Title 1. PEPTIC ULCER DISEASE.pdf ✅

PHARMD GURU Page 1 PEPTIC ULCER DISEASE INTRODUCTION:  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. First part of duodenum (Duodenal ulcer). 3. Lower end of esophagus (as a result of reflux from the stomach into the esophagus).  The ratio of incidence in duodenal ulcer and peptic ulcer is 4:1. GASTROINTESTINAL SYSTEM
PHARMD GURU Page 2 DEFINITION: Peptic ulcer disease (PUD) refers to a group of disorders characterized by circumscribed lesions of the mucosa of the upper gastrointestinal (GI) tract (particularly the stomach and duodenum). The lesions occur in regions exposed to gastric juices. 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. ETIOLOGY: 1. 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). 2. 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 output. 3. 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. 4. 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 treatment to prevent ulcers and ulcer related complications, such as bleeding.
PHARMD GURU Page 3 5. 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 ulcers. 6. Smoking: People who regularly smoke tobacco are more likely to develop peptic ulcers compared to non-smokers. 7. 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. Other notable factors influencing HCl secretion include, calcium, alcohol, coffee, acidity and food fat. PATHOPHYSIOLOGY: Ulcers develop when an imbalance exists between factors that protect gastric mucosa and factors that promote mucosal corrosion. Approximately 90% of patients with duodenal ulcer and 70% of patients with gastric ulcer have H. pylori infection. 1. Protective factors a) Normally, the mucosa secretes a thick mucus that serves as a barrier between luminal acid and epithelial cells. This barrier slows the inward movement of
PHARMD GURU Page 4 hydrogen ions, and allows their neutralization by bicarbonate ions in fluids secreted by the stomach and duodenum. b) Alkaline and neutral pancreatic biliary juices also help buffer acid entering the duodenum from the stomach. c) An intact mucosal barrier prevents back-diffusion of gastric acids into mucosal cells. It also has the capacity to stimulate local blood flow, which brings nutrients and other substances to the area and removes toxic substances (e.g., hydrogen ions). Mucosal integrity also promotes cell growth and repair after local trauma. 2. Corrosive factors. Peptic ulcer disease reflects the inability of the gastric mucosa to resist corrosion by irritants, such as pepsin, HCl, and other gastric secretions. a) Exposure to gastric acid and pepsin is necessary for ulcer development. b) Disrupted mucosal barrier integrity allows gastric acids to diffuse from the lumen back into mucosal cells, where they cause injury. 3. Physiological defects associated with peptic ulcer disease. Researchers have identified various physiological defects in patients with duodenal and gastric ulcers. a) Duodenal ulcer patients may have the following defects:  Increased capacity for gastric acid secretion a. Some duodenal ulcer patients have up to twice the normal number of parietal cells (which produce HCl). b. Nearly 70% of duodenal ulcer patients have elevated serum levels of pepsinogen I, and a corresponding increase in pepsin-secreting capacity.  Increased parietal cell responsiveness to gastrin  Above-normal postprandial gastrin secretion  Defective inhibition of gastrin release at low pH, possibly leading to failure to suppress postprandial acid secretion  Above-normal rate of gastric emptying, resulting in delivery of a greater acid load to the duodenum.