PEPTIC ULCER DISEASE

   
                                         
                            

PEPTIC ULCER DISEASE

(By DR.S.UMA DEVI.M.D)

Introduction

A breach in the lining of the upper GI tract in certain specific sites, caused by the action of acid and pepsin.

Sites of occurance:

1.Duodenal bulb(DU) first few inches of duodenum

2. Stomach lesser curvature(Gastric ulcerGU)

Other locations:

Esophagus

Pyloric channel,

Duodenal loop,

Jejunum

Meckles diverticulum

                                       Fig.1.Normal stomach

Pathogenesis

A defect in the mucosa,submucosa and muscular layer of UGI tract

Normally a balance exists between acid secretion and gastroduodenal  mucosal defences

 Here-Imbalance between Aggressive factors and defensive factors in protecting normal gastric mucosa

Aggressive factors:

1.Gastric acid

2.Pepsin

3.Bile acids

Defensive factors

1.Gastric mucosal barrier

2.Bicorbonates

3.Normal mucosal blood flow

4.Ability of nucosa to regenerate(cell restitution)

5.  Gastric Mucus

Risk factors

Smoking

Heredity

Blood group ‘O’and ‘A’

Imbalance between aggressive and defensive hactors  results in peptic ulcer

1.On aggressive side - Gastrinoma (Zollinger –Ellison syndrome)

2.On defensive side -2 factors

                                      A) NSAID

                                      B)H.Pylori infection

These external factors are not necessarily additive.

Etiology of ulcer

Commonest:  Helicobactor .pylori

Next common: NSAID induced

Less common: hyper secretory state-Zollinger Ellison syndrome

                          (+ Gcell hyperplasia,mastocytosis,basophilic  leukemias)

Present classification of ulcer disease:

(According to true cause)

1.H.Pylori related

2.NSAID induced

3. Related to Zollinger-Ellison syndrome.(Acid stimulating cancer)

Role of acid in ulcer production

Acid is fundamentally “causative” only in Zollinger Ellision syndrome

In other 2 types though ‘not causative’ acid is essential permissive factor

(without presence of acid, ulcer cannot develop in these 2)

So in all 3 types powerful Anti secretory therapy required  Suppression of acid secretion is main stay of treatment

 

Other factors

Cigarette smoking most important and worsening factor

Severe physiological stress-Burns,CNS trauma,surgery,severe medical illness

Tobacco chewing

Alcohol excess

 Process of Ulcer healing

1.Angiogenesis of granulation tissue in the base of the ulcer

2.Replication of epithelial cells at ulcer margin

3.Final reestablish ment of glandular architecture

Clinical features                                                  

Age:

Peptic ulcer common in younger age

Gastric ulcer in old age

PUD can also occur in children

Symptoms

The most outstanding  symptom-

epigastric pain

Relived by food /antacids

Severity –variable-mild/moderate/severe

Nature-aching/burning

Location
generally epigastric

But may be high up under xiphisternum

Or low down around umbilicus

DU pain-typically-right epigastrium

GU pain in left epigastrium(but overlap occurs)

If pain radiates to back consider penetration

Typical rhythm of the pain

Comes after food and

eased by antacids,vomiting or food

In DU-

2hrs after meals

In GU-within ½ hr to 1hr after meals

In DU-typical nocturnal pain inmiddle of night disturbing sleep.

Periodicity

Most characteristic feature

Symptoms last for a few days to weeks alternate with

periods of remission Same or longer duration)

Relief of pain with milk alkaliesD.D.gallstones or hyperacidity

Associated symptoms:

Heartburn. Waterbrash ,eructation’s ,vomiting

Vomiting often relieves the pain

Apetitite is usually good but patient is afraid to eat.

Constipation common

Loss of weight common in GU .

Atypical features

.1.No pain but bouts of heartburn,waterbrash or vomiting

2.Hemetemesis;perforation( early voluntary guarding or muscular rigidity)

3.Pain may be totally unrelated to food

4.In some –severe steady continuous pain+vomiting of highly acis gastric juice

5.Post bubar duodenal ulcer: pain in the back and may be unrelated to food.

It may manifest  only with attacks of intermittent vomiting /intermittent obstruction

6.Pyloric channel ulcer:can cause obstruction,penetration and run accelerated  course.

They are difficult to treat medically.;periodicity ,rhythmicity absent

Pain comes immeadiately after eating  with frequent vomiting.

Clinical examination:                                                                          

(History is more important).

·         .tenderness in epigastrium  on deep palpation

·         .Guarding or muscular rigidity over ulcer

                  It signifies involvement of peritoneum

·         Mass ;A tender mass may be palpable

When ulcer has leaked outside

·         Visible gastric peristalsis when there is obstruction

·         Succusion splash may be heard after taking fluid/food(gastric obstruction)

 Complications;                                                                           

·         Bleeding

·         Obstruction

·         Penetration causing pancreatitis

·         Perforation

·         Intractability

·         Frequent recurrences

Mortality causes:                                                     -

Bleeding related:

 Uncontrolled bleeding,during surgery for bleeding,within 48 hrs after endoscopy,from surgical complications (within 1month),endoscopy related motality.

Non bleeding related:

Cardiac,pulmonaruy causes,CVD,multiorgan failure,malignancy related

Treatment for peptic ulcer                        -

Cure of Helicobactor Pylori Infection

Avoidance of NSAID

Appropriate use of antisecretary therapy

Differential Diagnosis:                        

Cholecystitis

Crohn’s disease

Pancreatitis

Zollinger –Ellison syndrome

Functional dyspepsia

Gastritis

Duodenitis

Gastric carcinoma

Investigations

Routine lab tests specially anemia is alarm sign for early endoscopic study

Imaging study:

A double contrast barium study by expert –

Can accurately diagnose the ulcer

Test for H.pylori-invasive and non invasive

Plain xray chest in erect posture to diagnose perforation

Imaging studies contra indicated in pregnancy

Disables biopsy

Cannot diagnose ulcers less than half centimeter.

Procedures            

EGD-Esophago –gastro- duodenoscopy

Advantage-

direct visualistion,biopsy enabled,enables endoscopic therapy for bleeding ulcers

 repeat endoscopy after 6 Wks to ensure healing and to rule out malignancy

Brush cytology to increase biopsy yield especially in the risk of bleeding (in coagulopathy )

 Urgent Indication for endoscopy

Those presenting with alarm symptoms

Treatment options

Aim:

Healing the ulcer

Curing the ulcer diathesis

Medical

Empiric antisecretary therapy

Empiric triple therapy for H.pylori

Endoscopy  and appropriate therapy based on findings

H.pylori serology  followed by triple therapy in infected persons

 Note : perform endoscopy  early in patients >40-50 yrs

Surgical care                                        

Indications
Refractory cases

Perforation

Obstruction( Endoscopic balloon dilatation)

Massive hemorrhage

Appropriate surgical procedure:

 Depends on nature and location

1.Simple oversewing of ulcer with treatment for h.pylori/cessation of NSAID

2. Vagotomy and pyloroplastywith

(Billroth I -_Antrectomy with gastroduodenal reconstruction

Billroth II- gastrojejunal reconstruction

Highly selective vagotomy

Medications

For h.pylori related PUD

Triple therapy PPI  based

Consists of  one  PPI+Amoxy +clarithromycin -14 days course

Replace amoxy with metronidazole only in penicillin allergic cases-

because metronidzole resistance is high.

 For NSAID related- cessation of NSAID

Appropriate course of PPI

In cases with known ulcer and if NSAID are unavoidable-

Lowest possible dose and  duration of NSAID and cotherapy with a PPI and Misoprostol

 List of PPIs (proton Pump inhibitors)

Omeprazole-  20mgPO-bid or

Rabeprazole-  20 mg-PO -bid

Lansoprazole- 30mgPO –bid/qd or

Esome-prazole- 40mg-PO qd

Action of PPIs

Irreversibly inhibit proton pump on parietal cell membrane

Proton pump is an enzyme (H⁺/K^+-ATPase)

This enzyme actively secretes hydrogen ions into gastric lumen

Used as capsules or enteric coated granules

Side effects: diahrrea,skin rash, headache

Interaction Only omeprazole interacts with diazepam,phenytoin &warfarin;not other PPIs

PPI and  antibiotics  combination  is used in triple therapy

2 types   therapy available

1.PPI based (more commonly used)

2.Bismuth based

Antibiotics usable

Clarithromycin-500mg-PO-bid (macrolide antibiotic)

Amoxicillin-  1gm PO-bid

 Drugs used in quadriple therapy in case of failure of triple therapy

Bismuth 525 mg-PO-qid

Metronidazole 500mg –Po-bid

Tetracycline-  500mg Po-qid

Cytoprotectants

Prostaglandin analogue(in NSAID related PUD)

Prostaglandins are weak inhibitors of gastric acid secretion

Prostaglandins are cytoprotective

Misoprostol-200micro gram PO-qid (Side effect uterine cramps)

 Drugs that do not directly inhibit acid production

Bismuth salts                                                                    

Mechanism not known

But heal H.pylori ulcers

Form an insoluble protective layer over ulcer base

Thus prevent damage by acid and pepsin              

This drug not recommended for long term or repeated use.

Sucralphate

(Sucrose aluminium octasulphate)

Mechanism of action not known

? coats ulcer base ?stimulates local prostaglandin release.

 H2 receptor blockers

Ranitidine      150mg-Po-bid 

Famotidine    20mg PO-bid

Nizatidine    150mg Po-bid

(gastrin stimulates parietal cells by releasing histamine

Follow up

Minimum healing time for ulcer is 8 wks

6-8 wks after initial diagnosis-

Endoscopy –to confirm healing and to r/o malignancy

Documentation of cure with non invasive tests for H.pylori

Inpatient and outpatient Medication

For recurrent/refractory/complicated ulcers:

Half the standard dose of H2 receptor antagonist at bed time

When to use prophylactic therapy?

Patients requiring chronic NSAID therapy /NSAID induced ulcers

Patients older than 60 yrs

Patients with history of PUD or GI bleed

Patients taking concomitant steroids/anti coagulants/or with severe comorbid conditions

Drugs for prophylactic use

Misoprostol 100microgram PO 4 times per day

Omeprazole20 mg  PO  daily once

Lansoprazole15mg Po every day.

Antacids

Do not effectively heal ulcer but relieve the symptoms of ulcer

Antacids inter act with many drugs

Many antacids contain a combination of magnesium and aluminium hydroxide

Aluminium hydroxide-

Ill effects-

 constipation,

binds with phosphates in the GI tract causing fall in blood phosphate(so weakness)

Magnesium hydroxide

More effective than ALOH

More than 4 doses a day cause diahrroea

Antacid must be used with caution in kidney disorder,heart disease and hypertension

Other diseases Commonly associated:

Cirrohis, renal failure,PT.

H.Pylori related Peptic ulcer

Helico bactor pylori   

                  

                                  

Introduction

1.Urase producing organisms;spiral ;gram negative;

2. colonises where there is gastric metaplasia                                                                 

3.Found in almost all cases of DU(2nd part part with gastric metaplasia)

4.In 70% of GU cases

5.Also in normal persons;about 50% of worlds population is infected with H.Pylori

Infection persists for many years.;leads to ulcer disease in 10-15% of people.

6.Always associated with active chronic gastritis –histologically

7. Spreads by feco-oral root through contaminated water.

8. According to WHO- h.pylori is Type I carcinogen

9. Causes gastritis/peptic ulcer/gastric carcinoma

10.The spiral shape and flagella facilitates penetration into mucus layer and

attachment to epithelial layer.

Discovery of H.pylori has shown that peptic ulcer is a  simple infectious  disease

Old dictim was :  NO ACID                        No ulcer

Present dictim :  No H.Pylori                       No Ulcer

Role in ulcer pathogenesis:

·         On invading stomach  releases toxins and enzymes injuring gastric epithelium

·         Stomach and duodenal mucosa become vulnerable to damage by aggressive factors

·         Thrives in alkaline medium so produces urase which generates ammonia from urea

·         Ammonia+water=form free hydroxyl radicles:free raicle disrupt epithelial integrity

·         Production of alkaline medium-enables its survival in alkaline medium

·         Attracts nutrophils and monocytes.,liberating  interleukin and TNF  damaging gastric epithelium

·         Liberates proteinases and phospholipases 

·         These damage protective mucosal coat exposing  underlying epithelium for damage

·         A cytotoxin associated gene(cagA)  found often in this,is associated with severity and carcinogenesis-gastric cancers and lymphoma

Diagnosis  of H.pylori

Non Invasive tests

1.Blood test : detects specific antibodies to h.pylori ELISA test- best

2.Urea  Breath test:-

 Patien drinks  urea  solution labeled with radio active Carbon

  that is broken down by  H.Pylori 

Hydrolysis of urea------ produces labeled CO2

CO2 is rapidly absorbed in blood and appears in breath

Breath test requires certain special prepations and indications   

Unusable in pregnancy

Accuracy may be impaired by antibiotic and PPI use.   

3.Stool test: to detect H.pylori proteins in the stools

Non invasive tests do not indicate if active infection is ongoing.

Antibodies persist for long;so elisa test not useful to ascertain erradications

Invasive tests:

Endoscopic  biopsy with histological exam,culture and PCR

In asymptomatic patients and in patients with no past history of PUD:

No test required.

H.pylori Treatment:

1. Includes several medicines ( because world wide bacterial resistance  is a major problem)

2.Two medicines are antibiotics to kill the bacteria (Two to avoid antibiotic resistance)

The other medication is antisecretory which helps the ulcer to heal.

Most are cured after finishing the course

Some need a second course

Try all medicine to ensure cure. Patient’s compliance is very important

 Follow up: Ensure all bacteria are killed   by follow up tests after tmt-breath or stool test(4 wks after tmt)

Drug regimen available:                                /

Principle  involved :

Use drugs

             That kill the bacteria ,Reduce stomach acid,andProtect stomach and duodenal lining

 Medicines that reduce Stomach acid

·         PPIs  halts pumping of acid into stomach

·         H2 blockers –work by blocking histamine.

               But PPIs have shown to work better.

·         Bismuth sub salicylates coats ulcer and protects from acid

(Though it might be bacteriocidal,it is used  with antibiotics ,not in place of antibiotic)

In Britain Clarithromycin  based triple therapy (triple therapy in short) is standard tmt.

Triple therapy consists of (base on proton pump inhibitor)

1.       One PPI    

2.      Clarithromycin

3.      Second  bacteriocidal  Amoxycillin or metronidazole 

Duration of therapy-  for 14 days (not 10 days- lesser cure rates))    

Quadriple therapy

Used in US.consists of (for 14 days)

1.      PPI

2.      Bismuth subsalicylate

3.      Tetracycline

4.      metrnidazole

   Situation in which used

  Penicillin allergy

Resistance to clarithromycin and

Failure of triple therapy

 Limitations – all  regimens have. No single regimen of choice.

6 regimens were approved by FAD

	.I. Triple drug regimen( LAC) II.four drug regimen – a new combination (LOAD)                LAC-(Lansoprazole ,amoxy and clarithromycin) LOAD( Levofloxacin,omeprazole,Alinia(Nitrazoxanide) and Doxycyclin) 14 days therapy Shorter duration of LOAD is recommended but  further studies are needed.

 

I.

Dosing Schedules for All 3 Therapies

Dosing Schedule	LOAD (10 and 7 Day)	LAC (10 Day)
Before breakfast	Omeprazole 40 mg	Lansoprazole 30 mg
With breakfast	Levofloxacin 250 mg + nitazoxanide 500 mg	Amoxicillin 1000 mg + clarithromycin 500 mg
With dinner	Nitazoxinide 500 mg + doxycycline 100 mg	Amoxicillin 1000 mg + clarithromycin 500 mg Treatment failure:

Treatment failure

In 20% treatment failure occurs after first regimen(non compliance or drug resistance)

A second regimen is indicated in these

4weeks  after completion of  therapy, perform tests for persistence of H.pylori

During retreatment at least one of the antibiotic must be different from the one  used before

Side effects  of regimen:

Nausea,dyspepsia, metallic taste , head ache diahrrea,darkened stools.antabuse like effect.

                                                        

Zollinger-Ellison syndrome(Gastrinoma)

Introduction

Adenoma/hyperplasia of Islet cells of pancreas

Arise from-multipotent  endodermal stem cells

Excessive gastrin secretion from tumor(Gastrinoma)

Result-excessive stimulation of parietal cells to secrete acid

In upper small intestine this hyperacidity  inactivates pancreatic lipase

+Bile acids are precipitated-effect-steatorrhea,diahrrhea

 Clinical features

Features of peptic ulceration

Ulcers –severe/multiple/

Ulcer location-unusual-esophagus,jejunum

Intractable recurrent ulceration occur following surgery for peptic ulcer

Bleeding and perforation common

1/3^rd tumors malignant-spread to  liver and L.nodes

Multiple endocrine hyperplasia in1/3^rd (in pitutory,parathyroid,pancreas)

Investigations

Barium meals-showing coarse gastric mucosal folds/ulcers

Endoscopy-shows multiple ulcers at atypical sites

Abdominal CT

Blood levels of gastrin markedly raised>110pg/ml

Secretin stimulation test

Investigations for MENI (multiple endocrine neoplasia

Treatment

Surgical removal of tumor if possible(single without regional nodes)

High doses and long duration of Omeprazole therapy

Total gastrectomy in unresponsive cases (rarely necessary these days)

                                           

Differences  between gastric and duodenal ulcer

	Gastric ulcer	Duodenal Ulcer
Age	More than40 yrs	20-59 yrs
Sex	Equal in both sexes	More in males
Course of illness	Less remittant	More remittent
Episodes of pain	Relatively longer in duration	Shorter in durationRel
Antacids	Relief of pain not consistent	Relief prompt
food	Provokes pain	Relieves pain
heartburn	Less common	More common
Night pain	Less common	More common
Anorexia,nausea	More common	Less common

 Major types of Gastritis:

1.Erosive gastritis

2.Non erosive gastritis

 Sub types

Superficial gastritis

Atrophic gastritis

Gastric atrophy

Benign ulcers versus malignant  Gastric ulcers                            

	Benign Ulcers	Malignant ulcer
1.CLINICAL	Age<40 o:p="" usually="">

Long h/o yrs of duration

Remissions and relapses  a rule

Relief of pain with food,vomiting

Loss of appetite less common

Normal or high acidity

Occult blood rare ,transitory

Over40 yrs

Short history

Not so

Not so

Loss of appetite common

Anacidity or low acidity

Frequent and persists for long time

Site of ulcer in images

Mostly on vertical part of lesser curvature ;rare on  horizontal part

Crater projects outside the margins of the stomach

Crater smooth

Generally on horizontal part or lesser curvature or on greater curvature

Crater usually within the line of stomach

Crater irregular,ragged

Endoscopy

Sharp edge deep ulcer smooth base converging folds

Ill defined edge,irregular floor with nodules in vicinity

 ************************