acid peptic disorders

Gastro Intestinal Gastro Intestinal TractTract

Gastro Intestinal Tract

Organs of GIT

Oral cavityPharynxEsophagusStomachSmall intestineLarge intestine


Accessory Organs

Liver

Gallbladder

Pancreas

Spleen


EsophagusEsophagus is a muscular, collapsible tube about 10

inches long, extending from the pharynx to the stomach.

Lower Esophageal Sphincter It is the physiological not the anatomical sphincter at

the lower end of esophagus that joins the stomach.

There is only thick layer of circular muscle that relaxes only on swallowing to propel the food to the stomach otherwise it is tonically contracted.


Stomach

Dilated part of the GIT between the esophagus and small intestine.

A J-shaped distended organ.

Has two openings; cardiac and pyloric openings.

Has two curvatures; greater and lesser curvatures.


Parts of Stomach

Fundus

Body

Pylorus


Small Intestine Duodenum Jejunum Ileum

Large Intestine Caecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Anal canal


Wall of the GIT

A hollow system throughout.

Right from esophagus till rectum, the wall of GIT has three layers :

Mucosa (inner most)Muscular Layer (middle)Serosa (outer most)

Layers of GI Tract


LIVER

The largest gland in the body.

Functions

Production and secretion of bile.

Involvement in many metabolic activities.

Filtration of blood. Synthesis of blood clotting

factors.

Digestion and AbsorptionDigestion and Absorption

Digestion and Absorption

Digestion is the process by which the large and complex food substances are broken down into the simpler and smaller form, so that they can be easily absorbed.

Food on which the body mainly lives consists of the following:

CarbohydratesProteinsFats


These substances can not be absorbed in their natural forms so they are broken down into smaller particles with the help of various enzymes and secretions.

Carbohydrates Glucose, Galactose, FructoseProteins Amino acidFats Fatty acids

These substances are then absorbed in the small intestine.


Throughout the GIT, secretory glands are present that secrete various secretions and serve many functions for digestion and absorption of food. They are

SalivaPancreatic secretionBileGastric secretion


It is the secretion of the stomach.

The stomach mucosa has two important types of tubular glands:

Pyloric Gland Oxyntic gland

Pyloric Glands

Pyloric glands are located in the pylorus of the stomach.

They secrete :

Mucus (secreted by Mucus Cells)Pepsinogen (secreted by Chief

Cells)Gastrin (secreted by G - Cells)

Oxyntic Glands

Oxyntic glands are located in the mucous membrane of the body and fundus of the stomach.

An Oxyntic gland is composed of three different types of cells:Mucous neck cellsPeptic (chief) cellsParietal (oxyntic) cells

Oxyntic Glands

Mucous Cells secrete mainly mucus.

Chief Cells secrete pepsinogen.

Parietal Cells mainly secrete HCl.

Oxyntic Glands

The Parietal Cell

Parietal Cell

Cl-H+/K+ ATPase

Gastrin Acetylcholine

H+ K+

Na+ Na+

Na+

Na+

Na+Na+

Na+

Na+ Na+

Cl- Cl-

Histamine

Parietal Cell

Parietal Cell

Receptors on a parietal cell

Three receptors are present on the membrane of a parietal cell:

Histamine receptors Acetylcholine receptors Gastrin receptors

Parietal Cell

Stimulation of gastric acid (HCl) secretion

• The Parietal cells are stimulated by three different things:

Nervous stimulation Histamine Gastrin

Parietal Cell

Inhibition Of Gastric Acid Secretion

LOW pH

• Low pH , less than 3.0 in the stomach inhibits Gastrin secretion and thereby inhibits acid secretion.

Drugs Atropine H2 receptor blockers Proton Pump Inhibitors

Mechanism of HCl secretion by parietal cell

When parietal cell is stimulated, a series of changes take place in the cell.

Step 1Chloride ions ( Cl -) are

transported from cytoplasm into the lumen of the canaliculi to create a negative potential.

The initial stimulation for the transport of these chloride ions is not known however histamine appears to be an important factor.

Step 2

This negative potential causes diffusion of positively charged potassium ions (K +) from the cell cytoplasm into the canaliculi.

Step 3

Water (H2O) in the cytoplasm dissociates in to hydroxyl ions (OH-) and hydrogen ions (H+)

Mechanism of HCl secretion by parietal cell

Step 4 Hydrogen ions ( H +) are then exchanged in

the canaliculi for potassium ions ( K + ).

This exchange process is brought about through the presence of an enzyme

( H +, K + , adenosine triphosphatase ), which is also called PROTON PUMP.

Mechanism of HCl secretion by

parietal cell

Thus potassium ions are reabsorbed in to the cell cytoplasm and hydrogen ions take their place in the canaliculi.

Hydrogen ions then combine with Chloride ions to make HCl.

The final secretion in the canaliculi is extremely high in HCl.

Mechanism of HCl secretion by

parietal cell

Acid Related Diseases

Acid Related Diseases

• Peptic ulcer

• Gastroesophageal reflux disease (GERD)

• Gastritis

• NSAIDs and Peptic Ulcer

Ulcer

Ulcer can be defined as breach in

the continuity of the superficial

epithelium and exposure of deeper

tissues to the external environment.

Ulcer

• Ulcer is an imbalance between Aggressive and Defensive factors

The Aggressive Factors (gastric acid secretion)

&The Defense Mechanisms (mucosal resistance to acid)

of the GI-mucosa

Aggressive Defensive

Gastric Acid

Pepsin

Mucus

HCO3

Prostaglandins

Gastric MucosalBlood Flow

Peptic Ulcer

Duodenum90 -95 % of duodenal ulcers occur in first portion of duodenum

StomachMore than 90% of gastric ulcers occur in the lesser curvature

EsophagusLower end of Esophagus in reflux esophagitis

Jejunum In zollinger Ellison syndrome

Sites

Peptic Ulcer

Peptic Ulcer

ETIOLOGYHeredityAcid pepsin vs mucosal resistance.Factors reducing mucous

resistanceAssociation with other diseases

Peptic Ulcer

Heredity

Peptic ulcer tends to run in families.

Gastric and duodenal ulcers are inherited as separate disorder.

In case of family history, duodenal ulcer develops below the age of 20.

Peptic Ulcer

Acid Pepsin Vs Mucosal Resistance

• An ulcer forms when there is imbalance between the aggressive factors (e.g. acid and pepsin) and defensive forces (e.g. mucus, HCO3 and Prostaglandins)

a) Abnormal Acid Pepsin Secretion

• Increase secretion of acid is due to the increase secretion of Gastrin Histamine Acetylcholine.

Peptic Ulcer

b. Reduced mucous resistance• Gastric cells secrete mucus , bicarbonates

and prostaglandins as protective agents against the acid.

• Following factors reduce the mucus resistance

Helicobacter Pylori NSAIDs Smoking Reflux of bile and intestinal secretions.

Peptic Ulcer

Association With Other Diseases Or Known

Factors

• Higher incidence in patients with COPD, CRF, Cirrhosis.

• Steroids in higher dose.

• Severe burns

Peptic Ulcer

Signs & Symptoms

• Pain in epigastrium• Heart burning• Nausea• Anorexia• Haematemesis due to ulcer perforation• Weight loss• Vomiting

Peptic Ulcer

• Both duodenal and gastric ulcer has the same signs & symptoms but they differ in the character of pain.

– In Gastric ulcer pain starts within 15 -20 min after eating.

– In Duodenal ulcer pain starts 2-3 hours after eating.

D:\ateeq.CCL\My Documents\Documents 2008\Espra Relaunch\video157 (Gastric Ulcer).swf

Gastro- Esophageal Reflux Disease (GERD)

• GERD develops when esophageal mucosa is exposed to the gastric contents for prolonged period of time resulting in inflammation and heart burn.

Gastro- Esophageal Reflux Disease (GERD)Signs & Symptoms

• Heart burn

• Regurgitation of food

in mouth

• Iron deficiency anemia

Gastro- Esophageal Reflux Disease (GERD)

Complications

• Esophagitis• Benign esophageal sphincter• Barrett’s esophagus• Anemia• Aspiration

GASTRITISIt is the inflammation of gastric mucosa and if persists leading to the gastric ulcerations and erosions.

Etiology Aspirin and other NSAIDS Severe stress Burns Excessive alcohol consumption

GASTRITIS

Signs & symptoms• It may be asymptomatic• Anorexia• Nausea• Epigastric pain• Heart burn• Slow loss of blood may lead to anemia• hemorrhage

NSAIDs and Peptic Ulcer

• Some peptic ulcers are caused by prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as

– Aspirin – Ibuprofen – Diclofenac sodium– Indomethacin– Naproxen sodium


• Normally the stomach has three defenses against digestive juices: – Mucus– The chemical bicarbonate and Prostaglandins – Blood circulation to the stomach lining that

aids in cell renewal and repair.

• NSAIDs hinder all of these protective mechanisms, therefore digestive juices can damage the stomach lining and cause ulcers.


• Prostaglandins are the chemical mediators of Inflammation and Pain

• NSAIDs inhibit the enzyme Cyclo-Oxygnase that plays an important for the production of Prostaglandins

• Some Prostaglandins are gastro-protective and work as house keeping enzyme


• Inhibition of those PGs is associated with a decrease in GMBF, HCO3 and Mucus

• Ultimately when the defenses of the stomach are weak, Ulcer can occur

• NSAID-induced ulcers usually heal once the person stops taking the medication.

ZOLLINGER ELLISON’S SYNDROME

In this uncommon disorder, ulceration occurs due to gastric acid hypersecretion as a result of gastrin secreting tumor mainly arising in pancreas.

Signs & symptoms Diarrhea may be the presenting feature Epigastric pain Heart burn Bleeding and perforations are common

Helicobacter Pylori & Peptic Ulcer

• H.Pylori infection is the most important factor in peptic ulcer disease.

• It is spiral shaped, flagellated, bacteria found in stomach and duodenum.

• It accounts for 90% of duodenal ulcer and 70% of gastric ulcer.

Helicobacter Pylori & Peptic Ulcer

H. Pylori causes its effects by:

• Increase in fasting and meal stimulated gastrin release.

• Increase in parietal cell mass.

• Increase in pepsinogen.

Management of Acid Related Diseases

General Measures

Peptic Ulcer

No smoking Avoid alcohol Avoid aspirin

General Measures

• GERD Weight reduction Stop smoking Meals should be of in small volume Avoid heavy lifting and bending after

meals Avoid late night meals to reduce reflux

during sleep.

Pharmacological Treatment

It can be divided into the :

• Drugs enhancing the mucosal defense

• Acid suppression drugs.

a. Drugs enhancing the mucosal defense

• These drugs act by strengthening the defensive forces of gastric mucosa by increasing the prostaglandin synthesis , increase in mucus and bicarbonate production.

• They include the following groups : Sucralfate Antacids Prostaglandin analogues


SucralfateMechanism Of Action• It forms an adherent complex with proteins

in the ulcer base and protects it from further digestion .

• It also stimulates mucus , prostaglandin and mucus production.

• Available Brands

• Ulsanic, Ulcocid, Sucrafate, Sucemed.


AntacidsMechanism Of Action

• They contain the Aluminium Hydroxide, calcium carbonate , magnesium salts , sodium bicarbonate. They cause the neutralization of gastric acid and local cooling effect.

Available Brands

• Gaviscon, Tricil, Aluphagel, Magalcid


Prostaglandin analogues

• Misoprostol is a prostaglandin analogue that promotes ulcer healing by stimulating mucus and bicarbonate secretion and inhibition of acid secretion.

b. Acid Suppression Drugs

• H2 receptor antagonists

• Proton Pump Inhibitors

H2 Receptor Antagonists

Mechanism Of Action

They are the competitive inhibitors of histamine at H2 receptors on the parietal cells there by decreasing the acid production. They inhibit about 60 – 65% acid production.

H2 Receptor AntagonistsMajor drugs Available

• CimetidineDose 400 mg BD or 800 mg at nightAvailable Brands Cimet , Tagamet, Ulcerex

• RanitidineDose 150 mg BD or 300 mg at nightAvailable Brands Zantac, Anzol, Renulcid, Ranax

• FamotidineDose 20 mg BD or 40 mg at nightAvailable Brands Famopsin, Polypep, Nocid, Peptiban

Proton Pump Inhibitors

Mechanism Of ActionThey bind with the acid secreting enzyme called H+ K+ ATPase (Proton Pump) and inactivate it, thereby inhibiting acid secretion. The PPIs inhibit approximately 90 – 95% of acid production.

Proton Pump InhibitorsMajor Drugs Available• Omeprazole

Dose 20 mg ODAvailable Brands Risek, Omega , Ruling, Omezol

• LansoprazoleDose 30 mg ODAvailable Brands Selanz, Inhibitol, lanzac

• PantoprazoleDose 40 mg ODAvailable Brands Zotonix, Zopent, Protium, Pantazol

• EsomeprazoleDose 20 – 40 mg ODAvailable Brands Espra, Esopra, Nexium, Esso

• RebprazoleDose 10-20 mg ODAvailable Brands Bepra, Rabicid, Zechin, Prompto