the stomach can occur for several reasons: (1) The outlet to the stomach (the pylorus and duodenum) may be obstructed by an ulcer or tumour or by something large and indigestible that was swallowed. (2) The pyloric sphincter at the exit to the stomach may not open enough or at the right times to allow food to pass through. This sphincter is controlled by neurological reflexes to insure that only very tiny particles leave the stomach and also to insure that not too much acid or sugar leaves the stomach at one time, which could irritate or injure the small intestine. These reflexes depend on nerves which sometime become damaged. (3) The normally rhythmic, 3/minute contractions of the lower part of the stomach can become disorganized so that the contents of the stomach are not pushed towards the pyloric sphincter. This also usually has a neurological basis; the most common cause is long-standing diabetes mellitus, but in many patients the cause of delayed gastric emptying is unknown, so the diagnosis given is idiopathic (meaning cause unknown) gastroparesis.
Tests used to evaluate patients with delayed gastric emptying usually include endoscopy to look inside the stomach, and gastric emptying (a nuclear medicine study) to measure how quickly food leaves the stomach. The test of gastric emptying involves eating food that has a radioactive substance added to it, so that the rate of emptying of the stomach can be measured with a type of geiger counter (gamma camera). Another, less frequently used tests is the electrogastrogram which measures small electrical currents that come from the stomach muscle and that indicate whether the 3/min contractions of the lower stomach are occurring normally. The contractions of the stomach can also be measured directly by passing a tube with pressure sensors on it down the nose and into the stomach.
Functional Dyspepsia Many patients have pain or discomfort which is felt in the centre of the abdomen above the belly button. Some examples of discomfort that is not non-painful are fullness, early satiety (feeling full soon after starting to eat), bloating, or nausea. There is no single motility disorder that explains all these symptoms, but about a third of patients with these symptoms have delayed gastric emptying (usually not so severe that it causes frequent vomiting), and about a third show a failure of the relaxation of the upper stomach following a swallow (abnormal gastric accommodation reflex). About half of the patients with these symptoms also have a sensitive or irritable stomach which causes sensations of discomfort when the stomach is filled with even small volumes. A gastric emptying study (see above) can show whether there is poor emptying of the stomach. The other motility disorders are more difficult to detect, but scientists have developed a computer-controlled pump called the barostat which can show (1) whether the upper stomach relaxes adequately during eating and (2) how much filling of the stomach it takes to cause pain or discomfort.
Intestinal Dysmotility, Intestinal Pseudo-Obstruction Abnormal motility patterns in the small intestine can lead to symptoms of intestinal obstruction (blockage). These symptoms are bloating, pain, nausea, and vomiting. They vary in how severe or how frequent they are, but there are usually periods during which the patient is free of symptoms. These symptoms can result either from weak contractions or from disorganized (unsynchronised) contractions.
Weak contractions of the small intestine are due to abnormalities in the muscle and are usually associated with diseases such as scleroderma. These connective tissue disorders may cause the intestine to balloon out in places so that the contractions of the muscle are not able to move the contents downstream. Other patients have contractions that are
strong enough, but they are too disorganized or nonperistaltic to move food along. This type of motility disorder is due to abnormalities in the nerves which coordinate (synchronize) the contractions of the intestine. This abnormality is easiest to detect by recording the housekeeper waves because these are easily identified peristaltic contractions. In intestinal pseudo-obstruction of the neurological variety, these bursts of contractions occur simultaneously over large parts of the intestine or they may actually
move upstream. The test which is used to detect either of these intestinal motility abnormalities is a small bowel motility study. This involves putting down a long tube with pressure sensors on it which passes through the stomach and into the small intestine. It is important to record several of the housekeeper wave fronts to be sure of the diagnosis. In some clinics this is done by recording for five hours or more while the patient lies on a bed in the clinic, but in other clinics, the pressure sensors are connected to a battery-operated computer and the patient is sent home to return the next day.
Small Bowel Bacterial Overgrowth This means that there are too many bacteria in the upper part of the small intestine. This leads to symptoms of bloating, pain, and diarrhea that occur immediately after eating because the bacteria in the intestine begin to consume the food in the small intestine before it can be absorbed. These bacteria give off hydrogen and other gases which cause bloating and diarrhea. Small bowel bacterial overgrowth is a result of abnormal motility in the small intestine; when the housekeeper waves do not keep the bacteria swept out because the contractions are too weak or disorganized, the bacteria grow out of control. Bacterial overgrowth is most easily detected by the hydrogen breath test: The patient drinks a sugar solution and breathes into a bag every 15 minutes for two hours. If the bacteria are present in large amounts in the small intestine, they give off hydrogen, some of which is absorbed into the blood, carried to the lungs, and breathed out where it can be detected.
Focal ablation of residual Barrett’s tissue may be conducted with the HALO360 device or a focal ablation device, the HALO90 device, capable of more selective tissue ablation. The HALO90 is substantially equivalent to the HALO360, having the same electrode design and delivering the same energy density and power density to the tissue. The difference is that the surface area is smaller, allowing more focal selective ablation of residual Barrett’s tissue, and this device is attached to the endoscope, rather than to a balloon catheter. The following images depict the ablation catheter. The generator is similar to the HALO360 energy generator.