Esa 3 - Gi - Session 4 & 5 - Stomach

Front 1

Describe the gross structure, parts and curvatures of the stomach.

Back 1

The adult stomach can hold 2 to 3 litres of food. The size and position of the stomach changes depending on posture, degree of distension and body shape.
The empty stomach has folds known as rugae on its inner surface which flatten when the stomach expands. The gastric wall comprises of :
- Mucosa: columnar epithelium with tight junctions, lamina propria containing gastric pits (glands), muscularis externa
- Submucosa
- Muscularis mucosa: circular, oblique and longitudinal smooth muscle
- Serosa
- peritoneum
It is comprised of 2 curvatures and 5 parts:
- Cardia – the oesophageal opening
- Fundus – above the level of the oesophageal opening
- Body – the central cavity of the stomach
- Antrum - the lower part
- Pylorus - the most distal part opening into the duodenum. A ring of connective tissue separates the pylorus from the duodenum.
There is a lesser curvature, the upper concave border where the left and right gastric arteries anastomose and the greater curvature, the lower convex border where the left and right gastroepiploic arteries anastomose.

Front 2

Describe the histologicial differences between different parts of the stomach.

Back 2

The cardia contains mostly mucus secreting glands. The fundus has largely a storage function. The mucosa of the fundus and body is lined by simple columnar mucus-secreting epithelium invaginated by gastric glands which are lined with mucous neck cells, acid producing parietal (oxyntic) cells and pepsinogen producing chief (zymogenic) cells.
The antral region controls the movement (or emptying) of gastric contents into the duodenum. The mucosa of the antrum and the pylorus contain mainly mucus producing glands and gastrin producing g cells. The antrum and pylorus are also more muscular than other regions of the stomach.

Front 3

Describe the gastric pits.

Back 3

The gastric pits penetrate the columnar epithelial surface of the gastric mucosa. These are short ducts into which more deeply lying gastric glands secrete their secretions into the neck of these ducts.

Front 4

Describe the disposition of circular smooth muscle in the stomach wall

Back 4

Circular smooth muscle is a very thin layer in the fundus and body but a thick layer in the antrum where strong muscular contractions aid the mixing of food. It is also very thick in the pylorus where it forms the pyloric sphincter controlling the emptying of the stomach.

Front 5

Describe the structure and function of the oesophageal/gastric sphincter and the pyloric sphincter.

Back 5

There are no specialised muscle fibres at the cardia of the stomach. Instead the gastroesophageal sphincter is achieved by several mechanisms prevent reflux of acid from the stomach into the oesophagus.
- Angulation of oesophageal entry into cardia
- Valves in cardia
- Lower intra-gastric pressure than oesophageal pressure
- Tug of the right crus of the diaphragm at the oesophageal sphincter
If relux occurs heartburn may occur and inflammation with ulceration may result. Chronic acid reflex can lead to baretts oesophagus – squamous -> columnar metaplasia, which increases risk of oesophageal carcinoma.
The pyloric sphincter is formed by thickened circular muscle at the pylorus and it controls the flow of stomach contents into the duodenum.

Front 6

Describe the functions of the stomach.

Back 6

- Stores food and regulates release into duodenum
- Disinfects it
- Breaks it down to chyme by peristaltic action and enzymes
- Endocrine (gastrin), exocrine (gastric juice) and paracrine (histamine) secretions

Front 7

Describe the stomach secretions.

Back 7

The stomach secretes HCL from parietal cells in gastric pits and proteolytic enzymes eg pepsin from chief cells to break down the food into chyme. These secretions create a luminal ph of less than 2. Therefore the stomach also secretes mucus from luminal end neck cells and HCO3- alkali to protect the stomach mucosa.

Front 8

Describe the mechanism of acid secretion.

Back 8

Nowhere else in the body produces acid so to make an acid alkali needs to be produced. In the mitochondria of parietal cells H+ ions are formed by the splitting of water. This also produces OH- which reacts with CO2 to form HCO3-. 1 mole of H+ions are made for every mole of HCO3 produced. The H+ ions enter the stomach via proton pumps on canaliculi. Canaliculi are invaginations of the cell wall and they expel H+ ions against their gradient into the stomach lumen. The HCO3- ions enter the blood and are then recycled into the 2nd part of the duodenum via the common bile duct from the liver and the major pancreatic duct. This is called the alkaline tide.
Parietal cells, along with chief cells are mainly found in the fundus and body. The lower antral region and pylorus is where gastrin is released from G cells.

Front 9

Describe the chief cells.

Back 9

Chief cells are mainly found with parietal cells in the fundus and body and secrete pepsinogen, an inactive precursor, which becomes cleaved by acid in the stomach to pepsin.

Front 10

Describe gastrin.

Back 10

Gastrin is the hormone secreted by g cells in the stomach, mainly in the antrum and pylorus. It is a 17 amino acid polypeptide which binds to the parietal cell and stimulates acid and intrinsic factor secretion via second messenger pathway. Instrinsic factor is important in the uptake of vitamin B12 at the terminal ileum. Gastrin secretion is stimulated by peptides and acetyl choline. Gastrin release is inhibited by somastatin released from D cells when ph is low. Food buffers the acid increasing the ph and so removes inhibition. In pernicious anaemia, antibodies target parietal cells and thus prevent secretion of intrinsic factor

Front 11

Describe the act of histamine in the stomach

Back 11

Histamine is released from mast cells and binds to H2 surface receptors on parietal cells, which are good drug targets as they are only found in the stomach (H1 receptors found everywhere else). They stimulate acid secretion via cAMP. The mast cells are stimulated by gastrin and acetylcholine.

Front 12

Describe the act of acetylcholine in the stomach.

Back 12

Acetylcholine is released from post ganglionic parasympathetic neurones in response to gastric distension as food arrives. It targets muscarinic receptors on parietal cell surface membranes and triggers acid release via second messenger pathway. Acetylcholine release is also stimulated in the cephalic phase where the sight and smell of food and swallowing food activates the parasympathetic neurones. Ach stimulates the release of gastrin from g cells and histamine from mast cells.

Front 13

Describe the control of acid secretion.

Back 13

Gastrin, histamine and acetyl choline work together to stimulate the parietal cells to secrete acid. Gastrin is stimulated by ACH and peptides and inhibited by low ph levels be negative feedback. Histamine is stimulated by ACH and gastrin. Ach release is stimulated by distension of the stomach and CNS –sight, smell swallowing.

Front 14

Describe the cephalic, gastric and intestinal phase of acid secretion control.

Back 14

The cephalic phase is the anticipatory phase where the smell and sight of food as well as the act of swallowing stimulates parasympathetic nerves to release ach which activates parietal cells to release acid directly or via stimulation of histamine release from mast cells.
The gastric phase is when food reaches the stomach. Food buffers the acidic environment increasing the pH. This increase removes the inhibition of gastrin due to low ph. As the stomach distends, intrinsic nerves release ACH which stimulate the release of gastrin as well as the release of acid. As the food is broken down peptides are released which further stimulate the release of gastrin. Histamine is stimulated by gastrin and ACH.
The intestinal phase is when food as chyme begins to empty from the stomach into the duodenum, it stimulates the intestines to release cholecystokinin and gastric inhibitory polypeptide which reduce acid secretion from the stomach. The accumulation of acid in empty stomach also inhibits gastrin secretion. The low ph between meals can aggravate ulcers due to food not buffering its contents. This is why food can ease pain caused by gastic ulcers.

Front 15

Describe stomach defences against low ph.

Back 15

The luminal ph is below 2 and this would dissolve the mucosa if it was not protected. The mucosa is covered by a continuous layer of mucus. H+ ions dissolve into the mucus and are neutralised by the HCO3- released from epithelial cells. The ph of the surface cells is then 6.5. Mucus and alkali secretions are stimulated by prostaglandins. Prostaglandins are produced from membrane phospholipids - phospholipase -> arachydonic acid –COX -> prostaglandins. They are promoted by most factors stimulating acid secretion.

Front 16

How may mucus and alkali defences of the stomach be stopped?

Back 16

Alcohol dissolves the mucus causing acute gastritis, chronic gastritis is caused by infection of helicobacter pylori, N-SAIDS. These all result in peptic ulcers.

Front 17

How could you reduce acid secretion in the stomach?

Back 17

- Histamine 2 receptor antagonists such as cimetidine can be used as H2 receptors are specific to the stomach.
- Proton pump inhibitors such as omeprazole can be used to prevent the transport of H+ ions from the mitochondria of the parietal cells.
- If the peptic ulcers are caused by helicobacter pylori breaking down the mucus lining, then they can be treated with antibiotics.
 PAC ( Proton pump inhibitors, amoxicillin, clarithromycin) or metronidazole

Front 18

Describe the vagal reflex involved in gastric motility.

Back 18

Swallowing a bolus stimulates a vagal reflex to produce receptive relaxation, causing the rugae of the gastric mucosa to flatten out. The resting tension in the walls of the stomach is reduced and the food fills the stomach without raising the intra-gastric pressure. This reduces the risk of acid reflux into the oesophagus.

Front 19

Describe the parasympathetic innervation of the stomach.

Back 19

The parasympathetic innervation of the stomach is via the anterior and posterior vagal trunks which enter the abdomen through the oesophageal hiatus.

The anterior vagal trunk( derived from left vagal nerve) enters as a single branch that lies on the anterior surface of the oesophagus. It runs towards the lesser curvature where it gives rise to the hepatic and duodenal branches which enter the hepatoduodenal ligament. The anterior vagal trunk continues along the lesser curvature, giving rise to the anterior gastric branches.

The posterior vagal trunk( derived from right vagal nerve) enters the abdomen on the posterior surface of the oesophagus and passes towards the lesser curvature. It supplies branches to the anterior and posterior surfaces of the stomach. It also gives off a celiac branch which passse to the celiac plexus and then continues along the lesser curvature giving rise to posterior gastric branches.

Bothe the anterior and posterior nerves control the opening of the pyloric sphincter.

Front 20

Describe the sympathetic innervations of the stomach.

Back 20

Sympathetic nerve supply from T6-T9 segments of spinal cord passes to the celiac plexus through the greater splanchnic nerve and is distributed through the plexuses around the gastric and gastroomental arteries.

Front 21

Describe the major arteries that supply the stomach.

Back 21

The stomach is a foregut derivative and so receives blood supply from celiac trunk.
Celiac trunk orginates from the aorta at T12 and has 3 branches: left gastric artery, common hepatic artery and splenic artery.
- The left gastric artery gives off the oesophageal branch and passes along the lesser curvature and anastomoses with the right gastric artery
- The common hepatic artery gives off the hepatic artery, the right gastric artery and the gastroduodenal artery.
-> the hepatic artery gives rise to the cystic artery which supplies the gall bladder, the cystic duct and the common bile duct
 The gastroduodenal artery gives rise to the right gastroepiploic artery and the superior pancreaticoduodenal artery
 The right epiploic artery runs along the greater curvature and anastomoses with the left gastroepiploic artery
- The splenic artery has a turbulent appearance along the posterior surface of the stomach.
 Short gastric artery
 Left gastroepiploic artery

Front 22

Describe the venous drainage of the stomach.

Back 22

The right and left gastric veins empty into the hepatic portal vein. The left gastroepipolic vein and short gastric veins drain into the splenic vein. The inferior mesenteric vein drains into the splenic vein also.
The splenic vein joins the superior mesenteric vein to form the hepatic portal vein.
The prepyloric vein ascends over the pylorus to the right gastric vein. This vein is used by surgeons to identify the pylorus.

Front 23

Describe the rhythmic contractions of the stomach.

Back 23

The full stomach begins regular peristaltic contractions, triggered by a pacemaker in the longitudinal muscle of greater curvature of the fundus which fires 3 times a minute. The wave of excitement spreads from cardia to fundus, to body to antrum and to pylorus. The peristalsis speeds up through the stomach. The chyme overtakes large lumps and these lumps are pushed back into the fundus. The chyme reaches the pylorus before the wave of peristalsis does allowing a small squirt of chyme into the duodenum and then the pylorus is closed when the wave reaches it.

Front 24

What is the "basal electrical rhythm" (BER) of the stomach? Where does it normally originate?

Back 24

Waves of depolarization propagate towards the pylous (3/minute). Rate is affected by vagus and gastrin. Myogenic pacemakers (possibly oscillation of Cl¯ conductance) in the longitudinal muscle of the greater curvature region of the fundus.

Front 25

What is the effect of vagotomy upon the BER?

Back 25

Vagotomy disorganizes rhythm and appearance of “spikes”

Front 26

Describe the control of gastric emptying.

Back 26

3 squirts of chyme enter the duodenum every minute. The volume of each quirt is affected by the rate of acceleration of peristaltic wave and by feedback from the duodenum.
Gastric emptying is slowed by
- Fat in duodenum,
- low pH in duodenum,
- hypertonicity eg high concentration chyme in duoedenum.
This is done so that the rate of stomach emptying matches the rate of digestion.

Front 27

Why might a patient with a cancer of the stomach present with obstructive pancreatic drainage?

Back 27

The cancer may have invaded the pancreas, posterior to the stomach, and caused blockage of its duct system.

Front 28

Describe a vagotomy.

Back 28

The secretion of acid by parietal cells is under vagus nerve control. Therefore in people suffering from chronic or recurrent ulcers, surgical section of vagus nerves is performed to reduce acid secretion.
- A truncal vagotomy is rarely performed as the innervations of other abdominal organs would also be sacrificed
- A selective gastric vagatomy involves the stomach being denervated but the vagus innervations to the liver, billary ducts, pylorus, intestines and celiac plexus.
- A selective proximal vagotomy denervates the supply specifically to the parietal cells sparing the motility of the stomach.

Front 29

Describe the importance of helicobacter pylori in causing chronic gastritis and modifying gastric physiology.

Back 29

Gastric ulcers are open lesions of the mucosa of the stomach whereas peptic ulcers (duodenal ulcers) are lesions of the mucosa of the pyloric canal or the duodenum. People experiencing severe chronic anxiety are most prone to the development of peptic ulcers as they have gastric acid secretion rates that are markedly higher than normal between meals (when there is no food to buffer the acid). High acid levels overwhelm the bicarbonate, usually secreted into the duodenum via the common bile duct, and reduce the efficacy of the protective mucus lining, so it is more vulnerable to helicobacter pylori infection.
This causes inflammation of the gastric mucosa – chronic atrophic gastritis, gastric ulcers and predisposes gastric adenocarinomas and MALT lymphomas.
Helicobacter can’t colonise duodenal mucosa however the gastric inflammation increases acid secretion. The increased acid secretion eventually can cause metaplasia of the duodenal cap producing gastric mucosa which can then be colonised by helicobacter pylori.
If the ulcers erode into the gastric arteries, it can cause life threatening bleeding. The gastroduodenal artery lies posterior to the duodenal cap so a peptic ulcer can cause serious bleeding. A gastric ulcer which erodes through the posterior stomach wall into the pancreas, eroding the splenic artery can result in severe haemorrhage into the peritoneal cavity.

Front 30

How does helicobacter pylori survive the acidic conditions of the stomach?

Back 30

Helicobacter pylori is a spiral, gram negative bacteria which secretes urease.
- Urease breaks Urea into Ammonia and CO2 (there is urea in the stomach)
- Ammonia becomes Ammonium by taking a H+ from water (leaving a OH- ion)
- The OH- ion reacts with water to form Bicarbonate (OH- + H2O =H2CO3)
- Bicarbonate buffers the area around H Pylori from the stomach acid, allowing it to survive in the stomach
Helicobacter pylori erodes the proctective mucus lining of specifically gastric mucosa making it more vulnerable to gastric acid and pepsin.

Front 31

Define the term Dyspepsia.

Back 31

Dyspepsia is any symptom referable to the upper GI tract that is present for at least 4 weeks. These symptoms may be heartburn, pain, acid reflux,

Front 32

What are the symptoms, complications and risk factors of peptic ulcer disease?

Back 32

Symptoms: Dyspepsia, malaena, haematemesis, anaemia, vomiting, severe abdominal pain – peritonitis
Complications: perforation, bleeding, pyloric stenosis, malignancy
Risk factors: helicobacter pylori, NSAIDS, smoking

Front 33

How can you diagnose helicobacter pylori infection?

Back 33

- Serology – antibodies, latex agglutination
- Endoscopic biopsy – histology and culture
- Urea breath test - Patients swallow radio-labelled urea and twenty minutes later if you can detect radio-labelled CO2 it demonstrates that Urea was split by urease. Indirectly this can tell you if H Pylori is present.
-

Front 34

Detail helicobacter pylori infection treatement.

Back 34

One week of 2 antibiotics: amoxicillin, clarithromyocin, metronidazole
And proton pump inhibitor eg omeprazole
PAC

Front 35

Describe antacids.

Back 35

Antacids are very weak bases eg gaviscon, rennies etc. They can be bought over the counter and work will with acid suppressants. In extreme overdose they can cause metabolic alkalosis. They should not be taken with renal failure.

Front 36

Describe H2 antigonists. what are the side effects?

Back 36

H2 antagonists eg cimetidine reversibly compete with histamine for binding to H2 receptors on the basolateral membrane of parietal cells. They suppress basal & to lesser extent stimulated acid secretion and are particularly effective in suppressing nocturnal acid secretion when parasympathetic activity is increased.
Side effects: GI upset, Headache, Confusion, Skin rash, Gynaecomastia – large mamillary glands in men (androgen receptor antagonist), Specific inhibitor of cytochrome P450 enzyme prolonging the half life of many drugs.

Front 37

Describe proton pump inhibitors and their side effects.

Back 37

Proton pump inhibitors eg omeprazole enter parietal cells from blood, accumulate in the secretory canaliculi, are activated & covalently bind sulfhydryl groups in extracellular domain of the proton pump inhibiting its activity.
Side effects: may reduce clearance of warfarin and other drugs metabolized by cytochrome P450 system, nausea, abdominal pain, constipation, flatulence and diarrhea

Front 38

List some causes of GORD – Gastro oesophageal reflux disease.

Back 38

It is a disease if symptoms occur more than once a week – heartburn, dysphagia, regurgitation.
Reduced oesophageal pressure
- Fatty acids
- Progesterone
- Anticholinergics
- Cafferine
- Scleroderma
Increased abdominal pressure
- Pregnancy
- Obesity
These will result in reflux as LOS is hindered. Physiological reflux happens all the time but the oesophageal mucosa quickly removes the acid.

Front 39

What are the common risk factors for GORD?

Back 39

Male, old age, obese, caucasion, family history, high dietary fat intake, high salt intake, smoking

Front 40

Name some non-pharmacological measures to reduce GORD and list complications of reflux disease

Back 40

Elevate head in bed, avoid fatty or spicy food, avoid alcohol, avoid caffeine, avoid eating 2-3 hrs before bedtime.
Medical – h2 antagonists and proton pump inhibitors.
Complications of reflux disease – anaemia, stricture, baretts oesophagus -> carcinoma, aspiration pneumonia.

Front 41

Why are Proton pump inhibitors (PPI) more effective than H2 antagonists at reducing stomach acid production?

Back 41

If you can visualise a picture of the Parietal cell it will be a lot easier. There are several ways to stimulate a Parietal to produce H+ ions. Receptors for Ach (muscarinic receptors), Gastrin receptors and Histamine receptors will all, when stimulated, result in the production of acid. By blocking the H2 receptors, there are still other inputs on the parietal cells that will result in acid production. If you block the proton pump then you are effectively blocking all these receptor inputs, as the common path ends at this point. This is why PPIs are more effective.