Leukemia (Blood Cancer)

Peptic Ulcer 

         Peptic refers to the stomach, and an ulcer is a sore or break in a membrane, so peptic ulcer disease describes having one or more sores in the stomach - called gastric ulcers - Or duodenum - called duodenal ulcers- which are actually more common. Normally, the inner wall of the entire gastrointestinal tract is lined with mucosa, which consists of three cell layers. The innermost layer is the epithelial layer and it absorbs and secretes mucus and digestive enzymes. The middle layer is the lamina propria and it has blood and lymph vessels. The outermost layer of the mucosa is the muscular mucosa, and it’s a layer of smooth muscle that contracts and helps with the breakdown of food.

Now in the stomach, there are four regions - the cardia, the fundus, the body, and the pyloric antrum. There’s also a pyloric sphincter, or valve at the end of the stomach, which closes while eating, keeping food inside for the stomach to digest. The epithelial layer in different parts of the stomach contains different proportions of gastric glands which secrete a variety of substances; the cardia has mostly foveolar cells that secrete mucus which is a mix of water and glycol-proteins. The fundus and the body have mostly parietal cells that secrete hydrochloric acid and chief cells that secrete pepsinogen, which is an enzyme that digests protein. Finally, the antrum has mostly G cells that secrete gastrin in response to food entering the stomach. These G cells are also found in the duodenum and the pancreas, which is an accessory gland of the gastrointestinal tract. Now, gastrin stimulates the parietal cells to secrete hydrochloric acid and also stimulates the growth of glands in the epithelial layer.

In addition, the duodenum has Brunner glands which secrete mucus rich in bicarbonate ions. In fact, with all of the digestive enzymes and hydrochloric acid floating around, the stomach and duodenal mucosa would get digested if not for the mucus coating the walls and bicarbonate ions secreted by the duodenum which neutralizes the acid. Since the stomach walls are constantly exposed to the acid, they have a thick mucus layer than the duodenum which is only momentarily exposed to the acid. In addition, the blood flowing to the stomach and duodenum brings in even more bicarbonate which again helps neutralize the hydrochloric acid. Finally, small signaling molecules called prostaglandins to get secreted in the stomach and duodenum. And they stimulate mucus and bicarbonate secretion, as well as vasodilation of the nearby blood vessels which allows more blood to flow to the area, and this promotes new epithelial cell growth, it also inhibits acid secretion.

The main cause of gastric and duodenal ulcers is infection with H. pylori bacteria, especially in low-income countries and settings. H. pylori are gram-negative bacteria that colonize the gastric mucosa and release adhesions that help them adhere to gastric foveolar cells as well as proteases that cause damage to mucosal cells. The majority of individuals with H. pylori don’t develop any problems, but sometimes it causes a patchy pattern of damage that starts in the antrum and then spreads to the rest of the stomach and eventually into the duodenum. Over time the damage erodes deeper and deeper into the mucosa, eventually causing ulcers. Another cause of gastric ulcers, and less so duodenal ulcers, is non-steroidal anti-inflammatory drugs, or NSAIDs, like ibuprofen. NSAIDs inhibit the enzyme cyclo-oxygenase which is involved in the synthesis of inflammatory prostaglandins.

Reducing the level of prostaglandins over a prolonged period of time, though, leaves the gastric mucosa susceptible to damage, and over time ulcers can start to develop. A rare cause of peptic ulcer disease is Zollinger Ellison syndrome, which is due to a tumor called a gastrinoma. A gastrinoma is a neuroendocrine tumor that is typically located in the duodenal wall or pancreas and secretes abnormal amounts of gastrin. Excess gastrin stimulates parietal cells to release excess hydrochloric acid, which overwhelms normal defense mechanisms and allows ulcers to develop in the first portion of the duodenum or even in the distal duodenum or jejunum.

Peptic ulcers that result from any of these mucosa-damaging mechanisms are usually small, round “punched out” holes in the mucosa. The ulcers usually have a clean base because the hydrochloric acid secretions and the constant churning are a bit like a dishwasher actually keeping debris out of the ulcer! Typically, beneath the base is a layer of scar tissue and blood vessels, and occasionally the ulcers can bleed if the erosion goes deep? Gastric ulcers typically form in the lesser curvature of the antrum. Duodenal ulcers on the other hand usually develop right after the pyloric sphincter and there’s usually Brunner gland hypertrophy - which is a consequence of the body trying to produce more mucus to protect the damaged area. Very deep ulcers can erode into underlying blood vessels and can cause bleeding, which is a problem that is extremely dangerous when there’s a nearby artery. That’s because hemorrhage into the gastrointestinal tract can happen and this rapid loss of a lot of blood can ultimately lead to shock. Two well-known dangerous spots are when there’s a gastric ulcer on the lesser curvature of the stomach eroding into the left gastric artery, and a duodenal ulcer on the posterior wall of the duodenum eroding into the gastro-duodenal artery.

Another complication is perforation, which is when an ulcer erodes all the way through the wall of the stomach or duodenum, allowing gastrointestinal contents –like undigested food and gastric secretions to get into the peritoneal space – which is usually sterile. Perforation is a well-known complication of duodenal ulcers on the anterior wall of the duodenum. When they perforate, air starts to collect under the diaphragm, irritating the phrenic nerve, and sending referred pain up to the shoulder. Finally, and very rarely, long-standing duodenal ulcers near the pyloric sphincter can sometimes have so much edema or scarring that they obstruct the normal passage of gastric contents into the intestines resulting in gastric outlet obstruction, this can quickly lead to nausea or vomiting since the food literally can’t get by.

The main symptom of gastric and duodenal ulcers is epigastric pain, which is an aching or burning in the upper abdomen. Other symptoms are bloating, belching, and vomiting. Classically, gastric ulcer pain increases while eating a meal due to the physical presence of the food, as well as the hydrochloric acid production stimulated by the process of eating, on the other hand, duodenal ulcer pain decreases while eating a meal. This may be why gastric ulcers are associated with weight loss, while duodenal ulcers are associated with weight gain. Peptic ulcers can be diagnosed with upper endoscopy, which is when a tube is snaked through the esophagus, into the stomach, and then the proximal duodenum in order to see the ulcer itself. Usually, during the procedure, a biopsy is done to make sure that there are no signs of malignant cells and to see if there are signs of an H. pylori infection. Treatment of peptic ulcers depends on the underlying cause. If there’s an H. pylori infection, it’s usually cured with a combination of antibiotics and acid-lowering medications, specifically proton pump inhibitors. Substances that can worsen peptic ulcers include NSAIDs, as well as alcohol, tobacco, and caffeine, so it’s best to stop using all of those as soon as possible. And in really extreme cases, surgery may be needed.