Upper GI Tract Disorders Flashcards
What is included in the foregut?
- distal oesophagus to 2nd part of duodenum
What is included in the midgut?
- 3rd part of duodenum to 2/3 of transverse colon
What is included in the hindgut?
- 3rd part of transverse colon to rectum
What are the main arteries that supply the foregut, midgut and hindgut?
- foregut = coeliac artery
- midgut = superior mesenteric artery
- hindgut = inferior mesenteric artery
What are the 2 main features of swallowing?
- deliver food bolus to stomach
- protect airway from aspiration of food into lung
What is dysphagia?
- general term for swallowing difficulties
Which aspect of the oesophagus is responsible for stopping acid going back up the oesophagus?
- lower oesophagus sphincter
Which cells in the stomach secrete HCl?
- parietal cells
What is the primary protein channel in the membrane of parietal cells that is responsible for creating acid in the stomach?
- H+ / K+ ATPase is the proton pump of the stomach
Is the stomach function generally controlled by the sympathetic or parasympathetic nervous system?
- parasympathetic
What are the 3 ways in which parietal cells secrete HCl?
1 - ACh from vagus nerve (Gaq)
2 - Gastrin (Gaq)
3 - Histamine (Gas) due to gastrin stimulation
What is the direct and indirect action of gastrin on stimulating parietal cells to secrete gastric juice?
- direct = gastrin stimulates parietal cells directly
- indirect = gastrin stimulates histamine release that stimulates parietal cells
Gastrin is able to stimulate parietal cells both directly and indirectly, what type of cell signalling is the direct and indirection action of gastrin on stimulation parietal cells?
- direct = endocrine
- indirect = paracrine (nearby cells)
ACh, gastrin and histamine all work on different receptors on parietal cells, which receptors are present on parietal cells for each of the stimulus?
- ACh = Gaq and ⬆️ Ca2+
- gastrin = Gaq and ⬆️ Ca2+
- histamine = Gas and ⬆️ cAMP and phosphokinase A
What is gastro-oesophageal reflux disease (GORD)?
- leakage of acid from stomach into oesophagus
What are the main cuases of gastro-oesophageal reflux disease (GORD)?
- failure of the lower oesophageal sphincter to close fully
- temporary relaxations of the lower oesophageal sphincter
- failure of the diaphragmatic sphincter
- hiatal hernia
- increased intra-abdominal pressure
How common is gastro-oesophageal reflux disease (GORD)?
- very common
- 20-30% in western world will have regular GORD
- 50% of people will have at least one case of GORD
What is the most common bacterial infection that is a risk factor for Gastro-oesophageal reflux disease (GORD)?
- helicobacter pylori
What are the 3 most common risk factors that can increase intrabdominal pressure and therefore the risk of developing Gastro-oesophageal reflux disease (GORD)?
- obesity
- pregnancy
- ascites
What are some of the most common lifestyle risk factors for developing Gastro-oesophageal reflux disease (GORD)?
- alcohol
- smoking
- physcial activity/exercise
- depression/anxiety
What is the one non-modifiable risk factor for developing Gastro-oesophageal reflux disease (GORD)?
- age
- older people are more at risk
Do all patients with gastro-oesophageal reflux disease (GORD) present with symptoms?
- no
- majority are asymptomatic
Of the patients who do experience gastro-oesophageal reflux disease (GORD) related symptoms, what are the 3 most common symptoms?
1 - acid reflux (”heartburn”) medical term is dyspepsia
2 - burning in chest/throat
3 - reflux of acid into mouth with sour taste
Patients with gastro-oesophageal reflux disease (GORD) may experience the globus sensation, what is this?
- a persistent sensation of a lump in the throat
Patients with gastro-oesophageal reflux disease (GORD) may experience some generic symptoms, what are the most common?
- upper abdominal or non-cardiac chest pain
- respiratory symptoms due to aspiration and bronchospasm that may be worse at night
- persistent nausea and vomiting
- poor dentition (enamel erosion on inside of teeth)
What is the most common method for diagnosing patients with suspected gastro-oesophageal reflux disease (GORD)?
- mostly clinical
When diagnosing patients with suspected gastro-oesophageal reflux disease (GORD), clinical interpretation of symptoms is the most commonly approach, however if needed an endoscopy - oesophago-gastro-duodenoscopy (OGD), can be performed, what is this?
- camera down the throat
- able to travel to upper duodenum
When diagnosing patients with suspected gastro-oesophageal reflux disease (GORD), clinical interpretation of symptoms is the most commonly approach. However if needed an endoscopy - oesophago-gastro-duodenoscopy (OGD), can also be performed, but if a patient cannot have a OGD what older methods can be used for diagnosis?
- X-ray using contrast dye (barium)
- oesophageal manometry and pH studies
- faeces or breath testing for H. pylori
Do all patients who are colonised with Helicobacter pylori (H. pylori) present with symptoms?
- no
- greater than 70% have no symptoms
Helicobacter pylori (H. pylori) is not able to live in the stomach due to the acid conditions, but what is it able to do to ensure its survival in the stomach?
- flagella help navigate to higher pH areas (fundus) and lining
- releases urease that converts urea to CO2 and ammonia
- ammonia neutrilises stomach pH
Helicobacter pylori (H. pylori) are microaerophilic, what does this mean?
- requires only a little O2
- die with high O2 levels
Some strains of Helicobacter pylori (H. pylori) are able to produce cytotoxin-associated gene A (CagA), what is this?
- a virulence factor associted oncogene
- associated with inflammation, increased risk of ulcers and cancer
All strains of Helicobacter pylori (H. pylori) are able to produce vacuolating toxin A (VacA), what is this?
- protein secreted by H. pylori
- all strains produce active VacA as need cofactors
- can causes cell damage
What are the 4 main diseases that can be causes by Helicobacter pylori (H. pylori)?
1 - gastritis (inflammation of stomach)
2 - dyspepsia (chronic acid reflux)
3 - peptic ulceration
4 - gastric cancer
Peptic ulcers are one of the main diseases that can be causes by Helicobacter pylori (H. pylori). What are the 2 most common types of ulcers?
- 70-85% gastric ulcers
- 90-95% duodenal ulcers
Gastric cancer is one of the main diseases that can be caused by Helicobacter pylori (H. pylori). What are the 2 most common types of cancer caused by H. pylori?
- adenocarcinoma (starts in mucus-producing glandular cells)
- mucosa-associated lymphoid tissue (MALT) lymphoma (92-98% cases), can also cause non-hodgkins lymphoma
In patients with gastro-oesophageal reflux disease (GORD) what lifestyle factors can they be advised to change?
- alcohol
- smoking
- diet
- weight loss
In patients with gastro-oesophageal reflux disease (GORD) what pharmacotherapies can be used?
- proton pump inhibitors
- H2 receptor antagonists
In patients with gastro-oesophageal reflux disease (GORD) proton pump inhibitors and H2 receptor antagonists can be prescribed. Do these drugs stop reflux?
- no
- they reduce acid secretion
- do not stop cause of reflux
If a patient has been diagnosed with Helicobacter pylori (H. pylori), what treatment would they be prescribed?
- “Triple therapy” 7 days – PPI plus 2 antibiotics (e.g. amoxicillin and metronidazole)
- 66% effective
- high rates of metronidazole resistance in treatment failures
Proton pump inhibitors are a drug that is used to reduce acid production in the stomach. What is the most commonly used drug that we need to be aware of called?
- omeprazole
- other drugs include lansoprazole, esomeprazole
- all end in prazole
Proton pump inhibitors are a drug that is used to reduce acid production in the stomach. Omeprazole is the most commonly used drug that we need to be aware of, what is the mechanism of action of this drug and what does it help with?
- direct permanent binding to H+/K+ ATPase (“the proton pump”)
- inhibits H+ and K+ exchnage
- significant reduces HCl secretion (>95%)
Proton pump inhibitors are a drug that is used to reduce acid production in the stomach. Omeprazole is the most commonly used drug that we need to be aware of. It is able to bind with the H+/K+ pump and inhibit the release of H+ that form HCl in the stomach. Although side effects are rare, what are the most common side effects?
- diarrhoea
- increased risk of GI infection (e.g. C. difficile)
If a patient is unable to tolerate proton pump inhibitors, what drug could be used as an alternative?
- H2 receptor antagonist
- ranitidine
- educes histamine stimulation of acid production but not gastrin of ACh
Surgery can be considered for patients with Gastro-oesophageal reflux disease (GORD), but only in specific circumstances, what are they?
- medication and lifestyle has failed
- patients doesnt want medication for rest of their lives
- proof of reflux is required
What is a hernia?
- protrusion of all or part of a viscus through its coverings and into an abnormal position
- essentiually an internal part of the body pushing through a weakness in the muscle or surrounding tissue wall
A hiatal hernia is probably the second most common condition of the upper GIT. What is a hiatal hernia?
- hiatal refers to the hiatus opening in diaphragm
- stomach push through the diaphragm and into the oesophagus
There are 2 types of hiatal hernias, what are these called?
1 - sliding
2 - rolling
There are 2 types of hiatal hernias, a sliding hernia is the most common, accouting for 85-95% if hiatal hernias. What is a sliding hernia?
- gastrooesophageal junction (GOJ) is mobile
- GOJ slides into oesophagus and part of stomach follows through the oesophageal hiatus
- diaphragmatic sphincter is lost
- negative thoracic pressure pulls gastric contents into the oesophagus causing reflux
In a sliding hiatus hernia the gastrooesophageal junction (GOJ) (which is where the oesophagus and stomach meet) is mobile and slides through the diaphragm sphincter and part of the stomach follows into the oesophagus. What are the most common symptoms of this?
- mostly asymptomatic
- reflux/dyspepsia (indigestion)
- regurgitation or vomiting
- dysphagia (swallowing difficulties)
What is a rolling hiatal hernia that accounts for between 5-15% of hiatal hernias?
- gastrooesophageal junction (GOJ) remains fixed in its normal position below the diaphragm
- part of the stomach pushes up and roles through the hiatus in the diaphragm next to the oesophagus
What symptoms does a rolling hiatal hernia that accounts for between 5-15% of hiatal hernia present with?
- often asymptomatic
- chronic non specific symptoms/signs
- abdominal pain, early satiety, anaemia, dysphagia
- risk of strangulation (1%) causing a surgical emergency
What is gastritis?
- inflammation of the protective lining of the stomach called the gastric mucosa
Does gastritis only have one cause?
- no it is multifactoral
- can be caused by GORD and/or H.pylori
What is the main cause of gastritis?
- H.pylori
What are the 2 serious problems that can be caused by chronic gastritis?
1 - gastric cancer
2 - gastric ulcers
H. pylori is the most common cause of gastritis, what are some of the less common causes?
- smoking
- ingested agents (NSAIDs, alcohol, caustics)
- autoimmune gastritis
- non H. pylori infections (e.g. Epstien Barr Virus)
- inflammatory conditions (Crohns, sarcoid, vasculitis)
How is gastritis treated?
- remove causal agent if possible (especially H. pylori and NSAIDs)
- acid suppression therapy (PPI)
Non-steroidal anti-inflammatories, such as aspirin, ibuprofen, naproxen, diclofenac are commonly used by people for a number of conditions. What is the common mechnaism of action they all use?
- inhibition of COX enzymes
COX-1 produces prostaglandins, which are protective in the GIT. How is COX-1 protective?
- cycloxygenase (COX) breaks down arachadonic acid (AA) from diet
- COX-1 converts AA into prostoglandins that contribute towards platelet and kidney function and stomach protection
How does COX-2 that produces prostaglandins that are involved in pain and inflammation?
- cycloxygenase (COX) breaks down arachadonic acid (AA) from diet
- COX-2 converts AA into prostoglandins that contribute towards pain, swelling and inflammation
In the stomach what do the prostoglandins do that are converted from arachoanoic acid by COX-1 do to help protect the stomach?
- trigger the secretion of bicarbonate
- involved in mucus production
- improve blood supply
- help repair and maintain stomach walls
NSAIDs are designed to inhibit COX-2, but also inhibit COX-1, which converts protective prostoglandins from arachodonic acid. What happens we prolonged use of NSAIDs in the stomach?
- reduce mucous production
- reduce blood flow
- reduce bicarbonate secretion
- reduce repair and maintenance in the stomach
If a patient is going to be taking NSAIDs for a prolonger period of time, what other medication should they consider taking in regards to the stomach?
- gastric protection
- proton pump inhibitors
What is a peptic ulcer?
- a break in the inner lining of the stomach
What infection is a commonly associated with peptic ulcers?
- H.pylori
In addition to H.pylori, what is the other main cuase of peptic ulcers?
- NSAIDs
What is a stress ulceration, which is a cause of peptic ulcers. What is a stress ulceration?
- erosions of the stomach lining
- caused by trauma, critical illness, major surgery
What malignancy is associated with peptic ulcers?
- gastric cancer
In addition to NSAIDs what other medication commonly prescribed is associated with peptic ulcers?
- steroids
- bisphosphonates (bone thinning drugs)
- chemotherapeutic agents
Zollinger-Ellison syndrome can cause peptic ulcers, what is this syndrome?
- a neuroendocrine tumor of G cells of the pancreas
- gastrin causes stomach to produce too much acid
- too much acid results in peptic ulcers
- find tumour to diagnose disease
What are the 2 main types of peptic ulcers?
- gastric - lesser curve
- duodenum = 1st part and is the most common
Between a gastric and duodenum ulcer, which is the most common, and which is more likley to be associated with a tumour?
- gastric = more likley to be associated with cancer
- duodenum = most common
Patients can present with ulcers in an acute or chronic manner. In chronic symptoms, what are the most common symptoms?
- upper abdominal pain
- gastric ulcer pain increases 2-3 hours after meal
- duodenal ulcer pain reduces after eating
- patient becomes anaemic (chronic blood loss)
- weight loss due to association between pain and food
Patients can present with ulcers in an acute or chronic manner. In chronic symptoms, why do patients with gastric ulcers have more pain following a meal?
- more acid is produced due to meal
- acid causes pain
Patients can present with ulcers in an acute or chronic manner. In chronic symptoms, why do patients with duodenal ulcers have less pain following a meal?
- pancreatic juice is secreted following meal
- pancreatic juice increases low pH which was causing pain
Patients can present with ulcers in an acute or chronic manner. In acute symptoms, what are the most common symptoms?
- acute upper GI bleeding
- haematemesis (vomiting fresh blood)
- coffee-ground vomiting
- melaena (dark sticky faeces)
- rectal bleeding
- perforation of ulcer causing peritonitis and systemically unwell
Patients can present with ulcers in an acute or chronic manner. In acute symptoms, what are the 3 key symptoms?
1 - haematemesis (vomiting fresh blood)
2 - coffee-ground” vomiting
3 - melaena (dark sticky stool)
How are ulcers diagnosed?
- clinical assessment
- medical history and examination are important
In addition to medical history and examination, what other invasive approach can sometimes be used?
- endoscopy - oesophago-gastro-duodenoscopy (OGD)
If a patient has suspected gastric or duodenal ulcer, what infection should be tested for?
- H.pylori
- normally gastric sample taken during gastro-esophageal oscopy
- urease is measured in sample
- campylobacter-like organism (CLO) test
How are peptic ulcers treated?
- proton pump inhibitors and H. pylori eradication therapy
- lifestyle adjustment (smoking, alcohol)
- stop NSAIDS/other implicated medications (if possible!!)
In the case of bleeding in the upper GI bleeding, which can originate from the oesophagus, stomach or duodenum there are 2 types of a bleed, what are they called?
1 - variceal
2 - non-variceal
What are varices?
- veins that have become large and swollen
Upper GIT bleeding can be subdivided into variceal and non-variceal bleeding, which is more common?
- non-variceal
- accounts for aprox 89% of bleeding
Variceal bleeding in the upper GIT is rare, but if it occurs what is generally the cause?
- increased portal venous pressure
Variceal bleeding in the upper GIT is rare, but if it occurs it is generally due to increased venous portal pressure. How can this be treated?
- stop the bleeding and reduce the portal pressure
- medication (β blockers reduce portal pressure)
- radiological intervention
- endoscopic treatment
Non-variceal bleeding is by far the most common type of upper GIT bleed and can occur in the oesophagus, stomach or upper duodenum. Peptic ulcers are a common cause of this, but is this serious in patents?
- can be
- patients may need to be resuscitate
- may need a transfusion
Non-variceal bleeding is by far the most common type of upper GIT bleed and can occur in the oesophagus, stomach or upper duodenum. Peptic ulcers are a common cause of this. How can non-variceal bleeding be treated?
- reverse anticoagulation
- endoscopy using adrenaline injection, clips or heater probes
Non-variceal bleeding is by far the most common type of upper GIT bleed and can occur in the oesophagus, stomach or upper duodenum. Peptic ulcers are a common cause of this. If a patient is suscpected of having non-variceal bleeding what bacterial infection must we always consider?
- H.pylori
The gastroduodenumal artery (GDA) is one of the key reasons why we get bleeding when patients have peptic ulcers, especially duodenal peptic ulcers. Where does the gastroduodenumal artery run and why can this cause bleeding?
- GDA passes behind 1st part of duodenum (D1)
- ulcers can erode duodenum and then the GDA
The gastroduodenumal artery (GDA), which runs posterially to the duodenum is one of the key reasons why we get bleeding when patients have peptic ulcers, especially duodenal peptic ulcers. If the duodenum peptic ulcer and gastroduodenumal artery can be seen during an endoscopy, what can be done?
- can be clipped or burned
- radiological embolisation
- if not possible surgery is needed
In addition to bleeding which is caused by peptic ulcers, what else can happed to the ulcers?
- perforation of the ulcer (gas collection and rupture)
- can occur anterior or posterior to duodenum
In addition to bleeding which is caused by peptic ulcers a perforation may occur. If this can be repaired using endoscopy, what is normally done?
- omentum can spontaneously seals hole
- posterior (retroperitoneal) seals duodenum
In addition to bleeding which is caused by peptic ulcers a perforation may occur. If perforation occurs and surgery is rquired what is the aim of surgery?
- closure of the ulcer if possible
- omentum can be placed over hole (omental patch)
In addition to bleeding which is caused by peptic ulcers a perforation may occur. If perforation occurs and surgery is performed, what other medication should be considered alongside?
- high dose PPI (historically vagotomy)
What is metaplasia?
- cells differentiate into a different cell
- generally due to stimulus
- change occurs at the basal cells
What is dysplasia?
- greek for bad formation
- cells develop abnormally and unorganised
- often precursor to cancer
What is Barrett’s oesophagus?
- metaplastic replacement of normal oesophageal squamous epithelium with columnar epithelium
- occurs in distal oesophagus
Is Barrett’s oesophagus common?
- unusual
- occurs in 1-2% of the population
What is the most common cause of Barrett’s oesophagus?
- chronic gastro-oesophageal reflux
- diagnosed from a biopsy showing columnar epithelium taken from lower oesophagus
In Barrett’s oesophagus, caused by chronic gastro-oesophageal reflux a diagnosis is made from a biopsy showing columnar epithelium taken from lower oesophagus. How is metaplasia and dysplasia involved in this disease?
- premalignant condition
- metaplasia can occur but chronic leads to dysplasia
- dysplasia can lead to adenocarcinoma sequence
What are the main risk factors for developing Barrett’s oesophagus?
- being male
- age (more common in older patients)
- history of reflux
- less common obesity, smoking and family history
If a patient has a history of reflux and they are suspected of having Barrett’s oesophagus, will their reflux symptoms get worse?
- no
- could get better due to metaplasia of cells
- columnar cells are more resistant to acid
If a patient has Barrett’s oesophagus, what are the 2 levels of dysplasia that can occur?
1 - low grade dysplasia
2 - high grade dysplasia
If a patient has Barrett’s oesophagus, this can develop into low and high grade dysplasia. In high grade dysplasia what are the 2 most common outcomes in relation to cancer?
- up to half already have invasive cancer
- minority will develop cancer if left (but not all progress)
If a patient has Barrett’s oesophagus, this can develop into low and high grade dysplasia. In low grade dysplasia what are the 2 most common outcomes in relation to cancer?
1 - some may progress to high grade dysplasia and cancer
2 - most will not progress or will revert to non-dysplastic mucosa
If a patient has Barrett’s oesophagus, this can develop into low and high grade dysplasia. There are a multitude of factors that contribute to Barrett’s oesophagus, what gene mutation is commonly involved and how common is this gene?
- p53 tumour suppressor gene mutation prevalence increases
- low incidencd of p53 in in-dysplasic Barrett’s mucosa 5%
- incidence increases in LGD 10-20%
- incidence is highest in HGD >60%
How is Barrett’s oesophagus managed if a patient has metaplasia or low grade dysplasia that is found on the biopsy?
- observe and monitor
How is Barrett’s oesophagus managed if a patient has high grade dysplasia that is found on the biopsy?
- management becomes part of MDT
- radiofrequency ablation
- endoscopic removal +/- ablation
- surgery
- PPI therapy may reduce progression of Barrett’s
