Pathophysiological Mechanisms and Preclinical Models of Peptic Ulcer

A Peptic ulcer is a mucosal lesion of the stomach or duodenum in which the acid and pepsin play major pathogenic roles. The major forms of peptic ulcer are gastric ulcer and duodenal ulcer, both of which are chronic diseases often caused by Helicobacter pylori. The term peptic ulcer also encompasses gastric ulcers and duodenal ulcers associated with stress or the ingestion of drugs, most commonly aspirin and non-steroidal anti-inflammatory drugs (NSAIDs). Ulcer associated with Zollinger-Ellison Syndrome (ZES), caused by gastrin secreting is also considered a form of peptic ulcer. Whether an ulcer develops, depends on the balance between aggressive factors ( mainly gastric acid and pepsin) and factor that participate in mucosal defense or resistance to ulceration. Peptic ulcer develops when gastro duodenal mucosal defenses are unable to protect the epithelium from the corrosive effects of acid and pepsin. Gastric acid catalyses the cleavage of inactive pepsinogen molecules to proteolytically active pepsins and also provides the low pH for pepsin activity. Peptic ulcer effect of plant drugs and herbal formulations are studied against chemicals ( ethanol, acetic acid, histamine), drugs (dimaprit, indomethacin, aspirin, reserpine) and stress induced ulcer in rats as they virtually mimic any form of occurring gastric ulcer in stomach. The level of pH, total acidity, ulcer index reflects damage to stomach mucus as well as protective effect of plant drugs. INTRODUCTION A peptic ulcer is a hole in the gut lining of the stomach, duodenum, or oesophagus. An ulcer occurs when the lining of these organs is corroded by the acidic digestive juices which are secreted by the stomach cells. A peptic ulcer of the stomach is called a gastric ulcer, of the duodenum, a duodenal ulcer; and of the esophagus, an esophageal ulcer. TYPES OF PEPTIC ULCERS 2 Peptic ulcers are the areas of degeneration and necrosis of GIT mucosa exposed to acidpeptic secretions. Though they can occur at any level of the alimentary tract that is exposed to Hcl and pepsin, They occur most commonly(98-99%) in either the duodenum or in the stomach in the ratio of 4:1 Each of the two main types may be acute or chronic. Acute peptic ulcers or stress ulcers are multiple, small mucosal erosions, seen most commonly in the stomach but occasionally involve in the duodenum. Pathogenesis It is not clear how the mucosal erosions occour in stress ulcers because actual hyper secretion of gastric acid is demonstrable in only crushing’s ulcers occurring from intracranial such as due to brain trauma, intracranial surgery and brain tumor. In all other etiologic factor, gastric acid secretion is normal or below normal .in these conditions the possible hypotheses for genesis of stress ulcers are as under: 1. Ischaemic hypoxic injury to the mucosal cell. 2. Depletion of the gastric mucus barrier rendering the mucosa susceptible to attack by acid-peptic secretion. Chronic peptic ulcers i.e gastric and duodenal ulcer Duodenal ulcers There is conclusive evidence to support the role of high acid pepsin secretion in the causation of duodenal ulcers. Besides this, a INTERNATIONAL JOURNAL OF PHARMACEUTICAL AND CHEMICAL SCIENCES ISSN: 22775005 Vol. 2 (2) Apr-Jun 2013 www.ijpcsonline.com 772 few other noteworthy features in the pathogenesis of duodenal ulcers are as follows:1. There is generally hyper secretion of gastric acid into the fasting stomach at night which is takes place under the influence of vagal stimulation. There is high basal as well as maximal acid output in response to various stimuli. 2. Patient of duodenal ulcer have rapid emptying so that the food which normally buffers and neutralise the gastric acid ,passes down into the small intestine, leaving the duodenal mucosa exposed to aggressive action of gastric acid. Gastric ulcer Gastric ulceration is a commonly encountered clinical problem and occurs due to a disturbance of the delicate balance between HCL and mucosal resistance. Alteration in the activity of CNS ,peripheral neurotransmitters and autocoids as well as several chemical substance can increase H+ concentration resulting in ulcer formation. The pathogenesis of gastric ulcer is mainly explained on the basis of impaired gastric mucosal defences against acid pepsin secretion some other features In the pathogenesis of gastric ulcer are as follows:1. Hyperacidity may occur in gastric ulcer due to increased serum gastrin level in response to ingested food in an atomic stomach. 2. However many patients of gastric ulcer have low to normal gastric level. Ulcerogenesis in such patients is explained on the basis of damaging influences of other factors such as gastritis, bile reflux, etc. 3. The normally protective gastric mucus barrier against acid pepsin is dearranged in gastric ulcer there is depletion in the quantity as well as quality of gastric mucus. Distinguishing features of two major forms of peptic ulcer. Features Duodenal ulcer Gastric ulcer 1. Incidence a. Four times more common than gastric ulcers and b. Usual age 25-50 years. Less common than duodenal ulcers and Usually beyond 6th decade. 2. Etiology Most commonly as a result of H.pylori infection and other factors-hyper secretion of acid-pepsin, association with alcoholic cirrhosis, tobacco, hyperparathyroidism, chronic pancreatitis, blood group O, genetic factors. Gastric colonisation H.pylori asymptomatic but higher chances of development of duodenal ulcer. Disruption of mucus barrier most important factor. Association with gastritis, bile reflux, drugs, alcohol,