Peptic Ulcer

A peptic ulcer is defined as a disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation. The word peptic refers to pepsin a stomach enzyme that breaks down proteins. A peptic ulcer in the stomach is called a gastric ulcer.

Epidemiology of Peptic ulcer

Peptic ulcers used to be a rare disease before the 19th century. Acute perforations of gastric ulcers were first reported in young girls at the beginning of the 19th century. With the progress of the 19th century, peptic ulcer disease became frequent both in men and women.

In the West, this disease affects equally men and women whereas men are affected 18 times more commonly than women in India.  Broadly, in developing countries like India, it is impossible to obtain exact figures for disease incidence, and differences are bound to exist between regions.

A peptic ulcer is more prevalent in Jammu and Kashmir, followed by Southern India. North India comes next, and East and North East have a comparatively lower prevalence

Pathogenesis of Peptic Ulcer

Peptic ulcers occur because of an imbalance between aggressive factors (gastric acid and pepsin) and defensive factors (gastric mucus, bicarbonate, Prostaglandins). Gastric ulceration occurs when mucosal defenses fail, as when mucosal blood flow drops, gastric emptying is delayed, or epithelial restitution is impaired

The factors produce ulceration by aggravating gastric acid and pepsin secretion- 2 categories:

a. Endogenous factors: These include different visceral neurotransmitters, hormones (acetylcholine, gastrin, histamine, somatostatin, and cholecystokinin), second messengers (Ca2+), and genetic factors.

b. Exogenous factors: These include bacterial infection (H. Pylori), NSAID, alcohol, psychogenic factors, and dietary habits.

Endogenous Factors

1. Acetylcholine (Ach)
2. Gastrin
3. Histamine
4. Somatostatin and Cholecystokinin:
5. Ca2+ as second messengers
6. Genetics: Increased familial history – 20-50% of patients. Ulcers are also more common in blood group O subjects and in those who do not secrete blood group antibodies into gastric secretions.

Exogenous Factors

1. H. pylori: Pylori is a curved or S-shaped gram-negative bacterium approximately 0.5 by 3 µm in size containing four to seven sheathed flagella at one pole.
2. Non-steroidal Anti-inflammatory Drugs (NSAID): NSAIDs interferes with the following lines of mucosal defense-
   • Mucous cell secretion of mucin and surface-active phospholipid. Both PGE and PGF induce the secretion of polysaccharide material in the stomach known as mucin, which acts as a protective agent against potential stomach ulceration induced by HCl and pepsin. This implies that NSAIDs cause gastric ulcers by inhibiting the secretion of this cytoprotective substance.
   • Basal bicarbonate secretion from gastric mucosa.
   • Mucosal proliferation is necessary for ulcer healing.
   • Regulation of mucosal blood flow.
   • Physiological regulation of gastric acid secretion via feedback inhibition.

   NSAID may also cause ulceration by the generation of oxygen-derived free radicals and products of the lipo-oxygenase pathway. COX inhibition by NSAID results in the diversion of arachidonic acid metabolism towards the lipo-oxygenase pathway, resulting in increased leukotriene synthesis. These leukotrienes can contribute to gastrointestinal ulceration, through two mechanisms, firstly, by a reduction in prostaglandin level and secondly, through the release of oxygen radicals mediated mucosal injury produced in this pathway.

3. Ethanol:  Ethanol damage to the gastrointestinal mucosa starts with micro-vascular injury, namely disruption of the vascular endothelium resulting in increased vascular permeability, edema formation, and epithelial lifting. These effects are secondary to ethanol-induced slowing or cessation of gastric mucosal flow. Alcohol causes the stomach cells to oversecrete both acid and histamine which makes the stomach linings vulnerable to ulcer formation. Ethanol also reduces prostaglandin levels and increases the release of histamine and the influx of calcium ions.
4. Cigarette Smoking: Continued smoking with advancing age augments the secretion of HCl and pepsin and is also expected to modify the contents of gastric juice and pepsin isoenzyme patterns. The increased gastric acid secretion is mediated through the stimulation of the H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking causes mucosal injury by increasing the content of free oxygen radicals, PAF, pituitary vasopressin, gastric endothelin, and pituitary vasopressin. Smoking and nicotine stimulate pepsinogen secretion also by increasing the chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, NSAID or cold restrain stress. Smoking also alters processes important in gastric and duodenal mucosal integrity or protection such as mucosal bicarbonate secretion, prostaglandin content, mucosal blood flow, or epidermal growth factor.
5. Diet: All foods are capable of stimulating gastric acid secretion through distention of the stomach, but proteins are the major stimulants. Digested proteins in the form of peptides, peptones, and amino acids act primarily through the stimulation of gastrin from antral G cells. The aromatic amino acids are the most potent of the amino acids. Amino acids absorbed into the circulation stimulates acid secretion by directly stimulating parietal cells or via gastrin release in humans. Caffeinated beverages (eg. tea, coffee), cola-type beverages, beer, and milk are potent stimulants of gastric acid secretion. Coffee produces acid output equal to 70 percent of peak acid output as compared to Penta gastrin. 5% aqueous tea and coffee beverages act by decreasing PGI2 synthesis. A low-fiber diet, and high dietary consumption of salt and red/black peppers also cause peptic ulcers.
6. Psychological Factor (Stress Ulcers): There is considerable evidence that supports the role of stressful life events in the etiology of PUD. Stress-induced ulcers are due to an increase in free radical generation apart from acid pepsin factors. Stress causes an increase in gastric motility, vagal overactivity, and mast cell degeneration, reducing gastric mucosal blood flow. Stress may also produce ulceration by the release of histamine with enhanced acid secretion and reduced mucous production. Cold-restrained stress-induced ulcers are the result of autodigestion of the gastric mucosal barrier, accumulation of HCl, and generation of free radicals.

Types of Peptic Ulcer

Based on location, peptic ulcers are categorized as follows:

1. Gastric Ulcer: Occurrence of ulcer in the stomach, more commonly in older age group.
2. Duodenal Ulcer: Occurrence of ulcer in the duodenum. They occur commonly in younger individuals and are evenly distributed among various socioeconomic groups. These patients have higher than normal levels of acid secretion rates. Depending on the severity, peptic ulcers are classified as:

• Acute Peptic Ulcer: These ulcers involve tissues to the depth of the submucosa. They may arise in the form of single or multiple lesions. They are found in many sites of the stomach and the first few centimeters of the duodenum.
• Chronic Peptic Ulcer: These ulcers penetrate through the epithelial and muscle layers of the stomach wall and may include the adjacent pancreas or liver. In the majority of cases, they occur singly in the pyloric antrum of the stomach and the duodenum.

Symptoms

The most common symptom of a peptic ulcer is abdominal discomfort. This discomfort comes and goes for several days of the week, generally occurring 2 to 3 hrs after a meal, in the middle of the night, when the stomach is empty. Other symptoms include blood loss leading to anemia, weight loss, poor appetite, bloating, burping, nausea, and vomiting. In patients with an advanced-stage emergency, symptoms are sharp, sudden, and persistent accompanied by stomach pain, bloody or black stools, blood in vomit, etc

ACUTE PEPTIC ULCER

They are usually multiple erosions due to disruption of the mucosal barrier.

Causes- Stress, drugs like analgesics, steroids, surgeries.

Clinical Features

• Sudden onset of acute pain and tenderness in the epigastric region.
• Vomiting with or without haematemesis.
• Often acute peptic ulcers can lead to perforations.
• Acute ulcers after cerebral trauma or neurosurgeries are called Cushing ulcers.
• Acute ulcers after major burns are called curling ulcers.

Diagnosis is by gastroscopy.

Treatment

• Intravenous ranitidine 50 mg, 8th hourly.
• IV fluids.
• Blood transfusions if there is bleeding.

Curling’s ulcers

They are acute ulcers that develop after major burns, presenting as pain in the epigastric region, vomiting, or haematemesis. Treatment is conservative- IV ranitidine. IV pantoprazole 80 mg in 100 ml DNS low, later 40 mg IV maintenance.

Note: curling ulcer occurs when burn injury is more than 35%.

Cushing ulcers

They are acute ulcers that develop after cerebral trauma or after neurosurgical operations. Treatment is conservative by IV Ranitidine. It is commonly a single, deeper ulcer that more frequently perforates. It can occur in the esophagus and duodenum also.

GASTRIC ULCER

Etiology

It occurs due to an imbalance between protective and damaging factors of the gastric mucosa.

• Atrophic gastritis.
• Smoking, alcohol.
• Helicobacter pylori infection (70%).
• There is either normal chlorhydria or hypochlorhydria.
• Altered mucosal barrier mechanism.
• Lower socioeconomic group.

Factors involved in Gastric Ulcer Formation

•  Duodenal-gastric reflux containing bile salts and lysolecithin breaks the mucosal barrier making it more vulnerable to injury, the action of drugs, and pepsin injury.
• Gastric stasis.
•  Ischaemia of the gastric mucosa.

Types of Gastric Ulcer (Daintree Johnson)

Type          Location                                                                               Incidence                      Acid level

1      In the antrum, near the lesser curve                                                55%                       Normal

2  Combined gastric ulcer with duodenal ulcer                                   25%                       High

3     Prepyloric ulcer                                                                                 15%                         High

4    Gastric ulcer in the proximal stomach or cardia                           5%                             Normal

Note: Often in a lesser curve, saddle-shaped ulcers can occur.

Clinical Features

• Equal in both sexes.
• Pain in the epigastric region after taking food, lasting up to two hours. Pain is uncommon during the night. Relieved by vomiting or by inducing vomiting.
• Periodicity: symptom-free intervals maybe 2-6 months. Often with seasonal variation.
• Vomiting relieves pain.
• Haematemesis and melaena: Haematemesis is more common.
• Their appetite is good but hesitant to eat because eating induces pain and that results in loss of weight.

Differential diagnosis

• Hiatus hernia
• Cholecystitis
• Chronic pancreatitis
• chronic gastritis
• dysphagia
• carcinoma stomach

Investigations

• Barium meal X-ray to see niche and notch.
• Gastroscopy – for location, type of ulcer, and also to take a biopsy.
• US abdomen mainly to rule out other diseases and to confirm the associated diseases.

Treatment

• Drugs like H2 blockers, proton pump inhibitors, and carbenoxolone help in reducing or eliminating the symptoms but asymptomatic ulcers may exist silently and may turn into malignancy So surgery is the preferred line of treatment. Partial gastrectomy and Billorth I gastroduodenal anastomosis is done.
• Type 4 proximal gastric ulcer is difficult to manage.

Complications of gastric ulcers

• Hourglass contracture; which occurs exclusively in women is due to the cicatricial of lesser curve ulcers.
• Tea-pot deformity: (Hand-Bag stomach) is due to cicatrization and shortening of the lesser curvature.
• They present with features of pyloric stenosis.
• Perforation.
• Bleeding by erosion into the left gastric and rarely splenic vessels or to vessels in the wall of the ulcer.
• Penetration posteriorly into the pancreas, anteriorly into the liver.
• Malignant transformation is usually into adenocarcinoma of the stomach (2-5%).

Clinical features

1.  Loss of periodicity.
2.  Persistent pain.
3.  Vomiting.
4.  Loss of appetite and weight

Diagnosis

• Barium meal: It shows filling only in the proximal stomach or double-pouched stomach.
• Gastroscopy.

 Treatment

Partial gastrectomy wherein gastric ulcer with a lower compartment of the stomach is removed and Billroth-I anastomosis is done.

DUODENAL ULCER

Etiology

•  Common in people with blood group O +ve.
• Stress, anxiety hurry, worry, curry.
•  Helicobacter pylori infection is an important etiology for duodenal ulcers (90%).
•  NSAIDs, steroids
•  Endocrine causes: Zollinger Ellison syndrome, MEN syndrome, hyperparathyroidism.
•  Other causes: Alcohol, smoking, and vitamin deficiency.

Pathology

1.  An ulcer occurs in the first part of the duodenum, usually within the first inch, involving the muscular layer.
2. Sites: a. In the bulb (bulbar)95%.    b. Post bulbar (5%).
3.  Eventually, it shows cicatrization causing pyloric stenosis. Serosa overlying the site of the duodenal ulcer shows petechial hemorrhages with speckled red dots, appearing like sprinkled cayenne pepper

Clinical Features

•  In India, the ratio of duodenal ulcer to the gastric ulcer is 30: 1. A very high incidence.
• It is common in all socio-economic groups, more with stressed professionals (Type A personality).
• Pain is more before food, in the early morning, and decreases after taking food. Food relieves the hunger pain. Night pains are common.
•  Common in males.
•  Periodicity is more common than in chronic gastric ulcers with seasonal variation.
•  Water brash, heartburn, and vomiting may be present.
•  Melaena is more common, haematemesis also can occur.
• Their appetite is good and there is a gain in weight.
• It decreases once stenosis develops.
•  Eats more frequently without any restriction.
•  Chronic duodenal ulcers can be uncomplicated or complicated.

Differences between clinical features of gastric ulcer and duodenal ulcer

Gastric ulcer                                                                    Duodenal ulcer

Pain after food intake                                                     Pain before food intake

Periodicity less common                                                Periodicity more common

Haematemesis is more common                                        Malena is more common

Weight loss occurs                                                          Weight gain occurs

Equal in both sexes                                                         Common in males

No pain in empty stomach                                                 food realize pain [hunger pain]

Food never reduces pain                                                   Food reduces pain

No pain at night                                                                   Incidence of nocturnal pain

Vomiting is common so it releases the pain                  After taking he feels better so he takes a frequent diet

Tenderness left to the midline of EPG                                Tenderness at duodenal point

Complications of  Duodenal Ulcer

1. Pyloric stenosis: Due to scarring and cicatrization of the first part of the duodenum.

2. Bleeding (10%).

3. Perforation (5%). Both acute and chronic ulcers can perforate. Anterior ulcers perforate.

4. Residual abscess.

5. Penetration to the pancreas.

Investigations

Barium meal X-ray shows deformed or absence of duodenal cap (because of spasm). The appearance of trifoliate duodenum is due to secondary duodenal diverticula which occurs as a result of scarring of the ulcer.

Gastroscopy reveals the type, location of the ulcer, and narrowing if any.

Biopsy for the presence of Helicobacter pylori.

Estimation of serum gastrin level, and serum calcium level.

Treatment

I. General measures: Avoid alcohol, NSAIDs, smoking, and spicy foods. Have more frequent food.

II. Specific measures:

Drugs

• H2 Blockers: Promotes ulcer healing in 4-8 weeks, by reducing acid secretion.
• Proton pump inhibitors: Inhibit parietal cell H+, K+ ATPase enzyme responsible for acid secretion. . They stop acid secretion completely.
• Antacids: Neutralises the HCl to form water and salt and also inhibit peptic activity.
• Sucralfate is an aluminum salt of sulfated sucrose that provides a protective coat to ulcer craters, promoting healing. It inhibits peptic activity. The dose is 1 g qid for 6 weeks (Before food). It is an effective drug.
• Anti-Helicobacter pylori regime: It is very useful, given for 7-14 days later the proton pump inhibitors are continued.
• Colloid bismuth sulfate is a good drug for ulcers, but it stains the oral cavity and mucosa.
• Misoprostol is the only prostaglandin agonist accepted. A Follow-up gastroscopy is a must, to confirm that the ulcer has healed.

Surgery for Uncomplicated DU

•  Highly Selective Vagotomy (HSV).
• Selective vagotomy with pyloroplasty (SV + P).
• Truncal vagotomy with gastrojejunostomy (TV + GJ).
• In HSV, only fibers supplying the parietal cells are ligated. The nerve of the Latar jet which supplies the antrum pump is retained and so no drainage procedure is required in HSV. HSV is also called parietal cell vagotomy or super-selective vagotomy. Here nerve fibers in the last 6 cm of the stomach, just proximal to the pylorus are preserved (Crow’s foot). A vagotomy reduces acid secretion, hence ulcer heals. No acid, no ulcer.
• Posterior truncal vagotomy with anterior seromyotomy—Taylor’s operation. It can be done through laparoscopy.