Oesophagus and Stomach Phil Thirkell + asfand baig

Anatomy Blood supply to the oesophagus and stomach? Coeliac artery – a branch off the abdominal aorta Which embryonic structure does the oesophagus derive from? Foregut Endoderm

Histology Cell Type Non- Keratinised Stratified Squamous Epithelium Upper 1/3 oesophagus Striated muscle Middle 1/3 oesophagus Striated muscle and Smooth muscle Lower 1/3 oesophagus Smooth muscle

Smooth Muscle Narrow, rod shaped cells No striations One nucleus per cell Striated Muscle Tubular cells Striations Multiple nuclei

Gastro-oesophageal Junction How can you tell where the junction is? Change from non-keratinised stratified squamous to simple columnar What forms the lower oesophageal sphincter? Compression from the diaphragm (right crus) Angle of entry into the stomach Intra-abdominal pressure Mucosal folds (but I don’t know how these help form the junction)

Pathology Gastro-Oesophageal Reflux Disease Barrett’s Oesophagus Failure of lower sphincter causes reflux of acid Oedema/white cell infiltration Increases risk of cancer Barrett’s Oesophagus Metaplasia from stratified squamous to simple columnar Goblet cells Produce mucus to protect against acid environment Considered a pre-malignant condition Association with adenocarcinoma Oesophageal Cancer Late presentation Can cause obstruction Poor prognosis Risk Factors: Age, male, FH, smoking, alcohol, reflux, Barrett’s, hot drinks Oesophageal Varices Dilated veins of portal system Form due to portal hypertension Risk of bleeding Difficult to treat

Stomach Functions of the stomach? What are the folds in the stomach? Storing food Killing bacteria Regulate food entry into duodenum Dissolve and partially digest macromolecules into food To secrete intrinsic factor the only indispensable role of the stomach What are the folds in the stomach? Rugae – same name for the folds in the bladder, which do the same – allow increase in size without increasing the pressure within

Stomach Anatomy

Stomach Secretions Contents of stomach secretions? Chief cell Hydrochloric acid Enzymes – pepsinogen, gastric lipase Mucus Bicarbonate Water Intrinsic Factor Chief cell Pepsinogen Parietal cell HCl G-cell Gastrin Mucus cell Mucus D-cell Somatostatin ECL-cell Histamine Histamine and Gastrin – stimulate acid secretion Somatostatin – inhibits gastrin/acid secretion

Parietal Cell

Stimulation of Acid Secretion Stimulates acid secretion Inhibits acid secretion Histamine Somatostatin Gastrin Prostaglandins Acetylcholine Enteric hormones - VIP

Dysphagia difficulty swallowing Disease of mouth/tonsils Inflammation or cancer Stricture Pharyngeal pouch Hiatus hernia Achalasia – problem with peristalsis co-ordination. (sorry to those I told wrong, I was getting confused with oesophageal atresia) Goitre Infections (oesophagitis) Aortic aneurysm

Peptic Ulcer Causes: Helicobacter pylori NSAIDs Crohn’s disease Cancer Zollinger-Ellison syndrome A non-beta islet cell, gastrin-producing tumour of the pancreas. Loads of gastrin causes huge acid secretion all the time, making patients really prone to ulcers Urease enzymes Break down urea into CO2 and ammonia. The ammonia then neutralises the stomach acid, allowing bacteria to survive more readily. How to test for H.pylori? Urease breath test Blood antibody serology Biopsy and urease test Stool antigen

Peptic Ulcer Epigastric pain – what happens on eating? Nausea A gastric ulcer gets worse on eating. Food enters stomach, acid is released and it comes into contact with the ulcer, aggravating it and causing pain. A duodenal ulcer is made better on eating as the pyloric sphincter closes and bicarbonate is released from the pancreas. The pain then starts again after 2-3 hours when the contents of the stomach is released and the acid comes into contact with the ulcer. Nausea Bloating/flatulence Epigastric tenderness Anaemia – chronic bleeding from the ulcer

Why do NSAIDs cause ulcers? Normally, prostaglandins are released when gastric mucosa is damaged, causing increased production of mucus and bicarbonate. Cyclo-oxygenase enzyme 1 (COX-1) creates prostaglandins. NSAIDs inhibit COX-1, reducing prostaglandin production. This decreases the mucus and bicarbonate secretion This increases the damage by acid on gastric mucosa  ulcers

Stomach Pharmacology Antacids Alginates Bismuth chelates Prostaglandin analogues H2 antagonist Proton pump inhibitors H. pylori eradication therapy

Antacids React chemically to neutralise stomach acid (acid + base  salt + water + carbon dioxide) Magnesium hydroxide Calcium Carbonate e.g. Rennie S/E - gas

Alginates Polysaccharide which reacts with stomach contents to make a raft which floats on the surface to prevent reflux and protects mucosa E.g. Sodium alginate Gaviscon is combined antacid and alginate

Bismuth Chelates Binds pepsin to prevent acid secretion Coats the mucosa Increases prostaglandin production S/E – can cause black tongue and black faeces

Prostaglandin Analogues Misoprostol Inhibits acid secretion Increases mucosal blood flow to generate HCO3 S/E: diarrhoea and stomach cramps Can’t be used in pregnancy – causes uterine contractions and can cause a termination women of child-bearing age should be using contraceptives if prescribed misoprostol as gastric acid treatment

H2-receptor antagonists (anti-histamines) Blocks the histamine receptor on the parietal cell to reduce acid secretion e.g. Cimetidine, ranitidine, nizatidine (not loratidine – only blocks H1, so used in allergies)

Proton Pump Inhibitors e.g. omeprazole, lansoprazole, pantoprazole Block the H+/K+-ATPase pump of the gastric parietal cell Used in patients with reflux, GORD, NSAID ulcers and as 2° prevention in pts who’ve had ulcers Used to control Zollinger-Ellison until something else can be done about it Acts systemically, in that it is absorbed into the blood stream, circulates and then acts on the parietal cells – instead of just acting directly on them in the stomach lumen In acidic conditions the drug can bind to the ATPase, but in neutral conditions it cant. S/E - ↑risk of infection due to ↓ acid secretion to kill bacteria, decreased vitamin B12 absorption due to less acid, decreased calcium absorption. Nausea + vomiting

H. Pylori eradication 1 week of: 1 proton pump inhibitor – omeprazole, lansoprazole 2 antibiotics – amoxicillin and either: clarithromycin or metronidazole Can’t use serology to check if the eradication therapy has worked because the antibodies will still be there even if all the bacteria are now dead To help remember: --Need 2 antibiotics because it could be resistant to one of them --Only 1 PPI because no resistance to them and they work really well