Session 4 Flashcards
Describe the route of hormones acting on the stomach
Peptides released from endocrine cells
Into portal circulation
Pass through liver
Enter systemic circulation
End up pretty close to where they were
Define paracrine. Give example for stomach:
Paracrine - Relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it.
Peptides released by endocrine cells
Act in local environment
Diffuse short distances E.g. somatostatin
Define Neurocrine. Give an example for the stomach
Peptides released by neurones in the GI tract
Released after action potential
Example: Gastrin releasing peptide (GRP)
GRP is released from the postganglionic fibres of the vagus nerve.
Increases release of Gastrin from G cells
What are the two broad categories of gastrointestinal hormones?
Gastrin family:
- Gastrin
G cells in antrum of stomach
Increases gastric acid secretion
- Cholecystokinin (CCK)
I cells in duodenum and jejunum
Increases pancreatic/gallbladder secretions by causing gall bladder contraction and stimulates the pancreas.
CCK is stimulated by fat and protein entering into the duodenum.
Bile used for emulsification/breakdown of fat and then enzymes from pancreas to break down proteins.
Secretin family:
- Secretin
S cells in the duodenum
Stimulated by H+ and fatty acids
Increases HCO3 from pancreas/gallbladder
Decreases gastric acid secretion
Chyme is very acidic so needs to be neutralised.
- Gastric inhibitory polypeptide (GIP)
Cells in the duodenum and jejunum
Stimulated by sugars, amino acids and fatty acids
Increases insulin
Decreased gastric acid secretion
What are the basic functions of the stomach?
Receive food - Short term storage facility - We eat faster than we can digest so short term storage is needed - Folds called rugae allow expansion of the stomach during eating and then contraction to avoid feeling of distension when not eating.
Disrupt food - 3 layers of smooth muscle which contract vigorously. Gives food larger surface area.
Continue/commence digestion - Mainly proteins through enzymes
Disinfect - acidic conditions guard against pathogens.
Describe the basic structure of the stomach. Describe the lining of the stomach.
From lower oesophagus to stomach:
Abrupt transition of stratified squamous to columnar - This is about secretion
Mucosa/submucosa thrown into non-permanent folds called Rugae.
Lots of little holes on its surface called gastric pits
Epithelial cells cover surface and extend into pits/glands
Mucous cells - secrete mucus - line stomach.
In the gastric pits:
Parietal cells - produce H
Chief cells - protease release
G cells -gastrin release
Stomach smooth muscle:
Extra oblique layer of muscle allows more vigorous contractions in order to mix/grind contents then move them along
Upper stomach - wall thinner - musclular wall thickens as we move inferiorly in the stomach.
Has sustained contractions
Creates basal tone
Lower stomach
Strong peristalsis mixes stomach contents
Coordinated movements
Contractions every 20 seconds (or so)
Proximal to distal
Shape of stomach:
Larger (proximal) to smaller (distal)
Contents accelerates
Lumps left behind (separates contents)
Liquid chyme ejected into duodenum
3 times a minute
What do Brunners glands do?
From the stomach, although still columnar going into the duodenum, when we dump chime from the stomach into the duodenum, it is still very acidic and hyper osmotic, so the body needs to make it isotonic and more neutral. Brunners glands are important to allow water to enter the duodenum.
What is the blood supply and drainage of the stomach and other organs around it? describe the route (draw)
Coeliac trunk arises from abdominal aorta at around and from it has three main branches: the splenic artery (Looks very wiggly), left gastric artery and common hepatic artery.
Left gastric artery anastomoses with the right gastric artery. These work to supply the lesser curve of the stomach.
Splenic runs posterior to the stomach and from this branches the left gastroepiploic artery which; together with the right gastroepiploic artery which branches from the gastroduodenal artery, supplies the greater curve of the stomach
Common hepatic gives off the right gastric artery and then the gastroduodenal artery which runs posterior to the duodenum.
Gastroduodenal artery is a massive haemorrhage risk if a peptic ulcer perforates near it.
After Gastroduodenal artery branches from common hepatic artery, the common hepatic artery is renamed the proper hepatic artery.
All veins from gut drain into the portal vein via correspondingly named veins e.g. Lesser curve of stomach supplied by left and right gastric arteries and drains via left and right gastric veins into the portal vein.
How does stomach act as storage?
We consume food faster than we can digest so we need to store it. Achieved through receptive relaxation
Vagally mediated relaxation of stomach
Allows food to enter stomach without raising intra-gastric pressure too much
Prevents reflux of stomach contents during swallow
Gastric mucosal folds (rugae) allow distension
How is digestion continued in the stomach?
Acidic conditions:
◦ Denatures proteins to make surface area bigger so its more easily broken down.
◦ Activates proteases (kept inactive to avoid self digestion) acidic conditions activate them. Pepsinogen to Pepsin
◦ Disinfect stomach contents
What does the stomach secrete?
HCL - Gives acidic conditions
Intrinsic factor - involved in VitB12 absorption.
Mucus/HCO3^- - Mucus coats stomach surface, bicarbonate secreted into mucus makes mucus an alkaline protective layer.
Pepsinogen (pepsin) for protein breakdown
Histamine - stimulates gastric acid secretion Somatostatin - inhibits G cells
How are cell types distributed across the stomach
Cardia: Predominantly mucus secretion
Fundus/body: Mucus, HCL, pepsinogen
Pylorus: Gastrin, somatostatin
However, lots of crossover
How is HCL production controlled in the stomach?
Parietal cell - produces H+ - Also called oxyntic cell
Stimulated by:
◦ Gastrin - acts on CCK receptor
◦Histamine - acts on H2 receptor to amplify gastrin function
◦ Ach - Ach from Vagus nerve acts on muscarinic receptors
Control of Gastrin secretion
G cells located mainly in Antrum
G cell stimulated by:
◦ Peptides/amino acids in stomach lumen
◦ Vagal stimulation - Acetylcholine (thought/sight/smell of food)
◦ Gastrin-releasing peptide (GRP)
Inhibition of HCL production
Essentially inhibition of G cells
◦ When food leaves stomach pH drops as presence of food acts as a buffer for the acid
◦ Low pH activates D cells
◦ D cells release somatostatin
◦ Somatostatin inhibits G cells (and ECL cells)
◦ Stomach distension reduces from reduced vagal activity
Summarise control of stomach secretions
How is HCL produced in the parietal cells?
Pumps acid against large gradient through H+/K+ ATPase and the result is H+ is pumped into the lumen.
Starts off by splitting water inside the cell into OH- and H+. The OH- can combine with CO2 to make bicarbonate ions (HCO3-) through carbonic anhydrase.
So bicarbonate being pumped out of the cell through the basolateral membrane (in exchange for chloride ions) and H+ out of the apical membrane (chloride ions also leave the cell through chloride channels).
Alkaline tide - When we have a meal and we have to produce lots of acid we make the venous blood leaving the stomach more alkaline which goes down and is used later on to neutralise the acid later in the GI tract.
Describe the phases of digestion
Cephalic (30% of total HCL)
◦ Parasympathetic stimuli
◦ Smelling, tasting, chewing, swallowing
◦ Direct stimulation of parietal cell by vagus nerve
◦ Stimulation of G cells by vagus (GRP released) ‘Anticipating food’
◦ Also increases gastric motility (slightly)
Gastric (60% of total HCL)
◦ Distension of stomach stimulates vagus which then stimulates parietal cells and G cells
◦ Presence of amino acids and small peptides - Stimulate G cells
◦ Food acts as a buffer in stomach - removes inhibition on Gastrin production
Enteric NS and Gastrin cause strong smooth muscle contractions
Intestinal (10% of HCL production)
◦ Chyme initially stimulates Gastrin secretion
◦ Partially digested proteins detected in duodenum
◦ Short phase
◦ Soon overtaken by inhibition of G cells
◦ Presence of lipids activate enterogastric reflex - Reduces vagal stimulation
◦ Chyme stimulates CCK and secretin (help suppress secretion)
How does the stomach protect itself from digestion?
Mucin is secreted by the foveolar cells
- Forms viscous mucus layer that adheres to epithelium and helps prevent physical damage from food
- HCO3 ions are secreted into mucus layer to provide a (pH neutral) barrier against the stomach acid
- Rich blood supply to gastric mucosa can remove and buffer acid that has breached mucus layer
- Prostaglandins are released that promote the above processes
- NSAIDS decrease prostaglandin release
High turnover of epithelial cells
◦ Helps keep epithelia intact
What can breach stomach defences?
Alcohol - Dissolves mucus layer
Helicobacter pylori - Chronic active gastritis
NSAIDS - Inhibits prostaglandin
Stress is major - physiological stress e.g. from burns not psychological stress.
What is dyspepsia?
The term ‘dyspepsia’ is used to describe a complex of upper gastrointestinal tract symptoms which are typically present for four or more weeks, including upper abdominal pain or discomfort, heartburn, acid reflux, nausea and/or vomiting
What is GORD? Triggers? Symptoms? Consequences? Treatment?
Gastro-oesophageal reflux disease
Symptoms: Chest pain, acid taste in mouth, cough
Consequences of GORD: •Nothing •Oesophagitis •Strictures •Barrett’s oesophagus
Triggers include: • Obesity (increased intra-abdominal pressure) • Pregnancy (increased intra-abdominal pressure) • Hiatus hernia • LOS function • Delayed Gastric emptying
Treatment
◦Lifestyle modifications (smaller meals, don’t eat before bed, lose weight, prop self up a bit with pillows when sleeping)
◦Pharmacological: Antacids H2 antagonists Proton pump inhibitors
◦Surgery (fundoplication - It involves wrapping the fundus of the stomach around your lower oesophagus - can cause dysphagia so rare)
What is the lower oesophageal sphincter?
Consists of:
- Muscular element
- Right crus of diaphragm
- Oblique angle of entry of oesophagus into stomach
- Intra-abdominal pressure collapses lumen in abdomen.
- LOS consists of distal 4cm of oesophagus
- Resting pressures are 10-30mm Hg (only 5-10mm Hg required) so at rest is tonically contracted
- Pressures vary: Lowest after meals, Highest at night
How does GORD relate to hiatus hernias
- Much higher rate of reflux oesophagitis with hiatal hernias
- Mechanism slightly unclear
- Moving LOS into thorax reduces:
Basal tone
The normal increase in LOS tone when straining
What is Gastritis?
- Symptom complex (pain, nausea, vomiting, bleeding)
- Endoscopic appearance - Inflammation of the stomach mucosa
- Has acute and chronic varieties
Describe acute gastritis
Acute mucosal inflammatory process
Caused by: ◦Heavy use of NSAIDS ◦Lots of alcohol ◦Chemotherapy - kills rapidly dividing cells ◦Bile reflux - irritant
Exposure of mucosa to chemical injury results in damaged epithelial cells and a reduction in mucus production
Mucosa responds by vasodilatation/oedema and appearance of inflammatory cells (mainly neutrophils)
Symptoms •Asymptomatic •Or abdominal pain, nausea, vomiting •Occasionally bleeding (which can be fatal)
Treatment •Removal of irritant
Describe chronic gastritis
Two main types:
Bacterial:
◦H-pylori infection (most common cause)
Autoimmune:
◦Antibodies to gastric parietal cells
◦Can lead to pernicious anaemia
Can also be caused by: Chemical/reactive (minimal inflammation)
◦ Chronic alcohol abuse, NSAIDS, reflux of bile
Symptoms: H-pylori •Asymptomatic or similar to acute gastritis
•Symptoms may develop due to complications such as: Peptic ulcers, adenocarcinoma, MALT lymphoma
Autoimmune
•Symptoms of anaemia •Glossitis •Anorexia - uncomfortable to eat •Neurological symptoms from B12 deficiency
What is Helicobacter-pylori?
Helix shaped/gram negative/microaerophilic (perfect to live in stomach environment)
Spread: • Oral to oral/faecal to oral
Produces urease which converts urea to ammonium (basic in solution) so increases local pH
Has a flagellum so has good motility
• Lives in mucus layer/adheres to gastric epithelia
Problems: •Releases cytotoxins - direct epithelial injury
- Expresses enzymes: - Urease - Ammonia toxic to epithelia
- Possibly degrades mucus layer
- Promotes inflammatory response causing self injury
Describe how location of Helicobacter-pylori colonisation affects symptoms?
If in antrum (home of G cells)
- Increased Gastrin secretion (or decreased D cell activity)
- Increased parietal cell acid secretion so chime entering duodenum is very acid which can go on to cause, duodenal epithelial metaplasia, colonisation of duodenum and duodenal ulceration.
If in antrum and body:
• Asymptomatic
If predominantly in body:
• Atrophic effect • Gastric ulcer • Leads to intestinal metaplasia • Dysplasia • Cancer
Describe the diagnosis/treatment for helicobacter-pylori infection in the stomach
Diagnosis
- Urea breath test (using carbon 13)
- Stool antigen test
- Upper gastrointestinal endoscopy - biopsy then test for presence of H-pylori
Treatment
- Proton pump inhibitor
- Amoxicillin + (clarithromycin or metronidazole)
What is peptic ulcer disease? Describe differences between acute/chronic ulcers. Describe its morphology, clinical consequences, causes, symptoms and diagnosis/treatment
Defects in gastric/duodenal mucosa
◦ Must extend through muscularis mucosa
◦ Most common in first part of duodenum
◦ Commonly affects lesser curve/antrum of stomach
Acute ulcers
- Develop as part of acute gastritis Chronic ulcers
- Occur most frequently at mucosal junctions
- Where antrum meets body (on lesser curve)
- In duodenum where antrum meets small intestine
Morphology
- Generally less than 2cm diameter (but can be 10cm)
- Base of ulcer is necrotic tissue/granulation tissue
- Muscularis propria can be replaced by scar tissue
Clinical consequences
- Scar tissue shrinking can narrow stomach lumen or cause pyloric stenosis
- Perforation causing peritonitis
- Erosion into adjacent structure (liver or pancreas). Can cause fistulae.
- Haemorrhage from vessel in base of ulcer will cause haematemesis (vomiting blood)
- Malignancy (rare)
Caused by mucosal injury ◦ H-pylori ◦ NSAIDS ◦ Smoking (really only contributes to relapse of ulcer disease) ◦ Stress (only massive physiological stress) e.g. burns
Symptoms: • Epigastric pain (sometimes back pain - referred) • Burning/gnawing • Follows meal times • Often at night (especially DU)
Pain often delayed after eating if the patient has a duodenal ulcer as there’s a waiting time for food/chyme to enter duodenum.
If its a gastric ulcer then onset of pain will be fast.
Serious symptoms: • Haematemesis or melaena-Bleeding/anaemia • Early satiety from repeated scarring • Weight loss (reluctance to eat due to pain)
Diagnosis/Treatment
•Review symptoms then endoscopy •Lifestyle modification (change in diet) •Stopping any exacerbating medications (NSAIDs) •Testing for H-pylori (if present- eradicate) •Proton pump inhibitors (can increase risk to infection)
Describe the differences between duodenal ulcers and gastric ulcers
Describe the normal defence mechanisms of the stomach and then the pathogenesis of peptic ulcer disease
Normal defence mechanisms • Mucus • Bicarbonate • Adequate mucosal blood flow - can remove acid that diffuses through injured mucosa • Prostaglandins (stimulate above) • Epithelial renewal
Breakdown of normal defences more important than excessive acid
- Ulcers can develop in people with normal or low levels of acid
- Rapid gastric emptying/inadequate acid neutralisation (from bile/pancreas) has been implicated in duodenal ulcers
What is functional dyspepsia?
Have symptoms of ulcer disease
◦ No physical evidence of organic disease
It is a diagnosis of exclusion
How do we diagnose gastric pathology?
Upper GI endoscopy
• Biopsies • Benign/malignant ulceration • H-pylori Urease breath test - test for H-pylori
Erect chest X-ray
• Perforation - check for gas under diaphragm. Difficult as patient is very sick.
Blood test (FBC)
• anaemia from chronic bleeding
Describe pharmacological intervention for gastric pathology
H2 blockers:
•Cimetidine •Ranitidine
Proton pump inhibitors:
•Omeprazole
What is Zollinger-Ellison syndrome?
Non beta islet cell gastrin secreting tumour of the pancreas
Proliferation of parietal cells
• Lots of acid production • Severe ulceration of the stomach and small bowel • Abdominal pain, diarrhoea
What is stress related mucosal damage?
‘broad term used to describe the spectrum of pathology attributed to the acute, erosive, inflammatory insult to the upper gastrointestinal tract associated with critical illness’
Symptoms of gastritis/ulceration Following • Severe burns • Raised intracranial pressure • Sepsis • Severe trauma • Multiple organ failure
Give a small overview of stomach cancer?
Third most common cancer in the world
Usually presents late
- Has to be quite large before symptoms
- Dysphagia • Loss of appetite • Malaena • Weight loss • Nausea/vomiting/ • Virchow’s nodes - left supraclavicular node enlargement indicative of GI pathology
Huge geographical variation around the world
•High rates •Chile/Japan/South America - Have screening programs
Risk factors
• Male • H-pylori • Dietary factors - high salt • Smoking
What prevents food from going from the stomach back up the oesophagus?
Lower oesophageal sphincter prevents reflux of stomach - composed of a small amount of smooth muscle and a part of the diaphragm that surrounds it so when intra abdominal pressure increases the diaphragm flattens and constricts it.
Oesophagus goes through diaphragm at roughly T10 level. Oblique entry into stomach of oesophagus helps as if there’s an increased pressure in the stomach, pressure will be exerted more into the fundus than up towards the oesophagus. This angle of entry also gives rise to a flap valve which can help further to block reflux. Thorax pressure lower than abdominal pressure which helps close it.
What is pernicious anaemia?
Pernicious anaemia is a condition in which the body can’t make enough healthy red blood cells because it doesn’t have enough vitamin B12.
What are the different pathological features of gastritis?
