Luminal Infections and Disorders Flashcards
What are the three main groups of microorganisms in the GI tract?
- Commensal
- Opportunistic
- Pathogenic
What are commensal organisms?
Commensals – normal inhabitant of the human body, living in communities – they form the microbiota
Colonize a lot of different environments on our body – hair, skin, oral cavity, colon, vagina, etc.
Neither the host or the microbe is harmed – both derive benefits from their relationship
What event has a big impact on the our microbiota early on in life?
Microbiota is largely established by the mother during birth
Passage through the birth canal, from the skin, breast-feeding and food
This then continues to develop throughout life
What benefits do microbiota provide the human host?
- Bacteria can help digest and process food which we can then absorb
- Promotes postnatal differentiation of the mucosal structures
- Physical barrier function
- Stimulates the immune system – allowing for immune system development
- Regulation of metabolism
- Colonization resistance against pathogens – fight off potential pathogenic bacteria
What benefits do humans provide to the commensal microbiota?
- Provide nutrients and growth factor
- Provide a protected habitat
- Means for dispersal – grow and thrive in gut and spread from there onwards
What are the main bacterial phyla represented in the colon?
Colon – main bacterial species represented – Bacteroidetes and firmicutes
What is an opportunistic pathogen?
Opportunistic pathogens - these are commensal microorganisms that can become pathogenic in specific situaitons.
- When a bacteria are housed in the GI tract – they are considered commensal
- Only when they cause disease do they become pathogens
- Opportunistic bacteria – sometimes cause disease in certain instances – note that disease is not required for survival but rather an accident e.g. When protective mechanisms are absent/reduced these bacteria can thrive causing disease
Examples in the gut:
* Escherichia coli
* Bacteriodes fragilis
* Enterococcus faecium/faecalis
What is a pathogenic microorganism?
Obligate pathogen - Need to cause disease to transmit between hosts (—> evolutionary survival)
Can produce asymptomatic infection (but ≠ commensal)
Infections are not necessarily more severe than with opportunistic pathogens
Examples:
* Escherichia coli – many different types
* Shigella dysenteriae
* Salmonella Typhi
* Campylobacter jejuni/coli
What is the difference between zoonotic and environmental microorganisms?
Two other categories to help us understand where pathogens come from…
What are the different factors in the gut that prevent infections from arising?
- Barrier function – epithelium – tight junction
- Intestinal microbiota – colonization resistance
- Mucus secreted through goblet cells – creates thick layer making it hard for the pathogen to pass through
- Local immune cells – Gut associated Lymphatic tissue – APCs, lymphocytes, Paneth cells, etc. – providing protection + secreting antimicrobial peptides
- Lumen pH
- Low oxygen tension – low amount of oxygen in the gut – most microbes are anaerobes
- Flow rate – peristalsis – wash out bacteria
- Bile salts/ digestive enzymes – toxic to bacteria
What are some different factors that could impact the normal protective factors, increasing the risk of opportunistic infection?
- Immunosuppression
- Disruption of barrier function – sepsis
- Antibiotic – disrupting normal microbiota
- Ileus – lack of motility/propulsion (appendicitis) - peristalsis is reduced – increased ability of the bacterial colonization
- Antacid drugs – disrupt pH
Do obligate pathogens require the normal protective factors to be disrupted in order to cause infection?
Obligate pathogen – don’t need the protective mechanisms to be disrupted in order to cause infections, rather it disrupts these protective factors by itself
What are some examples of how obligate pathogens disurpt the normal functioning of the GI tract?
- Toxin production – many different effects – attack the epithelium, disrupting it, causing inflammation, causing a perturbation in the environment
- Increase the flow rate – diarrhea
- Direct invasion properties – virulence ability – reaching and bypassing the epithelium
- Resistance to bile salts, enzymes and intestinal microbiotia
- Capsule/LPS – avoidance of the immune system
- Adherence and motility mechanisms
Some opportunistic pathogens can become obligate pathogen by picking up virulence factors
How do pathogens (opportunistic or obligate) cause diarrhea or vomiting (mechanism)?
Diarrhea
* 3x day, liquid more than 80% water and >300g per 24 hours
Two mechanisms:
* Secretory - microorganisms and toxin produced cause water loss from epithelium.
* Inflammatory diarrhea - direct damage to epithelium - release of proteins, blood, WBCs and inflammation of the epithelium
Vomiting
* Reflex
* Mechanisms of protection
* Stimulated by humoral and neuronal mechanism
* Obligate pathogens create toxins in the GI tract - sends a message to the brain – drives vomiting response – relaxation of the esophagus and contraction of the stomach – vagal nerve mediated
What are the four organisms that can cause GI infections that we’ll be focusing on?
- H. Pylori
- Vibrio Cholerae
- Shigella
- Clostridioides difficile
H. Pyrlori
* Gram-staining
* Is it common?
* How is it transmitted?
* What area of the body does it colonize?
- Gram-negative
- Widespread across the world – present in 50% of western adults
- Transmitted through food and water
- Colonizes the human stomach (little bit of duodenum) – able to…
1. Survive in acid environment – microaerophile - needs oxygen but not too much – matches stomach
2. Motility (able to move through mucus to get through to the wall of the stomach)
3. Urease activity (enzyme transforms urea into ammonia – which is alkali, creating a H+ buffer)
What are the clinical features, method of diagnosis and treatment for a H. pylori infection?
Main clinical features
* Gastritis – mucosa becomes inflamed
* Gastric and duodenal ulcers
* Increased risk of carcinoma
Diagnosis
* Gastroscopy with biopsy (invasive)
and/or
* urea breath test (give radioactive protein to eat – if H.P present – we get radioactive ammonia in the breath)
and/or
antigen in stools
Treatment - Three antibiotics
Vibrio Cholerae
* Gram-staining
* How is it transmitted?
* What is the bacteria sensitive to?
* What area of the body does it colonize?
* Virulence factor
- Gram-negative
- Transmission < contaminated water or food (seafood!)
- Sensitive to drying out, sunlight and acid – need high bacterial load to transfer as a result
- Colonizes - Mainly acting the jejunum and the ileum
- Virulence factors - Secretes toxin and adheres to mucosae (Pili)
What is the mechanism that drives diarrhea production in V. Cholera infection?
Not invasive pathogen – produces toxin - consisting of a A and B subunit
B subunit – binds to the GM1 receptor – A subunit enters the cell where it activates adenylate cyclase – increase cAMP – increasing Cl- secretion and reduced absorption of Na+ - resulting in a net flow of water out
V. Cholera
What are the clinical features?
How is a diagnosis made?
What is the treatment?
Clinical features
* Watery secretory diarrhea (Rice-water stools) – Water and mucus – no protein, blood, WBCs, etc.
* Causes severe dehydration
Diagnosis - Clinical aspects and stool culture
Main treatment – rehydrates (IV ideally) and potentially antibiotic
Shigella
* Gram-staining
* How is it transmitted?
* What area of the body does it colonize?
* How many species are there? Which is the main?
* How does it cause pathology?
- Gram-negative
- Transmission - contaminated water or food, very low infectious load - very communicable
- Site - Large Colon
- Four species - S. dysenteriae, S. flexneri, S. boydii and S. sonnei
- Invasive pathogen - invades the epithelium and causes Inflammation of the gut. Does produce toxin but not the main mechanism.
How does shigella cause infeciton?
- Enter gut epithelium through M-cells (responsible for presenting antigens to immune cells) – trojan horse - allowing them to spread through the epithelium.
- They become ingested by macrophage at the basal side – macrophage dies releasing a huge amounts of cytokines resulting in tissue destruction
Shigella
* What are the clinical features?
* What are the complicaitons?
* How is a diagnosis made?
* What is. the treatment?
Clinical Features
* Bacterial dysentery – bloody diarrhea (+pus/mucus) + abdominal cramps and fever – three main features
* Complications – toxic megacolon and systemic – autoimmune (guillain barre syndrome)
Diagnosis – Stool culture + PCR
Treatment – supportive and antibiotics (Ciprofloxacin and azithromycin)
Clostridioides Difficile
* Gram-staining
* How is it transmitted?
* What area of the body does it colonize?
* What promotes/increases risk of C. Difficile infection?
* How does it cause pathology?
- Gram-positive
- Transmission - Environmental pathogen - forms resistant spores - common in health care facilities
- Site - Colon
- Promoted by antibiotic use - disrupts normal microbiota
- A combination of direct cellular damage and immunopathology
What impact do C. Difficile toxins have on gut epithelial cells?
GTP binding proteins belong to the Rho family – cytoskeleton regulatory proteins
Toxin drives glucosylation of GTPases (like Rho) causes the collpase of the actin cytoskeleton
What is this diagram of C. Difficile infection showing?
C. Difficile mechanism of action - Cellular damage and immunopathology
- B toxin is more important in physiopathology – lead glucosylation of GTPase – cell will die
- Toxins can also pass through the tight junctions and interact with neutrophils which are then recruited driving a large immune response
What is a common histological feature observe din C. Difficile infeciton?
Exudate of dead epithelial cells, fibrin and inflammatory cells – forms pseudo membrane
Is C. Difficile infection common?
The most common cause of nosocomial (originating in hospitals) diarrhoea, with a severity spectrum ranging from asymptomatic carriage, mild to moderate diarrhoea, to life- threatening pseudomembranous colitis
It has been steadily increasing from the 1980s to the 2010s, now endemic in healthcare institutions and in the community, but slightly decreasing
C. Difficile
* What are the clinical features?
* How is it diagnosed
* How is it treated?
Clinical features
* Asymptomatic carriage
* Diarrhoea / simple colitis
* Pseudomembranous colitis
* Fulminant colitis
Diagnosis
* Clinical features
* Stool analyses: Antigen (Toxin or Bacteria (enzyme))
* Culture
Treated
* Antibiotics - Metronidazole or vancomycin?
Fidaxomicin - needs to be specific as killing normal microbiota could promote C. Difficle
* “Faecal transplants” - Prevent bacteria from colonizing by replacing the microbiome back following antibiotics (prevention)
* Immunotherapy - not much evidence
Note - Probiotics not succesful
What are 4 different ways we could use drugs to treat C. Difficile infection?
What role does prevention and control play in controlling C. Difficile outbreaks?
Very important!
Infection control – removal of spores of C. difficile – hospital environment cleaning – spores resistant to alcohol – need to use bleach
Antibiotic stewardship – avoid antibiotics that promote CD infections
What is special about the UK hyper-virulent strain of C. Difficile?
Hypervirulent strains – tcdC gene deletion - negative regulator of toxin release – deletion leads to increase levels
Resistant to quinolone antibiotics - not directly used to treat C. Difficile but when people were treated with quinolone C.Difficile was left behind whereas everything else was killed
What organism could be responsible for the infeciton in the following patient case?
H. Pylori Infection
What organism could be responsible for the infeciton in the following patient case?
Vibrio Cholerae
What organism could be responsible for the infeciton in the following patient case?
Shigella
What organism could be responsible for the infeciton in the following patient case?
Clostridioides difficile
What is the definition of gastroenteritis? What are the three main causes?
Gastro-enteritis = inflammation of the digestive tract, causing nausea, vomiting, abdominal pain, diarrhea, eventually fever.
Can be upper or lower digestive tract
Can be caused by:
* Viral – quite common – stomach flu
* Bacterial causes – main group – microbial food poisoning – two big types within this category – infection (viable microorganism was ingested) & intoxication (ingest the toxin but not the whole viable microorganism)
* Parasite causes – less common in the western world – more common in the developing world
What are some examples of bacterial species that cause infective and/or toxic gastro-enteritis
Infective - Campylobacter spp, Salmonella spp, shigella
Both - E. Coli
Toxic/intoxication - Clostridium perfringens, Bacillus cereus, Staphylococcus aureus Clostridium botulinum and Vibrio cholerae
Difference between mild, moderate and severe gastroenteritis?
What are the general differences between small bowel and large bowel gastroenteritis?
Blood in diarrhea is dependent on the degree of tissue invasion - e.g. shigella and salmonella travel quite deep causing bleeding.
Organism(s) that causes watery diarrhea with no fever?
Organism(s) that causes watery diarrhea with fever?
Organism(s) that causes bloody diarrhea with no fever?
Organism(s) that causes bloody diarrhea with fever?
What are the typical modes of transmission for organisms causing gastroenteritis?
Endogenou pathogens in food - no cooked thoroughly
Drinking water contaminated with feces
Human to human - faecal contamination
What is the definition of infective dose?
The number of pathogens needed to cause disease in the new host
Varies with the pathogen
Relatively high for all bacteria whereas viruses require a lower load
Foodborne Infections - Campylobacter species
* Does it infect the small or large bowel?
* Main species causing infection?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Associated with what type of food/liquid?
* Diagnosis and treatment?
* Complications?
Campylobacter species - Commonest cause of diarrhoea in the developed World
- Infects both the small and large bowel
- C. jejuni and C. coli
- Mechanism - infective
- Typically gives bloody and fever but can give bloody with no fever or watery with fever
- Associated with poultry (grows well in the gut of chicken), wild birds and other animals and in their milk and water – zoonotic
- Diagnosis - Clinical and stool culture
- Treatment - Antibiotics
- Complications - !! Guillain-Barré Syndrome!!
Foodborne Infections - Non-typhi Salmonella spp
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Associated with what type of food/liquid?
* Diagnosis and treatment?
Non-typhi Salmonella spp - Major cause of foodborne disease world-wide (2nd after Campylobacter)
- Small and large bowel
- Infective mechanism
- Very wide range of clinical manifestations - all four combinations of fever and diarrhea - Often serious: fever, diarrhoea, vomiting
- Associated with poultry/eggs (Typhi: Only human reservoir)
- Diagnosis - clinical symptoms and stool culture
- Treatment - Antibiotics - Be careful due to MDR
Foodborne Infections - Clostridium perfringens
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Associated with what type of food/liquid?
* Diagnosis and treatment?
Clostridium perfringens
- Small bowel
- Intoxication - toxin - Bacteria sporulate in small intestine and produce an enterotoxin - destruction of villus tips with resultant pain and diarrhoea
- Symptoms - Watery no fever or Watery with fever - can also lead to myonecrosis (necrosis of the skin up to th muscle).
- Associations - Warm food contamination with spores - bulk cooking of meat
- Diagnosis – stool and detection of toxin
- Treatment – supportive
Foodborne Infections - Clostridium botulinum
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Source?
* Diagnosis and treatment?
Clostridium botulinum
- Small bowel
- Mechanism - Intoxication
- Symptoms - Watery with no fever or watery with fever - can be absorbed into the blood stream resulting in neuro-Botulism (toxin mediated paralytic illness) + wound botulism – toxin on the skin – seen in heroin users
- Associated - Widely distributed in nature - soils, lake sediments, vegetables, GI tract of mammals, birds and fish. Home-canned or fermented foods.
- Diagnosis - Stool culture + Detection of toxin
- Treatment - Supportive + (Anti-Toxin)
Foodborne Infections - Staphylococcus aureus
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Source?
* Complications?
* Diagnosis and treatment?
Staphylococcus aureus
- Small bowel
- Mechanism - intoxication - heat stable toxin
- Symptoms - Very acute vomiting response often followed by diarrhoea - watery with or without fever
- Source - Contaminates salted foods and dairy produce
- Complication - sepsis
- Diagnosis - Not necessary
- Treatment - supportive
Foodborne Infections - Bacillus cereus
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Source?
* Diagnosis and treatment?
Bacillus cereus
- Small bowel
- Mechanism - Intoxicating - toxin
- Symptoms - Acute vomit response followed by diarrhoea - watery with or without fever
- Source - Spore germinate in warm cooked rice
- Diagnosis - Not necessary
- Treatment - supportive
Cool Fact - Separate toxins for vomiting and diarrhoea responses! (ingestion of toxin directly for vomiting response)
Foodborne Infections - Norovirus
* Does it infect the small or large bowel?
* Mechanism - infection or intoxication (toxin)?
* Symptoms?
* Source?
* Diagnosis and treatment?
Norovirus - Most common viral cause of epidemic gastroenteritis worldwide - Winter vomiting disease
- Small bowel and large bowel?
- Mechanism - infective and intoxication
- Symptoms - Vomiting, diarrhoea, low grade fever - watery with or without fever
- Source - Direct contact with fecal matter or vomit – direct contact but some outbreaks associated with shell-fish
- Diagnosis - Clinical and PCR
- Treatment - supportive
Foodborne - What are the four different strains of E. Coli that you should remember? Mechanism - infective or intoxication?
E. Coli – many different strains that result in different clinical manifestations - all the different types of diarrhea
Intoxication - Enterotoxigenic E. Coli
Three different invasive types:
EPEC – children – small intestine
EIEC – more like shigella
EHEC – more severe manifestations (colon)
How are the infective strains of E. Coli transmitted (EHEC, EPEC and EIEC)?
- Food-borne (faecal contamination)
- Faecal-oral transfer
- Environmental contamination by domestic animals
EHECs are highly infectious agents - Infectious dose c. 10 bacteria
How do EHECs and EPECs infect the GI tract - mechanism?
- Attachment to microvilli
- Use type III secretion system which will inject the toxin into the cell
- Results in the formation of its own gene – intimin
- Results in micro-villi destruction and pedestal formation due to the formation of polymerized actin
In what season are E. Coli, Salmonella, Campylobacter and Norovirus infections more common?
E. Coli - Summer
Salmonella - Summer
Campylobacter - Spring
Norovirus - Winter
What are the common oesophagal disorders that we are interested in?
GORD ( gastro-oesophageal reflux disease)
These are different ways GORD can manifest:
* Oesophagitis
* Barrett’s oesophagus
* Benign oesophageal stricture
Oesophageal Motility disorders ( e.g. Achalasia)
Eosinophilic oesophagitis
Oesophageal cancer
Outline how the oesophagus normally functions.
Deglutition (swallowing( is performed by striated muscle
- Bolus is formed
- The upper oesophageal sphincter relaxes
- Food enters the esophagus
- Primary peristaltic wave is triggered all the way down
- Lower oesophageal sphincter relaxes
- Food enters into stomach
What is high resolution manometry?
Allows us to track pressure changes in the oesophagus.
High pressure areas shown in red and low pressure in green/blue
What are some examples of common symptoms seen in oesophageal disease?
- Main symptoms is dysphagia – alarm symptom – manifestation of severe disease – inability/reduced ability to swallow
- Often if there is inflammation, it is accompanied by odynophagia (pain on swallowing)
- Heartburn – burn retrosternally – acid reflux into esophagus
- Acid regurgitation – acid is felt and tasted
- Waterbrash – characteristic symptom of increased saliva production due to the aforementioned symptoms
- Dental erosions
What are the two classifications for dysphagia?
Dysphagia - difficulty swallowing solids or liquids - alarm symptom – we want to exclude cancer
Can be…
1. Oropharyngeal - difficult bringing the bolus from the mouth to the oesophagus - usually neurological cases - stroke
2. Oesophageal
When someone presents with dysphagia, what hints can point us towards a diagnosis?
Elderly – think neurological causes if intermittent/long standing or sinister esophageal cancer if new, progressive with regurgitation and weight loss
Cancer – problems with solids first and then liquids – progressive dysphasia
Younger people – can’t swallow – same difficulty with solid and liquids – think about dysmotility – number one is achalasia but can also be secondary to acid reflux
Young patients – food bolus obstruction – think eosinophilic eosophagitis
Extra…
Hoarse voice – think of ENT causes (or advanced tumour left recurrent laryngeal nerve is infiltrated/impacted by advanced oesophageal cancer)
Pharyngeal pouch (posterior to the larynx) – pouch that accumulates and prevents food movement – think of this when people get regurgitation of food from previous days
What investigations do we use if someone presents with oesophageal disease?
Investigations
- Endoscopy and biopsy - gold standard
- Barium swallow – swallowing a barium meal – gives us a more dynamic information about the way esophagus contracts – can’t tell us about inflammation or potential cancers
- Oesophageal function test – manometry (measure pressure), pH (reflux) and impudence monitoring (looking for material refluxing that isn’t acidic) – look at motility and look at the exposure of acid
What are the two main reasons for GORD to arise?
- Transient lower oesophageal relaxations (sphincter becomes relaxed) – daytime reflux, small or no HH and often no esophagitis (no inflammation of the lining) – more common
- Reflux with low lower esophageal sphincter pressures – less common, nocturnal reflux – associate with the hiatus hernia (hernia slides up and down) – disrupts the lower esophageal sphincter function – causes esophagitis and much more likely to suffer Barret’s
Other mechanisms also potentially involved…
* Increased acid production by the stomach
What are the typical symptoms of GORD?
TYPICAL symptoms of GORD
* Heartburn – behind the sternum
* Acid regurgitation
* Waterbrash – excessive salivation
Precipitating factors - after a meal and postural (bending over, at night)
What does the treatment of GORD look like?
- Lifestyle measures – smoking, alcohol, diet (staying away from triggers - caffeine, high fat, carbonated drinks, etc. ) weight reduction
- Mechanical – posture, prevent lifting heavy weights, elevate head in bed
- Antacids are commonly used
- Acid suppression - Proton-pump inhibitors or H2 antagonists
- Complex GORD – particularly in young people – surgical operation – reconstruct the lower Oesophageal sphincter
What are the complications associated with GORD?
Complications of GORD
* Oesophagitis
* Oesophageal Stricture – narrowing of the esophagus in response to continuous inflammation
* Barret’s Oessophagus
* Adenocarcinoma (Most arise from Barrets)
What are some benign and malignant causes of oeophageal strictures?
OESOPHAGEAL STRICTURE= narrowing of Gullet
Benign
* GORD up to 10% - most common cause
* Barrett’s
* Extrinsic compression – tumours in the mediastinum or lung
* Post-radiotherapy
Malignant
* Oesophageal cancer
How is a benign oesophageal stricture treated?
Treatment
1. PPI – omeprazole
2. Dilate the narrowed oesophagus - Dilatation – opening up – stretch – push dilators - CRE balloons or push dilators
What is barret’s oesophagus?
Barret’s esophagus – growth of a stomach like epithelium up into the esophagus – gastric columnar epithelium growing into the esophagus (squamous epithelium replaced) – esophagus is made more robust
Problematic – prone to develop of dysplastic changes – adenocarcinoma – premalignant condition - increased risk.
Commonest in obese men >50
Often asymptomatic – symptoms of Acid reflux
How is barrett’s oesophagus treated?
- Ablation – stop the development of barrets – burn the area - especially if there is a high risk fo cancer.
- Long term treatment people with proton pump inhibitors
What are the two main types of oesophageal cancer?
Two cancer types
- Adenocarcinoma is becoming more common – more in younger (average age still 60) - found in the lower third of the esophagus – more associated with obesity and Barret’s.
- Squamous cell -– mid/upper eosophagus – more in the older population - associated with smoking and alcohol – becoming less common
How is a diagnosis of oesophageal cancer performed?
Gold standard - Upper endoscopy + biopsies used for diagnosis
TMN Staging…
* CT - metastases and lymph nodes
* Endoscopic ultrasound – used to stage the tumour – depth of invasion of the tumour
How can we help cancer patients if it is too advanced?
Oesophageal cancer – 2/3 of cases there isn’t much we can do about it
Palliation measures – relieve the difficulty swallowing – leads to ill-health due to malnutrition
Entermetal sheet/stent opening the esophagus – improves quality of life but doesn’t change the prognosis
What investigations do we perform to diagnose achalasia?
Normally… normal upper GI endoscopy
Perform a barium swallow - dilated oesophagus with accumulation of barium above sphincter (hypertonic/tight sphincter) with trickle into the stomach
Futher tests - Manometry which is used to confirm the diagnosis
What is achalasia?
Achalasia is a motility disorder
Definition of achalasia – failure of the LOS to relax and absence of peristalsis – resulting in food staying in the esophagus.
Dysphagia to liquid and solid with weight loss and chest pain.
More common in young
Endoscopic appearance is normal
Complications – food and liquid back log into wind pipe – causing respiratory complications/infections
What does high resolution manometry look like for achalasia?
How is achalasia treated?
Best way to treat is to stretch the LOS (Endoscopic pneumatic dilatation) – Can cause acid reflux but relieves swallowing problems
Other options
- Surgical myotomy - Weaken the sphincter muscle
- Botox injection – need multiple – not long lasting
- POEM – non-invasive way to perform a myotomy
What is eosinophilic oesophagitis?
Eosinophilic esophagitis is an allergic condition that happens in the esophagus - asthma of the esophagus
The esophagus becomes inflamed and does not contract properly.
There is a build up of eosinophiles in the oesophagus.
How does eosinophilic oesophagitis typically present?
- Presents in children and young adults
- Presents as dysphagia or food bolus obstruction, regurgitation
- Associated with atopy
- More common in males – 3:1
- Can see endoscopic signs - furrows, rings and strictures
How is eosinophilic oesophagitis diagnosed?
Diagnosis with biopsy
Take 6 biopsies – 3 from the lower esophagus and 3 from the upper esophagus – 15 eosinophils per 15 powered field
What is the treatment for eosinophilic oesophagitis?
- Topical steroid – Budesonide (Jorvesa) or flucticasone dry powder inhaler – wipes out eosinophiles – first line
- Children – elimination diet – dairy, eggs, nuts, soya, shellfish and wheat
- PPI therapy
- Sometimes get strictures – narrowing – these need to be dilated
How do proton pump inhibitors and H2 antagonists work?
Proton pump inhibitors - block H+/K+ ATPase in parietal cells from pumping out protons
- PPI are unstable in acidic environments so they are enteric coated
- Ingested in an inactive form and become trapped and activated by the acidic pH inside parietal cells
- This is where they irreversibly bind to proton pumps (H+/K+ ATPase) – preventing them from pumping protons and new pumps take 24hr to synthesize (do not work via receptors)
- But we get rebound hypersecretion upon PPI cessation
H2 Antagonists
* H2 antagonists bind to histamine type 2 receptors on the basolateral (antiluminal) surface of gastric parietal cells, interfering with pathways of gastric acid production and secretion
Should PPIs be perscribed with NSAIDs or aspirin?
NICE recommends all patients taking NSAID or COX-2i should be given a PPI.
Effective prevention of NSAIDs ulcers and complications
What are some adverse effects associated with proton pump inhibitors?
Iron deficiency - simply supplement with more iron.
Potential diagnoses for the following patient case?
Probably upper GI pathology with chronic blood loss!
Peptic ulcer ( gastric or duodenal)
In view of age gastric cancer needs excluding.
If someone if suspected of having peptic ulcers, what investigation do we perform?
Upper GI endoscopy
What is one of the most common causes of peptic ulcers?
H. Pylori – cause of peptic ulcer disease – resides in the gastric pits
H. Pylori disrupts the epithelium – leading to ulcer formation
H. Pylori - Has the ability to live along the epithelium of the stomach – produces bicarbonate and ammonia – buffers the acidic microenvironment
How can we test for H. Pylori?
Testing for H. Pylori - Number one cause of peptic ulcer disease
Non-invasive
* Make a diagnosis H. Pylori using a breath test – administer radiolabelled urea (C-13) – urea is split by H. Pylori into bicarbonate – this can then be picked up in the breath as radiolabelled CO2
* Antibody measurement
* Stool Antigen test – primary care
Invasive
* Culture – not commonly done – only used to determine antibiotic sensitivities
* Histology
* CLO test - Take a biopsy – place onto CLOtest kit – immediately see whether H. Pylori is present as it will cause a pH change
How do NSAIDs and aspirin influence risk of ulcers and bleeding in HP positive patients?
Aspirin/NSAIDs increase risks of ulcers and bleeding in HP-positive patients
Test for and eradicate if positive
Note - HP can also be linked to…
* unexplained iron deficiency anaemia
* Immune thrombocytopenic purpura - I.T.P
* vitamin B12 deficiency
Consider eradication therapy if positive
How is helicobacter pylori treated?
Triple therapy!
1x PPI and 2x Antibiotic
Eradication confirmed using breath test or stool antigen test
What are some different causes of mucosal injury?
Bulk of the pathology occurring in the GI tract is mucosal-based
- GI tract secretions – acid, pepsin , biliary and pancreatic secretions can all injure the muscosa
- The mucosa of the GI tract is sensitive to ischaemia – blood supply from outside in, so luminal aspect most at risk – this combined with high metabolic injury – makes it sensitive to ischaemia
- Many drugs damaging to GI tract (as shown above) – NSAIDs, antibiotics, steroids and chemotherapy agents
- Immunological causes – coeliacs disease
- Infections - . Helicobacter, Salmonella, Shigella, E. coli, C. difficile, CMV
- Radiation
- Trauma - endoscopic procedures
- Idiopathic - Ulcerative colitis and Crohn’s disease
What are the different ways mucosal injury can manifest?
- Inflammation
- Apoptosis or necrosis - Apoptosis a useful diagnostic feature as not many conditions associated with this – suggests HIV, GVHD (graft versus host disease) and reaction to some drugs e.g. mycophenolate
- Erosion and ulceration
- Hypoplasia and atrophy
- Hyperplasia
- Metaplasia
- Dysplasia +/- neoplasia
What is gastritis? What can we divided it into?
Gastritis is inflammation in your stomach lining
Can be acute or chronic
What are the causes of acute gastritis?
Acute gastritis
* Acute erosive / haemorrhagic gastritis - Ingestion of irritant chemicals
* Acute H. pylori infection - Usually no or minor symptoms, so seldom seen in biopsies
What are the two main types of chronic gastritis?
Chronic Gastritis
Non-atrophic gastritis – associated with chronic H. Pylori Infection
Atrophic gastritis – associated with autoimmune gastritis (antibodies generated against the parietal cells – can be detect in blood – serology diagnostic) and chronic H. Pylori infection.
Atrophic gastritis characterised by loss of parietal (acid secreting) and peptic (pepsin secreting) cells in gastric body.
Extra…
Loss of intrinsic factor secretion also possible leading to low vitamin B12 absorption – can lead to megaloblastic anaemia
Intestinal type metaplasia and neuroendocrine cell hyperplasia are common features in atrophic gastritis
What are some examples of special forms of chronic gastritis?
What is coeliac disease?
A hypersensitivity reaction to glutamine-rich proteins in wheat, barley and rye (gliadins, hordeins and secalins) - gluten
Inflammation in the small intestinal mucosa impairs the absorption of nutrients
Strong link to HLA haplotypes – class 2 – MHC on antigen presenting cells
How is coeliac disease diagnosed?
Requires…
1. Histological changes of the duodenum
2. Detection of auto-antibodies
3. Response to gluten free diet
Often picked up in asymptomatic individuals in iron deficiency anemia – malabsorption
What are some extra-intestinal conditions that coeliac disease is linked to? What are the complications associated with coeliac disease?
Autoimmune diseases often go hand-in-hand
Not unusual to diagnose dermatitis herpetiformis first followed by coeliac disease diagnosis
What are the histological features of coeliacs disease?
Histological features
* Variable villous atrophy
* Chronic inflammation in lamina propria
* Increased CD8+ T-lymphocytes in epithelium
* Epithelial damage
* Crypt hyperplasia
Can bacterial, viral, fungal and parasitic infections be picked up in histology?
Bacteria
* Some bacterial infections – bacterial species are visible in biopsy - H. Pylori and Mycobacterium
* Some produce a characteristic pattern of injury – pseudomembranous colitis in C. Difficile and neutrophil rich granuloma in Yersinia enterocolitica
Viral infection
* Infected cells can contain inclusion bodies – HSV and CMV can be diagnosed on a biopsy
Fungal, Parasitic and Helminths
* Fungal, protozoal and helminths are large enough to be seen in biopsies
* Candida can be seen in esophageal biopsies
What is the most common organism to cause pseudomembranous colitis?
Organism responsible – C. Difficile - cause volcano lesions
What is the aetiology of IBD?
IBD - refers to Ulcerative colitis and Crohn’s disease
Causes not fully understood
1. Loss of tolerance to normal commensal bacteria
2. Familial and genetic component – involved in immune pathways such as bacterial recognition
3. Environmental – food antigens and smoking (makes Crohn’s worse but protective for UC)
4. Infection – no single organism identified
What is the role of biospsies in IBD diagnoses?
Biopsies in IBD
1. Allows one to make an initial diagnosis
2. Exclude other aetiologies
3. Distinguish between Crohn’s and UC
4. Reponse to treatment
5. Complications/any other pathology
Biopsies ideally taken from multiple sites
How does UC typically present?
- Show Chronic relapsing and remitting course
- Presentation is normally rectal bleeding
- Incidence in peaks at 15-25 y/o and later peak between 60-70
- Confined to the mucosa
- Involve rectum +/- left colon
- Mainly limited to the large intestine and rectum
- Continious inflammation
- Whole colon in a continious distribution - pancolitis
What are the histological features of UC?
Histology
* Erythema
* Ulceration
* Granular appearance
* Flat - loss of mucosal folds
* Inflammatory polyps and pseudopolyps (arise from ulceration)
* Chronic architectural changes
What are the common sites of inflammation in UC?
Commonly – rectum and left colon length
Most severe cases – involvement of entire colon and rectum
How does Crohn’s disease typically present?
Chronic, multifocal, relapsing condition that can affect any part of the GI tract
Peak incidence 20-30 years with smaller peak 60-70 years. No gender difference
Variety of presentations depending on part of GI tract involved e.g. abdominal pain, diarrhoea, weight loss, strictures and obstruction, fistulae
Transmural inflammation (affecting all parts of the GI wall) that is often patchy and discontinuous (“skip lesions”)
What are the most common sites for Crohn’s disease?
Most common – small intestine, colon and anus whereas upper GI is less common
Why are granulomas for CD diagnoses?
One of the most useful features – granulomas – aggregates of activated macrophages – 70% of cases
Most common in the earlier stages of the disease – can be seen in the GI tract and draining lymph nodes
What are examples of histological features seen in CD?
- Aphthous ulcers in Crohn’s Disease - mouth
- Ulceration extending into the anal canal and perianal skin
- Discontinuous patchy nature of inflammation - skip lesions
- Deep knife like fissuring ulcers (UC - flat bottomed ulcers)
- Stricture formation - healing response narrows gut tube
- Fistula formation - connection between two structures.
- Granulomas
- Transmural inflammation
- More severe - cobblestone mucosa
Which of the following IBD complications applies to UC and CD?
Intestinal obstruction (stricture), fistulae and malabsorption (small bowel involvement) are typically only seen in Crohn’s disease
Note:
* Toxic dilatation – emergency – dilates and wall becomes thin and perforates easily
* Amyloidosis – protein plaque formation
Does UC and CD increase your risk of cancer?
Risk increased in both UC and CD (highest in UC)
Most commonly colorectal carcinomas but also increased risk of small bowel carcinomas and other malignancies e.g. bile duct carcinomas, leukaemias
How do UC and CD differ for the following features?
How do UC and CD differ for the following features?
What are some examples of IBD mimics?
- Infective colitis – mimic CD
- Ischaemic colitis – any part in large bowel – more common in splenic flexure – histology helps to distinguish
- Diverticular disease – can result in fistulas
- Drug-induced colitis – ileocolic inflammation with NSAIDs
- Radiation colitis
- Neoplasia
What are five causes of colonic stirctures?
- Crohn’s disease
- Ischaemic colitis
- Diverticular disease
- Diaphragm disease – NSAIDs
- Neoplasia
What is microscopic colitis? How does it typically present? Causes? How is it treated?
Microscopic colitis - Normal appearance of colonic and rectal mucosa at endoscopy but increased in chronic inflammatory cells in lamina propria - affects the large bowel
Two types
* Collagenous colitis
* Lymphocytic colitis
Presentaiton
* Typically in older patients
* Watery diarrhea over several months – need biopsy for diagnosis
Causes
* Often not identified
* Lymphocytic colitis associated with coeliac
* Drugs - lansoprazole and NSAIDs
Treatment
* steroids (budesonide)
What is a qFit test?
qFit - immunochemical test for small quantities of blood
If qFit positive - patients sent for a colonoscopy
When performing a colonoscopy, what are we looking for?
Looking for polyps – can be raised or flat – some of these may turn into colorectal cancer if not treated
How do polyps look like?
- Polypoid lesion on a stalk (can also be flat), projecting into the lumen of the colon
- Smooth surface
- Well circumscribed
- No obvious ulceration or haemorrhage
How is staging of a adenocarcinoma performed?
The patient should be staged with CT scan or MRI scan - TMN staging
What are the two categories of polyps? Do they all progress to a adenocarcinoma?
- Adenomatous polyps – highest progression to malignancy (adenocarcinoma)
-
Hyperplastic metaplastic polyps - don’t have malignant potential
* Third - classified as hyperplastic but has a serrated polyp – problem is that they are often flat making them hard to recognise
So no, not all colonic polyps progress to adenocarcinoma
What does the adenoma –carcinoma sequence refer to (mutations)?
Theadenoma-carcinoma sequencerefers to a stepwise pattern of mutational activation of oncogenes (e.g.K-ras) and inactivation oftumour suppressor genes(e.g.p53) that results in cancer.
APC – tumour suppressor – negative regulator of cell division/growth – once this genes is deleted, we see a higher predisposition of cancer
What is the commonest cause of iron deficiency anemia?
Commonest cause of iron deficiency anaemia is blood loss
Commonest cause of blood loss is GI bleeding
What are the colorectal cancer alarm features?
- Rectal bleeding – exclude colorectal cancer especially in older patients
- Weight loss – is a late presentation – not a good sign
- Anaemia/thrombocytosis
- Alteration in the bowel habit – vast majority of cases is persistent diarrhoea – more common in the cancers of the right-side bowel (ascending colon)
- Frequent diarrhoea is the middle of the night – indicates an organic problem rather than functional
- New Onset over 50 years
- Family history of bowel cancer
- Past medical history of IBD
What are some potential diagnoses for the following case?
Haemorrhoids
Colon polyps
Colon Cancer
Inflammatory bowel disease
What is the difference between cancer grading and staging?
GRADE of the cancer – depends on the pattern of cancers cells under the microscope – higher grade = more aggressive
Stage – standard way to sum up how far the cancer is spread
What system do we use for staging?
TNM staging system
* T refers to how far the primary tumor has grown into the wall of the GI tract and into nearby organs.
* N refers to cancer spread to nearby lymph nodes.
* M indicates whether the cancer has metastasized (spread to distant organs).
What are the most common sites of metastases for colorectal cancer?
Liver (most common for colorectal cancer), Lungs and Brain – main sites of metasteses
How do we perform the ‘T’ part of the TMN staging system?
- T1- mucosa and submucosa
- T2 – Muscularis propria
- T3 - Serosa
- T4 (associated with metastatic disease) – spread to nearby structures past the serosa – in the peritoneum and vasculature (bad news)
Note
* T1-T3 – contained within the lining of the organ
* In T3 tumours – you still can get positive lymph nodes as cells may end up there
What treatment can be used to treat colon cancer?
- Surgery - common
- Chemotherapy
- Radiotherapy
What are the risk factors for colon cancer?
- Diet high in redmeatsand processedmeats raises colorectal cancer risk.
- Cookingmeatsat very high temperatures (frying, broiling, or grilling) creates chemicals that might raise cancer risk.
- Diet low in fibre
- Obesity
- Physical inactivity.
- Smoking
- Alcohol excess.
- A family history of colorectalpolypsor colorectal cancer.
- History ofinflammatory bowel disease.
10./ Older age
What are the most common locations for bowel cancer?
- Recto-sigmoid area – account for 1/3 – most common
- Right side of the colon – account for 20/30%
How is colorectal cancer screening performed?
- Population over the age of 50 routinely and regularly checked for occult blood (qFIT)
- If positive they get a colonoscopy
Aim – prevent spread, screen and act early - improved outcomes
Is colorectal cancer common and significant cause of morality in Scotland?
Yes!
* Third commonest cancer in Scotland
* Colorectal is the second most common cause of cancer morality
What is the definition of hyperplasia?
Hyperplasia - Tissue growth to an increase in cell number
(increase in cell size = hypertrophy)
Can be physiological or pathological
What is the definition of metaplasia?
Metaplasia - A change from one fully differentiated cell type to another fully differentiated cell type
What is the definition dysplasia?
Descriptive term used by pathologists to indicate a pattern of disordered growth, architecture and maturation within a tissue (usually epithelial in nature)
Unlike metaplasia and neoplasia, it does not describe a pathological process, rather an appearance seen down the microscope
Important to recognise as it reflects underlying abnormalities in the regulation of cell growth and differentiation - may show pre-neoplastic or neoplastic changes (note dysplasia can also revert back to normal)
What is the definition neoplasia?
The development of a neoplasm, i.e. an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue, and which persists even after the evoking stimulus (if known) is removed
Neoplasms may be benign or malignant
How can dysplasia be categorized?
Dysplasia is commonly divided into low grade and high grade based on the extent by which the growth pattern deviates from that of normal tissue
In epithelial cells, what is a severe dysplasia called?
In epithelial tissues, severe dysplasia is often referred to as carcinoma in situ (also known as intraepithelial neoplasia)
What are the histological features of dysplasia?
- Hyperchromatism - Dark staining of nuclei reflecting an increase in DNA content, e.g. polyploidy
- Nuclear pleomorphism - Variation in nuclear shape (and size)
- Loss of orientation - Many normal epithelial cells show “polarity”
- Cell crowding and stratification - Reflects a loss of normal contact inhibition
- Increased and/or abnormal mitotic figures
Reflects increased cell proliferation
What do you call cancers from epithelial cells, soft-tissue and blood?
What is the difference between an adenocarcinoma and squamous cell carcinoma?
Adenocarcinoma - Adenocarcinomas start in glandular cells called adenomatous cells. Glandular cells produce mucus/fluids to keep tissues moist.
Squamous cells carcinoma - starts in squamous cells. These are the flat, surface covering cells found in areas such as the skin or the lining of the throat or food pipe (oesophagus).
What are different factors that can drive neoplasia formation?
- Chemical carcinogens
- Physical agents
- Infections
- Inherited susceptibility
- Hormonal stimulation
What mechanisms drive neoplasia formation?
- Direct or indirect damage to DNA
- Reduced ability to repair DNA damage
- Increased stimuli to proliferate
- Reduced ability to inhibit growth
- Defects in apoptosis
What is the difference between benign and malignant neoplasia/cancers?
What are 5 different routes of metasteses?
- Lymphatic
- Vascular
- Perineural and intraneural
- Spread across cavities
- Iatrogenic
Can benign tumours have a negative clinical consequences?
Not unproblematic - can have serious clinical consequences
- Bleeding – erosion and ulceration
- Space occupying lesions within skull
- Compression of adjacent structures - Obstruction of lumina - e.g. intussusception in GI tract
- Hormonal effects
a) increased production
b) decreased production
What is intussusception?
Telescoping effect due to the presence of a polyp in the small and large bowel – compresses the veins and arteries in that area causing ischemia
Can it sometimes be difficult to differentiate between malignant and benign tumours?
It can be difficult to predict the behaviour of some neoplasms (tumours)
These are often referred to as tumours of uncertain (or borderline) malignant potential.
What are the two main categories of borderline tumours?
Tumours fall into 2 main categories:
1. Show extensive local invasion but almost never metastasize – prone to local recurrence if incompletely excised
2. Tumours that appear benign which can develop distant metastases – often presenting many years after initial diagnosis
What is cancer grading? What is the difference between a high and low grade tumour?
An attempt to predict the aggressiveness of a cancer based on its microscopic features
- High grade cancers are typically poorly differentiated and tend to have a worse prognosis
- Low grade cancers are well differentiated and tend to have a better prognosis
What are the symptoms associated with a GI neoplasm?
- Tiredness (anaemia)
- Bleeding
- Anorexia and vomiting
- Weight loss
- Pain caused by obstruction
- Dysphagia
- Alteration in bowel habit (colorectal)
What are the two types of oesophageal carcinoma?
- Squamous Cell Carcinoma - 90% of oesophageal cancers worldwide with 80% of cases occur in developing countries
- Adenocarcinoma - Commonest type in the UK
What are the risk factors for squamous cell oesophageal carcinoma?
Risk factors include
* Tobacco and alcohol
* Diet
* Infection - ?Fungal oesophagitis (Candida)
Evidence for the role of human papillomavirus (HPV) is lacking
* Genetic factors
What is oesophageal adenocarcinoma associated with? What are two key risk factors?
Most associated with acid reflux and barrett’s esophagus (Squamous epithelium to columnar epithelium)
Risk factors – obesity and male sex
For oesophageal carcinomas, what is the more important prognostic factor?
Tumour STAGE is the most important prognostic factor for both squamous cell carcinomas and adenocarcinomas
Good prognosis for tumours confined to the mucosa
Many tumours picked up late
10-20% survival for adenocarcinomas involving deep muscularis propria
What are the risk factors for gastric adenocarcinoma? What is the aetiology?
- Incidence increases with age
- Males > females
- Familial link in about 10%
- Small percentage have germline mutations e.g. TP53, CDH1 genes
Often presents late
Aetiology multifactorial: diet, H. pylori, bile reflux - chronic gastritis is a common theme
Tumour can grow quite large until symptoms are caused – stomach can accommodate size - reason why it is picked up late
What are the two main subtypes of gastric adenocarcinomas?
Intestinal
* The majority of cases in high incidence areas - Japan, east Asia, eastern Europe and parts of S America
* Increased risk in patients with FAP (Familial adenomatous polyposis)
Diffuse
* Relatively more common in low incidence areas
* Often younger patients
* Female > male
* Mutation or inactivation of CDH1 gene a common feature
Can you get gastric polyps?
Gastric polyps are intraluminal projections of mucosal or submucosal tissue.
They are generally asymptomatic.
While these lesions are typically benign, they do have the potential of containing local dysplasia and progression to invasive cancer.
Are cancers in the small intestine common? What are the different types?
Uncommon
- Adenocarcinoma
- Neuroendocrine tumours
- Gastrointestinal stromal tumor (GIST)
- Lymphoma - Enteropathy type T-cell lymphoma (EATL) in coeliac disease
What are neuroendocrine tumours (NETs)?
Epithelial tumours associated with the synthesis of hormone or neurotransmitter-like substances.
Can be difficult to predict their behaviour
Risk depends on… size (bigger – more aggressive), site (appendix – less aggressive / small intestine – more aggressive), grade (1-3 – based on proliferative activity)
What are sastrointestinal stromal tumours (GISTs)?
GISTs - Soft tissue tumour that can arise anywhere in the GI tract - Borderline tumour type
- Related to “pacemaker” cells in the muscularis propria
- Malignant tumours are a type of sarcoma
- High proportion have activating mutaiton in the KIT receptor tyrosine kinase gene
- Stomach is the commonest site
What are some examples conditions that give rise to non-neoplastoc colorectal polyps?
Colonic polyps are common
- Inflammatory - IBD, lymphoid
- Hamartomatous – contain normal components of the Gi tract but in an abnormal proportion or arranged differently - e.g. Juvenile polyps, polyposis and Peutz-Jegher syndrome
- Hyperplastic
- Lesions in the submucosa presenting as a “polyp”
What are two categories of neoplastic colorectal polyps?
Adenomas - benign
* Tubular
* Tubulovillous
* Villous
Adenocarcinomas - malignant
Adenocarcinoma - Peak age, gender differences and common sites?
- Peak incidence 60-79
- No gender difference with exception of rectal cancers (M>F)
- 55% of tumours rectum/sigmoid
- 22% of tumours caecum/ascending colon
Most sporadic - no family history
About 5% are associated with a known familial syndrome (FAP, HNPCC) or IBD
What are the dietary risk factors for colorectal adenocarcinomas?
- Excessive calories relative to requirement
- Low fibre
- High intake of refined carbohydrates
- High intake of red meat
- Low intake of protective micronutrients e.g. vitamins A, C, D and E
What are non-dietary risk factors for a colorectal adenocarcinoma?
Other risk factors:
* First degree relative with Colorectal cancer
* Inherited syndromes (FAP, HNPCC etc.)
* Alcohol in rectal carcinomas
* Smoking
* Inflammatory bowel disease
* Occupational factors e.g. solvents
* Radiation
What is a common gene mutation seen in colorectal cancers?
Inactivation of APC (Adenomatous Polyposis Coli) tumour suppressor gene seen in about 80% of colorectal carcinomas
Mutation is typically an early event in the transition from adenoma to carcinoma
Apart from the adenoma-carcinoma sequence, what other pathways are potentially involved in colorectal cancers?
- Microsatellite instability pathway – inactivation of DNA mismatch repair genes – increase the mutation rate – not associated with the typical adenoma-carcinoma sequence - more common in right colon
- “Serrated neoplasia” pathway - typically have a mutation in either BRAF or KRAS proto-oncogenes - More common in the right colon
What genetic factors increase the risk familial colorectal carcinomas?
FAP - About 1% of colorectal carcinomas are associated with FAP
HNPCC - Up to 5% associated with Hereditary nonpolyposis colorectal cancer (lynch syndrome)
Of sporadic carcinomas, ≥30% may be associated with an inherited defect
What factors can be used for colorectal carcinoma prognosis?
How is colorectal screening performed in Scotland?
Bowel screening – ages 50-74 – uses qFit test with referral to colonoscopy if positive result
Summary of the pathology and clinical presentaiton of Ulcerative colitis.
Ulcerative Colitis
Pathology
* Always starts from the rectum
* Continuous manner - Inflammation spreads to various areas of the colon
* Passed the splenic flexure = pan-colitis (important implications in terms of outcome – more parts of the colon affecting – longer term prognosis is worse)
* Mucosal inflammation (lining of the wall)
Presentation
* Rectal bleeding - mucosal inflammation starting from the rectum – leads to rectal bleeding)
* Diarrhea (due to irritation of lining)
* Left lower abdominal pain
* Young patients with rectal bleeding, diarrhea – we think UC (perform colonoscopy)
Summary of the Pathology and clinical presentaiton of Crohn’s Disease.
Crohn’s Disease
Pathology
* Starts at the ileocecal junction
* Can spread to any part of the GI system -Many instances it doesn’t affect the rectum
* Discontinuous inflammation (skip lesions)
* Trans-mural inflammation
* Possibility of creating an abscess, perforation and fistula formation (usually in the rectum)
* Formation of strictures (inflammation and replacement of tissue by fibrous tissue)
Presentation
* Only show rectal bleeding when there is inflammation in rectal region
* Different diarrhea - small bowel affected – increased motility but also because of malabsorption
* Crohns leads to malabsorption - B12, folate, iron, etc
* Lower right abdominal pain
How to differentiate microscopic colitis from the other types of IBD? What is it associated with?
Microscopic colitis – profound diarrhea but no other classical signs of IBD
Taking biopsy you see lymphocytes and fibrous deposition
Associated with taking medication (PPIs) – responds to classical treatments
How can UC cause bowel dilation?
When severe, toxic megacolon (dilation) may occur
Dilation caused by significant inflammation that impacts the bowel’s ability to contract
Summary - What are the macroscopic features seen in UC?
- Diffuse abnormality of the mucosal surface of the colon - inflammation
- Pseudopolyps present between areas of ulceration
What are the microscopic features observed in UC?
- Pseudopolyp with adjacent mucosal ulceration - mucosal ulceration create polyps
- Ulceration - break in the mucus membrane
- Crypt abscess formation - inflammatory cells build up
- Granulation tissue - healing response
- Inflammation confined to the mucosa/submucosa
What are the macroscopic abnormalities seen in Crohn’s Disease?
- Thickening of the bowel wall
- ‘Cobblestone’ appearance of the small bowel mucosa
- May see ‘fat wrapping’ - movement of fat into the intestinal wall
What are the microscopic features seen in Crohn’s disease?
- Fissuring ulceration (deep-knife like) with purulent exudate (white blood cell accumulation)
- Accompanying chronic inflammation and fibrosis - causing strictures
- Granulomata (non-caseating) with giant cells
- Lymphoid follicles also present
Which of the highlighted areas represents an adenoma and adenocarcinoma?
Blue areas – Dysplastic glands forming tubular and villous structures – adenoma
Red area - Abnormal glands invading the wall of the colon with a stromal reaction – adenocarcinoma - more abnormal looking
What is the best treatment if a patient has a adenoma or early-stage adenocarcinoma?
Surgery
What are the macroscopic change seen in liver cirrhosis?
- Numerous nodules of variable size
- Nodules present throughout the whole liver
- Yellow colour implies the presence of fat
- May be large (earlier) or small (late stage)
What are the microscopic features seen in liver cirrhosis?
- Nodular architecture affecting the whole slide with disruption of normal lobular relationships
- Nodules of hepatocytes separated by bands of fibrous tissue (shown on image)
- Bridging fibrosis between nodules – from one portal triad to another
- Mild inflammation, particularly within fibrous bands
