2 Upper GI disorders - Mouth and Oesophagus

Structure of the GI system

key sites for therapeutic intervention incude :

• mouth

• oesophagus

• stomach

• pancreas

• small intestine

• large intestine

• liver

Gastrointestinal Disorders

• GORD

• oral cavity ulceration and stomatitis

• peptic ulcer disease

• duodenal ulcer

Dysfunctional physiology of the mouth

• oral ulceration - break in oral epithelium - exposes nerve endings in underlying connective tissue

• Stomatitis - inflammation of the lining of the mouth caused by poor oral hygiene, heat burns

• Leukoplakia - painless white patches on side of tongue or cheeks

• Dysphagia - difficulty swallowing

Oesophagus structure

• UOS - prevents air entering oesophagus and oesophagopharyngeal reflux

• LOS prevents gastroesophageal reflux

• high intraluminal pressure keeps it closed until food needs to be dumped into the stomach

Dysfunctional physiologies and diseases of the oesophagus

• GORD

• Hiatal Hernia

• Motility Disorders - problems with sphincters and uncoordinated contraction

• Achalasia caused by inadequate LOS relaxation

GORD causes

• Transient LOS relaxation in the absence of swallowing

• acid escaping - oesophageal epithelium damage

3 Types of GORD

• non erosive reflux disease - heartburn

• Erosive oesophagitis - acute inflammatory disease

• Barrett’s oesophagus - metaplasia (transformation) of the mucosa - cancer risk

Mechanism of Acid Secretion

Gastric Anatomy - stomach

OXYNTIC gland area :

• mucous cells

• chief cells (pepsinogen)

• ECL cells (histamine)

• Parietal cells (HCl, intrinsic factor)

PYLORIC gland area :

• mucous cells

• G cells (gastrin- hormone that stimulates acid secretion)

• D cells (somatostatin)

• NO parietal cells

Cells key to acid secretion in the body (oxyntic gland) of the stomach

Cells key to acid secretion in the pyloric region of the stomach

• include the purpose the cells*

Gastric or Oxyntic Gland - mechanism of parietal cells

• translaocation of the H+/K+ ATPase proton pump to the apical membrane

• at rest they are in cytoplasmic vesicles

• when stimulated they are membrane fused

• increased surface area and membrane pumps

Stimuli for Acid secretion - up regulation

• Acetylcholine - enteric neurons

• Histamine - ECL cells

• Gastrin - G cells

Stimuli for Acid Secretion - down regulation

• Somatostatin- D cells - directly inhibits parietal cell secretion - inhibits gastrin and histamine release

Acid secretion Pathways

• ACH - Ca activated

• Gastrin - Ca activated

• Histamine - PKA activated - more powerful and fastest

Phases of Acid Secretion

• Cephalic Phase - sight, smell, thought

• Gastric Phase - food neutralises ph - G cell stimulation, food prevents D cell activity

• Intestinal Phase - chyme enters duodenum - duodenal stimulation of hormones, less food and lower pH stimulate D cell activity

gastric secretion following a meal

• food buffers stomach acid and raises pH

• suppresses somatostatin from D cells causing gastrin and HCl release

• digestion trigger huge secretion volume and HCl

• As food leaves stomach, acid increases and pH falls - D cell stimulation, less HCl produced as somatostatin

HCl secretion control

• vagovagal reflex - increases parietal cell acid production and stomach distention :

• direct stimulation of ECL cell to release histamine

• direct stimulation of G cells to release gastrin via GRP ( gastrin releasing peptide)

Mechanism of HCl secretion

• CO2 diffuses into parietal cell from plasma

• hydrated to carbonic acid by carbonic anhydrase

• carbonic acid dissociates to H+ and H2CO3-

• proton pump actively transports H+ and K+ in

• Na+ actively reabsorbed

• K+ recycles to gastric lumen via K+ channel

• Cl- exists passively from cell via Cl- channel

How is the Na+ and K+ gradient maintained on the absolute real side of the stomach’s membrane ?

• proton pump

• exchanger promotes HCO3- exit and Cl uptalke, maintains cellular pH

slight rise blood pH = alkaline tide

negative gastric artero-venous carbon dioxide gradient

Regulation of HCl secretion

How’s does mucus protect the stomach’s lining ?

• vagal stimulation and irritation stimulate gastric mucous cells to secrete mucin ( a glycoprotein that is part of the mucosal barrier)

• gastric surface epithelial cells secrete HCO3- when stimulated by ACh, HCl and PGs

• HCO3- accumulates near cell surface

• mucus protects by trapping HCO3- rich fluid near apical border of epithelia

How and Why is mucus layer continually produced ?

prostaglandin Acid regulation - how do they do this ?