Gastroduodenal ulcer disease

From WikiLectures

A disease characterized by the presence of one or more ulcers in the wall of the stomach or duodenum.

  • ulcer (ulcus) – a mucosal defect, reaching deeper into the submucosa,
  • erosion – mucosal defect limited to the mucosa (does not penetrate through the muscularis interna into the submucosa).

Location of ulcers

The ulcer extends into the submucosa
  • Type I – small curvature mediogastrically,
  • Type II – combined chronic duodenal and gastric ulcer,
  • Type III – prepyloric ulcer up to a distance of 2 cm from the pylorus,
  • Type IV – ulcer high on a small curvature near the GE junction.
  • duodenal ulcer – 95 % in the bulb of the duodenum on the anterior and/or posterior wall (kissing ulcer),
  • multiple duodenal ulcers – especially in Zollinger-Ellison syndrome,
  • ulcers on a large curvature – suspected malignancy.

Note: Duodenal ulcers are four times more common (80 %) than gastric ulcers, they also bleed more often.

Etiology

Helicobacter pylori infection disrupts the protective mucus barrier and thus creates a terrain for ulceration
  1. the main etiological agent is Helicobacter pylori,
  2. abusus NSAID,
  3. imbalance between protective and aggressive factors acting on the mucosa:

Protective factors

  • Mucus and bicarbonates (from saliva, food - the best neutralizer),
  • prostaglandins,
  • mucosal regenerative capacity,
  • good mucosal perfusion.

Aggressive factors

Note: HP infection is the main cause of the gastric ulcer and HCl in duodenal hypersecretion.

Special types of ulcers

  • Cushing's ulcer – for trauma or CNS surgery (vagus irritation - HCl hypersecretion),
  • Curling's ulcer – for burns (hyperhistamina - hypersecretion HCl),
  • Zollinger-Ellison syndrome - ↑ gastrin production (stimulates HCl secretion) in pancreatic gastrinoma,
  • Stress ulcer – a disorder of mucosal perfusion.

Dividing ulcers

  • acute – funnel-shaped defect with sharp edges, often multiple, with a black base (digested blood),
  • chronic – round defect with bulging edges, light base (cleaned with enzymes and HCl, red-pink - granulation tissue, white - connective tissue), it is solitary, algae of the surrounding mucosa converge radially to it..

Clinical manifestations

  1. Gastric ulcer,
    • pain (visceral) in the epigastrium after a meal (Antacids do not usually bring relief),
    • anorexia, feeling full, heartburn, occasional vomiting with bile - the sick prefer to starve for fear,
    • affects older individuals,
  2. Duodenal ulcer,
    • epigastric pain on an empty stomach (often wakes the patient at night - nocturnal hunger pains),
    • food and antacids bring relief,
    • typical seasonal occurrence with exacerbation in spring and autumn (duration 1-2 weeks),
    • affects younger individuals.
Multiple duodenal ulcerations in a patient with Zollinger-Ellison syndrome

Diagnostics

  1. history (pain, nausea , vomiting, heartburn , loss of appetite, weight loss, foetor ex ore + physical examination (palpable pain in the epigastrium),
  2. imaging methods,
    • endoscopy – endoscopy - in uncomplicated ulcer (incl. biopsy, pH of the gastric mucosa and evidence of HP), bleeding,
    • Native X-ray - evidence of pneumoperitoneum during perforation,
    • Contrasting X-ray - in case of stenosis, event. during perforation (KL flow into the peritoneal cavity),
  3. biochemical examinations,
    • Helicobacter pylori identification:
      • invasive - rapid urease test, biopsy (microscopy, culture, PCR),
      • non-invasive - breath test with labeled urea, antibodies against HP in serum and urine, eventually saliva PCR, fecal HP antigens.

Peptic ulcer therapy

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Chronic antral gastric ulcer

Ulcer disease is a chronic disease characterized by recurrent relapses over many years. The incidence of duodenal ulcer is 4-5 times higher compared to gastric ulcer. The etiology of the disease is not yet recognized.

Current prevention or treatment is possible as
  • Inhibition of factors leading to irritation and erosion of the mucosa.
  • Support of protective endogenous factors.
Factors influencing the formation of peptic ulcer
Inhibition of factors leading to irritation and erosion of mucous membranes.
  1. It is mainly protection against hydrochloric acid.
  2. Food plays an important role in increasing HCl production but also binding it. Of the basic foods, HCl meat stimulates gastric secretion the most, but it also has a strong binding ability. Therefore, it is recommended in small portions. Meals must be regular.
  3. Some habits can be harmful. It is mainly smoking (induces vasoconstriction in the stomach wall and reduces the effect of protective mechanisms), strong alcohol and coffee, which must be rejected (1 beer, a glass of wine per day is allowed, but no distillate).
  4. Substances with erosive effects on the GIT mucosa should be avoided . These are mainly salicylates and a group of non-steroidal anti-inflammatory drugs.
  5. The presence of Helicobacter pylori correlates with the onset and recurrence of duodenal ulcer. It occurs in 95% of patients with duodenal ulcer, most often in the antrum of the stomach, where it is also the cause of antral gastritis. Its eradication brings relief to the sick. The role of H. pylori is not clearly understood, as this microorganism also occurs in asymptomatic humans (60 %). However, eradication of H. pylori in patients with peptic ulcer disease leads to a reduction in disease recurrence.
  6. Pharmacotherapy.

Substances neutralizing gastric pH - antacids

Locally acting, non-absorbable

They neutralize HCl in the stomach and inactivate pepsin. Magnesium and aluminum compounds are used. Magnesium-containing antacids have a laxative effect, aluminum compounds are rather constipating, so they are often combined.

  • algeldrate (aluminum hydroxide in hydrated active form), simaldrate (magnesium aluminum silicate), hydrotalcite (basic magnesium aluminum carbonate), magnesium aluminate, aluminium phosphate.

Advantages: they are very cheap, disadvantages: they leave the stomach contents very quickly, therefore they only lead to a temporary reduction in stomach acidity, they act briefly (1,5–2 hours).

Total antacids

  • sodium bicarbonate and and calcium carbonate

They are used, for example, for heartburn. It cannot be used for a long time because: it could lead to systemic alkalosis, it is absorbed, CO2 is released upon reaction with HCl , which can lead to secondary mucosal irritation and hypersecretion of HCl.

Compounds acting as antagonists at the receptor level

Stimulation leading to HCl secretion is provided by 3 types of receptors:

Only the first two types can be damped.

Parasympatholytics

Drugs with stronger affinity for gastric receptors are used (M1). It is used pirenzepine. Its effects are equal to H2 lytics, recurrences are less frequent.

H2 antagonists

  • famotidine and ranitidine

Histamine H2 receptor antagonists, unlike their predecessor cimetidine, do not have antiandrogenic effects. Famotidine is more effective than ranitidine.

  • cimetidine

It is the first drug in this group to enter clinical use. Cimetidine has been shown endoscopically to lead to the healing of 85% of duodenal ulcers within 8 weeks of treatment, compared with 30% of those treated with placebo. The shortest time needed for healing is around 4 weeks, while the pain disappears within a few days. Healing of gastric ulcers reaches 75-80%. A more complication of treatment is more frequent recurrence of the ulcer (in 5-30%), then a long-term maintenance evening dose is chosen to suppress HCl secretion at night on an empty stomach. Smoking reduces the effects of cimetidine.

Omeprazole

The main side effect of cimetidine is its antiandrogenic effect and subsequent gynecomastia.


Proton pump inhibitors

More detailed information can be found on the page |Proton pump inhibitors

  • omeprazole (eg HELICID®)

Irreversible H+/K+ ATPase inhibitor - proton pumps. The pump exchanges K+, which travel into cells, for H+, which are secreted into the gastric lumen. Cl- forms HCl. Omeprazole is a lipophilic weakly basic substance that, after absorption, reaches the parietal cell via the bloodstream. Because the binding is irreversible, the enzymatic activity is restored only with the newly formed enzyme, ie after 18 hours. Omeprazole is the most effective inhibitor of HCl secretion. 70% of duodenal ulcers heal within 14 days, 95-100% within 4 weeks. Gastric healing is slower (depending on size and location), but practically all of them heal within 8 weeks. Doses of 20-40 mg daily are used for treatment. Omeprazole is also effective in H2 lytic resistant ulcers , severe reflux oesophagitis and Zollinger-Ellison syndrome. Omeprazole also appears to reduce the incidence of H. pylori. Tolerance of omeprazole is very good, there are no serious drug interactions during treatment. A newer related substance with similar effects is pantoprazole.

Promoting protective factors

They support the production of mucin, form a protective layer of mucus, stimulate the production of prostaglandins E2, which induce local vasodilation, improve mucosal nutrition and accelerate its healing.

Substances which inhibit to eliminate H.pylori

  • colloidal Bi

Complex salt of citric acid. In an acidic gastric environment, it precipitates with proteins released by the erosive action of HCl in the ulcer area. The stable complexes thus formed adhere to the base of the ulcer and form a protective layer. It also prevents the activation of pepsinogen, inactivates the finished pepsin chemically. Bismuth salts have a direct toxic effect on H. pylori strains.

Agents acting as "local dressing"

  • sucralfate

They form a protective layer of mucus, have a special affinity for the base of the ulcer, which they cover and protect against the effects of HCl. It binds bile acids and pepsin, stimulates the production of endogenous prostaglandins, and increases mucus production. Co-administration of antacids is not recommended. Ulcer healing follows after 4 weeks of treatment in 80%, after 6 weeks in 90%. Relapse is less common. Side effects: 2.2% constipation (most common), less common: dry mouth, dyspepsia.

Synthetic prostaglandin analogs (E1)

They reduce HCl secretion and have a cytoprotective effect. The main use is in preventive administration in patients treated with non-steroidal anti-inflammatory drugs.


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Taken from

References

  1. BERARDI, RR, RM TANKANOW and TT NOSTRANT. Comparison of famotidine with cimetidine and ranitidine  [online]. [feeling. 2012-10-24]. < https://www.ncbi.nlm.nih.gov/pubmed/2896559 >.
  2. ↑ SANTOSH, Kumar. www.pharmainfo.net  [online]. Last revision 27.8.2010, [cited. 2012-10-24]. < http://www.pharmainfo.net/santosh-kumar-jh/drug-advice-cimetidine-ranitidine-famotidine >.
  3. ↑ FUNDER, John W and Julie E MERCER. Cimetidine, and Histamine H2 Receptor Antagonist, Occupies Androgen Receptors *  [online]. [feeling. 2012-10-24]. < https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem-48-2-189 ,>.
  4. ↑ - SÚKL: Drugs database  [online]. [feeling. 2012-10-24]. < http://www.sukl.cz/modules/medication/search.php >.