PEPTIC ULCERPEPTIC ULCER

DefinitionDefinition

• Acid peptic digestion of alimentary mucosa resulting in an Acid peptic digestion of alimentary mucosa resulting in an ulcer is called peptic ulcer disease.ulcer is called peptic ulcer disease.

• The corrosive effects of acidThe corrosive effects of acid

++

• Proteolytic effect of pepsinProteolytic effect of pepsin

Gastritis is the precursor to PUD and it is clinically difficult to Gastritis is the precursor to PUD and it is clinically difficult to differentiate the twodifferentiate the two

Stomach (called gastric ulcer)Stomach (called gastric ulcer)Duodenum (called duodenal ulcer)Duodenum (called duodenal ulcer)Esophagus (called Esophageal ulcer)Esophagus (called Esophageal ulcer)Meckel's Diverticulum (called Meckel's Diverticulum Meckel's Diverticulum (called Meckel's Diverticulum ulcer)ulcer)Anastomotic ulcer after GJ. Anastomotic ulcer after GJ.

Peptic Ulcer DiseasePeptic Ulcer Disease

Gastric Mucosa & SecretionsGastric Mucosa & Secretions

The inside of the stomach is bathed in about 2 liters of The inside of the stomach is bathed in about 2 liters of gastric juice every daygastric juice every day

Gastric juice is composed of digestive enzymes & Gastric juice is composed of digestive enzymes & concentrated hydrochloric acid, which can readily tear concentrated hydrochloric acid, which can readily tear apart the toughest food or microorganismapart the toughest food or microorganism

The gastroduodenal mucosal integrity is determined by protective (defensive) & damaging

(aggressive) factors

Gastric Mucosa & SecretionsGastric Mucosa & Secretions

The Defensive ForcesBicarbonate

Mucus layer

Mucosal blood flow

Prostaglandins

Growth factors

The Aggressive ForcesHelicobacter pylori

HCl acidPepsinsNSAIDs

Bile acidsIschemia and hypoxia. Smoking and alcohol

When the aggressive factors increase or the defensive factors decrease, mucosal damage will result, leading to erosions & ulcerations

Because of ImbalanceBecause of Imbalance

Imbalance primarily between Aggressive factors Imbalance primarily between Aggressive factors and Defensive factors:and Defensive factors:

Aggressive

factors, e,g,

acid, pepsin,

bile etc.

Defensive

factors, e.g.

mucus,

HCO3, PG

Phases of gastric Phases of gastric secretionsecretion

Phase Stimuli Pathway

Cephalic (stimulate) Sight, smell, taste or thought of food

1) Vagus (M3 receptors)2) Histamine (H2 receptor)3) Gastrin

Gastric (stimulate) Food in the stomach 1) Stretch: local reflex (M3 receptors)

2) Chemical substances in food (gastrin)

3) Increase pH: Inhibition of somatostatin (GHIH) release

Intestinal (inhibit) Chyme in the duodenum

Gastric secretionsGastric secretions

1.1. Pepsinogens Pepsinogens (Chief cells).(Chief cells).

2.2. HCl and intrinsic factor HCl and intrinsic factor (Parietal cells).(Parietal cells).

3.3. Gastrin Gastrin (G-cells).(G-cells).

4.4. Mucus, bicarbonate Mucus, bicarbonate (mucus-secreting cells).(mucus-secreting cells).

What may contribute What may contribute imbalance ?imbalance ?

Helicobacter pyloriHelicobacter pylori

NSAIDsNSAIDs

EthanolEthanol

TobaccoTobacco

Severe physiologic Severe physiologic

stress (Burns, CNS trauma,stress (Burns, CNS trauma,

Surgery, Severe medical illness)Surgery, Severe medical illness)

SteroidsSteroids

EtiologyEtiology

Other uncommon causes include:Other uncommon causes include:Gastrinoma (Gastrin secreting tumor)Gastrinoma (Gastrin secreting tumor)Stress ulceration (trauma, burns, critical illness)Stress ulceration (trauma, burns, critical illness)Viral infectionsViral infectionsVascular insufficiencyVascular insufficiency

ETIOLOGIC FACTORS OF PUD

Who are they ?Who are they ?

Barry J Marshall J. Robin Warren

Nobel Laureates of Medicine – 2005

Discovery of H. pylori & its role in peptic

ulcer

Etiology Etiology

The two most common causes of PUD are:The two most common causes of PUD are:Helicobacter pyloriHelicobacter pylori infection ( 70-80%) infection ( 70-80%)Non-steroidal anti-inflammatory drugs (NSAIDS)Non-steroidal anti-inflammatory drugs (NSAIDS)

H.pyloriH.pylori as a cause of PUD as a cause of PUD

Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection

H. pyloriH. pylori is Gram-negative, spiral & is Gram-negative, spiral & has multiple flagella at one endhas multiple flagella at one end

Transmitted from person-to-person Transmitted from person-to-person by Oro–oral or feco-oral spreadby Oro–oral or feco-oral spread

Rhesus monkey is the Rhesus monkey is the only natural reservoir.only natural reservoir.

Dynamics of H.pylori Dynamics of H.pylori infectioninfection

Dr.T.V.Rao MDDr.T.V.Rao MD 1818

Pathogenesis of Pathogenesis of H. pyloriH. pylori infectioninfection

Any acidity is buffered Any acidity is buffered by the organism's by the organism's production of the enzyme production of the enzyme urease, which catalyzes urease, which catalyzes the production of the production of ammonia (NH3) from urea ammonia (NH3) from urea & raises the pH there& raises the pH there

The bacterium stimulates The bacterium stimulates chronic gastritis by chronic gastritis by provoking a local provoking a local inflammatory response.inflammatory response.

Pathogenesis of Pathogenesis of H. pyloriH. pylori infection infection

- ↓ Somatostatin production from antral D-cells due to antral gastritis- Low somatostatin will ↑Gastrin release from G-cell hypergastrinemia- This will stimulate acid production by the parietal cells leading to further duodenal ulceration.

Effects of H. pylori on gastric Hormones

This effect is exaggerated among smokers!

Carcinogenic effect of Carcinogenic effect of H. pylori H. pylori

H. pylori

Host Factors

Other environmental Factors

Antral gastritis Pangastritis

DU GU Gastritis Cancer

NSAIDSNSAIDS

Symptomatic GI ulceration occurs in 2% - 4% of patients Symptomatic GI ulceration occurs in 2% - 4% of patients treated with NSAIDs for 1 yeartreated with NSAIDs for 1 year

In view of the million of people who take NSAIDs annually, In view of the million of people who take NSAIDs annually, these small percentages translate into a large number of these small percentages translate into a large number of symptomatic ulcerssymptomatic ulcers

The effects of aspirin & NSAIDs on the gastric mucosa ranges The effects of aspirin & NSAIDs on the gastric mucosa ranges from mucosal hemorrhages to erosions & acute ulcersfrom mucosal hemorrhages to erosions & acute ulcers

NSAIDSNSAIDS

Inhibits the production of Inhibits the production of prostaglandinsprostaglandins precursor from membrane fatty acids precursor from membrane fatty acids resulting in:resulting in:

1. Decrease mucus & HCO3 production1. Decrease mucus & HCO3 production

2. Decrease mucosal blood flow2. Decrease mucosal blood flow

3. Reduce cell renewal3. Reduce cell renewal

The drugs also generate oxygen-free radicals The drugs also generate oxygen-free radicals & products of the lipoxygenase pathway that & products of the lipoxygenase pathway that may contribute to ulcerationmay contribute to ulceration

NSAIDSNSAIDS

Gastric acid probably aggravates NSAID-induce mucosal Gastric acid probably aggravates NSAID-induce mucosal injury by injury by

- Converting superficial injury to deeper mucosal necrosis,- Converting superficial injury to deeper mucosal necrosis,

- Interfering with haemostasis & platelet aggregation- Interfering with haemostasis & platelet aggregation

- Impairing ulcer healing- Impairing ulcer healing

• Users of NSAIDs are at approximately 3 times greater relative Users of NSAIDs are at approximately 3 times greater relative risk of serious adverse gastrointestinal events than nonusersrisk of serious adverse gastrointestinal events than nonusers

Psychological Stress Psychological Stress UlcersUlcers

Gastric mucosa of body of stomach undergoes Gastric mucosa of body of stomach undergoes a period of transient ischemia in a period of transient ischemia in association withassociation with

HypotensionHypotensionSevere injurySevere injuryExtensive burnsExtensive burnsComplicated surgery Complicated surgery

Psychological Stress Psychological Stress UlcersUlcers

Ischemia due to ↓ capillary blood flow or Ischemia due to ↓ capillary blood flow or shunting of blood away from GI tract so shunting of blood away from GI tract so that blood flow bypasses gastric mucosathat blood flow bypasses gastric mucosa

Imbalance between destructive properties of Imbalance between destructive properties of HCl acid and pepsin, and protective factors HCl acid and pepsin, and protective factors of stomachof stomach’’s mucosal barriers mucosal barrier

TypesTypes

Acute Acute

ChronicChronic

Acute peptic ulcer Acute peptic ulcer (DUODENAL OR(DUODENAL OR

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

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

Sudden onset of acute pain and tenderness in epigastric Sudden onset of acute pain and tenderness in epigastric region.region.

Vomiting with or without haematemesis.Vomiting with or without haematemesis.

Often acute peptic ulcers can lead to perforations.Often acute peptic ulcers can lead to perforations.

Acute ulcers after cerebral trauma or neurosur geries Acute ulcers after cerebral trauma or neurosur geries are called as Cushing’s ulcers .are called as Cushing’s ulcers .

Acute ulcers after major burns are called as Curling’s Acute ulcers after major burns are called as Curling’s ulcers .ulcers .

Diagnosis is by gastroscopy.Diagnosis is by gastroscopy.

TreatmentTreatment

Intravenous ranitidine 50 mg, 8th hourly.Intravenous ranitidine 50 mg, 8th hourly.

IV fluids. IV IV fluids. IV pantoprazole/rabeprazole/omeprazole.pantoprazole/rabeprazole/omeprazole.

Blood transfusions if there is bleeding.Blood transfusions if there is bleeding.

Most of the time surgery is not required Most of the time surgery is not required for acute ulcers.for acute ulcers.

During follow-up patients are advised to During follow-up patients are advised to take antiulcer drugs for 4-6 weeks—take antiulcer drugs for 4-6 weeks—ranitidine, omeprazole or lanso prazole.ranitidine, omeprazole or lanso prazole.

Curling’s UlcersCurling’s Ulcers

They are acute ulcers which develop after They are acute ulcers which develop after major burns, presenting as pain in major burns, presenting as pain in epigastric region, vomiting or epigastric region, vomiting or haematemesis.haematemesis.

Treatment is conservative—IV ranitidine. IV Treatment is conservative—IV ranitidine. IV pantoprazolepantoprazole

80 mg in 100 ml DNS—slow, later 40 mg IV 80 mg in 100 ml DNS—slow, later 40 mg IV maintenance.maintenance.

Cushing’s UlcersCushing’s Ulcers

They are acute ulcers which develop after They are acute ulcers which develop after cerebral trauma or after neurosurgical cerebral trauma or after neurosurgical operations. operations.

It is commonly single, deeper ulcer more It is commonly single, deeper ulcer more frequently perforates. frequently perforates.

It can occur in oesophagus and duodenum It can occur in oesophagus and duodenum also. Treatment is conservative by IV also. Treatment is conservative by IV ranitidine.ranitidine.

Chronic ulcersChronic ulcers

Two major variants in peptic ulcers are commonly encountered in the Two major variants in peptic ulcers are commonly encountered in the clinical practice:clinical practice:

1)1) Duodenal UlcerDuodenal Ulcer (DU) (DU)

2)2) Gastric UlcerGastric Ulcer (GU) (GU)

Gastric ulcerGastric ulcer It occurs due to imbalance between protective and It occurs due to imbalance between protective and damaging factors of gastric mucosa.damaging factors of gastric mucosa.

Atrophic gastritis, duodenogastric bile reflux, Atrophic gastritis, duodenogastric bile reflux, gastric stasis, gastric stasis, abnormalities in acid and pepsin abnormalities in acid and pepsin secretion. secretion.

Acid becomes ulcerogenic even to normal gastric Acid becomes ulcerogenic even to normal gastric mucosa. Smoking, alcohol, NSAIDs, steroids.mucosa. Smoking, alcohol, NSAIDs, steroids.

Helicobacter pylori infection (70%).Helicobacter pylori infection (70%).

There is either normochlorhydria or There is either normochlorhydria or hypochlorhydria.hypochlorhydria.

Altered mucosal barrier mechanism.Altered mucosal barrier mechanism.

Lower socioeconomic group.Lower socioeconomic group.

Gastric ulcerGastric ulcer

Factors Involved in Gastric Ulcer FormationFactors Involved in Gastric Ulcer Formation

Duodenogastric reflux—reflux containing bile salts Duodenogastric reflux—reflux containing bile salts andand

lysolecithin break the mucosal barrier making it morelysolecithin break the mucosal barrier making it more

vulnerable for injury, action of drugs and pepsin vulnerable for injury, action of drugs and pepsin injury.injury.

Gastric stasis.Gastric stasis.

Ischaemia of the gastric mucosa.Ischaemia of the gastric mucosa.

Type II and III gastric ulcers show acid Type II and III gastric ulcers show acid hypersecretion.hypersecretion.

Pathology Pathology

Gastric ulcer is large in size, usually lies Gastric ulcer is large in size, usually lies in the lesser curvature, its floor being formed in the lesser curvature, its floor being formed by the muscular layer.by the muscular layer.

Posteriorly it may penetrate into the Posteriorly it may penetrate into the pancreas; it may cause torrential bleeding by pancreas; it may cause torrential bleeding by eroding left gastric (commonly) vessles or eroding left gastric (commonly) vessles or splenic vessels or vessels in the gastric ulcer splenic vessels or vessels in the gastric ulcer wall.wall.

Microscopically, it shows ulcer crater with Microscopically, it shows ulcer crater with chronic inflammatory cells and granulation chronic inflammatory cells and granulation tissue, endarteritis obliterans and epithelial tissue, endarteritis obliterans and epithelial proliferation.proliferation.

(Ulcer to the right of the incisura is malignant (Ulcer to the right of the incisura is malignant unless proved otherwise).unless proved otherwise).

Gastric ulcer > 3 cm is called as giant gastric Gastric ulcer > 3 cm is called as giant gastric ulcer. It has got 6-23% chances to turn into ulcer. It has got 6-23% chances to turn into malignancy.malignancy.

Grossly, margin of the benign gastric ulcer is Grossly, margin of the benign gastric ulcer is clear; deep; near lesser curve; edge is not everted clear; deep; near lesser curve; edge is not everted with gastric mucosal folds converging towards the with gastric mucosal folds converging towards the base of the ulcer.base of the ulcer.

95% of benign gastric ulcer occurs towards lesser 95% of benign gastric ulcer occurs towards lesser curve, as it takes more burden of passage of food curve, as it takes more burden of passage of food and so more of wear and tear. Benign gastric ulcer and so more of wear and tear. Benign gastric ulcer is rare in greater curvature, fundus and cardia.is rare in greater curvature, fundus and cardia.

Clinical featuresClinical features

Equal in both sexes. It is becoming more Equal in both sexes. It is becoming more common in common in females.females.

Common after the age of 40 years.Common after the age of 40 years.

PainPain in epigastric region after taking in epigastric region after taking food, lasting up to two hours. Pain is food, lasting up to two hours. Pain is uncommon during night. It is relieved by uncommon during night. It is relieved by vomiting or by inducing vomiting.vomiting or by inducing vomiting.

PeriodicityPeriodicity: Symptom free interval may be 2-6 : Symptom free interval may be 2-6 months.months.

Often with seasonal variation.Often with seasonal variation.

VomitingVomiting relieves pain and often it is induced by relieves pain and often it is induced by the patient for relief of pain.the patient for relief of pain.

Haematemesis and melaenaHaematemesis and melaena: Haematemesis is more : Haematemesis is more common.common.

Appetite is good but hesitant to eat, because eating Appetite is good but hesitant to eat, because eating induces pain and that results in loss of weight. induces pain and that results in loss of weight.

But once complications occur, appetite decreases. But once complications occur, appetite decreases. Aversion to spicy, fried foods occurs.Aversion to spicy, fried foods occurs.

On deep palpation, tenderness is felt in epigastric On deep palpation, tenderness is felt in epigastric region.region.

Differential Differential diagnosisdiagnosis

Hiatus hernia.Hiatus hernia.

Cholecystitis.Cholecystitis.

Chronic pancreatitis.Chronic pancreatitis.

Chronic gastritis.Chronic gastritis.

Dyspepsia.Dyspepsia.

Carcinoma stomach.Carcinoma stomach.

Barium meal X-rayBarium meal X-rayBarium meal showing Niche in Barium meal showing Niche in the lesser curve as the lesser curve as benign benign gastric ulcer.gastric ulcer.

Niche on the lesser curve with Niche on the lesser curve with notch on the greater curvaturenotch on the greater curvature

Ulcer crater projects beyond Ulcer crater projects beyond the lumen of the ulcerthe lumen of the ulcer

Regular/round margin of the Regular/round margin of the ulcer crater—stomach spoke ulcer crater—stomach spoke wheel patternwheel pattern

Overhanging mucosa at the Overhanging mucosa at the margins of a benign gastric margins of a benign gastric ulcer—projects inwards towards ulcer—projects inwards towards the ulcer—Hamptom’s linethe ulcer—Hamptom’s line

Converging mucosal folds Converging mucosal folds towards the base of the ulcertowards the base of the ulcer

Symmetrical normal gastric Symmetrical normal gastric mucosal foldsmucosal folds

GastroscopyGastroscopy

Gastroscopy is Gastroscopy is done to see the done to see the location, type of location, type of ulcer and also to ulcer and also to take biopsy (10 take biopsy (10 biopsies).biopsies).

Gastric ulcer in the body Gastric ulcer in the body of the stomach.of the stomach.

TreatmentTreatment

Drugs like H2 blockers, proton pump Drugs like H2 blockers, proton pump inhibitors, carbenexolone (Biogastrone, inhibitors, carbenexolone (Biogastrone, Sucralfate, prostag landins which coats the Sucralfate, prostag landins which coats the ulcer and so creates a mucosal barrier) ulcer and so creates a mucosal barrier) helps in reducing or eliminating the helps in reducing or eliminating the symptoms.symptoms.

But asymptomatic ulcer may exist silently But asymptomatic ulcer may exist silently and may turn into malignancy.and may turn into malignancy.

So surgery is the preferred line of So surgery is the preferred line of treatment. Partial gastrectomy and Billroth treatment. Partial gastrectomy and Billroth I gastroduodenal anastomosis is done.I gastroduodenal anastomosis is done.

Type IV proximal gastric ulcer is difficult to manage. Type IV proximal gastric ulcer is difficult to manage. It is treated by subtotal gastrectomy. Often distal It is treated by subtotal gastrectomy. Often distal gastrectomy with selective sleeve like extension cut gastrectomy with selective sleeve like extension cut along the lesser curve to remove the ulcer is done—along the lesser curve to remove the ulcer is done—Pauchet’s procedure.Pauchet’s procedure.

Other surgical procedures:Other surgical procedures:

1. de Miguel’s antrectomy : Distal antrectomy, 1. de Miguel’s antrectomy : Distal antrectomy, pylorectomy with excision of ulcer along with pylorectomy with excision of ulcer along with gastroduodenal anastomosis is done. It preserves gastric gastroduodenal anastomosis is done. It preserves gastric reservoir function, shows less recurrence rate and less reservoir function, shows less recurrence rate and less operative morbidity.operative morbidity.

2. Mak’s pylorus preserving gastrectomy : 2. Mak’s pylorus preserving gastrectomy : Hemigastrectomy with excision of pyloric ulcer but Hemigastrectomy with excision of pyloric ulcer but retaining 2 cm prepyloric stomach. It is only used in retaining 2 cm prepyloric stomach. It is only used in type I gastric ulcer. Even though it has got fewer type I gastric ulcer. Even though it has got fewer incidences of postoperative diarrhoea and dumping, it incidences of postoperative diarrhoea and dumping, it has got high recurrence ratehas got high recurrence rate

3. HSV with excision of ulcer.3. HSV with excision of ulcer.

4. Kelling Madlener procedure : It is 4. Kelling Madlener procedure : It is antrectomy and excision of proximal gastric antrectomy and excision of proximal gastric ulcer Type IV.ulcer Type IV.

5. Csendes procedure : It is subtotal 5. Csendes procedure : It is subtotal gastrectomy with sleeve extended resection gastrectomy with sleeve extended resection along the lesser curve for along the lesser curve for type IV proximal type IV proximal gastric ulcer.gastric ulcer.

ComplicationsComplications 1. Hour glass contracture : 1. Hour glass contracture : It occurs exclusively in women It occurs exclusively in women , is due to cicatricial , is due to cicatricial contracture of lesser curve contracture of lesser curve ulcer. Here stomach is ulcer. Here stomach is divided into two compartments.divided into two compartments.

• Clinical features– Loss of Clinical features– Loss of periodicity. periodicity. Persistent pain.Persistent pain. Vomiting. Vomiting. Loss of appetite and Loss of appetite and weight.weight.

• DiagnosisDiagnosis– Barium meal: It – Barium meal: It shows fi lling only in the shows fi lling only in the proximal stomach or double proximal stomach or double pouched stomach.pouched stomach.– Gastroscopy.– Gastroscopy.

• TreatmentTreatment

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

• Tea-pot deformity Tea-pot deformity (Hand-bag stomach): (Hand-bag stomach): It is due to It is due to cicatrisation and cicatrisation and shortening of the shortening of the lesser curvature.lesser curvature.

• They present with They present with features of pyloric features of pyloric stenosis.stenosis.

• Treatment is partial Treatment is partial gastrectomy with gastrectomy with Billroth I Billroth I anastomosis.anastomosis.

• 3. Perforation— most frequent.3. Perforation— most frequent.

• 4. Bleeding by erosion into the left 4. Bleeding by erosion into the left gastric and rarely splenic vessels or to gastric and rarely splenic vessels or to vessels in the wall of ulcer —35%. It is vessels in the wall of ulcer —35%. It is common in type II and III gastric ulcers.common in type II and III gastric ulcers.

• 5. Penetration posteriorly into pancreas, 5. Penetration posteriorly into pancreas, anteriorly into liveranteriorly into liver

• 6. Malignant transformation usually into 6. Malignant transformation usually into adenocar cinoma of stomach (2-5%)..adenocar cinoma of stomach (2-5%)..

Duodenal ulcerDuodenal ulcer• AetiologyAetiology

• Common in people with blood group O +ve.Common in people with blood group O +ve.

• Stress, anxiety—‘hurry, worry, curry’.Stress, anxiety—‘hurry, worry, curry’.

• Helicobacter pylori infection is an important Helicobacter pylori infection is an important aetiology for aetiology for duodenal ulcer (90%).duodenal ulcer (90%).

• NSAIDs, steroidsNSAIDs, steroids

• Endocrine causes: Zollinger-Ellison syndrome, MEN Endocrine causes: Zollinger-Ellison syndrome, MEN syndrome, hyperparathyroidism.syndrome, hyperparathyroidism.

• Other causes: Alcohol, smoking, vitamin defi Other causes: Alcohol, smoking, vitamin defi ciency.ciency.

• Dragstedt dictum : “No acid – No ulcer”.Dragstedt dictum : “No acid – No ulcer”.

Duodenal ulcerDuodenal ulcer

• PathologyPathology• Ulcer occurs in the fi rst part of duodenum, Ulcer occurs in the fi rst part of duodenum,

usually with in the first inch,involving the usually with in the first inch,involving the muscular layer.muscular layer.

• Sites:Sites:

• a. In the bulb (bulbar)—95%.a. In the bulb (bulbar)—95%.

• b. Post-bulbar (5%).b. Post-bulbar (5%).

• Eventually it shows cicatrisation causing pyloric Eventually it shows cicatrisation causing pyloric stenosis. Serosa overlying the site of duodenal stenosis. Serosa overlying the site of duodenal ulcer shows petechial haemorrhages with speckled ulcer shows petechial haemorrhages with speckled red dots, appearing like sprinkled red dots, appearing like sprinkled cayenne pepper .cayenne pepper .

• Microscopically, ulcer with chronic Microscopically, ulcer with chronic inflammation with granulation tissue, inflammation with granulation tissue, gastric metaplasia of duodenal mucosa, gastric metaplasia of duodenal mucosa, endarteritis obliterans are visualised.endarteritis obliterans are visualised.

• Sometimes two opposing ulcers, i.e. over Sometimes two opposing ulcers, i.e. over anterior and posterior surfaces of duodenum anterior and posterior surfaces of duodenum are present and are called as kissing are present and are called as kissing ulcers.ulcers.

• An anterior ulcer perforates commonly, An anterior ulcer perforates commonly, posterior ulcer bleeds or penetrates posterior ulcer bleeds or penetrates commonly.commonly.

Clinical featuresClinical features• PainPain is more before food, in early morning and is more before food, in early morning and

decreases after taking food. It is classically called as decreases after taking food. It is classically called as hunger pain as it is relieved by taking food. Night hunger pain as it is relieved by taking food. Night pains are common.pains are common.

• PeriodicityPeriodicity is more common than in chronic gastric is more common than in chronic gastric ulcer with seasonal variation.ulcer with seasonal variation.

• In India, ratio of duodenal ulcer to gastric ulcer is In India, ratio of duodenal ulcer to gastric ulcer is 30 : 1. A very high incidence.30 : 1. A very high incidence.

• It is common in all socioeconomic group, more with It is common in all socioeconomic group, more with stressed professionals (Type A personality).stressed professionals (Type A personality).

• Common in males .Common in males .

• Water-brash, heart burn, vomiting may be present.Water-brash, heart burn, vomiting may be present.

• Melaena is more common, haematemesis also can occur.Melaena is more common, haematemesis also can occur.

• Appetite is good and there is gain in Appetite is good and there is gain in weight. It decreases once stenosis weight. It decreases once stenosis develops.develops.

• Eats more frequently without any Eats more frequently without any restriction.restriction.

• Chronic duodenal ulcer can be Chronic duodenal ulcer can be uncomplicated or complicated.uncomplicated or complicated.

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

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

• Biopsy also can be taken to look for the Biopsy also can be taken to look for the presence of Helicobacter pylori . presence of Helicobacter pylori .

• Usually biopsies are taken from duodenum, Usually biopsies are taken from duodenum, pylorus, antrum, body, fundus, and pylorus, antrum, body, fundus, and confirmed by rapid urease test or C13 or confirmed by rapid urease test or C13 or C14 breath tests.C14 breath tests.

• Estimation of serum gastrin level, serum Estimation of serum gastrin level, serum calcium level.calcium level.

Differential Differential diagnosisdiagnosis

• Carcinoma stomach (pylorus)Carcinoma stomach (pylorus)

• Dyspepsia due to other causesDyspepsia due to other causes

• – – Hiatus herniaHiatus hernia

• – – OesophagitisOesophagitis

• – – CholecystitisCholecystitis

• – – Chronic pancreatitisChronic pancreatitis

Duodenal ulcerDuodenal ulcer

Diagnosis:Diagnosis:

1)1) Diagnosis of ulcerDiagnosis of ulcer

2)2) Diagnosis of H. pyloriDiagnosis of H. pylori

EndoscopyEndoscopy Barium meal – contrast x-rayBarium meal – contrast x-ray Biopsy – bacteria & malignancyBiopsy – bacteria & malignancy H.Pylori:H.Pylori:

Endoscopy cytologyEndoscopy cytology Biopsy – Special stainsBiopsy – Special stains Culture - difficultCulture - difficult Urease Breath test.Urease Breath test.

PUD - DiagnosisPUD - Diagnosis

Diagnosis of PUDDiagnosis of PUD

In most patients routine laboratory tests are usually In most patients routine laboratory tests are usually unhelpfulunhelpful Diagnosis of PUD depends mainly on endoscopic and

radiographic confirmation

EndoscopyEndoscopy

• Most sensitive and specific . Most sensitive and specific .

• Direct visualization of the mucosa, Direct visualization of the mucosa,

• Biopsy to rule out malignancy or Biopsy to rule out malignancy or Hpylori.Hpylori.

• Identifies lesions too small to detect by Ba Identifies lesions too small to detect by Ba exam, for evaluation of atypical radiographic exam, for evaluation of atypical radiographic abnormalities, or to determine if an ulcer is abnormalities, or to determine if an ulcer is a source of blood loss.a source of blood loss.

Doudenal Ulcer on EndoscopyDoudenal Ulcer on Endoscopy

Doudenal UlcerNormal doudenal bulb

Gastric Ulcer on EndoscopyGastric Ulcer on Endoscopy

Chronic Gastric Ulcers

Diagnosis of Diagnosis of H. pyloriH. pylori

Non-invasiveNon-invasive

• CC1313 or C or C1414 Urea Breath Test Urea Breath Test

• Stool antigen testStool antigen test

• H. pylori IgG titer (serology)H. pylori IgG titer (serology)

InvasiveInvasive

• Gastric mucosal biopsyGastric mucosal biopsy

• Rapid Urease testRapid Urease test

Diagnosis of Diagnosis of H. pyloriH. pylori

Non-invasive 1. C13 or C14 Urea Breath Test

The best test for the detection

of an active infection

Diagnosis of Diagnosis of H. pyloriH. pylori

Non-invasiveNon-invasive

1)1) Serology for Serology for H pyloriH pyloria.a. Serum Antibodies (IgG) to Serum Antibodies (IgG) to H pylori H pylori (Not for active (Not for active

infection) infection) b.b. Fecal antigen testing (Fecal antigen testing (Test for active HPTest for active HP) )

Diagnosis of Diagnosis of H. pyloriH. pylori

InvasiveInvasive

• Upper GI endoscopyUpper GI endoscopy– Highly sensitive testHighly sensitive test– Patient needs sedationPatient needs sedation– Has both Has both diagnosticdiagnostic & & therapeutictherapeutic rolerole

Diagnosis of Diagnosis of H. pyloriH. pylori

Invasive (endoscopy)Invasive (endoscopy)– DiagnosticDiagnostic::– Detect the site and the size of the ulcer, even small Detect the site and the size of the ulcer, even small

and superficial ulcer can be detectedand superficial ulcer can be detected– Detect source of bleedingDetect source of bleeding– Biopsies can be taken for Biopsies can be taken for rapid urease testrapid urease test, ,

histopathologyhistopathology && cultureculture

Diagnosis of Diagnosis of H. pyloriH. pylori

Invasive (endoscopy)Invasive (endoscopy)

• Rapid urease test ( RUT)Rapid urease test ( RUT)o Considered the endoscopic Considered the endoscopic diagnostic test of choicediagnostic test of choiceo Gastric biopsy specimens are placed in the rapid Gastric biopsy specimens are placed in the rapid

urease test kit. If urease test kit. If H pyloriH pylori are present, bacterial are present, bacterial urease converts urea to ammonia, which changes urease converts urea to ammonia, which changes pH and produces a pH and produces a CCOOLLOORR changechange

Diagnosis of Diagnosis of H. H. pyloripylori

Invasive (endoscopy)Invasive (endoscopy)

* Histopathology* Histopathologyo Done if the rapid urease test result is negative Done if the rapid urease test result is negative

* Culture* Cultureo Used in research studies and is not available Used in research studies and is not available

routinely for clinical useroutinely for clinical use

TreatmentTreatment

• Aim of therapy:Aim of therapy:• To relieve symptoms; To relieve symptoms;

• To heal ulcer; To heal ulcer;

• To prevent recurrence.To prevent recurrence.

• I. General measuresI. General measures::

• Avoid alcohol, NSAIDs, smoking, spicy foods. HaveAvoid alcohol, NSAIDs, smoking, spicy foods. Have

• more frequent food.more frequent food.

• II. Specific measures:II. Specific measures:

• Intragastric pH should be maintained above 5.Intragastric pH should be maintained above 5.

Drugs of Ulcertreatment

Index…Index…

ClassificationClassification1.1. Acid Neutralizing agents: (ANTACIDS)Acid Neutralizing agents: (ANTACIDS)

• Systemic: Sodium Bicarbonate and Sod. CitrateSystemic: Sodium Bicarbonate and Sod. Citrate• Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium Nonsystemic: Magnesium hydroxide, Mag. Treisilicate, Aluminium

hydroxide gel, Magaldrate and calcium carbonatehydroxide gel, Magaldrate and calcium carbonate

2.2. Reduction in Gastric acid secretion:Reduction in Gastric acid secretion:

• H2 antihistamines: H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Cimetidine, Ranitidine, Famotidine, Nizatidine and RoxatidineNizatidine and Roxatidine

• Proton pump inhibitors: Proton pump inhibitors: Omeprazole, Lansoprazole Omeprazole, Lansoprazole Pantoprazole, Rabeprazole and EsomeprazolePantoprazole, Rabeprazole and Esomeprazole

• Anticholinergics:Anticholinergics: Pirenzepine, Propantheline and Pirenzepine, Propantheline and OxyphenoniumOxyphenonium

• Prostaglandin analogue: Prostaglandin analogue: MisoprostolMisoprostol

Classification – contd.Classification – contd.

3.3. Ulcer protectives: Sucralfate, Colloidal Bismuth sudcitrateUlcer protectives: Sucralfate, Colloidal Bismuth sudcitrate

4.4. Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, Anti-H. pylori Drugs: Amoxicillin, Clarithromycin, metronidazole, tinidazole and tetracycline metronidazole, tinidazole and tetracycline

AntacidsAntacids• Weak bases that neutralize acidWeak bases that neutralize acid

• Also inhibit formation of pepsin Also inhibit formation of pepsin

(As pepsinogen converted to pepsin at acidic pH)(As pepsinogen converted to pepsin at acidic pH)

• Acid Neutralizing Capacity:Acid Neutralizing Capacity: – Potency of AntacidsPotency of Antacids– Expressed in terms of Number ofExpressed in terms of Number of mEq mEq of of 1N HCl1N HCl that are brought that are brought

down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)

Antacids - The Oldest Antacids - The Oldest RemedyRemedy

• Sodium Bicarbonate:Sodium Bicarbonate:– Potent neutralizing capacity and acts instantlyPotent neutralizing capacity and acts instantly– ANC: 1 gm = 12 mEqANC: 1 gm = 12 mEq

• NOT USED ANYMORE FOR ITS DEMERITS:NOT USED ANYMORE FOR ITS DEMERITS:– Systemic alkalosisSystemic alkalosis– Distension, discomfort and belching – CO2Distension, discomfort and belching – CO2– Rebound acidityRebound acidity– Sodium overloadSodium overload

AntacidsAntacids• Present day antacids :Present day antacids :

– Aluminium Hydroxide (ANC 1-2.5mEq/g)Aluminium Hydroxide (ANC 1-2.5mEq/g)– Magnesium Hydroxide (ANC 30 mEq) – milk of magnesiaMagnesium Hydroxide (ANC 30 mEq) – milk of magnesia– Magnesium trisilicate (ANC 1mEq/g)Magnesium trisilicate (ANC 1mEq/g)

• Duration of action : 30 min when taken in empty stomach and 2 Duration of action : 30 min when taken in empty stomach and 2 hrs when taken after a mealhrs when taken after a meal

• Side effects :Side effects :– Aluminium antacids – Aluminium antacids – constipationconstipation (As they relax gastric smooth (As they relax gastric smooth

muscle & delay gastric emptying) – also hypophosphatemia and muscle & delay gastric emptying) – also hypophosphatemia and osteomalciaosteomalcia

– Mg2+ antacids – Osmotic Mg2+ antacids – Osmotic diarrhoeadiarrhoea

• In renal failure Al3+ antacid – Aluminium toxicity In renal failure Al3+ antacid – Aluminium toxicity & Encephalopathy & Encephalopathy

(Magaldrate – hydrated hydroxy magnesium aluminate)(Magaldrate – hydrated hydroxy magnesium aluminate)

Antacids – contd.Antacids – contd.

• SimethiconeSimethicone: Decrease surface tension thereby reduce bubble : Decrease surface tension thereby reduce bubble formation - added to prevent reflux formation - added to prevent reflux

• Alginates:Alginates: Form a layer of foam on top of gastric contents & Form a layer of foam on top of gastric contents & reduce refluxreduce reflux

• Oxethazaine:Oxethazaine: Surface anaesthetic Surface anaesthetic

Sucralfate – ulcer protectiveSucralfate – ulcer protective

• Salt of Salt of sucrose sucrose complexed to sulfated aluminium hydroxide complexed to sulfated aluminium hydroxide (basic aluminium salt)(basic aluminium salt)

• MOA:MOA:– In acidic pH In acidic pH polymerisespolymerises to viscous gel that adheres to ulcer crater - to viscous gel that adheres to ulcer crater -

more on duodenal ulcermore on duodenal ulcer– Precipitates protein on surface proteins and acts as physical barrierPrecipitates protein on surface proteins and acts as physical barrier– Dietary proteins get deposited on this layer forming another coatDietary proteins get deposited on this layer forming another coat– Delays gastric emptying and causes gastric PG synthesis – protective Delays gastric emptying and causes gastric PG synthesis – protective

actionaction

Sucralfate – contd.Sucralfate – contd.

• Taken on empty stomach 1 hr. before mealsTaken on empty stomach 1 hr. before meals

• Concurrent antacids, HConcurrent antacids, H22 antagonist avoided (as it needs acid for antagonist avoided (as it needs acid for activation)activation)

• Uses:Uses:– NSAID induced ulcersNSAID induced ulcers– Patients with continued smokingPatients with continued smoking– ICUICU– Topically – burn, bedsore ulcers, excoriated skinsTopically – burn, bedsore ulcers, excoriated skins

• Dose: 1 gm 1 Hr before mealsDose: 1 gm 1 Hr before meals

• ADRs: Constipation, hypophosphatemia ADRs: Constipation, hypophosphatemia

Chemical reactions of antacids with HCl in the Chemical reactions of antacids with HCl in the stomachstomach

AntacidsAntacids

Capsules & Tablets:Capsules & Tablets:

• PowdersPowders

• Chewable tabletsChewable tablets

• SuspensionsSuspensions

• Effervescent granules and tabletsEffervescent granules and tablets

HH22 Antagonists Antagonists• Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine Cimetidine, Ranitidine, Famotidine, Roxatidine, Nizatidine

andand

• MOA:MOA: – Reversible competitive inhibitors of HReversible competitive inhibitors of H22 receptor receptor– Highly selective, no action on HHighly selective, no action on H11 or H or H33 receptors receptors– All phases of gastric acid secretionAll phases of gastric acid secretion– Very effective in inhibiting nocturnal acid secretion (as it depends Very effective in inhibiting nocturnal acid secretion (as it depends

largely on Histamine )largely on Histamine )– Modest impact on meal stimulated acid secretion (as it depends on Modest impact on meal stimulated acid secretion (as it depends on

gastrin, acetylcholine and histamine)gastrin, acetylcholine and histamine)– Volume of pepsin content and IF are also reducedVolume of pepsin content and IF are also reduced– Volume reduced by 60 – 70% - anti ulcerogenic effectVolume reduced by 60 – 70% - anti ulcerogenic effect– No effect on motilityNo effect on motility

HH22 antagonists antagonists• Kinetics:Kinetics:

– All drugs are absorbed orally adequatelyAll drugs are absorbed orally adequately– Bioavailability upto 80 %Bioavailability upto 80 %– Absorption is not interfered by presence of foodAbsorption is not interfered by presence of food– Can cross placental barrier and reaches milkCan cross placental barrier and reaches milk– Poor CNS penetrationPoor CNS penetration– 2/32/3rdrd of the drugs are excreted unchanged in bile and urine of the drugs are excreted unchanged in bile and urine

• Preparations: available as tablets, injectionsPreparations: available as tablets, injections

HH2 2 antagonists - ADRsantagonists - ADRs• Extremely safe drugs and well toleratedExtremely safe drugs and well tolerated

• Main ADRs are related to Cimetidine:Main ADRs are related to Cimetidine:– Antiandrogenic Antiandrogenic effectseffects– Increases Increases prolactinprolactin secretion and inhibits degradation of secretion and inhibits degradation of estradiol estradiol by by

liverliver– Cytochrome P450 inhibition – theophylline, metronidazole, phenytoin, Cytochrome P450 inhibition – theophylline, metronidazole, phenytoin,

imipramine etc.imipramine etc.– AntacidsAntacids

• Others:Others:– Headache, dizziness, bowel upset, dry mouthHeadache, dizziness, bowel upset, dry mouth– Bolus IV – release histamine – bradycardia, arrhythmia, cardiac arrestBolus IV – release histamine – bradycardia, arrhythmia, cardiac arrest– Elderly - precautionElderly - precaution

HH2 2 antagonists - Usesantagonists - UsesPromote the healing of gastric and duodenal ulcersPromote the healing of gastric and duodenal ulcers• Duodenal ulcer – 70 to 90%Duodenal ulcer – 70 to 90%• Gastric Ulcer – 50 to 75% (NSAID ulcers))Gastric Ulcer – 50 to 75% (NSAID ulcers))• Stress ulcer and gastritisStress ulcer and gastritis• GERDGERD• Zollinger-Ellison syndromeZollinger-Ellison syndrome• Prophylaxis of aspiration pneumoniaProphylaxis of aspiration pneumonia• UrticariaUrticaria

Doses:Doses: • 300 mg/40 mg/150 mg at bed time of R, F, Rox respectively for healing300 mg/40 mg/150 mg at bed time of R, F, Rox respectively for healing• Maintenance: 150/20/150 mg BD of R, F, Rox Maintenance: 150/20/150 mg BD of R, F, Rox

HH22 blockers Tablets in blockers Tablets in Peptic ulcerPeptic ulcer

Cimetidine 800mg bedtime /400mgBd 400mg bedtime

Ranitidine 300 mg bedtime/150mg BD 150 mg bedtime

Famotidine 40 mg bedtime 20 mg bedtime

Roxatidine 150 mg bedtime 75 mg bedtime

Proton Pump Proton Pump InhibitorsInhibitors• Most effective drugs in antiulcer therapyMost effective drugs in antiulcer therapy

• Prodrugs Prodrugs requiring activation in acid environmentrequiring activation in acid environment

• Block enzymes responsible for secreting HCl - binds Block enzymes responsible for secreting HCl - binds irreversiblyirreversibly to to H+K+ATPase H+K+ATPase

• Prototype: Prototype: Omeprazole (Prilosec) Omeprazole (Prilosec)

• Examples:Examples:– Lansoprazole Lansoprazole – PantoprazolePantoprazole– Rabeprazole Rabeprazole – Esomeprazole Esomeprazole

Omeprazole

Pharmacokinetics - Pharmacokinetics - PPIPPI

Given on an empty stomach because food affects absorptionGiven on an empty stomach because food affects absorption They should be given 30 minutes to 1 hour before food They should be given 30 minutes to 1 hour before food

intake because an acidic pH in the parietal cell acid intake because an acidic pH in the parietal cell acid canaliculi is required for drug activation, and food stimulates canaliculi is required for drug activation, and food stimulates acid production acid production

Concomitant use of other antisecretory drugs - H2 receptor Concomitant use of other antisecretory drugs - H2 receptor antagonists – reduces action antagonists – reduces action

Highly protein bound and rapidly Metabolized by the liver Highly protein bound and rapidly Metabolized by the liver by CYP2C19 and CYP3A4 – dose reduction necessary in by CYP2C19 and CYP3A4 – dose reduction necessary in severe hepatic failuresevere hepatic failure

Excreted in Kidneys minimally (no dose reduction needed in Excreted in Kidneys minimally (no dose reduction needed in renal failure and elderly) renal failure and elderly)

Adverse EffectsAdverse Effects The most common are GIT troubles in the form of nausea, The most common are GIT troubles in the form of nausea,

abdominal pain, constipation, flatulence, and diarrheaabdominal pain, constipation, flatulence, and diarrhea

Subacute myopathy, arthralgias, headaches, and skin rashes Subacute myopathy, arthralgias, headaches, and skin rashes

Prolonged use:Prolonged use: Gynaecomastia, erectile dysfunctionGynaecomastia, erectile dysfunction Leucopenia and hepatic dysfunctionLeucopenia and hepatic dysfunction Vitamin B12 deficiencyVitamin B12 deficiency Hypergastrinemia which may predispose to rebound Hypergastrinemia which may predispose to rebound

hypersecretion of gastric acid upon discontinuation of therapy and hypersecretion of gastric acid upon discontinuation of therapy and may promote the growth of gastrointestinal tumors (carcinoid may promote the growth of gastrointestinal tumors (carcinoid tumors )tumors )

• Therapeutic uses:Therapeutic uses:1.1. Gastroesophageal reflux disease (GERD)Gastroesophageal reflux disease (GERD)2.2. Peptic Ulcer - Gastric and duodenal ulcersPeptic Ulcer - Gastric and duodenal ulcers3.3. Bleeding peptic Ulcer Bleeding peptic Ulcer 4.4. Zollinger ellison SyndromeZollinger ellison Syndrome5.5. Prevention of recurrence of nonsteroidal antiinflammatory drug Prevention of recurrence of nonsteroidal antiinflammatory drug

(NSAID) - associated gastric ulcers in patients who continue (NSAID) - associated gastric ulcers in patients who continue NSAID use.NSAID use.

6.6. Reducing the risk of duodenal ulcer recurrence associated with Reducing the risk of duodenal ulcer recurrence associated with H. pylori infectionsH. pylori infections

7.7. Aspiration PneumoniaAspiration Pneumonia

PPI – Dosage schedulePPI – Dosage schedule

• Omeprazole 20 mg o.d.Omeprazole 20 mg o.d.

• Lansoprazole 30 mg o.d.Lansoprazole 30 mg o.d.

• Pantoprazole 40 mg o.d.Pantoprazole 40 mg o.d.

• Rabeprazole 20 mg o.d.Rabeprazole 20 mg o.d.

• Esomeprazole 20 - 40 mg o.d.Esomeprazole 20 - 40 mg o.d.

Muscarinic antagonistsMuscarinic antagonistsAtropine:Atropine:

– Block the MBlock the M11 class receptors class receptors– Reduce acid productionReduce acid production– Abolish gastrointestinal spasmAbolish gastrointestinal spasm

Pirenzepine and TelenzepinePirenzepine and Telenzepine

Mechanism of action: Mechanism of action: • Reduce meal stimulated HCl secretion by reversible blockade of muscarinic Reduce meal stimulated HCl secretion by reversible blockade of muscarinic

(M1) receptors on the cell bodies of the intramural cholinergic ganglia(M1) receptors on the cell bodies of the intramural cholinergic ganglia

(receptors on parietal cells are M3).(receptors on parietal cells are M3).

• Unpopular as a first choice because of high incidence of Unpopular as a first choice because of high incidence of anticholinergic side effects (dry mouth and blurredanticholinergic side effects (dry mouth and blurred vision) vision)

Prostaglandin Prostaglandin analoguesanalogues

• Inhibit gastric acid secretionInhibit gastric acid secretion

• Exhibit ‘cytoprotective’ activityExhibit ‘cytoprotective’ activity

• Enhance local production of mucus or bicarbonateEnhance local production of mucus or bicarbonate

• Promote local cell regenerationPromote local cell regeneration

• Help to maintain mucosal bloodHelp to maintain mucosal blood

Prostaglandin analogues Prostaglandin analogues - Misoprostol- Misoprostol

Actions:Actions:Inhibit histamine-stimulated gastric acid secretionInhibit histamine-stimulated gastric acid secretionStimulation of mucin and bicarbonate secretionStimulation of mucin and bicarbonate secretionIncrease mucosal blood flowIncrease mucosal blood flow

(Reinforcing of mucous layer buffered by HCO3 (Reinforcing of mucous layer buffered by HCO3 secretion from epithelial cells)secretion from epithelial cells)

Therapeutic uses:Therapeutic uses:

Prevent ion of NSAID-induced mucosal injury Prevent ion of NSAID-induced mucosal injury (rarely used because it needs frequent (rarely used because it needs frequent administration – 4 times daily)administration – 4 times daily)

MisoprostolMisoprostol• Doses: 200 mcg 4 times a day (Misoprost)Doses: 200 mcg 4 times a day (Misoprost)

• ADRs:ADRs:– Diarrhoea and abdominal crampsDiarrhoea and abdominal cramps– Uterine bleedingUterine bleeding– AbortionAbortion– Exacerbations of inflammatory bowel disease and should Exacerbations of inflammatory bowel disease and should

be avoided in patients with this disorderbe avoided in patients with this disorder

Contraindications:Contraindications:

1.1. Inflammatory bowel diseaseInflammatory bowel disease

2.2. Pregnancy (may cause abortion)Pregnancy (may cause abortion)

ProglumideACh

PGE2Histamine Gastrin

Adenyl cyclase

_ +

ATP cAMP

Protein Kinase (Activated)

Ca++

+

Ca++

Proton pump

KK+ H+

Gastric acid

Parietal cellLumen of stomach

AntacidOmeprazole

Ranitidine

H2M3

Misoprostol

_

__

_

+

PGE receptor

+

+

Gastrin receptor+

+

+

Eradication of H.pylori

OmeprazoleAmoxicillinClarithromycinMetronidazole

Triple TherapyThe BEST among all the Triple therapy regimen is:

Omeprazole / Lansoprazole - 20 / 30 mg bd

Clarithromycin - 500 mg bd

Amoxycillin / Metronidazole - 1gm / 500 mg bd

Given for 14 days followed by P.P.I for 4 – 6 weeks

Short regimens for 7 – 10 days not very effective

Triple Therapy – cont …

Bismuth subsalicylate – 2 tab qid

Metronidazole - 250 mg qid

Tetracycline - 500 mg qid

Some other Triple Therapy Regimens are

Ranitidine Bismuth citrate - 400 mg bd

Tetracycline - 500 mg bd

Clarithromycin / Metronidazole - 500 mg bd

Bismuth Bismuth subsalicylatesubsalicylate

Pharmacological actions:Pharmacological actions:

• Undergoes rapid dissolution in the stomach into bismuth and Undergoes rapid dissolution in the stomach into bismuth and salicylatessalicylates

• Salicylates are absorbed Salicylates are absorbed

• Bismuth coats ulcers and erosions protecting them from acid Bismuth coats ulcers and erosions protecting them from acid and pepsin and increases prostaglandin and bicarbonate and pepsin and increases prostaglandin and bicarbonate productionproduction

• Uses:Uses:• Treatment of dyspepsia and acute diarrhoeaTreatment of dyspepsia and acute diarrhoea

Surgery for Surgery for Uncomplicated DUUncomplicated DU

• Indications for surgical intervention for Indications for surgical intervention for chronic DU (Uncomplicated chronic DU (Uncomplicated DU):DU):

• 1. Uncomplicated DU, not responding to drug 1. Uncomplicated DU, not responding to drug therapy of 8-12 weeks—intractable duodenal therapy of 8-12 weeks—intractable duodenal ulcerulcer

• 2. Repeated recurrences2. Repeated recurrences

• Presently most of the uncomplicated DU does Presently most of the uncomplicated DU does not require surgerynot require surgery

• Highly selective vagotomy (HSV). In HSV, only Highly selective vagotomy (HSV). In HSV, only fibres supplying the parietal cells are ligated. fibres supplying the parietal cells are ligated. Nerve of Latarjet which supplies the antrum pump Nerve of Latarjet which supplies the antrum pump is retained and so no drainage procedure is is retained and so no drainage procedure is required in HSV. required in HSV.

• HSV is also called as parietal cell vagotomy or HSV is also called as parietal cell vagotomy or superselective vagotomy . superselective vagotomy .

• Here nerve fibres in last 6 cm of stomach, just Here nerve fibres in last 6 cm of stomach, just proximal to pylorus are preserved (Crow’s foot). proximal to pylorus are preserved (Crow’s foot).

• Vagotomy reduces acid secretion, hence ulcer Vagotomy reduces acid secretion, hence ulcer heals. No acid, No ulcer .heals. No acid, No ulcer .

• Selective vagotomy with pyloroplasty (SV + Selective vagotomy with pyloroplasty (SV + P).P).

• Truncal vagotomy with gastrojejunostomy Truncal vagotomy with gastrojejunostomy (TV + GJ).(TV + GJ).

• Posterior truncal vagotomy with anterior Posterior truncal vagotomy with anterior seromyotomy— Taylor’s operation. seromyotomy— Taylor’s operation.

• Posterior truncal vagotomy with HSV without Posterior truncal vagotomy with HSV without drainagedrainage

• Linear gastrectomy with posterior truncal Linear gastrectomy with posterior truncal vagotomyvagotomy

Types of vagotomy. (A) Highly selective Types of vagotomy. (A) Highly selective vagotomy,vagotomy,

(B) Selective vagotomy with pyloroplasty, (B) Selective vagotomy with pyloroplasty, (C) Truncal vagotomy with(C) Truncal vagotomy with

gastrojejunostomy.gastrojejunostomy.

Evaluation/Follow-up/Evaluation/Follow-up/

• H. Pylori Positive: retesting for tx efficacyH. Pylori Positive: retesting for tx efficacy• Urea breath test—no sooner than 4 weeks after therapy to avoid false Urea breath test—no sooner than 4 weeks after therapy to avoid false

negative resultsnegative results• Stool antigen test—an 8 week interval must be allowed after therapy.Stool antigen test—an 8 week interval must be allowed after therapy.

• H. Pylori Negative: H. Pylori Negative: • evaluate symptoms after one month. Patients who are controlled evaluate symptoms after one month. Patients who are controlled

should cont. 2-4 more weeks.should cont. 2-4 more weeks.

ComplicationsComplications

• Upper digestive bleeding Upper digestive bleeding is the most common complication.is the most common complication.

• Sudden large bleeding can be life-threatening. Sudden large bleeding can be life-threatening.

• It occurs when the ulcer erodes one of the blood vessels, such as the It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery. gastroduodenal artery.

ComplicationsComplications

• PerforationPerforation often leads to catastrophic consequences. often leads to catastrophic consequences.

• Erosion of the gastro-intestinal wall by the ulcer leads to Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal spillage of stomach or intestinal content into the abdominal cavity. cavity.

• Perforation at the anterior surface of the stomach leads to Perforation at the anterior surface of the stomach leads to acute acute peritonitisperitonitis, initially chemical and later bacterial , initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal peritonitis. The first sign is often sudden intense abdominal pain.pain.

• Posterior wall perforation leads to Posterior wall perforation leads to pancreatitispancreatitis; pain in this ; pain in this situation often radiates to the back. situation often radiates to the back.

• Perforation in the CBD- aerobilia, Perforation in the CBD- aerobilia, cholangitischolangitis

ComplicationsComplications

• PenetrationPenetration is when the ulcer continues into is when the ulcer continues into adjacent organs such as the liver and pancreas. adjacent organs such as the liver and pancreas.

• Gastric outlet obstruction Gastric outlet obstruction - scarring and swelling - scarring and swelling due to ulcers causes pyloric narrowing. Patient due to ulcers causes pyloric narrowing. Patient often presents with severe vomiting. often presents with severe vomiting.

• CancerCancer is included in the differential diagnosis is included in the differential diagnosis (elucidated by biopsy), Helicobacter pilory as the (elucidated by biopsy), Helicobacter pilory as the etiological factor making it 3 to 6 times more etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer. likely to develop stomach cancer from the ulcer.

Diagnosis of Diagnosis of perforatedperforated

peptic ulcer diseasepeptic ulcer disease History and physical examination History and physical examination

Upright Upright chest radiographschest radiographs will show will show pneumoperitoneumpneumoperitoneum

((““free airfree air””) in 80) in 80––90% of the cases.90% of the cases.

If pneumoperitoneum is identified on plain radiographs, there is no need for further studies.If pneumoperitoneum is identified on plain radiographs, there is no need for further studies.

Ultrasound is less sensitive for detecting free air but could be used to identify Ultrasound is less sensitive for detecting free air but could be used to identify other indirect findings of perforationother indirect findings of perforation such as such as

free fluidfree fluid and and decreased peristalsisdecreased peristalsis when the diagnosis remains in question. when the diagnosis remains in question.

Computerized tomography (CT) scans are more sensitiveComputerized tomography (CT) scans are more sensitive

for detecting pneumoperitoneum than the other modalitiesfor detecting pneumoperitoneum than the other modalities

but should ideally be performed at least 6 h following the onsetbut should ideally be performed at least 6 h following the onset

of symptoms.of symptoms.

the use of the use of oral contrast medium with CT scanningoral contrast medium with CT scanning to identify to identify

the the site of perforationsite of perforation and the and the presence of ongoing leakage.presence of ongoing leakage.

Indications for surgery inIndications for surgery inpatients with peptic ulcer diseasepatients with peptic ulcer disease

The indications for surgery for PUD have The indications for surgery for PUD have recently been limited to the treatment of recently been limited to the treatment of complicated PUD. complicated PUD.

because of the high mortality rate following because of the high mortality rate following emergency surgery for perforated PUD, many emergency surgery for perforated PUD, many are suggesting nonoperative management are suggesting nonoperative management rather than surgical management in high-risk rather than surgical management in high-risk patients. patients.

High risk is defined as High risk is defined as the presence of severe comorbidities, the presence of severe comorbidities, perforation greater than 24 h, perforation greater than 24 h, and hypotension on presentation.and hypotension on presentation.

Crofts et al. determined that nonoperative Crofts et al. determined that nonoperative management with nasogastric suction, fluid management with nasogastric suction, fluid resuscitation, and antibiotics resuscitation, and antibiotics

can be effective in the treatment of can be effective in the treatment of perforated PUD if the site of perforation perforated PUD if the site of perforation has sealed.has sealed.

Failure to improve within 24 h should then Failure to improve within 24 h should then prompt an operation.prompt an operation.

Each case must be individualized, and Each case must be individualized, and nonoperative management should not be nonoperative management should not be undertaken if a contrast study of the upper undertaken if a contrast study of the upper gastrointenstinal tract shows gastrointenstinal tract shows continuing continuing free perforationfree perforation..

Treatment options forTreatment options forperforated peptic ulcer perforated peptic ulcer

diseasedisease Surgery for PUD has a long history with many Surgery for PUD has a long history with many

surgical options.surgical options.

Many procedures have gone out of favor due to Many procedures have gone out of favor due to complications, side effects, and inadequacy, complications, side effects, and inadequacy, leaving leaving

highly selective vagotomy (HSV) orhighly selective vagotomy (HSV) or Truncal vagotomy with pylorplasty or Truncal vagotomy with pylorplasty or

gastrojejunosotomy,gastrojejunosotomy, Vagotomy with antrectomy, and Vagotomy with antrectomy, and Omental patch closure Omental patch closure

as the current options.as the current options.

Omental patch Omental patch closureclosure

Omental patch closureOmental patch closure is a quick and simple procedure that is is a quick and simple procedure that is

very useful in perforated PUD. very useful in perforated PUD.

It has long been the recommended treatment in patients with It has long been the recommended treatment in patients with

multiple comorbiditiesmultiple comorbidities, those that are, those that are

hemodynamically unstablehemodynamically unstable and and

those with exudative peritonitis.those with exudative peritonitis.

It is not useful in It is not useful in Type IV gastric ulcersType IV gastric ulcers and may not be the and may not be the

optimal treatment in a stable patient with a perforated Type Ioptimal treatment in a stable patient with a perforated Type I

gastric ulcer gastric ulcer

Numerous authors in recent years have prospectively investigated peptic ulcer recurrence rates after simple patch Numerous authors in recent years have prospectively investigated peptic ulcer recurrence rates after simple patch closure and H. pylori eradication and have reported closure and H. pylori eradication and have reported high success rateshigh success rates

Highly selective Highly selective vagotomyvagotomy

HSV is a tedious but safe operation , that can be HSV is a tedious but safe operation , that can be performed laparoscopically, performed laparoscopically,

with minimal side effects. with minimal side effects.

It has a higher recurrent ulcer rate than It has a higher recurrent ulcer rate than

the other procedures (10the other procedures (10––20%). 20%).

It is not useful for Type II or Type III It is not useful for Type II or Type III

gastric ulcers or for complicated PUD.gastric ulcers or for complicated PUD.

Truncal vagotomyTruncal vagotomy Truncal vagotomy and drainage procedure is Truncal vagotomy and drainage procedure is

very useful in complicated ulcer disease. very useful in complicated ulcer disease.

It reduces peak acid secretion by 50%. It reduces peak acid secretion by 50%.

It has a significant side effect profile It has a significant side effect profile and has a recurrentand has a recurrent

ulcer rate of 10%.ulcer rate of 10%.

Truncal vagotomy.Truncal vagotomy.

Vagotomy with Vagotomy with antrectomyantrectomy

Vagotomy with antrectomy is Vagotomy with antrectomy is most effective at reducing acid most effective at reducing acid secretionsecretion and has a recurrence rate of 0 and has a recurrence rate of 0––2%. 2%.

But, this operation has a 20% rate of post-gastrectomy But, this operation has a 20% rate of post-gastrectomy

and post-vagotomy syndromes and has a significant associated and post-vagotomy syndromes and has a significant associated mortality. mortality.

The mortality risk increases with patient comorbidities The mortality risk increases with patient comorbidities

and with emergency surgery for complicated PUD. and with emergency surgery for complicated PUD.

It should be avoided in hemodynamically unstableIt should be avoided in hemodynamically unstable

paitents and those with extensive inflammation since the paitents and those with extensive inflammation since the anastamosis may be compromised.anastamosis may be compromised.

postoperative morbidity and mortality associatedpostoperative morbidity and mortality associated with repair of a perforated peptic ulcer diseasewith repair of a perforated peptic ulcer disease

Despite current advances in medical and surgical therapy, Despite current advances in medical and surgical therapy, the morbidity and mortality associated the morbidity and mortality associated

with perforated PUD remains very high andwith perforated PUD remains very high and

this area has remained a topic of current research this area has remained a topic of current research efforts.efforts.

Comorbidities Comorbidities and and preoperative shockpreoperative shock are well-established are well-established independent risk factors for a poor independent risk factors for a poor

outcome following emergency surgery.outcome following emergency surgery.

Kocer et al. added Kocer et al. added ageage, , time before surgerytime before surgery, and , and performance of a definitive operationperformance of a definitive operation to the list to the list

of significant risk factors. of significant risk factors.

Adjunctive medical treatments Adjunctive medical treatments following operation for perforated following operation for perforated

PUDPUD

Proton Pump InhibitorsProton Pump Inhibitors

Discontinuation of Nonsteroidal Anti-Discontinuation of Nonsteroidal Anti-inflammatory Drugsinflammatory Drugs

Medications for Mucosal CytoprotectionMedications for Mucosal Cytoprotection

Treatment of Helicobacter pylori and Treatment of Helicobacter pylori and verification of eradicationverification of eradication

keypoints to remember in managing keypoints to remember in managing patients with patients with perforated PUDperforated PUD

Biopsy of all perforated gastric ulcers is required.Biopsy of all perforated gastric ulcers is required.

No single approach is ideal for all patients. Surgeons No single approach is ideal for all patients. Surgeons must be prepared to individualizemust be prepared to individualize

all treatment plansall treatment plans

Any patient admitted to a hospital because of peptic Any patient admitted to a hospital because of peptic ulcer disease should be placed on lifelong acid ulcer disease should be placed on lifelong acid suppression.suppression.

Patients who regularly take NSAIDs or aspirin should take Patients who regularly take NSAIDs or aspirin should take concomitant acid suppressiveconcomitant acid suppressive medicationmedication if they are more if they are more than 60 years old.than 60 years old.

Lifelong acid suppressive medication may be equivalent to Lifelong acid suppressive medication may be equivalent to surgical vagotomy in preventing surgical vagotomy in preventing recurrent peptic ulcerrecurrent peptic ulcer or or ulcer complicationsulcer complications..

Management of Management of upper GI upper GI HemorrhageHemorrhage

Management Management Upper GIT Upper GIT BleedingBleeding

Complete history:Complete history: alcohol use, cirrhosis, heart burn, reflux, and alcohol use, cirrhosis, heart burn, reflux, and medications. medications.

ExamExam : : signs of signs of cirrhosiscirrhosis including spider angiomata, palmer including spider angiomata, palmer erythema, prominent abdominal veins, caput medusa, and erythema, prominent abdominal veins, caput medusa, and ascites. ascites.

mucous membranes for melanin spots associated with mucous membranes for melanin spots associated with Puetz-Jeghers syndrome. Puetz-Jeghers syndrome.

Physical ExamPhysical Exam

Vital signs:Vital signs: instability, respiratory instability, respiratory distress, beware of beta blockadedistress, beware of beta blockade

signs of anemia, dehydrationsigns of anemia, dehydrationAbdominal examAbdominal exam::Rectal examRectal exam: : Look for perianal causes of Look for perianal causes of bleeding. bleeding.

check for occult blood in the check for occult blood in the stool.stool.

Laboratory Laboratory studies:studies:

• Type and CrossType and Cross• CBC: anemia?CBC: anemia?• hepatic dysfunction and hepatic dysfunction and renal compromiserenal compromise

• Coags: coagulopathy Coags: coagulopathy • ABG: probe for acidosisABG: probe for acidosis

Interventions to Interventions to considerconsider

• ABCABC’’ss Ensure adequate Ensure adequate airwayairway protection protection and adequate respirations:massive and adequate respirations:massive bleeding considered for bleeding considered for intubationintubation

Start 2 large bore Start 2 large bore IVIV’’ss.. FluidFluid bolus either NS or LR bolus either NS or LR 3-for-1 rule: Replace each 3-for-1 rule: Replace each milliliter of blood loss with 3 mL milliliter of blood loss with 3 mL of crystalloid fluid. of crystalloid fluid.

PharmacotherapyPharmacotherapy

• Proton pump inhibitors (PPIs), (PPIs), orally or intravenously as an infusionorally or intravenously as an infusion

• Octreotide is a is a somatostatin analog: shunt blood away from analog: shunt blood away from the splanchnic circulation. variceal and non-variceal upper GI the splanchnic circulation. variceal and non-variceal upper GI hage. hage.

• vasopressin analog most commonly for variceal upper GI hage. analog most commonly for variceal upper GI hage.

• Anti-fibrinolytic drugsAnti-fibrinolytic drugs such as such as

tranexamic acid

• Factor VII for variceal hemorrhage for variceal hemorrhage

• If If Helicobacter pylori:: antibiotics and a PPI antibiotics and a PPI

TubesTubes

•Foley CatheterFoley Catheter•NG with gastric lavageNG with gastric lavage: : If the stomach contains bile If the stomach contains bile but no blood, UGIB is less but no blood, UGIB is less likely likely

•Iced saline lavageIced saline lavage• STAT Upper STAT Upper endoscopyendoscopy

Early Early Endoscopy

• Both As A Diagnostic And Therapeutic: Both As A Diagnostic And Therapeutic: 1.Injection of of adrenaline or or

sclerotherapy 2.2.Electrocautery: Electrocautery: thermal thermal

3.3.Endoscopic clipping Endoscopic clipping 4.4.Banding of varicesBanding of varices5. Argon plasma coagulation. . 6. Cryotherapy ablation is another ablation is another

possibilitypossibility

Stigmata of high Stigmata of high riskrisk

•Active bleedingActive bleeding•OozingOozing•Visible vessels Visible vessels •Red SpotsRed Spots

Visible vessels

oozing bleeding

Active bleeding

Red Spots

Contraindications to Contraindications to endoscopyendoscopy

•UncooperativeUncooperative• severe severe cardiaccardiac decompensation, acute decompensation, acute myocardial infarction myocardial infarction

•perforatedperforated viscus viscus ((eg, eg, esophagus, stomach, esophagus, stomach, intestineintestine). ).

Refractory casesRefractory cases

• Repeat Repeat esophagogastroduodenoscopy

•Angiography EmbolizationEmbolization the feeder the feeder vessel vessel

•Balloon tamponade

•Surgery, to oversew or remove, to oversew or remove

PU bleeding PU bleeding TREATMENTTREATMENT

•MedicalMedical• Anti-ulcer medicationAnti-ulcer medication• H. pylori treatmentH. pylori treatment• Stop NSAIDsStop NSAIDs• Follow up EGD for gastric Follow up EGD for gastric ulcer in 6 weeksulcer in 6 weeks

PU TREATMENTPU TREATMENT

•Endoscopic interventionsEndoscopic interventions• Thermal coagulationThermal coagulation• Injected agentsInjected agents Success rateSuccess rate

» 95% initailly95% initailly» 80% will not rebleed80% will not rebleed

PU TREATMENTPU TREATMENT

• Surgical interventionSurgical intervention– Only 10% of patientsOnly 10% of patients– IndicationsIndications

1.1.Failure of endoscopyFailure of endoscopy2.2.Significant rebleeding after 1Significant rebleeding after 1stst endoscopyendoscopy

3.3.Ongoing transfusion requirementOngoing transfusion requirement4.4.Need for >6 units over 24 hoursNeed for >6 units over 24 hours5.5.Earlier for elderly, multiple co-Earlier for elderly, multiple co-morbiditiesmorbidities

PU Surgical PU Surgical interventionintervention

• Doudenal ulcerDoudenal ulcer– Expose ulcer with duodenotomy or Expose ulcer with duodenotomy or

duodenopyloromyotomy duodenopyloromyotomy – Direct suture ligation,Direct suture ligation,– The gastroduodenal The gastroduodenal artery may be ligatedartery may be ligated if if

necessarynecessary– the pyloric channel is closed vertically resulting the pyloric channel is closed vertically resulting

in a in a Heineke-Mikulicz pyloroplastyHeineke-Mikulicz pyloroplasty

– Anti-secretory procedureAnti-secretory procedure» Truncal, parietal cell vagotomyTruncal, parietal cell vagotomy» can use medscan use meds

PU Surgical PU Surgical interventionintervention

• Gastric ulcerGastric ulcer– 10% are maliganant10% are maliganant– 30% will rebleed 30% will rebleed with simple ligationwith simple ligation

ResectionResection• Distal gastrectomyDistal gastrectomy Bilroth I or II Bilroth I or II • Subtotal gastrectomySubtotal gastrectomy

Angiographic obliterationAngiographic obliteration

• of the bleeding vessel is of the bleeding vessel is considered in patients with considered in patients with poor prognoses poor prognoses

Summary Summary A peptic ulcer is a break in superficial epithelial A peptic ulcer is a break in superficial epithelial cells penetrating down to muscularis mucosa cells penetrating down to muscularis mucosa

Duodenal > gastric ulcers Duodenal > gastric ulcers

Can be asymptomaticCan be asymptomatic

H pylori is a predominant risk factorH pylori is a predominant risk factor

H pylori diagnosed by c urea breath test, stool H pylori diagnosed by c urea breath test, stool antigen or if validated serology, treated with antigen or if validated serology, treated with PAC500 or PMC250 regimePAC500 or PMC250 regime

Complications of PUD can lead to acute emergency of Complications of PUD can lead to acute emergency of upper GI bleedupper GI bleed

H. pyloriH. pylori

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