Flashcards in Jan 23 - Peptic Ulcer Disease Deck (53):
Name the different layers of the stomach lining from deep to superficial (kinda)
Superficial epithelial cells
Enterochromaffin-like (ECL) cells
Describe the mucosal layer of the stomach lining
It faces the stomach
It's a thick layer of mucous that protects the layer of skin that surrounds the stomach
Describe the superficial epithelial cells of the stomach lining
They have a high turnaround time (similar to the skin, they just schluff off). They are critical for producing mucous
What is the role of the parietal cells?
They are critical for the production of stomach acid (HCl)
What is the role of the chief cells?
They are involved in digestion; they produce digestive enzymes (pepsinogen, chymotrypsin, gastric lipase)
What is the role of G cells?
They produce gastrin, a peptide hormone that is most potent in the stimulation of the secretion of gastric acid by parietal cells of the stomach and aids in gastric mobility.
What is the role of enterochromaffin-like cells?
ECL cells are critical for the release of histamine, which is important because, upon stimulation, it causes the parietal cells to further increase acid production
Why are blood vessels important
Bicarbonate is drawn out from the bloodstream
Name three gastric acid producers
Name two gastric acid reducers
How does acetylcholine work to produce gastric acid?
Cholinergic receptors are located on the parietal cell membranes. Vagal stimulation of muscarinic cholinergic parietal cells via muscarinic receptors activates the parietal cells to secrete gastric HCl
How does gastrin work to produce gastric acid? What stimulates gastrin release?
Gastrin binds to cholecystokinin B receptors (CCK2) to stimulate the release of histamines in ECL cells and it induces the insertion of K+/H+ ATPase pumps into apical membrane of the parietal cells (which in turn increases H+ release into the stomach cavity). Its release is stimulated by peptides in the lumen of the stomach.
It also causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin
It may impact lower esophageal sphincter (LES) tone, causing it to contract
How does histamine work to produce gastric acid?
Receptors located on the parietal cells and when stimulated by histamine, gastric acid secretion occurs. It is the most important gastric acid secretion stimulant and is released from ECL cells by gastric and cholinergic activity
How do prostaglandins work to reduce gastric acid?
Receptors located on parietal cells that when stimulated reduce gastric acid secretion
How does somatostatin work to reduce gastric acid?
It inhibits gastric acid secretion as receptors are located on the parietal cells
Besides mucous production, what is the role of superficial epithelial cells?
It draw bicarbonate from the blood and transfers it into the intermediate layer and protects superficial epithelial cells by neutralizing the acid
How does mucosal layer protect the stomach lining?
It acts as a physical barrier that pepsin and other proteases cannot penetrate and slows the diffusion of H+
What's so dangerous about gastric acid?
It has a pH of 1-2, which denatures and hydrolyzes protein, hydrolyzes TG and carbohydrates. It also has pepsin and other proteases rapidly hydrolyzes protein. If there is an imbalance between gastric acid and mucosal defenses, it can result in inflammation and damage to the stomach lining leading to ulcerations
What are the two stages of of mucosal damage?
Erosion and ulcer
Superficial injury of the gastrointestinal mucosa causes by decrease in mucosal defences or increase in gastric acid
Describe an ulcer
Complete erosion through the GI mucosa extends through the muscularis mucosa into the submucosa or deeper resulting in a GI bleed
What are the 3 main etiologies/causes peptic ulcer disease (PUD)?
Helicobacter pylori (most common)
NSAID-induced (second most common)
Stress induced (uncommon)
What is H pylori?
Gram-negative bacterium and 40% of individuals have them colonized in the stomach. It's spread from person to person by fecal-oral route. Of the 40%, most (90%) have inflammation of the stomach (gastritis) or duodeum (duodenitis), which is usually asymptomatic. Only 15% of these go on to develop ulcers. 85% to 100% of duodenal ulcers and 65% of gastric ulcers are associated with H pylori
What are the virulence factors of H pylori?
H pylori has genes that make it more capable of colonizing the stomach, penetrating through the mucus layer (to evade the low gastric pH) and causing inflammation and cell death
How does H pylori affect the mucus lining?
H pylori is a spiral-shaped bacterium commonly found in the stomach. The bacteria's shape and the way they move allow them to penetrate the stomach's protective mucus lining, where they produce substances that weaken the lining and make the stomach more susceptible to damage from gastric acid
What happens if the H pylori attaches to the cells of the stomach?
The bacteria can also attach to cells of the stomach, causing stomach inflammation (gastritis), and can stimulate the production of excess stomach acid. Over time, infection with the bacteria can also increase the risk of stomach cancer
What is the mechanism of H pylori infection?
H pylori produces urease, which produces ammonia. The ammonia neutralizes gastric acid, allowing transit through stomach to the gastric mucosa. The flagella allows penetration of the mucus layer to the epithelial cell. After, the bacteria starts producing the toxins Vac A and LPS
What is Vac A?
Vacuolating toxin; it induces inflammation/apoptosis, promotes formation of acidic vacuoles in cells, and it forms pores in the epithelial cell membrane
What is LPS?
Lipopolysaccharides; it recruits and activates the immune cells resulting in inflammation that kills epithelial cells
What is the most common symptom of peptic ulcer disease caused by H pylori?
Gnawing or burning abdominal pain, usually in the area just beneath the ribs. This pain typically gets worse when your stomach is empty and improves when you eat food, drink milk or take an antacid
What are less common symptoms of peptic ulcer disease caused by H pylori?
Loss of appetite
Vomiting (vomit may be bloody or look like coffee grounds)
Black tarry stools
Why can H pylori infection lead to stomach cancer?
The more repeated damage creates scar tissue and the repeated damage can cause mutation in the stomach cells and eroded area can become cancerous
What is more common, duodenal ulcer or gastric ulcer?
The duodenal ulcer is 4x more common than a gastric ulcer
Describe the duodenal ulcer pathogenesis
1. Antral H pylori infection
2. Antral inflammation stimulates increased release of gastrin
3. Gastrin induces acid secretion from the body of the stomach
4. Increased acid damages the duodenal mucosa, causing ulceration
5. Duodenal cells change into gastric-like cells (metaplasia)
6. Metaplastic duodenum becomes colonized by H pylori
Describe the gastric ulcer pathogenesis
1. H pylori infection throughout most of the stomach
2. Inflammation stimulates increased release of gastrin
3. Gastrin induces increased acid secretion from body of stomach at first
4. Increased acid and inflammation damages the gastric mucosa, causing ulceration
5. Infection and inflammation causes loss of parietal and chief cells called atrophy, H+ decreases
What are the symptoms of gastric ulceration?
Burning pain over a wide area below the breast bone
Precipitated by food (hurts when the patient eat); the food stimulates acid production
What are the symptoms of duodenal ulceration?
Focal pain between breast bone and umbilicus
Pain relieved by eating but reoccurs 1-3 hours after meals
Pain also worse at night
What is the main invasive method to diagnose H pylori PUD?
Histology - requires expert pathologist (and a biopsy)
What are other invasive methods to diagnose H pylori PUD?
Culture biopsy - allows culture and sensitivity
Rapid urease (CLO) test - cost effective, requires an additional test for confirmation of H pylori infection (still need a biopsy)
What the main noninvasive method to diagnose H pylori PUD?
Urea breath test - expensive, reliable test to evaluate success of treatment for H pylori
What are other noninvasive methods to diagnose H pylori PUD?
Fecal antigen test - simple test, not reliable for evaluation of treatment success
Serology - not reliable for routine screening; will test positive even after treatment due to immunological memory
What are lifestyle changes are recommended when someone has to make if they have PUD
Reduce alcohol consumption (alcohol causes irritation of the cell lining)
Quit smoking (smoking cause larger ulcers, higher recurrence and makes them harder to treat)
Quit cocaine/amphetamine consumption (it reduces blood flow to gastric mucosa, which results in less bicarbonate to be taken up by the superficial epithelial cells)
Stop using NSAIDs (they could be the cause of the ulcer)
What are NSAIDs?
Nonsteroidal anti-inflammatory drugs
What do NSAIDs do?
They inhibit prostaglandins synthesis
What do prostaglandins do in the stomach?
They stimulate bicarbonate secretion and mucus secretion
They stimulate mucosal cell growth and decrease acid production
How is H pylori-induced PUD treated?
Antibiotics - H-pac: lansoprazole/amoxicillin/clarithromycin. They produce long-term cure in 80% of non NSAID induced ulcers
What are other treatment options besides antibiotics for PUD?
Stop excessive alcohol consumption
Stop eating foods that cause pain
What are PUD complications?
Acute or chronic GI tract bleeding (vomiting blood, rectal bleeding or dark tarry stools, massive loss of blood which results in hypotension, tachycardia and fainting)
Gastric ulcer (gastric cancer)
What are three uncommon causes of PUD?
What is zollinger-ellison syndrome?
A gastrin secreting tumor that produces hyper-activity. It can cause ulcers from stomach to lieum
What causes vascular insufficiency?
Cocaine/crack use. It reduces gastric blood flow resulting in reduced HCO3- uptake
How does radiation therapy/chemotherapy cause PUD?
It kills rapidly growing gastric epithelial cells