Delta Sem (6) - GIT Lecture (5) - Peptic Ulcer & H. Pylori

- Peptic ulcers involve defects in the gastric or duodenal mucosa extending through the muscularis mucosa.
- Lower esophagus, distal duodenum, and jejunum (in Zollinger-Ellison syndrome), and ileum (with Meckel's diverticulum) may also be sites of peptic ulcers.
- Ulcers are lesions ≥ 5mm, while erosions are lesions < 5mm.

### Common Locations of Peptic Ulcers
- Duodenum: first portion, anterior wall.
- Stomach: typically in the antrum, lesser curvature (common), anterior and posterior walls, and greater curvature (less common).
- Margins of a gastroenterostomy (stomal ulcer) are also possible locations.
- Duodenum, stomach, or jejunum in patients with Zollinger-Ellison syndrome.
- Adjacent to a Meckel's diverticulum.

### Etiology of Peptic Ulcers
- Helicobacter pylori is the most common cause.
- NSAID-associated PUD is the second most common cause.
- Corticosteroids, bisphosphonates, potassium chloride, and fluorouracil are medications that can cause peptic ulcers.
- Smoking may contribute to duodenal ulcers.
- Alcohol can irritate the gastric mucosa, increasing acidity.

### Rare Causes
- Zollinger-Ellison syndrome
- Malignancy (gastric cancer, lymphomas)
- Stress (acute illness, burns, head injury)
- Viral infection
- Vascular insufficiency
- Radiation therapy & chemotherapy
- Crohn's disease.

### Helicobacter pylori-Associated PUD
- Gram-negative bacillus that lives in the mucous layer overlaying gastric epithelium, leading to inflammation.
- Found within epithelial and mucous cells.
- More prevalent in lower socioeconomic status, acquired commonly during childhood, with about 50% of the world population being infected.

### H. pylori Transmission
- Typically through oral (saliva, vomit), fecal, or waterborne routes.
- Iatrogenic infection can occur through inadequately sterilized endoscopes and nasogastric tubes.
- Transmission from mother to fetus is not observed.

### Pathogenesis
- H. pylori is only found in the gastric mucosa.
- It produces urease, which cleaves urea into ammonia to protect against gastric acid.
- The infection leads to gastric inflammation, resulting in nutrients for the bacteria.
- The gastric antrum is the primary site, but the gastric body can also be involved.
- H. pylori elevates serum gastrin, leading to increased HCL secretion.
- Acid hypersecretion and impaired duodenal bicarbonate secretion damages the mucosa in duodenum, creating gastric metaplasia areas where H. pylori can infect.
- Duodenitis can then becomes an ulcer.

### H. pylori virulence factors that promote colonization and pathogenesis
- Urease enzyme and flagella
- Adhesins facilitate attachment to the mucosa.
- Cytotoxin-associated antigen A (Cag A) is injected into mucosal cells, affecting cell shape, proliferation, and apoptosis.
    -H. pylori strains with Cag A are linked to both duodenal ulcer and gastric cancer.
- Vacuolating cytotoxin A (Vac A) is a pore-forming toxin that aids bacterial colonization.
    -Combined seropositivity for both Cag A and Vac A correlates with high morbidity.

### Complications of Peptic Ulcer Disease
- Chronic gastritis
- Peptic ulcer disease
- Non-ulcer dyspepsia
- Gastric malignancy (adenocarcinoma & Mucosal associated lymphoid tissue (MALT) lymphoma)
- Menterier disease is a rare disorder with thickened mucosal folds, diminished HCL secretion, increased mucous secretion, and protein loss with hypoalbuminemia.
    - In children, it's associated with CMV infection.
    - In adults, it's associated with H-pylori infection.
    - Overexpression of transforming growth factor (TGF)-alpha in gastric mucosa causes menetrier disease.
    - Menetrier Disease typically occurs in males older than 30 years.
        - Common presentation: Epigastric pain, fatigue, anorexia, weight loss, edema and vomiting, diarrhea, and gastrointestinal bleeding leading to ascites, pleural effusion, and pericardial effusion.
- NSAIDs are the second most common cause of PUD.
    - Prostaglandin protects the gastric mucosa.
    - NSAIDs block prostaglandin synthesis by inhibiting COX-1, decreasing gastric mucus, bicarbonate production, and mucosal blood flow.

### Hypersecretory Environment
- Conditions associated with hypersecretory environments: Zollinger Ellison syndrome, systemic mastocytosis, antral G cell hyperplasia.
- Burns, CNS trauma, surgery, and severe medical illness increase the risk for secondary (stress) ulceration.
- Serious systemic illness, sepsis, hypotension, respiratory failure, and multiple trauma increase risk for stress ulceration
    - Cushing ulcers are associated with brain tumors or injuries.
    - Curling ulcers are associated with extensive burns.

### Zollinger Ellison Syndrome (ZES) (Gastrinoma)
- Gastrin-producing endocrine tumors of the pancreas (non-beta cells) or duodenum.
- Gastrin stimulates parietal cells, causing hypersecretion of HCL, which leads to ulceration.
- Ulcers typically form in the duodenal bulb but can also be seen in the distal duodenum and jejunum and are often multiple.
- ZES causes diarrhea and malabsorption due to ulceration, inactivation of enzymes from acidic pH, and precipitation of bile salts.

### Suspecting Zollinger-Ellison Syndrome (ZES)
- Multiple ulcers.
- Ulcers in unusual locations.
- Family history suggests multiple endocrine neoplasia type I (MEN I).
- Elevated fasting serum gastrin level (off PPIs for 1 week).
- Perform Secretin stimulation test
    - Giving secretin produces a marked increase in gastrin (>200 ng/L).
- Elevated fasting gastric acid output.
- Tumor localization and extent assessment by CT or Octreotide scan.

### Treatment for ZES
- PPIs control gastric acid hypersecretion.
- Surgical resection for candidates to resect the tumor.
- Chemotherapy, interferon, and octreotide for metastatic disease can be helpful.
- More than 20% of patients have a family history of duodenal ulcers.
- There are weak associations between duodenal ulcers and blood group O.
- Patients who do not secrete ABO antigens in saliva and gastric juices are at higher risk.
- The reasons for these genetic associations is unclear.

### Classification of Peptic Ulcers Location
- Stomach: gastric ulcer
- Duodenum: duodenal ulcer
- Esophagus: esophageal ulcer
- Meckel's Diverticulum: Meckel's Diverticulum ulcer

### Modified Johnson Classification of Peptic Ulcers
- Type I: Ulcer along the lesser curve of the stomach.
- Type II: Two ulcers are present - one gastric, one duodenal/prepyloric.
- Type III: Prepyloric ulcer.
- Type IV: Proximal gastroesophageal ulcer.
- Type V: Anywhere (associated with chronic NSAID use).
- Peptic ulcer occurs when the balance between aggressive and defensive mechanisms is disrupted.

### Aggressive Factors
- H. pylori infection
- NSAIDs
- Alcohol
- Bile salts
- HCL and pepsin

### Defensive Mechanisms
- Tight intercellular junctions
- Mucus secretion
- Bicarbonate secretion
- Mucosal blood flow
- Cellular restitution
- Epithelial renewal
- Altered mucosal defense allows back diffusion of H ions, causing epithelial cell injury.
- Duodenal ulcers are four times more common than gastric ulcers and men are more susceptible.
- The ulcer extends beyond the muscularis mucosa.
- Gastric ulcers are mainly located on the lesser curvature
- Duodenal ulcers are commonly located in the duodenal bulb (first part).
- The ulcer is round to oval with a smooth base.
- Acute ulcers have regular borders, while chronic ulcers have elevated borders with inflammation.

### Clinical Picture of Peptic Ulcer
- Epigastric abdominal pain is the most common symptom, a gnawing, burning sensation after meals .
    - Weight loss results from gastric ulcers shortly after meals. 
    - Weight gain results from food relieving duodenal ulcer pain
    - Pain wakes you up at night
    - Pain follows a pattern
    - Pain radiates to the back implying posterior penetrating gastric ulcer that is being complicated by pancreatitis.
- Other symptoms - bloating, abdominal fullness, nausea and vomiting, weight loss (GU), weight gain (DU)

### Alarm Symptoms and Signs
- Iron deficiency anemia
- Unintentional weight loss
- Progressive dysphagia & odynophagia
- Overt gastrointestinal bleeding (Hematemesis, Melena)
- Recurrent vomiting
- Family history of upper gastrointestinal malignancy
- Evaluate any patient for PUD complications (bleeding, perforation, or cancer) if they have "alarm" symptoms or signs.
- Remember alarm symptoms: Anaemia (Iron deficiency), loss of weight, anorexia, recent onset/progressive symptoms, melaena/hematemesis, and swallowing difficulty.
- Epigastric abdominal tenderness and signs of anemia may be revealed on a physical examination.
- Partial or complete gastric outlet obstruction leads to succussion splash.

### Main Differences Between Gastric Ulcer (GU) and Duodenal Ulcer (DU)
- GU affects 50-60 age group unlike DU (20-50).
- GU and DU are almost equally prevalent in men and women, with DU occurring more in men as can be identified by the ratio (2:1).
- The location of the pain usually entails the site of the ulcer; GU- over the umbilicus, unlike DU- right to the midline.
- DU can radiate pain, while GU cannot.
- There is no weight loss in DU as the patient can feel better, while GU experiences reduced intake due a feeling of discomfort.
- Haematemesis is experienced in GU, unlike black bloody stool in DU.
- Common symptoms between the two include: bloating and indigestion.
- Gastritis is common as a precursor in Gastric Ulcer, while gas is rare in Duodenal Ulcers.
- There is presence of Aggravating/Ameliorating Factors where the ulcers are prominent.

### Complications
- A complication of peptic ulcers is GI bleeding and is the first sign in 15% of patients.
    - Characterized as having tarry stool or coffee-ground emesis
    - Characterized as Melena and/or haematemesis
        - Endoscopy is performed to not only test, but also treat at the same time.
- Perforation causes abdominal pain, and leads to peritonitis from the release of contents into abdominal cavity:
    - Serum amylase, lipase present in the liver pancreas become elevated.
- Gastric Outlet Obstruction
    - inflammation causes the patient to suffer from the increasing worsening of meals.
    - The obstruction is as a result of a build up of mass.
        - treatment usually includes a balloon surgery, to assist the patient.
- Gastric cancer is also a major cause.

### Differential Diagnosis of Peptic Ulcer
- Gastritis: inflammation of the gastric mucosa with upper abdominal presenting pain.
    - The two disease are very similar.
- GERD: burning pain with regurgitation of food material.
- Gastric Cancer: characterized by pain with alarm symptoms i.e. vomiting.
- Pancreatitis: epigastric pain made worse in a supine position.
    - Serum and lipase is useful as a diagnostic tool.
- Biliary Colic: severe pain by fatty food.
- Cholecystitis: with upper and epigastric pain that is exacerbated by nausea and vomiting, positive Murphy sign, plus issues.
- Myocardial Infarction (MI): patients sometimes experience similar symptoms- epigastric pain .
- Mesenteric Ischemia: epigastric pain and weightless alert the clinician to look out for.

### Investigations
- Esophago-gastro-duodenoscopy (EGD):
    - is considered a gold standard in not only diagnosing GU/DU correctly, but also with high sensitivity.
    - Gastric ulcers can be biopsied.
        - Indication on patients with new dyspeptic patients of 50 years plus,.
        - Or alarm symptoms.
- Barium Swallow is indicated.
- Complete bloodwork helps assess.
- Serum Gastrin is an indication.
- CT scan is another check list.

### H. pylori testing
- Includes a number of test with and without an invasive procedure.
- It is recommended to stop all PI medications a week prior to testing, else false negative results would show.
- It is also tested a month after management.
#### NON-INVASIVE
- Measures levels in the blood- with relative cheap advantages, plus disadvantages that don't present from distinction.

#### C12 and C14
- They are the opposite in many factors that show a complex result, and the other presenting radioactive is contraindicated.

#### Endoscopic
- They test for choice.
- Rapid urease test in the antral region where H. Polori is situated.
- Histology gives also as assessment.

### Medications For Treatment
- Prodrugs that, when activated by acid, bind to and inhibit the parietal cell H/K - ATPase.
- Effectively taken at certain hours especially for the best results.
- PPIs- prescribed for a number of reason such as triple therapy for H. pylori, prevention, etc:
    - H2-Receptor is a major ingredient; inhibit the acid while administrating between dinner and bedtime.
    - Prostaglandin is to prevent peptic duodenal.

- PPIs should have mostly replaced H2 in medication.
- NSAIDs can cause multiple ulcers if not careful.
- PUD indicates for bleeding during surgery.

### Endoscopic Treatment
- Can differentiate between A-C during treatment of the ulcer.

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