GI Flashcards
What 2 conditions make up the inflammatory bowel diseases
Crohns and Ulcerative Colitis
Define Crohn’s disease with epidemiology
Inflammatory bowel disease characterised by transmural inflammation of the ENTIRE GI tract (mouth to anus). Terminal ileum and colon most commonly affected.
North Europe, UK, North America, 20-40 years
Risk factors for Crohns
- Family history
- Smoking
- White people (particularly Jewish origin)
- Oral contraceptive pill
- Diet low in fibre
- NSAID
Causes of Crohns
Genetic: NOD2/CARD15 gene mutation
Environmental:
- Smoking
- Oral contraceptive pill
- NSAIDs
Bacterial: Mycobacterium paratuberculosis, Pseudomonas and Listeria
Pathophysiology of Crohns
Chronic inflammation of the GI tract. Pathogen is presented to GI immune cells causing T helper cells to bind to it. This causes the release of inflammatory cytokines such as Interferon Gamma and TNF-a, which further stimulate immune response and inflammation
It is thought that genetic abnormalities leads to a dysfunction, causing inflammation to be unregulated.
This causes transmural inflammation with areas of healthy bowel in between, known as skip lesions, providing a cobblestone appearance of the bowel. Inflammation of the bowels can lead to malabsorption.
Signs and symptoms of Crohns
Signs
- Aphthous mouth ulcers
- Abdominal tenderness
- Perianal lesions - Skin tags, fistulae, fissures, abscesses, ulcers
Symptoms
- Diarrhoea (prolonged and often)
- Abdominal pain
- Weight loss and failure to thrive
- Several extra-intestinal manifestations affecting skin, joints, eyes (next card)
Extra-intestinal manifestations of Crohns
Skin:
- Perianal/mouth ulcers
- Erythema nodosum (swollen fat under skin, looks red, usually on shins)
- Pyoderma gangrenosum (rapidly enlarging, very painful ulcer)
Musculoskeletal:
- Arthritis of the large joints
- Seronegative spondyloarthropathies
- Clubbing
Eyes:
- Conjunctivitis
- Iritis
Investigations in Crohn’s
Faecal calprotectin (inflammatory marker in GI tract) - Raised
Serum antibodies
- pANCA negative (more in UC)
- ASCA positive (more in Crohn’s)
Endoscopy/Colonoscopy + Biopsy GOLD
- Endoscopy: Skip lesions, cobblestoning, strictures
- Biopsy: Transmural inflammation, non caseating granulomas, goblet cells present
CT/MRI can be used to find skip lesions, fistulas, abscesses
Histology of Crohn’s
Transmural inflammation, non caseating granulomas, goblet cells present
Treatment of Crohn’s
Cease NSAID, smoking
Induce remission
- Elemental diet
- Glucocorticoids: Budenoside (mild), prednisolone (moderate), IV Hydrocortisone (very severe)
- Immunosuppressants (Azathioprine or methotrexate)
- Anti TNF antibodies (infliximab)
Maintain remission
- Azathioprine
Complications of Crohn’s (6)
- Peri anal abscesses
- Anal fissure/fistula
- Small bowel obstruction
- Colorectal cancer
- Osteoporosis
- Anaemia/malnutrition
Crohns vs UC mnemonic
NESTS (Crohn’s)
N - No blood (rarer but still possible!)
E - Entire GI tract
S - Skip lesions
T - Terminal ileum and transmural inflammation
S - Smoking Risk factor
CLOSEUP (UC)
C - Continuous inflammation
L - Limited to colon and rectum
O - Only mucosa affected
S - Smoking protective
E - Excrete blood and mucus
U - Use aminosalicylates
P - Primary Sclerosing Cholangitis
Define Ulcerative Colitis with important epidemiology
Relapsing and remitting inflammatory bowel disease that characteristically involves rectum, and can extend up large bowel, up to ileocaecal valve. Doesn’t affect anus
Similar epidemiology to Crohns but 3x more common in NON SMOKERS (smoking is protective)
Risk factors for Ulcerative Colitis (6)
- Family History
- HLA-B27
- NSAIDs
- Infections
- Not smoking
- Chronic stress/depression
Pathophysiology of Ulcerative Colitis (4)
- IBD involving continuous inflammation, affecting only the colon on its mucosal layers. Usually starts at the rectum, working its way proximally to the caecum but never going past the ileocaecal valve.
- Relapsing, remitting course (Flares with new damage to bowel wall, followed by tissue healing).
- Can affect rectum only (proctitis), extend up to splenic flexure (left-sided colitis) or entire colon (pancolitis)
- Pseudopolyps develop due to regenerating mucosa that forms a kind of scar that looks like a polyp.
Signs and symptoms of UC
Signs
- LLQ pain and tenesmus (Rectal pain, feeling like you need to poo when you dont)
- Bloody, mucusy diarrhoea
- Weight loss/malnutrition
- Relapsing, remitting course
Symptoms
- Abdominal pain
- Cramping
- Diarrhoea
- Fever,malaise during attacks
Extra intestinal manifestations of UC
- Erythema nodosum
- Pyoderma gangrenosum
- Uveitis
- Colorectal cancer
- Ankylosing spondylitis
Investigations in UC
Faecal calprotectin - high
Xray, CT may be used for imaging
Check for C.diff cause of diarrhoea
Antibodies
pANCA positive
ASCA negative (Crohns)
Colonoscopy and biopsy GOLD
- Colonoscopy - Continuous mucosal ulcers and goblet cell depletion
- Biopsy - Psuedopolyps, crypt abscesses, goblet cell depletion. Inflammation limited to mucosa + submucosa
Histology in UC
Psuedopolyps, crypt abscesses, goblet cell/mucin depletion. Inflammation limited to mucosa + submucosa
What severity scoring system is used in UC
Truelove + Witts
Treatment of UC
1st (induce remission) - aminosalicylate (mesalazine/sulfasalazine) Rectal in proctitis, oral otherwise
if moderate/not responding prednisolone first.
In severe, IV hydrocortisone.
Cyclosporin (immunosuppressant) and Infliximab (TNF-a inhibitor) can also be given.
Next (Maintain remission)
- Aminosalicylate + azathioprine
If severe or non responsive,
Colectomy can be done (Curative)
Complications of UC (6)
PRIMARY SCLEROSING CHOLANGITIS!
Toxic megacolon
Bowel perforation
Colonic adenocarcinoma
Strictures or bowel obstruction
Extra intestinal manifestations
Define fulminant UC with symptoms and treatment
Sudden onset acute, severe flareup of UC.
> 10 bowel movements a day
Continuous bleeding
Abdominal tenderness
Toxicity
Colonic dilation
Hospital IV corticosteroid (hydrocortisone)
IV Ciclosporin or infliximab
Consider colectomy
Define Coeliac disease
Systemic autoimmune type 4 hypersensitivity reaction affecting the small intestine, triggered by dietary gluten peptides such as those found in rye, barley, wheat. Malabsorption is hallmark of the disease.
Pathophysiology of Coeliac
Normally, gluten containing food is broken down in stomach into gliadin. Gliadin resistant to proteases, passes to small intestine. Tissue transglutaminase (tTG) cuts off an amide group forming De-amidated gliadin.
In coeliac, this is taken up by macrophages which present it via MHC-II. T helper cells bind to it, releasing inflammatory cytokines which damage the villi of the small intestine.
IgA: Anti-tTG and Anti-EMA (Endomysial)
IgG: Anti-DGP (Deamidated gliadin peptide)
Risk factors for Coeliac
Family history
HLA-DQ2 or HLA-DQ8
Autoimmune disease
IgA deficiency
Downs syndrome
Signs/symptoms of Coeliac
Should be suspected in all diarrhoea + weight loss/anaemia
Signs
- Diarrhoea caused by common triggers
- Smelly, fatty, floaty stools (Steatorrhoea)
- Malabsorption signs (anaemia, weight loss, failure to thrive)
- Dermatitis Herpetiformis (Itchy red raised patches of skin, commonly found on extensor surfaces of arms and legs. Suggests active disease)
Symptoms
- Anaemia (iron, B12, folate deficiency)
- Weight loss
- Fatigue
- Osteomalacia (softening of bones due to lack of phosphate, vit D, calcium)
- Abdominal bloating, constipation
Common triggers of coeliac
Gliadin
Wheat, barley, rye (gluten rich foods)
Investigations in Coeliac
Antibodies:
- IgA- Anti tTG (tissue transglutaminase)
- Anti EMA (East mids airport (but also Endomysial))
IgG (if IgA deficiency)- Anti DGP (Deamidated gliadin peptide)
Small bowel endoscopy+biospy:
Villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes, lamina propria infiltration with lymphocytes
Coeliac histology
Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes, lamina propria infiltration with lymphocytes
Management of Coeliac
Gluten free diet (pasta, bread, flour, barley, rye)
Vitamin/mineral supplementation
Dexa scan to check osteoporosis risk
Define Irritable bowel syndrome (IBS), with 3 types
Chronic condition featuring abdominal pain and bowel dysfunction. Functional bowel disorder (has no identifiable/known pathology - Tests always come back normal)
Has 3 types
IBS - C: Constipation
IBS - D: Diarrhoea
IBS - M: Mixed/alternating
Exacerbators and risk factors of IBS
- Stress
- Microbial dysbiosis
- High FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet (short chain carbs)
- Gastroenteritis
- Menstruation
- PTSD
- Family history
- History of abuse
- Previous enteric infection
Signs/symptoms of IBS
- Chronic abdominal discomfort and abnormal bowel habits
- Abdominal bloating, distention and tenderness
- Urgency of defecation
- Symptoms worse after eating, relieved by defecation
- Mucus in faeces
- Altered stool appearance
Pathophysiology of symptoms of IBS
Visceral hypersensitivity - Sensory nerves in bowel wall have strong response to stimuli (stretching during/after meal)
Abnormal bowel motility - Fodmaps act as solutes and draw water into GI tract. Excess water causes smooth muscle spasms of intestines
Spasm/pain/bloating - GI flora metabolise FODMAPS producing gas
Investigations in IBS
“Diagnosis of exclusion”
- Faecal calprotectin, ESR and CRP - Rule out IBD
- Coeliac serology - Rule out Coeliac autoimmunity
- Abdominal X ray - Check obstruction
- Colonoscopy - Rule out IBD or bowel cancer
- FBC - Check for anaemia
Management of IBS
1st - Lifestyle advice (seperate card)
IBS-D - Loperamide - opioid receptor agonist, decreases muscular contraction in intestine. (Material stays in bowel so more water absorbed)
IBS - C - Laxatives (linaclotide)
AVOID lactulose
2nd line
If severe, tricyclic antidepressants (amitriptyline) reduces gut sensitivity
Lifestyle advice in IBS
Adequate fluid intake
Small, regular meals
Reduced processed foods
Limit caffeine and alcohol
Low FODMAP diet
Increase fibre if constipated, reduce if diarrhoea
Eat oats
Reduce stress
Lose weight
Crohns vs Colitis vs Coeliac Histology
Crohns - Transmural inflammation, non caseating granulomas, goblet cells present
Colitis - pseudopolyps, goblet cell depletion, crypt abscesses. Inflammation is mucosa/sub only
Coeliac - Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes, lamina propria infiltration with lymphocytes
Give the infective causes of diarrhoea
Viral
- Rotavirus (MC children)
- Norovirus (MC Adults)
Bacterial
- Campylobacter jejuni (MC, travel associated)
- C.diff
- E. coli (children)
- Salmonella
- Shigella
Infective condition causing diarrhoea, nausea vomiting
Gastroenteritis - Inflammation from stomach to intestines
How do antibiotics cause diarrhoea
Antibiotics beginning with C (in general) can cause C. diff
- C. diff replaces normal gut flora, causing necrosis and giving rise to pseudomembranous colitis, causing diarrhoea
Risk factors for infective diarrhoea/gastroenteritis and pseudomembranous colitis
Foreign travel
Poor hygiene
Crowded area
Pseudomembranous colitis
- Elderly
- Antibiotics
- Long hospital admission
- PPI/H2 antagonist acid suppression
What are the 3 cell layers of the stomach and what do they contain?
Epithelial Layer (innermost) - Absorbs/secretes mucus and digestive enzymes
Lamina propria - Blood/lymph
Muscularis mucosa (outermost) - Smooth muscle
What are the 4 regions of the stomach and what do they contain
Cardia - Foveolar cells (secrete mucus)
Fundus and body - Parietal cells that secrete HCl and chief cells that secrete pepsinogen
Antrum - G cells that secrete gastrin (which stimulates parietal cells to secrete HCl)
Duodenum contains Brunner glands which secrete mucus rich in bicarbonate to neutralise acid
Prostaglandins function
The stomach and duodenum also secrete prostaglandins which:
- stimulate mucus and bicarbonate secretion,
- vasodilate nearby blood vessels allowing more blood to flow to the area,
- promote new epithelial cell growth
- inhibit acid secretion.
Causes of gastritis
Acute
- H pylori, NSAID, alcohol
Chronic
- Long term H pylori, chronic alcohol, bile reflux
Autoimmune
- Antibodies against parietal cells
- Caffeine
- Smoking
- Extreme stress
- Increased acid
Risk factors for gastritis
Alcohol
NSAIDs
H Pylori infection
CMV and herpes
Reflux
Hiatus hernia
Zollinger-Ellison syndrome (tumours cause stomach to release too much acid)
Signs/symptoms of gastritis
Epigastric pain
Vomiting
Indigestion
Signs of B12 deficiency
Bloating
Investigations for gastritis
Endoscopy and biopsy - Will show gastritis
H pylori investigations
- H Pylori Urea breath test/ CLO test (patient given a meal containing radioactively labelled 13C urea. H Pylori will break the urea into radioactive CO2 which can be detected on exhalation)
- H Pylori Stool antigen test
Anti parietal cell/ anti IF antibodies - check for autoimmune cause
Differentials of Gastritis pain
Peptic ulcer disease
GORD
Non-ulcer dyspepsia
Gastric cancer (lymphoma, carcinoma)
Management of gastritis
Lifestyle: Reduce stress, alcohol, caffeine, NSAID
If H pylori
1st - H pylori eradication therapy (CAP - 2 antibiotic + PPI)
- Clarithromycin, amoxicillin, omeprazole
+ ciprofloxacin if fails
H2 receptor antagonist - Ranitidine
If autoimmune,
B12 injections for malabsorption
What is phlegmonous gastritis and how is it treated
Staph. Aureus, Streptococci, E. coli, Enterobacter infection. Normally, gastric acid prevents growth of bacteria, but in atrophic gastritis, less acid produced so ingested bacteria can invade and form pus on the gastric walls
- ICU admission and surgical resection of stomach
H. pylori Pathophysiology
- H Pylori secrete urease, splitting urea in stomach into CO2 and ammonia
- Ammonia + H+ = Ammonium and ammonium is toxic to the gastric mucosa > less mucous produced
- Somatostatin decreased, so less inhibition of acid secretion
- G cells stimulated to release more gastrin and histamine, so acid release from parietal cells increased
- Inflammatory effects further weaken mucosal protection
- Destruction to mucin layer causes decrease in HCO3-, less buffering of acid
What does H pylori do to substances in stomach (put simply)
- Releases urease, causing Ammonium production, damaging mucus
- Increases gastrin production, increasing stomach acid release by parietal cells
- Decreases somatostatin and HCO3-, so acid is inhibited/neutralised less
H Pylori investigations (3)
H pylori investigations
- H Pylori Urea breath test/ CLO test (patient given a meal containing radioactively labelled 13C urea. H Pylori will break the urea into radioactive CO2 which can be detected on exhalation)
- H Pylori Stool antigen test
- Biopsy urease test can be done too but is invasive
How is a H. pylori infection treated
H pylori eradication therapy (CAP - 2 antibiotic + PPI)
- Clarithromycin, amoxicillin, omeprazole
+ ciprofloxacin if fails
Consequences of H. pylori infection
Inflammation (Gastritis)
Peptic ulcer disease
Gastric carcinoma
Define a peptic ulcer
A break in mucosal lining of stomach or duodenum of 5mm in diameter or more. Usually due to an imbalance in factors promoting mucosal damage (NSAID, H. pylori, gastric acid) and protective defences (prostaglandins, mucus, bicarbonate (HCO3-))
Causes of peptic ulcers
- H. pylori
- NSAID
- Zollinger-Ellison syndrome (Gastrinoma causing excess acid release)
- Smoking and alcohol
- Stress
Where are Gastric and Duodenal ulcers commonly found?
Gastric ulcers usually found in lesser curvature of antrum
Duodenal found just after pyloric sphincter and usually Brunner gland hypertrophy (glands which secrete bicarbonate rich mucous)
Pathophysiology of peptic ulceration causes (3)
H pylori - release adhesins to adhere to foveolar cells and proteases causing damage to mucosal membrane
NSAIDs - Inhibit COX, causing indirect inhibition of prostaglandin synthesis.
ZE syndrome - Tumour in stomach, duodenal wall or pancreas, which secretes abnormal amounts of gastrin
How do gastric and duodenal ulcers cause bleeding
Very deep ulcers cut into arteries
Gastric ulcers affect left gastric artery
Duodenal ulcers affect gastroduodenal artery
What are the pain characteristics of gastric and duodenal gastric ulcers?
Burning epigastric pain
Gastric - Worse after eating
Duodenal - Worse when hungry, food provides some relief
(posterior penetration into pancreas may make pain radiate to back)
Other signs/symptoms of peptic ulcers
Nausea/vomiting
Dyspepsia (indigestion)
Weight loss (secondary to eating less in gastric ulcer)
Epigastric tenderness
Haematemesis
If bleeding
Anaemia
Malaena
Hypotension/tachycardia (shock) if bleeding acute and severe
Red flag symptoms in peptic ulcers
ALARM D
Require urgent endoscopy
- Anaemia
- Loss of weight
- Anorexia
- Recent onset/progressive symptoms
- Malaena/haematemesis
- Dysphagia
Investigations in peptic ulcer disease
If >55, Red flag symptoms, bleeding or dysphagia
- Endoscopy and biopsy, to check for malignancy or H pylori (biopsy urease clo test) (Will also show Brunners gland hypertrophy in duodenal!)
- Repeat to confirm healing/no malignancy after 4-6 weeks
<55, no red flags, non invasive fine
- H Pylori urease breath test
