Acid Peptic Disorders
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Transcript of Acid Peptic Disorders
Gastro Intestinal Gastro Intestinal TractTract
Gastro Intestinal Tract
Organs of GIT
Oral cavityPharynxEsophagusStomachSmall intestineLarge intestine
Gastro Intestinal Tract
Accessory Organs
Liver
Gallbladder
Pancreas
Spleen
Gastro Intestinal Tract
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.
Gastro Intestinal Tract
Gastro Intestinal Tract
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.
Gastro Intestinal Tract
Parts of Stomach
Fundus
Body
Pylorus
Gastro Intestinal Tract
Small Intestine Duodenum Jejunum Ileum
Large Intestine Caecum Ascending colon Transverse colon Descending colon Sigmoid colon Rectum Anal canal
Gastro Intestinal Tract
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
Gastro Intestinal 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
Digestion and Absorption
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.
Digestion and Absorption
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
Digestion and Absorption
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
• 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.
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
NSAIDs and Peptic Ulcer
• 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.
NSAIDs and Peptic Ulcer
• 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
NSAIDs and Peptic Ulcer
• 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
a. Drugs enhancing the mucosal defense
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.
a. Drugs enhancing the mucosal defense
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
a. Drugs enhancing the mucosal defense
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