Gastrointestinal system

Chapter 10

Gastrointestinal system

 Introduction to Gastrointestinal Tract                                          

• The human gastrointestinal tract (GIT) is an organ system responsible for consuming and digesting foodstuffs, absorbing nutrients, and expelling waste. The whole system is under hormonal control, with the presence of food in the mouth triggering off a cascade of hormonal actions; when there is food in the stomach, different hormones activate acid secretion, increased gut motility, enzyme release etc.

• The upper gastrointestinal tract consists of the esophagus, stomach, and duodenum. The lower gastrointestinal tract includes most of the small intestine and all of the large intestine. Other accessory organs include liver, pancreas, gall bladder, salivary gland, teeth and tongue. Nutrients from the GI tract are not processed on-site; they are taken to the liver to be broken down further, stored, or distributed.

• Mouth: The digestive process begins in the mouth. Food is partly broken down by the process of chewing and by the chemical action of salivary enzymes (these enzymes are produced by the salivary glands and break down starches into smaller molecules).

• Esophagus: After being chewed and swallowed, the food enters the esophagus. The esophagus is a long tube that runs from the mouth to the stomach. It uses rhythmic, wave-like muscle movements (called peristalsis) to force food from the throat into the stomach. This muscle movement gives us the ability to eat or drink even when we are upside-down. 

• Stomach: It is usually “J” shaped situated at left side of body, anterior to the spleen and it connects esophagus to duodenum. It is mixing chamber and holding reservoir. 

                                                               

• Mucous membrane consists of gastric glands. Gastric pits are the numerous small indentations in the mucous membrane of the stomach which are the mouths of the gastric glands. Secretions of gastric glands flow into each gastric pit and then into the lumen of the stomach. The gastric glands contain three types of exocrine gland cells that secrete their products into the stomach lumen.

• Cephalic Phase: The cephalic phase of gastric secretion occurs in response to stimuli received by the senses, such as taste, smell, sight and sound. This phase of gastric secretion is entirely reflex in origin and is mediated by the vagus nerve.

• Gastric Phase: It is stimulated by the presence of food in the stomach to secrete gastrin. The gastric phase is mediated by the vagus nerve and by the release of gastrin. The acidity of the gastric contents after a meal is buffered by proteins so that overall it remains around pH-3 (acidic) for approximately 90 minutes. 

• Intestinal Phase: The intestinal phase is not fully understood, because of a complex stimulatory and inhibitory process. Amino acids and small peptides that promote gastric acid secretion are infused into the circulation, however, at the same time chyme inhibits acid secretion. The secretion of gastric acid is an important inhibitor of gastrin release. If the pH of the antral contents falls below 2.5, gastrin is not released. Some of the hormones that are released from the small intestine by products of digestion (especially fat), in particular glucagon and secretin, also suppress acid secretion.
• Jejunum: This is the midsection of the small intestine, connecting the duodenum to the ileum. It is about 2.5 m long, and contains the plicae circulares (also called circular folds or valves of Kerckring), and villi that increase the surface area of this part of the GI Tract. Products of digestion (sugars, amino acids and fatty acids) are absorbed into the bloodstream here. 

• Ileum: The jejunum and the ileum are the greatly coiled parts of the small intestine, and together are about 4-6 meters long; the junction between the two sections is not well-defined. The mucosa of these sections is highly folded (the folds are called plicae), increasing the surface area available for absorption dramatically. 

• Pancreas: The pancreas is a large gland located just inferior and posterior to the stomach. It is about 6 inches long and shaped like short, lumpy snake with its “head” connected to the duodenum and its “tail” pointing to the left wall of the abdominal cavity. The pancreas secretes digestive enzymes into the small intestine to complete the chemical digestion of foods

Peptic Ulcer 

• Peptic ulcers are open sores that develop in the inside lining of the esophagus, stomach and upper portion of small intestine (duodenum) as a result of erosion from stomach acids. A peptic ulcer of the stomach is called a gastric ulcer of the duodenum, a duodenal ulcer; and of the esophagus, an esophageal ulcer. Peptic ulcers occur when the lining of these organs is corroded by the acidic digestive (peptic) juices which are secreted by the cells of the stomach. A peptic ulcer differs from erosion because it extends deeper into the lining of the esophagus, stomach, or duodenum and excites more of an inflammatory reaction from the tissues that are eroded. It is an ulcer of gastrointestinal tract at an area exposed to the acid pepsin mixture (APM). The mucosa of gastrointestinal tract (GIT) in this area is digested by pepsin (peptic digestion). It is most often caused by Helicobacter pylori infection.
• Vast majority of peptic ulcer occurs in

1.  Stomach (Gastric ulcer). 2. 
2. First part of duodenum (Duodenal ulcer). 3. 
3. Lower end of esophagus (as a result of reflux from the stomach into the esophagus).

• Gastric mucus and bicarbonate secretion by gastric mucosal cells: Gastric mucus forms a layer over the epithelium of mucosa. Mucosal cells of pyloric region secrete bicarbonate ions which remain in between the epithelial cells and the mucus and pH at this region is 6 or 7. In the luminal surface of the mucus, the pH is low i.e. 2-3, therefore the peptic activity is high, digestion is possible. Near the epithelium, deep to the mucus layer, the pH is high therefore pepsin loses its activity.

Components of Aggressive Mechanism:

• Helicobacter pylori (H. Pylori): It is gram –ve bacteria found in gastric and duodenal mucosa of most person, particularly elderly. They, while in the mucosa, split urea into ammonia and thus elevate the local pH and damage the local region of the mucosa by high alkalinity. In this way, they strongly help the peptic ulcer development (PUD). 

• Acid: Hydrochloric acid (HCl) is secreted by the parietal cells of the gastric glands. Excess acid production from gastrinomas (it is a tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration), tumors of parietal cells of stomach increases acid outpu.

• Non-steroidal anti-inflammatory drugs (NSAID): Non-steroidal antiinflammatory drugs, such as aspirin, naproxen, ibuprofen, and many pain medications can irritate or inflame the lining of stomach and small intestine. Even safety coated aspirin and aspirin in powered form can frequently cause ulcers.

• Stress: Emotional stress is no longer thought to be a cause of ulcers, however, people with ulcers often report that emotional stress increases ulcer pain. Physical stress may increase the risk of developing ulcers, particularly in the stomach. For example, people with injuries, such as severe burns, and people undergoing major surgery often require.

• Genetics: A significant number of individuals with peptic ulcers have close relatives with the same problem, suggesting that genetic factors may also be involved. The genetic disorder Zollinger-Ellison syndrome (ZES) is responsible for some ulcers. Zollinger-Ellison syndrome is a rare disorder in which tumors secrete large amounts of the hormone gastrin. This hormone causes the stomach to produce excess acid which attack the lining of the stomach and cause ulcer.

• Smoking: People who regularly smoke tobacco are more likely to develop peptic ulcers compared to non-smokers.

• Alcohol consumption: Regular heavy drinkers of alcohol have a higher risk of developing peptic ulcers. In normal person, the defense mechanism is adequate, no ulcer develops. Where the defense mechanism is weakened or, is the aggressive mechanism, i.e. APM strengthened, peptic ulcer develops.

• Stimulants/Inhibitors of HCl Secretion: Parietal cells are supplied by vagal fibers. Stimulation of vagus causes HCl secretion from parietal cells. Parietal cell also contains gastrin receptors on their surface. Combination of gastrin with these receptors causes parietal cell stimulation and production of HCl. Histamine produced by mast cells is situated very close to parietal cells. Histamine stimulates HCl secretion by stimulating histamine receptors on parietal cells. 

Epidemiology 

• Higher prevalence of peptic ulcer is in developing countries. Helicobactor Pylori is sometimes associated with socioeconomic status and poor hygiene. 

• According to latest WHO data, peptic ulcer disease death in India reached to 1.20% of total death. The age adjusted death rate is 12.37 per 1,00,000 of population ranks India 5th in the world. Mortality rate has decreased dramatically in the past 20 years. 

Pathophysiology  

• The normal stomach maintains a balance between the protective factors (i.e.: mucus and bicarbonate secretion, blood flow) and aggressive factors (i.e. acid secretion, pepsin). Gastric ulcers develop when aggressive factors overcome the protective mechanism.

• n addition to an increase in acid secretion, H. pylori also predisposes patients to PUD by disrupting mucosal integrity. The bacterium’s spiral shape, flagella and mucolytic enzymes, which it produces facilitate its pasage through mucous layer to gastric surface epithelium. Subsequently, it releases phospholipase and proteases, which cause further mucosal damage. A cytotoxin-associated gene (cag A) has been isolated in approximately 65% of the bacteria. The products of this gene are associated with more severe gastritis, gastric ulcer, gastric cancer and lymphoma.

• NSAID-induced ulcers account for approximately 26% of gastric ulcers, and they are believed to be secondary to a decrease in prostaglandin production resulting from the inhibition of cyclooxygenase. The topical effects of NSAIDs are superficial gastric erosions and petechial lesions. However, the risk of gastroduodenal ulcer is not diminished with parental or rectal use of NSAIDs indicating injury occurring from the systemic effect of NSAIDs on the gastrointestinal mucosa. The greatest risk of developing an ulcer occurs during the first three months of NSAID use; thereafter, the risk decreases but continues to be present. Whether concurrent H pylori infection and NSAID use are synergistic in producing gastric ulcers, it remains unclear. 

• Cigarette smoking can affect gastric mucosal defense adversely. Cigarette smoking is believed to play a facultative role in H pylori infection, that is, people who smoke tend to develop frequent and recurrent ulcers and their ulcers are more resistant to therapy.

Clinical Manifestations 

• Mild inflammation due to small ulcers may not cause any major symptoms and may heal on their own like mouth ulcers do. However, some ulcers can cause serious symptoms.

• Stomach pain is the most common symptom. The type of pain can vary from mild to severe and may occur typically at night. It may become severe as the stomach empties and in some cases may be relieved after having food. In some cases, pain may disappear for a few days and then reappear.

Other less common signs include:

• Bloating, 
• Heartburn
• Nausea or vomiting

In severe cases, symptoms can include: 

• Dark or black stool (due to bleeding)
• Vomiting blood
• Weight loss
• Severe pain in the mid to upper abdomen 

Complications 

• Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.

• Perforation (a hole in the wall of the GIT) often leads to catastrophic consequences if left untreated. Erosion of the gastrointestinal wall by the ulcer leads to spill of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. 

• Gastric outlet obstruction is the narrowing of pyloric canal by scarring and swelling of gastric antrum and duodenum due to peptic ulcers.

• Cancer is included in the differential diagnosis elucidated by biopsy. Helicobacter pylori as the etiological factor make it 3 to 6 times more likely to develop stomach cancer from the ulcer. 

Tests and Diagnosis

Diagnosis is mainly dependent on characteristic symptoms and the severity of ulcer. Stomach pain is usually the first signal of a peptic ulcer. Some tests will be ordered so that diagnosis can be confirmed, such as: 

• General Investigation: Physical examination and recording of patient’s history. There are no established blood tests that can reliably predict the presence of peptic ulcer disease. However, a complete blood count and blood chemistries (including liver function tests, amylase, lipase and serum calcium levels) are generally obtained.H. Pylori can be diagnosed by urea breath test, blood test, stool antigen assays, and rapid urease test on a biopsy sample.

• Blood, urea breath, and stomach tissue tests: These tests are performed to detect the presence of H. pylori. Although some of the tests for H. pylori may occasionally give false-positive results or may give false-negative results in people who have recently taken antibiotics, omeprazole or bismuth. These tests can be helpful in detecting the bacteria and guiding treatment.

• Radiology: Upper GI series (also called barium swallow): A diagnostic test that examines the organs of the upper part of the digestive system: the esophagus, stomach, and duodenum. Fluid called barium (a metallic, chemical, chalky, liquid used to coat the inside of organs so that they will show up on an X-ray) is swallowed. X-rays are then taken to evaluate an ulcer, scar tissue, or a blockage that is preventing food from passing through the digestive organs normally.

• Endoscopy: Endoscopy is the most accurate diagnostic test for peptic ulcer disease. It involves inserting a small, lighted tube (endoscope) through the throat and into the stomach to look for abnormalities. Endoscopies are also performed if the patient has other signs or symptoms, such as weight loss, vomiting (especially if blood is present), black stools, anemia, and swallowing difficulties.
• Endoscopic biopsy: During the endoscopy, a piece of stomach tissue is removed, so that it can later be analyzed for exact cause of peptic ulcer development. This type of test is typically used for older people, or those that have experienced weight loss or bleeding. 

Treatment

The type of treatment is usually determined by what caused the peptic ulcer. Treatment is focused on either lowering stomach acid levels so that the ulcer can heal, or eradicating the Helicobactor pylori infection.

Treatments can include:  

• Antibiotic medications to kill H. pylori: Antibiotic combination drug therapy regimen commonly used to treat if H. pylorus is found in digestive tract. It likely needs to take antibiotics for two weeks, as well as additional medications to reduce stomach acid. eg. Metronidazole, Amoxycillin, tetracycline etc.

• Medications that block acid production and promote healing: Proton pump inhibitors reduce stomach acid by blocking the action of the parts of cells that produce acid and include: Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole, and pantoprazole.

• Medications to reduce acid production: Acid blockers, also called histamine (H2) blockers, they reduce the amount of stomach acid released into digestive tract, which relieves ulcer pain and encourages healing include: Ranitidine, Famotidine, Cimetidine and Nizatidine.

• Antacids that neutralize stomach acid: Antacids neutralize existing stomach acid and can provide rapid pain relief include Aluminum hydroxide, Magnesium hydroxide, Calcium carbonate and Sodium bicarbonate.

• Medications that protect the lining of stomach and small intestine: In some cases, medications called cytoprotective agents that help to protect the tissues that line stomach and small intestine include Sucralfate and misoprostol. Another nonprescription cytoprotective agent is bismuth subsalicylate can also be used. 

• Pyloroplasty: Pyloroplasty is an elective surgical procedure in which the lower portion of stomach, the pylorus, cut and resutured, to relax the muscle and widen the opening into small intestine, enabling contents to pass more freely from the stomach. It may be performed along with a Vagotomy.

• Antrectomy: It involves the removing of lower part of the stomach (antrum), which produces a hormone that stimulates the stomach to secrete digestive juices. A Vagotomy is usually done in conjunction with an antrectomy. 

Prevention

• Peptic ulcers can be prevented by avoiding things that break down the stomach’s protective barrier and increase stomach acid secretion. These include alcohol, smoking, aspirin, non-steroidal antiinflammatory drugs and caffe.

• Preventing infection with H. pylori is a matter of avoiding contaminated food and water and adhering to strict standards of personal hygiene. Wash hands carefully with warm water and soap every time the bathroom is used, diaper changed, and before and after preparing food. Certain lifestyle changes can reduce risk of developing peptic ulcers by properly managing emotional and physical stress.