GI & Liver Flashcards
Describe the pathology of Gastro-oesophageal reflux disease?
- An increase in transient lower oesophageal sphincter relaxations (due to reduced tone of LOS) –> results in reflux of gastric acid, pepsin, bile and duodenal contents back into the oesophagus
- Lower oesophageal sphincter relaxes independently of a swallow, allowing gastric acid etc. to flow back into the oesophagus
- Prolonged contact of gastric contents with the mucosa results in clinical symptoms
- this may cause oesophagi’s, stricture (narrowing) or Barrett’s oesophagus
What are the causes of GORD?
• Acid reflux often happens as the lower oesophageal sphincter become less competent in many cases
This may occur due to:
- Obesity
- Hiatus hernia
- Lower oesophageal sphincter hypotension
- Loss of oesophageal peristaltic function
- Overeating
- Systemic sclerosis
What is a hiatus hernia?
LOS sphincter can’t close properly - (the gastro-oesophageal junction and part of the stomach ‘slides’ up into the chest via the hiatus so that it lies above the diaphragm)
What are the risk factors for GORD?
- Obesity
- Male
- Increased abdominal pressure e.g. pregnancy or obesity
- Smoking
- Hiatus hernia
What are the symptoms of GORD?
- Heart burn – burning chest pain
- Odynophagia – painful swallowing
- Hoarse throat
- Wheezing
- Regurgitation
- Acidic taste in mouth
What are the signs of GORD?
- Chest pain aggravated by bending, stooping and lying
* Nocturnal asthma – due to aspiration of gastric contents into lungs
What is the differential diagnosis of GORD?
- Coronary artery disease (CAD)
- Biliary colic
- Peptic ulcer
- Malignancy
• Usually diagnosed on clinical findings as long as there are no alarm bells e.g. weight loss, haematemesis and dysphagia
What investigations are used to diagnose GORD?
- Oesophago-gastro-duodenoscopy (endoscopy) – may show oesophagitis and hiatus hernia
- 24-hour intraluminal pH monitoring
- Diagnosis can be made without investigation provided there are no alarm bell signs
What is the management of GORD?
- Lifestyle changes – weight loss, stop smoking, small regular meals
- Antacids e.g. Gaviscon – help relieve symptoms
• Proton pump inhibitor e.g. lansoprazole, omeprazole
- (Inhibit gastric hydrogen release, preventing the production of gastric acid)
• H2 receptor antagonists e.g. cimetidine
- (Blocks histamine receptors on parietal cells reducing acid release)
• Surgery
What are the complications of GORD?
• Barret’s Oesophagus – the epithelium of the oesophagus undergoes metaplasia and changes from squamous to columnar epithelium (with goblet cells)
–> Risk of progressing to oesophageal cancer – premalignant for adenocarcinoma of oesophagus
• Peptic stricture – inflammation of the oesophagus resulting from gastric acid exposure, causing narrowing and stricture of the oesophagus
What is Mallory-Weiss Tear?
A linear mucosal tear occurring at the oesophagogastric junction and produced by a sudden increase in intra-abdominal pressure
• It often follows a bout of coughing or retching and is classically seen after
alcoholic ‘dry heaves’
• Most common in MALES
• Seen mainly in age 20-50
What are the risk factors for Mallory-Weis tear?
- Alcoholism
- Forceful vomiting
- Eating disorders
- Male
- NSAID abuse
What is the pathology of Mallory-Weis tear?
• Vomiting, coughing, retching etc.
–> increases intra-abdominal pressure which forces stomach contents into the oesophagus, dilating it and causing a tear
How does Mallory-Weis present?/ What are the signs and symptoms?
- Vomiting
- Abdominal pain
- Haematemesis
- Retching
- Postural hypotension
- Dizziness
- Melena
What is the differential diagnosis of Mallory-Weis tear?
- Gastroenteritis
- Peptic ulcer
- Cancer
- Oesophageal varices
What investigations are needed to diagnose Mallory-Weis tear?
Endoscopy
What is the management of Mallory-Weis tear?
• Most bleeds are minor and heal in 24 hours
• Surgery – If surgery is required then it involves the oversewing of the tear but this is
rarely needed
What is Dyspepsia?
One of the following:
- Postprandial (after eating) fullness
- Early satiation
- Epigastric pain or burning for more than 4 weeks
- Affects upto 25% of the population each year
Describe the pathology of dyspepsia?
- Dyspepsia is an inexact term used to describe a number of upper abdominal symptoms such as; heart burn, acidity, epigastric pain or discomfort, fullness or belching
- Patients may use to the term INDIGESTION to describe their symptoms
What are the causes of dyspepsia?
- GI tract disorders - functional dyspepsia affects around 75% with no known cause
- Other causes of dyspepsia are PEPTIC ULCERS
How does dyspepsia present?
- Reflux when lying flat
- Heartburn
- Acid taste – due to reflux
- Bloating
- Indigestion
What are the red flag symptoms for cancer?
- Unexplained weight loss
- Anaemia
- Evidence of GI bleeding e.g. melaena (dark tar like black stools) or haematemesis
- Dysphagia
- Upper abdominal mass
- Persistent vomiting
What is the management of dyspepsia?
- Reassurance
- Dietary review
- Endoscopy to find clear picture of whats going on
• Antidepressants e.g. selective serotonin reuptake inhibitors e.g. CITALOPRAM (low doses are used to reduce the sensitivity of the gullet)
What is a peptic ulcer?
- A break in the epithelial cells which penetrates down to the muscularis mucosa of either the stomach or duodenum
Describe the epidemiology of peptic ulcers?
- More common in elderly
* More common in developing countries – due to H. Pylori
What are the two types of peptic ulcers?
- Duodenal ulcers most common (90%):
o Relieved by eating
o 2-3 times more common than gastric ulcers
- Gastric ulcers – (50-80%):
o Worsened by eating, also associated with NSAIDs/aspirin
- Ulcers are a risk factor for gastric cancer due to chronic inflammation – gastric carcinoma and lymphoma
Describe the pathology of peptic ulcers?
• Usually gastric mucosa is protected by a layer of mucin that is produced by gastric cells
• Increased acidity overwhelms the protective mucin resulting in mucosal
damage and ulceration
• Ulcers result in gastritis (inflammation of gastric cells)
What are the causes of peptic ulcers?
- H.Pylori– most common
- NSAIDS e.g. aspirin
- Mucosal Ischaemia
- Increased acid
- Bile reflux
- Alcohol
How does H.Pylori cause peptic ulcers?
o H. Pylori = most common cause
o Lives in gastric mucus
o Secretes urease which splits urea in stomach into CO2 + ammonia
o Ammonia + H+ –> ammonium
o Ammonium, proteases, phospholipases and vacuolating cytotoxin A damages gastric epithelium
o Causes inflammatory response reducing mucosal defense –> mucosal damage
o Also causes increased acid secretion –> Gastrin release (from G cells) –> more acid secretion
o Triggers release of histamine –> more acid secretion
o Increases parietal cells mass –> more acid secretion
o Decreases somatostatin (released from D cells) more acid secretion
How do NSAIDS cause peptic ulcers?
o NSAIDS e.g. aspirin
o Mucus secretion
stimulated by prostaglandins
o COX-1 needed for prostaglandin synthesis
o NSAIDs inhibit COX-1
o No COX-1 = mucous isn’t secreted
o Reduced mucosal defense –> mucosal damage
How does mucosal ischaemia cause peptic ulcers?
o Stomach cells not supplied with sufficient blood
o Cells die off and don’t produce mucin
o Gastric acid attacks those cells
o Cells die –> formation of ulcer
o Treatment - H2 blocker
How does increased acid production cause peptic ulcers?
o Overwhelms mucosal defence
o Acid attacks mucosal cells
o Cells die –> formation of ulcer
o Stress can increase acid production
o Treatment – PPI and H2 blocker
How does bile reflux cause peptic ulcers?
o Duodeno-gastric reflux
o Regurgitated bile strips away mucus layer
o Reduced mucosal defense
What are the symptoms of peptic ulcers?
- Acquisition usually asymptomatic (but can cause nausea, vomiting and fever
- Burning epigastric pain
- Bloating
- Vomiting
- Haematemesis
- Dyspepsia
- Nausea
- Flatulence
What are the signs of peptic ulcer disease?
- Gastric ulcer pain often occurs when patient is hungry, eating and classically occurs at night, weight loss
- Duodenal ulcer pain often occurs several hours after meals, weight gain, relieved by eating
- Anorexia
What are the red flag symptoms for gastric cancer?
- Unexplained weight loss
- Anaemia
- Evidence of GI bleeding e.g. melaena or haematemesis
- Dysphagia
- Upper abdominal mass
- Persistent vomiting
What are the investigations for peptic ulcers?
- Endoscopy with biopsy
o Biopsy urease test e.g. CLO test
o Histology
- Stool antigen test – for H. Pylori
- Urea breath test
- Blood test for IgG antibodies (can be positive for a year after treatment)
What is the management of peptic ulcers?
- Lifestyle management – reduce smoking, reduce stress, drink less
- Stop NSAIDs
• Antibiotics for H. Pylori - CAP
o Clarithromycin
o Amoxicillin
o PPI e.g. omeprazole
- Proton pump inhibitors e.g. lansoprazole and omeprazole
- H2 antagonists e.g. cimetidine to reduce acid release
- Surgery for complications
What are the complications for peptic ulcers?
- Duodenal ulcers can grow deeper until it hits an artery (most commonly the gastroduodenal artery) –> massive haemorrhage –> shock
- Perforation – requires immediate surgical consult
- Obstruction
- Peritonitis as acid enters peritoneum
- Acute pancreatitis if ulcer reaches pancreas
What is gastritis?
- Gastritis is inflammation of the stomach lining that is associated with mucosal injury.
- Gastropathy indicates epithelial cell damage and regeneration WITHOUT inflammation - commonest cause is mucosal damage associated with Aspirin/ NSAIDs
What causes gastritis?
- H. Pylori infection – most common
- Autoimmune gastritis – the cause of pernicious anaemia associated with antibodies to gastric parietal cells and IF
- Viruses e.g. CMV and HSV
- Duodenogastric reflux – whereby bile salts enter stomach and damage mucin protection resulting in gastritis
- Crohn’s disease
- Mucosal ischaemia
- Increased acid
- Aspirin and NSAIDs e.g. naproxen
- Alcohol
What is autoimmune gastritis?
- Affects the fundus and body of the stomach –> atrophic gastritis mistakenly destroys a special type of cell (parietal cells) in the stomach –> loss of parietal cells = intrinsic factor deficiency –> in pernicious anaemia (low RBCs due to low B12).
How does Aspirin and NSAIDs cause gastritis?
They inhibit prostaglandins (which stimulate mucus production) via the inhibition of cyclo-oxygenase resulting in less mucus production and therefore gastritis
How does H.Pylori cause gastritis?
o H. Pylori Lives in gastric mucus
o Secretes urease which splits urea in stomach into CO2 + ammonia
o Ammonia + H+ –> ammonium
o Ammonium, proteases, phospholipases and vacuolating cytotoxin A damages gastric epithelium
o Causes inflammatory response reducing mucosal defense
o Also causes increased acid secretion
- Gastrin release (from G cells) –> more acid secretion
- Triggers release of histamine –> more acid secretion
- Increases parietal cells mass –> more acid secretion
- Decreases somatostatin (released from D cells) –> more acid secretion
What are the symptoms of gastritis?
- Epigastric pain
- Nausea or recurrent upset stomach
- Vomiting
- Indigestion
What are the signs of gastritis?
- Loss of appetite
- Abdominal bloating
- Haematemesis
What is the differential diagnosis of gastritis?
- Peptic ulcer disease
- GORD
- Non-ulcer dyspepsia
- Gastric lymphoma
- Gastric carcinoma
What are the investigations for gastritis?
- Endoscopy
- Biopsy and histology
- H. Pylori urea breath test
- H. Pylori stool antigen test
What is the management of gastritis?
• CAP
o Clarithromycin
o Amoxicillin
o PPI e.g. omeprazole
- H2 antagonists e.g. ranitidine or cimetidine – reduce acid release/ Antacids
- Prevention – give PPIs alongside NSAIDs – this also prevents bleeding from acute stress ulcers and gastritis often seen with ill patients – especially burn patients
What is malabsorption?
The failures to fully absorb nutrients in the small intestine either because of the destruction to the epithelium or due to a problem in the lumen meaning food cannot be digested.
What disorders of the small intestine result in malabsorption?
- Coeliac disease
- Tropical Sprue
- Crohn’s
- Parasitic infection
- Before malabsorption is diagnosed, insufficient intake must be ruled out to ensure its actually malabsorption
What are the causes of malabsorption?
- Insufficient intake- consider psychosocial cause
- Defective intraluminal digestion - due to pancreatic insufficiency (pancreatitis) or defective bile secretion
- Insufficient absorptive area - due to inflammation e.g. Crohn’s
- Lack of digestive enzymes
- Disaccharidase deficiency (lactose intolerance)
- Bacterial overgrowth – brush border damage
• Defective epithelial transport
o Abetalipoproteinemia
o Primary bile acid malabsorption – mutations in bile acid transporter protein
• Lymphatic obstruction
- Lymphoma
- TB
How does cystic fibrosis cause malabsorption?
- Cystic fibrosis results in the blockage of the pancreatic duct due to
excess mucus meaning enzymes fail to be released. - Whereas pancreatitis causes damage to most of the glandular pancreas
meaning less or no enzymes are released
How does an insufficient absorptive area arise?
o Villi and microvilli produce massive SA to absorb nutrients
o Gluten sensitive enteropathy (Coeliac Disease)
- Villous trophy and crypt hyperplasia
o Crohn’s – typically in terminal ileum
- Inflammatory disease of bowel
o Extensive surface parasitasion
- E.g. Giardia Lamblia
• Parasite eats food
• Metronidazole for a week
o Small intestinal resection or bypass
- Procedure for morbid obesity
- Crohn’s disease – coble stone mucosa –> can’t absorb anything
- Infarcted small bowel
What are the symptoms of malabsorption?
- Weight loss
- Steatorrhea
- Diarrhoea
What are the signs of malabsorption?
- Anaemia – decreased iron, B12, folate
- Bleeding disorders – decreased Vitamin K
- Oedema – decreased protein
- Metabolic bone disease – decreased vitamin D
- Neurological features
What are the investigations for malabsorption?
- FBC
o Increased/decreased MCV
o Decreased calcium/iron/B12 and folate
o Increased INR - Stool sample microscopy
- Coeliac tests
What is coeliac disease?
- Ingestion of gluten stimulates immune system to attack small intestine –> (due to genetic susceptibility) = inflammation of mucosa of the upper small bowel
- T-cell mediated autoimmune disease of the small bowel in which PROLAMIN (alcohol-soluble proteins in wheat, barley, rye and oats) intolerance causes VILLOUS ATROPHY + MALABSORPTION
- Prolamin is a COMPONENT of GLUTEN PROTEIN
- SUSPECT in ALL with DIARRHOEA, WEIGHT LOSS or ANAEMIA (especially if iron or B12 deficient)
What are the causes of coeliac disease?
• Gluten found in
o Wheat
o Barley
o Rye
What are the risk factors of coeliac disease?
- Other autoimmune diseases – T1DM, Thyroid diseases, Sjogren’s
- IgA deficiency
- Breast feeding
- Age of introduction into diet
- Rotavirus infection in infancy increases risk
How does coeliac disease present?
- 1/3 are asymptomatic (silent disease) and only detected on routine blood tests (raised MCV)
- Stinking stools/fatty stools (steatorrhoea)
- Diarrhoea
- Abdominal pain
- Bloating
- Nausea & vomiting
- Angular stomatitis - inflammation of one or both corners of mouth
- Weight loss
- Fatigue
- Anaemia
- Osteomalacia - softening of bones due to impaired bone metabolism due to lack of phosphate, calcium and vitamin D leading to OSTEOPOROSIS (40-60% risk in untreated patients leading to fracture risk)
- Dermatitis hepetiformis - red raised patches, often with blisters that burst on scratching, commonly seen on elbows, knees and buttocks
Describe the epidemiology of coeliac disease
- Most common age for presentation is 4th to 6th decade
- For every paediatric case diagnosed there are 9 adult cases
- Affects males and females equally
- Affects 1 in 100 individuals in European-derived populations – majority are undiagnosed
- Presentation is at any age but typically presents infancy (after weaning on to gluten-containing foods) and in adults aged 40-49
• Increasing prevalence
o Change in endoscopic techniques
o Antibody screening
o Increased awareness of spectrum of diversity in presentation of CD
• Associated with other autoimmune conditions e.g. T1DM and thyrotoxicosis
What is the classification of coeliac disease?
• Marsh Classification:
o 0 normal o 1 raised intra epithelial lymphocytes (IEL) o 2 raised ILE + crypt hyperplasia o 3a partial villous atrophy (PVA) o 3b subtotal villous atrophy (SVA) o 3c total villous atrophy (TVA)
Describe the pathology of coeliac disease?
- A-gliadin is the toxic portion of gluten and is resistant to proteases in the small intestinal lumen
- Gliadin binds to secretory IgA in mucosal membrane
- Gliadin-IgA is transcytosed to the lamina propria via HLA DQ2 and DQ8
- Gliadin binds to tissue transglutaminase (ttG) and is deaminated which increases its immunogenicity
- Deaminated gliadin is taken up by macrophages and expressed on MHC II complex
- T helper cells release inflammatory cytokines and stimulate B cells
- This causes villous atrophy, crypt hyperplasia and intraepithelial lymphocyte infiltration –> reduced SA to absorb nutrients –> B12, folate and iron cannot be absorbed –> pernicious anaemia
What are the investigations for coeliac disease?
- Should maintain gluten for at least 6 weeks before testing to get true results:
1) FBC:
• Low Hb
• Low B12
• Low ferritin
2) Duodenal biopsy is the gold standard for diagnosis:
• See villous atrophy, crypt hyperplasia and increased intraepithelial
white cell count - seen histologically
• All reverse on gluten free diet
3) Serum antibody testing:
- Indications include; persistent diarrhoea, folate or iron deficiency and a family history of coeliac disease or associated autoimmune disease
- Most sensitive test (95% sensitive unless patient is IgA deficient)
What is the treatment/management for coeliac disease?
- Lifelong gluten free diet i.e. no prolamins - use serum antibody testing for monitoring
- Eliminate wheat, barley and rye - results in days/weeks
- Dietitian review –> Correction of vitamin and mineral deficiencies e.g. B12, folate, iron, calcium and vitamin D
- DEXA scan to monitor osteoporotic risk
- Inform 10% risk in 1st degree relatives
What are the complications of coeliac disease?
- A few patients do not improve on a strict diet and are said to have non- responsive coeliac disease
- Anaemia
- Secondary lactose intolerance = T-cell lymphoma
- IgA antibodies elevated
- Vitamin deficiency
- Osteoporosis
What is tropical sprue?
- Severe malabsorption (of two or more substances) accompanied by diarrhoea and malnutrition
- Occurs in residents or visitors to tropical areas where the diseases in endemic – most of Asia, some Caribbean islands, Puerto Rico and parts of SA
- Epidemics can break out in villages, affecting thousands at the same time
Describe the pathology of Tropical Sprue
- Partial villous atrophy with malabsorption
* Onset is acute and occurs either a few days or many years after being in the tropics
What are the causes of tropical sprue?
- Cause is UNKNOWN but is likely to be infective because the disease occurs in epidemics and patients improve on antibiotics
What are the symptoms of tropical sprue?
- Diarrhoea
* Anorexia
What are the signs of tropical sprue?
- Weight loss
- Severe malabsorption
- Abdominal distension
What are the investigations for tropical sprue?
- Bloods – anaemia due to malabsorption of B12, folate and iron (nutritional deficiency)
- Jejunal biopsy – abnormal showing partial villous atrophy
What is the management of tropical sprue?
- Leave region
* Folic acid daily and tetracycline antibiotic for up to 6 months
What is Inflammatory Bowel Disease (IBD)?
• Two major forms, these are both chronic autoimmune conditions:
1) Ulcerative colitis (UC) - which affects ONLY the COLON
2) Crohn’s disease (CD) - can affect ANY PART of the GI tract (mouth-anus)
• IBD occurs when the mucosal immune system exerts an inappropriate response to luminal antigens, such as bacteria, which may enter the mucosa via a leaky epithelium
What is Crohn’s Disease?
A chronic inflammatory GI disease characterised by transmural (goes deep into mucosa) granulomatous inflammation affecting ANY part of the gut from mouth to anus (especially in TERMINAL ILEUM and PROXIMAL COLON)
• Unlike in UC, there is unaffected bowel BETWEEN areas of active disease - these are SKIP LESIONS
Describe the epidemiology of Crohn’s disease?
- Highest incidence and prevalence in Northern Europe, UK and North America
- F>M
- Presents mostly at 20-40
- Smoking increases risk by 3-4 x
- 1 in 5 patients with CD have a first-degree relative with the disease
- Presentation mostly at 20-40 yrs
- Lower incidence than UC per year
Describe the pathology of Crohn’s disease?
- Originates in mucosa and works through layers of bowel (mucosa, submucosa, muscularis propria + fat)
- Affects any part of gut from mouth to anus – commonly terminal ileum and proximal colon
• Macroscopically
o Skip lesions
o Cobblestone appearance due to ulcers and fissures in mucosa
o Thickened and narrow
• Microscopically
o Transmural – affects all layers of bowels
o Non-caseating granulomas (aggregations of epithelioid histiocytes)
o Goblet cells
What are the risk factors for Crohn’s disease?
- Family history - mutation on NOD2 gene of chromosome 16
- Smoking
- Female
- Chronic stress
- NSAIDs
What are the signs of Crohn’s disease?
- Blood in stool
- Malabsorption
- Mouth ulcers
- Extra-intestinal features
o Erythema nodosum
o Anal fissures
o Episcleritis
CHRISTMAS • Cobblestones • High temperature • Reduced lumen • Intestinal fistulae • Skip lesions • Transmural • Malabsorption • Abdominal pain • Submucosal fibrosis
What are the symptoms of Crohn’s disease?
- Diarrhoea
- RLQ abdominal pain (ileum)
- Fatigue, fever, Nausea, vomiting
- Tenderness
What is the differential diagnosis for Crohn’s disease?
• Alternative causes of diarrhoea should be excluded
o Salmonella spp.
o Giardia intestinalis
o Rotavirus
• Chronic Diarrhoea
What are the investigations for Crohn’s disease?
- Tenderness of RIGHT ILIAC FOSSA
- Colonoscopy – diagnostic
- Biopsy
- Barium enema
- Stool sample – rules out infectious diseases
• FBC
o Raised ESR/CRP white cell count
o Often low Hb due to anaemia
• Faecal calprotectin – indicates IBD but not specific
What is the management of Crohn’s disease?
- Oral corticosteroids e.g. budesonide and prednisolone
- IV hydrocortisone in severe flare ups
• Add anti-TNF antibodies e.g. Infliximab if no improvement
o Has predisposition for TB – night sweats, haemoptysis (coughing up blood) and weight loss
- Consider adding azathioprine or methotrexate to remain in remission if there are frequent exacerbations
- Surgery (80%) – doesn’t cure disease
What are the complications of Crohn’s disease?
o Malabsorption:
- Disease extent
- Surgical resections
o Obstruction:
- Abscesses
- Acute swelling
- Chronic fibrosis
o Perforation – acute abdomen
o Fistula formation
o Anal
- Skin tags
- Fissure
- Fistula
o Neoplasia – colorectal cancer
- Systemic – amyloidosis (rare)
- Resection at worst areas but can result in short bowel syndrome (leading to diarrhoea (since little colon to absorb fluids) and malabsorption lifelong)
What is ulcerative colitis?
- Relapsing and remitting inflammatory disorder of the COLONIC MUCOSA UP TO the ILEOCAECAL VALVE
- Ulcers form along lumen of intestine
- It may affect just the rectum - proctitis (50%)
- It may affect the rectum and left colon - left-sided colitis (30%)
- It may affect the entire colon (entire large bowel) UP TO the ILEOCAECAL VALVE - pancolitis/extensive colitis
Describe the epidemiology of ulcerative colitis?
- Highest incidence in Northern Europe, UK and North America
- Affects males and females equally
- Presents mostly at 15-30
Describe the pathology of ulcerative colitis?
- Remains in mucosa (does not go through full wall of bowel)
- Only affects colon
• Macroscopically
o Continuous inflammation (no skip lesions)
o Ulcers
o Pseudo-polyps
• Microscopically o Mucosal inflammation o No granulomata o Depleted goblet cells o Increased crypt abscesses
• Paneth cells are involved in innate immunity and suggest an inflammatory condition when found in the descending colon.
What are the risk factors for ulcerative colitis?
- Family history
- NSAIDs – associated with onset of IBD and flares of disease
• Chronic stress and
depression triggers flares
• Smoking relieves UC
What are the symptoms of ulcerative colitis?
- LLQ abdominal pain
- Fever
- Diarrhoea with blood and mucus
- Cramps
What are the signs of ulcerative colitis?
- Rectal tenesmus – incontinence, urgency, bleeding
- Tender distended abdomen
- Clubbing
- Erythema nodusum
ULCERATIONS • Ulcers • Large intestine • Carcinoma – risk of • Extra-intestinal manifestations – uveitis, erythema nodosum, sclerosing cholangitis • Remnants of older ulcers - pseudo polyps • Abscesses in crypts • Toxic megacolon – risk of • Inflamed, red, granular mucosa • Originates at rectum • Neutrophil invasion • Stool is bloody and has mucous
What is the differential diagnosis for ulcerative colitis?
• Alternative causes of diarrhoea should be excluded
o Salmonella spp.
o Giardia intestinalis
o Rotavirus
What are the investigations for ulcerative colitis?
- Colonoscopy - diagnostic
- Biopsy – crypt abscesses
- Barium enema
• Bloods
o FBC – raised ESR and CRP, low Hb
o Test for pANCA – negative in Crohn’s
o Iron deficiency anaemia
- Faecal calprotectin
- Stool sample – rule out infectious causes
- CT/MRI
- Abdominal X-ray
What is the management of ulcerative colitis?
• Anti-inflammatory e.g. sulfasalazine – 5-aminosalicylic acid (5-ASA) absorbed in small intestine
o Or mesalamine
- Immunosuppressors – corticosteroids, azathioprine
- Anti-TNF drugs - infliximab
- Colectomy with ileo-anal anastamosis indicated in patients with severe UC not responding to treatment
- Surgery – indicated for severe colitis that fails to respond to treatment
What are the complications of ulcerative colitis?
• Liver
o Fatty change
o Chronic pericholangitis
o Sclerosing cholangitis
• Colon
o Blood loss
o Toxic dilation
o Colorectal cancer
• Skin
o Erythema nodosum
o Pyoderma gangrenosum
• Joints
o Ankylosing spondylitis
o Arthritis
• Eyes
o Iritis
o Uveitis
o Episcleritis
Differentiate between Crohn’s disease + Ulcerative Colitis?
PRESENTATION AGE
- Crohn’s disease: 15-35
- Ulcerative colitis : Throughout lifespan
SITE OF APPEARANCE
- Crohn’s disease: Mouth to anus
- Ulcerative colitis: Colonic, rectal mucosa
TYPE OF LESION
- Crohn’s disease: Transmural inflammation
- Ulcerative colitis: Superficial ulcers
MICROSCOPIC FINDINGS
- Crohn’s disease - Non-caseeating granulomas
- Ulcerative colitis - crypt ulcers, abcesses
CHARACTERISTIC PATTERN
- Crohn’s disease - skip lesions
- Ulcerative colitis - continuous lesions
CHARACTERISTIC APPEARANCE
- Crohn’s disease -Cobblestone pattern, creeping fat, string sign on barium x-rays
- Ulcerative colitis - Loss of haustra on imaging (lead pipe appearance), friable mucosa
CLINICAL PRESENTATION
- Crohn’s disease - right lower quadrant pain fistulas, phelgom
- Ulcerative colitis - left lower quadrant pain, gross bleeding
DISEASE MECHANISM
- Crohn’s disease - transmural inflammation along GI tract
- Ulcerative colitis - destruction of colonic mucosa, submucosa
TREATMENT
- Crohn’s disease - corticosteroids, azathioprine, metronidazol, infliximab, adalimumab
- Ulcerative colitis - mesalamine, infliximab, surgical resection
What is Irritable bowel syndrome (IBS)?
IBS denotes a mixed group of abdominal symptoms for which no organic cause can
be found
What is the epidemiology of IBS?
- Age of onset <40
- F>M
- Common in Western world – affects 1 in 5
- Symptoms are exacerbated by stress, food, gastroenteritis or menstruation
Describe the pathology of IBS?
- Dysfunction in the brain-gut axis results in disorder of intestinal motility and/or enhances visceral sensitivity
- Recurrent abdominal pain with NO inflammation
- 3 types
1) BS-C – with constipation
2) IBS-D – with diarrhoea
3) IBS-M – with constipation and diarrhoea
What are the causes of IBS?
- Psychosocial – stress, depression, anxiety
- Psychological stress and trauma
- GI infection - gastroenteritis
- Sexual, physical or verbal abuse
- Eating disorders
What are the risk factors for IBS?
- Female
- Stress
- Gastroenteritis
- Previous severe and long diarrhoea
- High hypo-chondrial anxiety and neurotic score at time of initial illness
What are the symptoms of IBS?
- Abdominal pain relieved by defecating or passing of wind
- Bloating
- Alternating bowel habits
- Constipation
- Diarrhoea
What are the signs of IBS?
- Mucus in stools
- Change in stool frequency
- Change in stool consistency
- Sensation of incomplete emptying
- Urgency
- Worsening symptoms after food
What is the differential diagnosis of IBS?
- Coeliac disease
* Lactose intolerance – especially in IBS-D, bile acid malabsorption, IBD or colorectal cancer
What are the investigations for IBS?
• Since there is nothing physical to be found, diagnosis made by ruling out the differentials
• Bloods
o FBC – for anaemia
o ESR and CRP – biomarkers for inflammation (IBD)
o Coeliac serology for EMA and tTG – if either positive –> high chance of coeliac disease
- Faecal calprotectin – raised in IBD
- Colonoscopy – to rule out IBD or colorectal cancer
What is the management of of IBS?
• Lifestyle modification – fluids, avoid caffeinated drinks, alcohol and fizzy drinks, fibre (in wind and bloating NOT diarrhoea and bloating)
• Treat symptoms
o Pain/bloating – Buscopan
o Constipation – laxative e.g. Senna
o Diarrhoea – anti-motility e.g. Loperamide
• If none of the above work - amitriptyline (tricyclic antidepressant)
What are the three main symptoms for detecting IBS?
If patient reports any of ABC:
- A - Abdominal pain or discomfort - B - Bloating
- C - Change in bowel habit
What are the red flag symptoms for cancer?
- Unexplained weight loss
- PR bleed/blood in stool
- Family history of bowel or ovarian cancer
- Change in bowel habit and aged over 50
- Nocturnal symptoms
- Rectal or abdominal mass
- Anaemia
- Raised inflammatory markers - IBD
- If any found then refer to secondary care for further investigations
Compare Irritable bowel syndrome (IBS) with Irritable bowel disease (IBD)?
- IBS - Normal investigation results
- IBD - Abnormal investigation results
- IBS - Persistent/fluctuating symptoms
- IBD - Persistent/fluctuating symptoms
- IBS - Wouldn’t really get fever
- IBD - More likely to get fever
- IBS - No symptoms outside GI tract
- IBD - Symptoms outside GI tract
- IBS - No blood in stool
- IBD - Blood in stools
- IBS - No Melena
- IBD - Meleana - black poo, indicative of blood higher up in tract
- Both = food triggers
- IBS - No weight loss
- IBD - Weight loss
- IBS - No mouth ulcers
- IBD - Mouth ulcers
- IBS - Constipation more common
- IBD - Constipation but less common than in IBS
- IBS - Exacerbated by stress
- IBD - Can also be exacerbated by stress
- IBS - Bloating
- IBD - Bloating much less common than in IBS
- IBS can also mimic ovarian cancer in middle aged (50s) women.
What bacteria are found in GI tract?
- > 400species (around 100 trillion micro-organisms)
- Predominantly anaerobes
- The GI microbiome weighs more than your brains
What is the point of the microbiome?
- Gastric acid kills most swallowed pathogens
- Bacteria are protective against luminal infection HOWEVER can also be pathogenic if in the wrong part of the peritoneum
- The microbiome is protective against “against invaders” but is vulnerable to systemic antibiotics
• Less gastric acid or
broad-spectrum antibiotics –> increased risk of intra-luminal infection
What is Diarrhoea?
- Abnormal passage of loose or liquid stool more than 3 times daily
- Acute – lasts less than 2 weeks
- Chronic – lasts more than 2 weeks
What are the mechanisms of Diarrhoea?
1) Sudden onset of watery bowel frequency associated with crampy abdominal pains and a fever = INFECTIVE CAUSE (proximal small bowel)
2) Bowel frequency with loose, mucoid, blood-stained stools = INFLAMMATORY CAUSE (colon)
3) Passage of pale, offensive stools that float often accompanied by a loss of appetite and weight loss = STEATORRHEA
What are the causes of diarrhoea?
1) Viral
o Most cases caused by viruses e.g. rota/norovirus
2) Bacterial
o Campylobacter o Shigella o Salmonella o C.perfringens o S.aureus o B.cereus o E.coli o C.diff
o Parasites (e.g. giardia, cryptosporidium)
3) Children – rotavirus
4) Adults – norovirus, campylobacter
5) Antibiotics – these can give rises to antibiotic induced C. Diff diarrhoea o Rule of C’s: - Clindamycin - Ciprofloxacin (quinolones) - Co-amoxiclav (penicillins) - Cephalosporins (particularly 2nd and 3rd generation)
6) Infective
o Intraluminal infection
o Systemic infections e.g. sepsis, malaria
7) Non-infective
o Cancer o Chemical e.g. poisoning, sweeteners, side effects o IBS/malabsorption o Endocrine e.g. T4 o Radiation
What are the risk factors for diarrhoea?
• Immunosuppressed
o Particularly to:
- Cryptosporidium
- Mycobacteria
- Microsporidia
- CMV
- HSV
What is the first line investigation for diarrhoea?
• HISTORY IS KEY
o Onset/duration
- Acute – viral/bacterial
- Chronic – parasites and non-infectious
o Family History
o Characteristics of stool
1) Floating – fat content, malabsorption/coeliac
2) Blood or mucus – inflammatory, invasive infection, cancer
3) Watery small bowel infection
o Food/drink
- Dodgy takeaways – food poisoning
- Meat/BBQs – campylobacter
- Poultry – salmonella
o Travel
- No cholera in UK
- Foreign travel?
- Very common and self-limiting
o Immunocompromised e.g. HIV, diabetes, chemo, transplant, steroids – crypto, CMV etc.
o Unwell contacts – more likely to be infective
o Fresh water/swimming – cryptosporidian, giardia
o Animals
- Reptiles – salmonella
- Puppies – campylobacter
o Medications – recent antibiotics
- C diff. or side effects
o Any neuro signs
- Clostridium botunilum (descending weakness)
- C. jejuni –> GBS 1-3 weeks after diarrhoeal episode (ascending weakness)
What are the 2nd line investigations/after history?
• Stool tests
o Stool culture o Faecal calprotectin o Faecal occult blood o Microscopy o Ova, cysts and parasites o Toxin detection
• Blood tests
o FBC
o Inflammatory markers (FBC/CRP)
o Blood culture
What is infective diarrhoea?
- 2nd leading cause of death in children globally – after pneumonia
- Highest prevalence in S. Asia and Africa
What are the causes of infective diarrhoea?
- Enterotoxigenic E.coli (30-70%)
- Campylobacter (5-20%)
- Shigella (5-20%)
- Non-typhoidal Salmonella (5%)
- V.parahaemolyticus (shellfish)
- Viral (10-20%)
• Cholera o Vibrio cholerae o Contaminated food/water o Cholera toxin o Profuse watery “rice water” diarrhoea --> up to 20L a day o Vomiting o Rapid dehydration o Doxycycline and fluids
• Parasites o Protozoal (5-10% more chronic) - Cyrpto - Giardia - Entamoeba
o Worms
- Schistosomiasis
- Strongyloides
What are the risk factors for infective diarrhoea?
- Foreign travel
- PPI or H2 antagonist use
- Crowded area
- Poor hygiene
What are the symptoms of infective diarrhoea?
- Recurrent diarrhoea
- Vomiting and nausea
- Fever
- Fatigue
- Muscle pain
- Steatorrhea
What is the differential diagnosis for infective diarrhoea?
- Appendicitis
- IBD
- UTI
- Coeliac Disease
- Volvulus
What is the investigations for infective diarrhoea?
• Diagnosis - 3 or more unformed stools per day plus one of the following: o Abdominal pain o Cramps o Nausea o Vomiting o Dysentery
• Blood – suggests bacteria
o E. Coli and Shigella ALL cause bloody stools
- Stool sample
- If chronic, sigmoidoscopy and bloods
What is the management of infective diarrhoea?
- Rehydration
- Antibiotics – metronidazole or oral vancomycin
- Barrier nursing – side room, gloves and apron
• Fluids + electrolytes monitoring and replacement
o E.g. oral rehydration sachets
o IV replacement
- Antiemetics – treat vomiting e.g. metoclopramide
- Antimotility agents – NOT IN INFLAMMATORY DIARRHOEA
What are Diarrhoea Red Flags?
- Dehydration
- Electrolyte imbalance
- Renal failure
- Immunocompromise
- Severe abdominal pain
What are cancer risk factors?
- Over 50
- Chronic diarrhoea
- Weight loss
- Blood in stool
- FH cancer
What is the epidemiology of colorectal cancer?
- 3rd most common cancer worldwide
- Usually adenocarcinoma
• Majority occur in distal colon
o More distal the cancer, the more visible blood and mucus will be
- Majority of presentations >60
- M>F
What are the risk factors for colorectal cancer?
- Increasing Age
- Family history
• Genetic predisposition
o Familial adenomatous polyposis
- Apc bound to GSK
- Beta catenin binds apc complex in high levels of apc
- In mutations, apc protein misfolded so can’t bind to beta catenin
- Beta catenin able to move into nucleus –> endothelial proliferation –> adenoma
o Hereditary non-polyposis colorectal cancer (HNPCC)
- Normally two DNA protein repair genes
- Some individuals born with just one which leaves them susceptible
- Colorectal
- Ulcerative
What is the pathology of colorectal cancer?
• Progression
o Normal epithelium (prevention) –> adenoma (endoscopic resection) –> colorectal adenocarcinoma (surgical resection)–> metastatic colorectal adenocarcinoma (chemotherapy palliative care)
- Nearly all are adenocarcinoma (+RECTAL)
- Polypoid mass with ulceration
- Spreads by direct infiltration through the bowel wall then spread to lymphatic and blood vessels and metastasise to liver and lung
What is the staging and prognosis of colorectal cancer?
- R0 – tumour completely excised locally
- R1 – microscopic involvement of margin by tumour
- R2 – macroscopic involvement of margin by tumour
What is the Duke stage: criteria?
- A – 95% 5 year survival, limited to muscularis mucosae (mucosa)
- B - 75% 5 year survival, traverses bowel lining and into submucosa (not lymph)
- C - 35% 5 year survival, involvement of regional lymph nodes
- D - 25% 5 year survival – metastatic
What is the presentation of colorectal cancer?
• Right-sided carcinoma o Usually asymptomatic until they present with iron deficiency anaemia due to bleeding o May present with a mass o Weight loss o Abdominal pain
• Left sided and sigmoid carcinoma o Change in bowel habit with blood and mucus in stools o Diarrhoea o Alternation constipation and diarrhoea o Thin/altered stool
• Rectal carcinoma
o Rectal bleeding and mucus
o When cancer grows, it will have thinner stools and tenesmus (cramping rectal pain)
• Emergency o Obstruction - Absolute constipation - Colicky abdominal pain - Abdominal distension - Vomiting (faeculent)
What is the differential diagnosis of colorectal cancer?
• Anorectal pathology
o Haemorrhoids
o Anal fissue
o Anal prolapse
• Colonic pathology
o Diverticular disease
o Irritable bowel disease (IBD)
o Ischaemic colitis
• Small intestine and stomach pathology
o Massive upper GI bleed – haematochezia
o Meckel’s diverticulum
What are the investigations for colorectal cancer?
• Colonoscopy – gold standard
• Digital Rectal exam
o 38% of colorectal cancers can be detected by DRE
• Double contrast barium enema
What is the management of colorectal cancer?
- Surgery
- Endoscopic stenting
- Radiotherapy
- Chemo
Describe the epidemiology of oesophageal cancer?
- 6th most common cancer worldwide
- Squamous cell carcinoma occurs in middle third (40%) and upper third (15%) of the oesophagus
• Adenocarcinomas occur in lower third of
oesophagus and cardia of stomach and account for majority of oesophageal tumours (45%)
- Presents mostly between 60-70
- More common in males
What are the causes of squamous cell carcinomas?
o High levels of alcohol consumption o Achalasia – disorder where oesophagus has reduced/no ability to do peristalsis and transport food down o Tobacco use o Obesity – since this increases reflux o Smoking o Low fruit and veg consumption
What are the causes of Adenocarcinoma?
o GORD o Smoking o Obesity o Achalasia o Barrett’s oesophagus
What is the pathology of Oesophageal Cancer?
- Oesophagus lined by squamous epithelium
- Stomach lined by columnar glandular epithelium
- Oesophageal epithelium undergoes metaplasia (change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type) to stomach epithelium
- SCC in upper 2/3rds
- Adenocarcinoma in lower 1/3rd
What are the symptoms of Oesophageal Cancer?
• Pain – due to impaction of food or infiltration of cancer into adjacent structures
• Dysphagia – difficulty swallowing solids at first then fluids
o If there is dysphagia to solids AND liquids from start this indicates benign disease
What are the signs of Oesophageal Cancer?
- Majority have no physical signs – detectable when advanced
- Lymphadenopathy
- Anorexia
- Weight loss
What are the investigations for Oesophageal Cancer?
- Oesophagoscopy with biopsy
- Barium swallow – to see strictures
- CT/MRI/PET for tumour staging
Describe the epidemiology of Benign Oesophageal Tumours?
- Account for 1% of oesophageal tumours
- Leiomyomas most common
- Papillomas
- Fibrovascular polyps
- Haemangiomas
- Lipomas
What are the symptoms of Benign Oesophageal Tumours?
- Usually asymptomatic – usually found incidentally on barium swallowing
- Dysphagia
- Retrosternal pain
- Food regurgitations
- Recurrent chest infections
What are the investigations for Benign Oesophageal Tumours?
- Endoscopy
- Barium swallowing
- Biopsy
What is the management of Benign Oesophageal Tumours?
- Endoscopic removal
* Surgical of larger tumours
What is the epidemiology of SI cancer?
- 1% of all malignancies
- Adenocarcinoma most common
- Lymphomas (NHL) most frequently found in the ileum
What are the risk factors for SI cancer?
- Family history
- Coeliac Disease
- Crohn’s Disease
What are the symptoms of SI cancer?
- Abdominal pain
- Diarrhoea
- Weight loss
What are the signs of SI cancer?
- Anorexia
- Anaemia
- Palpable mass
What are the investigations of SI cancer?
- Ultrasound
- Endoscopic biopsy
- CT/MRI scan
What is the management of SI cancer?
- Surgical resection
* Radiotherapy
Describe the epidemiology of gastric cancer?
- Falling incidence
- Mainly affects Eastern Europe and Asia
- Affects more males than females
What are the causes of gastric cancer?
o Unknown
o Smoking
o H/ Pylori increases risk at population level
–>Increases risk of peptic ulcers –> gastric cancer
• Affects more males than females
What signs/symptoms does gastric cancer present with?
o Epigastric pain – constant and severe
o Vomiting, nausea, anorexia
o Weight loss
o Dysphagia – if tumour is in fundus
o Anaemia from occult blood loss
o Liver metastasis –> jaundice
What investigations should take place to diagnose gastric cancer?
o Gastroscopy with biopsy
o Endoscopic ultrasound
o CT/MRI
o PET scan
What is the management of gastric cancer?
o Nutritional support
o Surgery and combination chemo
What are the variations in adenocarcinoma?
• Early
o Can be classified as early gastric cancer even when it reaches lymph nodes
o 90% 5 year survival rates
• Late
o 60% - 5 year survival rate
What are the investigations for Liver Cancer (Hepatocellular Carcinoma)?
• CT/MRI liver • Biopsy • Raised AFP • Bloods o Clotting abnormalities o Deranged LFTs
What is the management of Liver cancer?
- Surgical resection
- Radiofrequency ablation
- TACE, chemotherapy
What is the epidemiology of pancreatic cancer?
- 99% of pancreatic cancer occurs in exocrine component of pancreas
- UK incidence rising
- More common in males
- Typically presents >60
- Majority are adenocarcinoma and are of ductal origin
