Lecture ILO’s Flashcards
Where does an upper GI bleed take place?
Anywhere above duodenum
Where does lower GI bleed take place?
Jejunum, ileum, colon, rectum
Potential upper GI bleed causes
• 36% Peptic Ulcer (duodenal and gastric)
• 24% Oesophagitis
• 22% Gastritis - inflammation in stomach lining
• 13% Duodenitis
• 11% Variceal Haemorrhage
• 4.3% Mallory Weiss Tear - vomiting too much causing a tear in lower oesophageal sphincter
• 3.7% Malignancy
• 2.6% Vascular malformations e.g. Angiodysplasia
• Others: Ingested blood from epistaxis, aorto-enteric fistula, haemobilia
• Drugs- NSAIDs, Aspirin, steroids, Bisphosphonates – anti-coagultants/anti-platelets etc.
What is the Glasgow Blatchford scoring system for GI bleed?
- Predicts need for medical intervention
- Score 1 or more indicates higher risk and need for inpatient endoscopy
- Score of 0 indicates low risk and unlikely to need urgent intervention
Measures:
Blood urea
Haemoglobin
Systolic blood pressure
Pulse
Melaena?
Syncope?
Hepatic disease?
Cardiac failure?
Upper GI Bleed Management
• 26 yr old man
• Coffee-ground vomiting • BP= 70/40, P= 120
• Hb= 58
• PLT= 34, INR= 1.6
• LFTs= grossly derranged
•General Management?
Upper GI Bleed: General Management
1• Resuscitate (correct hypovolaemia):
– IV fluids
– Blood transfusion
– Group and save/cross match
2• Reverse coagulopathy:
– Vitamin K, FFP (fresh frozen plasma)
– Platelets if less than 50
– Reverse medications (if possible)
• Warfarin: Vitamin K and prothrombin complex (e.g. Beriplex)
• Heparin: Protamine Sulphate
• Terlipressin (helpful in variceal bleeds(oesophageal) DO NOT GIVE TO HEART PROBLEM PATIENTS
• Somatostatin analogues (helpful in variceal bleeds)
• IV PPI (helpful in peptic ulcer disease)
• IV Antibiotics E.g. Ciproloxacin/Tazocin (helpful in variceal bleeds)
• Endoscopy
• Mesenteric angiography with coil embolization
• Surgery
50 year old man presents with recurrent haematemesis. He is tachycardia, hypotensive and peripheries are cold. You find the following on examination:
Spider nevi on face, chest and upper limbs
Distension of the abdomen
Yellow tint
Oesophageal Varices (liver cirrhosis)
What is oesophageal varices caused by?
Portal hypertension (commonest cause being liver cirrhosis)
Varices can burst -> upper GI bleed
• Portal Hypertension Causes:
– Pre-hepatic
– Intra-hepatic
– Post-hepatic
Oesophageal Varices:
Treatment
(Active Bleeding)
- Resuscitate
Correct coagulopathy - Terlipressin: Vascoconstrictor
- Constricts splanchnic vessels
- Caution in arterial disease
- Broad spectrum antibiotics (Tazocin/Ciprofloxacin) for SBP prophylaxis
- Gastroscopy (URGENT):
- Variceal banding- Band on tip of endoscope, varix is sucked into the band which then compresses the bleeding varix (preferred to sclerotherapy)
- Scleroptherapy- inject varices with sclerosing agent which thromboses varices
- Balloon Tamponade: Used if OGD therapy failed/contra-indicated or if exsanguinating haemorhage
- Sengstaken-Blakmore tube: Passed into stomach and balloon inflated and pulled up to lower oesophagus to compress bleeding varix
- Oesophageal tube inflated if bleeding fails to stomach with stomach balloon
Treatment of chronic oesophageal varices:
- Non-selective beta blockers E.g. Propanolol:
- Reduces portal inflow and thus portal pressure by: reducing cardiac output; and causing splanchnic arterial dilatation.
- Endoscopic Treatment: Endoscopic surveillance
- Repeated courses of banding at 2 week intervals
- Transjugular intrahepatic portosystemic shunt (TIPSS): - Via jugular vein, guidewire passed to liver and shunt forced open to form a channel from portal to systemic system and thus reduces portal pressure
22 year old student presents with 3 episodes of haematemesis over 3 hours preceded by recurrent episodes of vomiting following a heavy alcohol binge. Clinically he is euvolaemic and the haematemesis seems to have resolved.
Mallory - Weiss Tear
What is a Mallory - Weiss tear?
• Mucosal tear at lower oesophageal junction
• Usually secondary to coughing or retching
• Haemorhage may be large but majority stop sponatenously
Doesn’t normally need active treatment
40 year old man presents with haematemesis. Has had a four week history of epigastric pain worse just before eating food and radiates to his back, pain is relieved eating, especially milky foods
Duodenal Ulcer (worse just before eating food, relived by food especially milk)
40 year old man presents with haematemesis. Has had a four week history of epigastric pain worse after eating food and weight loss
Gastric Ulcer (worse after eating food and therefore causes weight loss)
Peptic Ulcer disease
• Cancauseacutebleed
• Dyspepsia
• Gastric Ulcer (GU)
– Commonest site= Lesser curvature – Pain after eatingàweight loss
• Duodenal Ulcer (DU)
– Four times commoner than GU
– Commonest site= duodenal cap
– Pain before eating/at night…relieved by eating/alkaline foods e.g. Milk
– Pain radiates to back
Risk factors of peptic ulcers
• H.Pylori (90% of DU; 80% of GU)
• Drugs: NSAIDs, Aspirin, steroids
• Smoking
• GU:
– Reflux of duodenal contents
– Delayed gastric emptying
– Stress: Cushing’s ulcer (neurosurgery); Curling’s ulcer (burns)
• DU:
– Increased gastric secretions & gastric emptying – Blood group O
How does H. Pylori cause peptic ulcers
• Impairs ulcer healing and causes ulcers
• Damages parietal cells -> gastrits/duodenitis/achlorhydria
• Spiral/helical shaped, gram negative
• Gastric epithelium because:
– Flagella allows quick movement through acidic lumen into the deep mucus surrounding of gastric epithelium
– Chemotaxis- Can sense the more alkaline areas in the epithelial lining and move towards these areas and contains adheisns that adhere to epithelial cells
– Secretes urease (catalyzes urea -> ammonia+CO2). Ammonia acts as a buffer to acid
40 year old man with known gastric ulcers presents with projectile vomiting. Dyspepsia now resolved but had worsening nausea over past month with vomiting in the past week, especially after large meals. Also finds food particles from the day before in vomitus.
Complication?
Gastric Outflow Obstruction
- Caused by: active ulcer with surrounding oedema, or fibrosis from healing ulcer
- Can lead to dehydration, metabolic alkalosis, electrolyte loss
- Management: NG tube, endoscopic dilatation, surgical
Peptic ulcer disease complications and management:
Bleeding
Malignancy
Conservative:
- Stop smoking, avoid precipitating drugs, food avoidance, reduces stress
Medical: - PPI
- H2- receptor antagonists
- Alginates (symptomatic treatment) ie gaviscon
Surgical:
- Vagotomy/highly selective vagotomy, pyloroplasty, gastrectomy
- Usually only done following complications
70 year old ex-smoker presents with weight loss and dysphagia for 6 weeks. He has suffered from GORD in the past, but the past 5 days he has had intermittent episodes of small volume haematemesis.
Oesophageal carcinoma
70 year old lady with history of pernicious anaemia presents with 1 month of weight loss and pain after eating food. Past 5 days has had haematemesis and melena, OE there is fullness in the epigastric region
Gastric carcinoma
80 year old lady
2 year history of worsening dyspepsia and burning central chest pain after eating, now presents with mild coffee ground vomiting
Cause?
GORD secondary to hiatus hernia (stomach has moved above diaphragm)
Oesophagitis
Oesophagitis
• Inflammation of oesophagus
• Commonest cause: oesophageal reflux
• Others:
– NSAIDs
– Irritant substances
– Infections:
• CMV,
• herpes simplex
• Candida
Duodentitis
Duodenitis
• Duodenal inflammation
• Causes similar to gastritis
• Difficult to distinguish between duodenitis and gastritis
Gastritis
Gastritis
• Inflammation of stomach lining
• Causes:
– NSAID, Aspirin, steroid use
– H.Pylori
– Autoimmune gastritis (causes pernicious anaemia)
– Duodenalreflux
– Viruses (CMV, herpex simplex)
• Can lead to atrophic gastritis (usually due to recurrent H.Pylori or autoimmune causes)
– Impaired gastric functioning -> Reduced secretions (IF, acid, pepsin) -> B12, iron and other nutrient deficiencies
– Riskofgastricadenocarcinoma
Gastro oesophageal reflux disease
• Dysfunction of lower oesophageal sphincter
• Causes reflux of food from stomach to lower oesophagus
• Risk Factors
– Hiatus hernia, Obesity, Gastric acid hypersecretion, smoking, alcohol, pregnancy, systemic sclerosis, H.Pylori, surgery in achalasia, Drugs (TCA, nitrates)
• If recurrent can lead to:
– Oesophagitis
– Baretts Oesophagus (metaplasia of lower oesophagus)
– Oesophageal stricture
Barrett’s oesophagus:
- Metaplasia of cells of lower oesophagus from squamous epithelium to columnar epithelium (mucus secreting)
Complete surveillance OGD’s to check not getting ademocarcinoma
What is inflammatory bowel disease?
– Inflammatory Bowel Disease mainly describes two conditions: Crohn’s Disease and Ulcerative Colitis
– Long-term conditions involving inflammation of the bowel
– Ulcerative Colitis only affects the colon (large intestine), whereas Crohn’s can affect anywhere from the mouth to the anus
Crohns disease symptoms:
– Diarrhoea/urgency
– Weight loss/failure to thrive
– Abdominal pain and tenderness
– Fever
– Malaise
– Anorexia
– Unlike in ulcerative colitis, there is unaffected bowel between areas of active disease – skip lesions (diseased part then normal part)
Crohn’s disease investigations:
– Bloods: FBC, ESR, CRP, U&E, LFT, INR, Ferritin, TIBC, B12, Folate
– Stool: MC&S and CDT (infection)
– Colonoscopy and rectal biopsy: even if mucosa looks normal, biopsy is needed
– Small bowel enema: detects ileal disease
– Barium enema: cobblestoning, ‘rose-thorn’ ulcers +/- colon
strictures (common exam question)
– Colonoscopy is used to establish disease extent
– MRI can assess pelvic disease
Crohns disease radiological findings:
– Small Bowel Enema: high sensitivity and specificity for examination of the terminal ileum
– Strictures: Kantor’s string sign is the string-like appearance of a contrast-filled bowel loop caused by severe narrowing
– Proximal bowel dilation
– ‘Rose-thorn’ ulcers
– Fistulae
– A colonoscopy will show diffuse erythema with deep ulcers in a patchy distribution
Chrohns disease management
– Stop smoking!!!
– To induce remission:
1. IV hydrocortisone
2. Budesonide (if hydrocortisone give bad side effects)
3. Mesalazine
– To maintain remission:
1. Azathioprine or Mercaptopurine
2. Methotrexate
3. Infliximab/adalimumab
Crohn’s disease inducing remission management:
– Stop smoking!!!
– To induce remission:
1. IV hydrocortisone
2. Budesonide
3. Mesalazine
Crohn’s disease maintaining remission management:
- Azathioprine or Mercaptopurine (immunosuppressive)
- Methotrexate
- Infliximab/adalimumab
Crohn’s disease monoclonal antibody therapy
– Under specialist supervision, monoclonal antibody therapies, adalimumab and infliximab, are options for the treatment of severe, active Crohn’s disease, following inadequate response to conventional therapies.
– Adalimumab and infliximab can be used as monotherapy or combined with an immunosuppressant although there is uncertainty about the comparative effectiveness and long-term side-effects of therapy.
– Side effects: numbness or tingling, vision problems, leg weakness, chest pain, shortness of breath, new joint pain, hives and itching.
Crohn’s disease management:
– ~80% Crohn’s patients will eventually have surgery – ileocaecal resection (usually worst affected part)
– About half of all patients who undergo surgery will develop recurrent disease within ten years
Ulcerative colitis symptoms:
– Bloody diarrhoea
– Urgency
– Tenesmus (rectus pain)
– Abdominal pain, especially in the left lower quadrant
– Extra-intestinal features include:
– Arthritis
– Uveitis (painful, red eye)
– Primary Sclerosing Cholangitis
Ulcerative colitis investigation
– Bloods: FBC, ESR, CRP, U&E, LFT, Blood Culture
– Stool: MC&S and CDT
– Abdominal X-ray: No faecal shadows
– Chest X-ray: Perforation
– Barium enema: Do not do during severe attacks or for diagnosis
– Colonoscopy: Shows disease extent and allows for biopsy
Ulcerative colitis - radiological findings
– Loss of haustrations – featureless , superficial ulceration, pseudopolyps
– Long-standing disease: colon is narrow and short a.k.a drainpipe colon
– Sacroiliitis
– Whole colon, without skips, irregular mucosa, loss of normal haustra markings
Ulcerative colitis severity assessment - Truelove & Witts
Common EQ
Mild
<4 stools a day +/- blood No systemic symptoms Normal ESR and CRP
Moderate
4-6 stools a day with moderate rectal bleeding
Minimal systemic symptoms e.g. temperature of 37.1- 37.8, HR of 70-90bpm, Hb of 105-110g/L
Severe
6 stools a day with severe rectal bleeding
Fever of >37.8, tachycardia >90bpm, Hb <105 g/L abdominal tenderness, distension, decreased bowel sounds
Hypoalbuminemia
Moderate: Topical 5-ASA +/- Oral 5-ASA +/- Oral Steroids -> Treat as severe if no better in 2 weeks
Severe: Admit, IV Hydrocortisone, IV Fluids -> Step-down to oral when well
Ulcerative colitis management:
– To induce remission:
1. Oral aminosalicyates – mesalazine, sulfasalazine
2. Distal disease: rectal mesalazine
– To maintain remission:
1. Oral mesalazine
2. Azathioprine
Significant side effect of mesalazine?
Acute pancreatitis
Crohn’s disease vs ulcerative colitis pathology
Pathology
Crohns disease
Lesions anywhere from mouth -> anus
‘Skip’ lesions
Ulcerative colitis
Inflammation always starts at the rectum and never spreads beyond the ileocaecal valve
Continuous Disease
Crohn’s Disease vs. Ulcerative Colitis
Histology
Histology
Crohn’s disease
Inflammation in all layers from mucosa to serosa
Increased goblet cells
Granulomas
Ulcerative colitis
No inflammation beyond submucosa
Depletion of goblet cells and mucin
Granulomas are infrequent
Crohn’s disease vs ulcerative colitis
Endoscopy
Crohn’s disease
Deep ulcers
Skip lesions – cobblestone
appearance
Ulcerative colitis
Widespread ulceration with preservation of adjacent mucosa - pseudopolyps
Crohn’s Disease vs. Ulcerative Colitis
Features
Features
Crohn’s disease
Diarrhoea (non-bloody)
Weight loss
Mouth ulcers
Perianal disease
Mass in RIF
Ulcerative colitis
Bloody Diarrhoea
Tenesmus – cramping rectal pain
Abdominal pain in LLQ
Crohn’s Disease vs. Ulcerative Colitis
Extra intestinal
Crohn’s disease
Extra-Intestinal
Gallstones – secondary to reduced bile acid reabsorption
Oxalate renal stones
Ulcerative colitis
Primary sclerosing cholangitis – chronic liver disease with ++ pain
Crohn’s Disease vs. Ulcerative Colitis
Complications
Complications
Crohn’s disease
Bowel obstruction
Fistula
Colorectal cancer
Ulcerative colitis
Risk of colorectal cancer increased in ulcerative colitis
Inflammatory bowel disease complications:
– Stoma formation (ileostomy or colostomy) - this may be needed after an operation to remove part of the bowel
– Persistent blood loss causing anaemia
– Perforation of the bowel wall
– Narrowing of the bowel causing obstruction (stricture), more common with Crohn’s disease.
– Ulceration and abnormal passages (fistulae) around the anus
– Severe dilatation of the colon - called toxic megacolon, this is more common with ulcerative colitis than Crohn’s disease
– Greatly reduced absorption of food from the bowel -> malnutrition
– Increased risk of bowel cancer, especially in ulcerative colitis
You are told by your registrar that one of your inpatients has been diagnosed with primary sclerosing cholangitis (PSC). Your registrar suspects that the patient may have an associated condition. Primary sclerosing cholangitis is associated with which disease?
Ulcerative colitis
You read a report which was handwritten in a patient’s medical notes who you suspect has inflammatory bowel disease. The report reads, ‘… there is cobblestoning of the terminal ileum with the appearance of rose thorn ulcers. These findings are suggestive of Crohn’s disease’. Select the most likely investigation that this report was derived from:
– A. Colonoscopy
– B. Sigmoidoscopy
– C. Barium follow through
– D. Abdominal CT
– E. Abdominal ultrasound
– C. Barium follow through
You are told by your registrar that one of the clinic patients has been admitted with a ‘flare up’ of ulcerative colitis (UC) which he reports as being severe. From the list of answers below, select the parameters which are likely to reflect a severe flare up of ulcerative colitis:
– A. Fewer than four bowel motions per day with large amounts of rectal bleeding
– B. Between four and six bowel motions per day with large amounts of rectal bleeding
– C. More than four bowel motions per day with large amounts of rectal bleeding
– D. More than five bowel motions per day with large amounts of rectal bleeding
– E. More than six bowel motions per day with large amounts of rectal bleeding
– E. More than six bowel motions per day with large amounts of rectal bleeding
A 28-year-old man undergoes a sigmoidoscopy for longstanding diarrhoea and weight loss. On visualization of the rectum, the mucosa appears inflamed and friable. A rectal biopsy is taken and the histology shows mucosal ulcers with inflammatory infiltrate, crypt abscesses with goblet cell depletion. What is the most likely diagnosis describing the histology report?
Ulcerative colitis
A 29-year-old anxious man is diagnosed with mild Crohn’s disease. Due to time constraints, the patient was asked to come back for a follow-up appointment to discuss Crohn’s disease in more detail. The patient returns with a list of complications he researched on the internet. Which of the following are not associated with Crohn’s disease?
– A. Cigarette smoking reduces incidence
– B. Fistulae formation
– C. Abscess formation
– D. Non-caseating granuloma formation
– E. Associated with transmural inflammation
– A. Cigarette smoking reduces incidence
You are asked to see a 29-year-old woman diagnosed with ulcerative colitis 18 months ago. Over the last 4 days she has been experiencing slight abdominal cramps, opening her bowels approximately 4–5 times a day and has been passing small amounts of blood per rectum. The patient is alert and orientated and on examination her pulse is 67, blood pressure 127/70, temperature 37.3°C and her abdomen is soft with mild central tenderness. PR examination is nil of note. Blood tests reveal haemoglobin of 13.5 g/dL and a CRP of 9 mg/L. The most appropriate management plan for this patient is:
– B. Topical 5-ASA +/- Oral 5-ASA +/- Oral steroids + discharge
IBS symptoms
O Common condition affecting the digestive system
O Symptoms:
O Abdominal cramping O Bloating
O Flatulence
O Diarrhoea
O Constipation
Common causes of IBS:
O Mixed group of abdominal symptoms with no clear organic cause
O The specific cause of IBS is currently unknown, but it has been linked to:
O Food passage being too fast/slow
O Oversensitive nerves in the large intestine
O Stress
O Family history of IBS
How is IBS diagnosed?
Common Exa Question
O Consider IBS if >6 months of
O Abdominal pain, and/or
O Bloating, and/or
O Change in bowel habit
O Remember: ABC
O Positive diagnosis if abdominal pain is relieved by defecation or is associated with altered bowel frequency/stool form plus 2/4 of:
O Altered stool passage (straining, incomplete)
O Abdominal bloating/distension
O Symptoms worse with eating
O Passage of mucus
Differential diagnoses of IBS
O Coeliac Disease
O Inflammatory Bowel Disease
O Crohn’s Disease
O Ulcerative Colitis
O Cancer
O Ovarian Cancer O Bowel Cancer
Red flags with common IBS symptoms
O Rectal bleeding
O Unexplained weight loss
O Family history of bowel/ovarian cancer
O If onset is >60 years old
Q: What would you do if you had a female patient age 55 present to clinic with IBS symptoms?
A: CA125 ?Ovarian Cancer
Tumour marker blood test
Investigations for suspected IBS to rule out differentials
O Full Blood Count
O Erythrocyte Sedimentation Rate
O C-Reactive Protein
O Liver Function Tests
O Tissue Transglutaminase Antibodies
O Coeliac Screen
If patient is >50 years or has any markers of organic disease – e.g. pyrexia, weight loss, PR blood a colonoscopy should be completed before diagnosing IBS. What further investigations should be complete?
O Upper GI Endoscopy – Dyspepsia, Reflux
O Small Bowel Radiology – Crohn’s
O Duodenal Biopsy – Coeliac disease
O Giardia Tests – Can trigger IBS
O ERCP/MRCP - Pancreatitis
when does a referral need to be made during an IBS diagnosis?
O Patient may need referral to various specialties; gastro, surgery, dieticians, psychology, dermatology, pain clinic
O If diagnosis is unclear
O If changing symptoms in established IBS O Rectal mucosal prolapse
O Food intolerance
O Stress/Depression
O Chronic pain
What are the 3 types of IBS?
O Diarrhoea-predominant (D-IBS) – may require further testing if ?small bowel disease,
O Constipation-predominant (C-IBS), and
O Alternating constipation and diarrhoea (A- IBS).
Management of IBS
O No known cure – treatment is rarely even 50% successful. Management aims to reduce symptoms
O Initial therapy should always be with lifestyle modification – centrally surrounding diet
O If lifestyle modifications alone are unsuccessful, targeted pharmacological approaches can be used
Lifestyle modification of IBS
O Regular meals – eaten slowly
O Avoid missing meals/having long gaps between meals
O 8 cups of liquid a day – water/uncaffeinated drinks
O Restrict tea, coffee, alcohol and fizzy drinks
O Limit fresh fruit to 3/day
O To reduce wind and bloating, increase intake of oats
Medication types for IBS
O First-line pharmacological treatment is according to the predominant symptom:
O Pain: Antispasmodic agents
O Constipation: Laxatives
O Diarrhoea: Loperamide
IBS constipation treatment
O Avoid insoluble fibre, such as bran – as it can worsen flatulence and bloating
O Bisacodyl and sodium picosulfate can aid constipation relief
O Ispaghula (fibre gel) should be used instead of lactulose, as lactulose can increase gas production
O For patients with constipation who are not responding to conventional laxatives, consider Linaclotide if:
O Maximum tolerated doses of previous laxatives from different classes have not helped, AND
O Constipation has been present for 12 months
Treatment for diarrhoea predominant IBS:
O Avoid sorbitol sweeteners
O Bulking agents – limited evidence
O Loperamide 2mg after each loose stool – max. 16mg/day
O Side effects:
O Colic
O Bloating
O Ileus
Treatment for pain caused by IBS
O Oral antispasmodics, e.g:
O Mebeverine 135mg/8hr (OTC)
O Alverine Citrate 60-120mg/8hr
O Dicycloverine 10-20mg/8hr
O Can also add simeticone – this is found in Imodium Plus!
What is meant by constipation?
• Defecation that is unsatisfactory because of infrequent stools, difficulty in passing stools or sensation of incomplete emptying
• Bowel movement less than 3 times a week Can be :
• Short term
• Chronic constipation - > 3months
• Faecal impaction – retention of faeces
What is the definition of diarrhoea?
What are sick day rules?
Acute <14 days – usually bacteria, viral, food , anxiety
Persistent >14 days -
Chronic > 4 weeks – IBS, Diet, IBD, Coeliac , bowel cancer
SICK day rules- stoping medication due to kidney function
Viral gastroenteritis causes
Noravirus
• Diarrhoea and projectile vomiting
• “Winter vomiting bug”
• Most common cause of viral gastroenteritis
• Outbreaks typically occur in semi-closed communities e.g. Care
homes, cruise ships
• Causes watery diarrhoea with vomiting, fever, abdominal pain
Rotavirus
What is the gold standard test for coeliac disease?
Endoscopy with duodenal-jejunal biopsy
Tissue transglutaminase autoantibodies
Chronic pancreatitis symptoms
Symptoms: Epigastric pain, radiates to back, eased lying forward, pain typically relapse and remit
– Symptoms of malabsorption (reduced pancreatic enzyme secretion): Bloating, steatorrhoea, weight loss
Causes of chronic pancreatitis
Causes
– Commonest: Alcohol
– Rarer causes: Cystic fibrosis, familial, haemochromatosis, pancreatic duct destruction (stones, tumor), Hyperparathyroidism
What two tissue types are the pancreas made up of?
Exocrine (digestive tissue approx 90%)
Endocrine (blood glucose tissue approx 10%)
Stages of non alcoholic fatty liver disease
1) Hepatic Steatosis
- Accumulation of fat globules within hepatocytes
2) Steatohepatitis
-Necrosis of hepatocytes
-Neutrophil-dominant inflammatory reaction
-Mallory bodies: Eosinophilic accumulations
-Continued exposure causes development of fibrosis mainly around central vein (initially)
3)Fibrosis and Cirrhosis
-Irreversible architectural disturbance
-Normal liver architecture replaced by nodules of regenerated liver cells separated by bands of collagenous fibrosis
General functions of the liver
• Protein synthesis
• Carbohydrate Metabolism
• Lipid metabolism
• Degradation of Ammonia -> urea
• Formation and excretion of bilirubin
• Hormone inactivation e.g. insulin, oestrogen
• Immunological functions
• Drug metabolism
Liver blood supply
Blood Supply
• The liver receives blood from two different sources
• Hepatic portal vein 2/3 : carries venous blood from the
intestines, pancreas and spleen.
• Hepatic artery 1/3 : brings oxygenated blood to the liver.
• With the bile duct, these two blood vessels form the portal triad.
What is ascites?
And what is its treatment?
• Increased hydrostatic pressure:
– portal hypertension + splanchnic vasodilation
• Salt and Water retention
• Reduced oncotic pressure:
– Hypoproteinaemia
• Treatment:
– Salt and fluid restriction
– Propanol
– Ascitic tap
– Oral diuretic (Spironalactone- 100mg/day, Furosemide- 40mg/day
– Large volume paracentesis (with Albumin)
– TIPSS for refractory ascites
Secondary disease to portal hypertension and angiogenesis
Oesophageal varices
What is Encephalopathy and how is it treated?
• Ammonia toxic to brain cells
• Precipitated by:
• sedatives, constipation, dehydration, infection, GI bleed, TIPSS
• Treatment:
• Treat underlying cause
• Lactulose + daily enemas(aim for 3 bowel motions/day)
• Rifaximin (non-absorbitive antibiotic, reduces gut bacteria and hence gut ammonia production): Can be used in second episode encephalopathy
How is acute liver failure identified?
Acute liver failure is a syndrome of acute liver dysfunction without underlying chronic liver disease.
ALF is characterised by the presence of coagulopathy (INR > 1.5) and hepatic encephalopathy. This is usually accompanied by transaminitis (i.e. deranged liver function tests ALT/AST) and hyperbilirubinaemia. ALF is usually initiated following a severe acute liver injury (ALI).
Classifications of acute liver failure
Hyperacute: HE within 7 days of noticing jaundice. Best prognosis as much better chance of survival and spontaneous recovery.
Acute: HE within 8-28 days of noticing jaundice
Subacute: HE within 5-12 weeks of noticing jaundice (ALF may be defined up to 28 weeks). Worst prognosis as usually associated with shrunken liver and limited chance of recovery.
Primary cause of ALF
Viruses (A, B, E)
Paracetamol
Non-paracetamol medications (e.g. Statins, Carbamazepine, Ecstasy)
Toxin-induced (e.g. Amanita phalloides - death cap mushroom that contains amatoxins and phallotoxins)
Budd-chiari syndrome
Pregnancy-related (e.g. fatty liver of pregnancy, HELLP syndrome)
Autoimmune hepatitis
Wilson’s disease
Acute liver failure clinical features
ALF is characterised by jaundice, confusion and coagulopathy.
Describe coeliac disease.
Coeliac disease is an autoimmune condition triggered by eating gluten. It can develop at any age and is thought to be caused by genetic and environmental factors. There is a link with other autoimmune conditions, particularly type 1 diabetes and thyroid disease.
TOM TIP: Remember for your exams that we test all new cases of type 1 diabetes and autoimmune thyroid disease for coeliac disease, even if they do not have symptoms.
Coeliac disease pathophysiology
In patients with coeliac disease, autoantibodies are created in response to exposure to gluten. These autoantibodies target the epithelial cells of the small intestine, leading to inflammation. These antibodies relate to disease activity and will rise with more active disease and may disappear with effective management. There are three antibodies related to coeliacs (particularly worth remembering the first two):
• Anti-tissue transglutaminase antibodies (anti-TTG) • Anti-endomysial antibodies (anti-EMA) • Anti-deamidated gliadin peptide antibodies (anti-DGP)
Inflammation affects the small bowel, particularly the jejunum. The surface of the small intestine is covered in projections called villi, which increase the surface area and help with nutrient absorption. Coeliac disease causes atrophy of the intestinal villi, resulting in malabsorption.
Presentation of coeliac disease
Presentation
Coeliac disease is often asymptomatic and is under-diagnosed, so have a low threshold for testing for coeliac disease in patients where it is suspected.
Presenting symptoms can include:
• Failure to thrive in young children
• Diarrhoea
• Bloating
• Fatigue
• Weight loss
• Mouth ulcers
Dermatitis herpetiformis is an itchy, blistering skin rash, typically on the abdomen, caused by coeliac disease. Anaemia occurs secondary to malabsorption and deficiency of iron, B12 or folate. Rarely coeliac disease can present with neurological symptoms: ○ Peripheral neuropathy ○ Cerebellar ataxia ○ Epilepsy
Diagnosis of coeliac disease
Diagnosis
The patient must continue eating gluten while being investigated. Antibodies and histology may be normal if the patient is gluten-free.
The first-line blood tests are:
• Total immunoglobulin A levels (to exclude IgA deficiency)
• Anti-tissue transglutaminase antibodies (anti-TTG)
Anti-endomysial antibodies (anti-EMA) are a second-line option where there is doubt (e.g., a borderline result). TOM TIP: Initial anti-TTG and anti-EMA antibody tests are IgA. Some patients have an IgA deficiency. When you test for these antibodies, it is important to test for total immunoglobulin A levels because if the total IgA level is low, the antibody test will be negative, even in a patient with coeliac disease. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies. Patients with a positive antibody test are referred to a gastroenterologist to confirm the diagnosis by endoscopy and jejunal biopsy. Typical biopsy findings are: ○ Crypt hyperplasia ○ Villous atrophy
Complications of coeliac disease
Complications
If someone with coeliac disease continues eating gluten, even in tiny amounts, it can lead to:
• Nutritional deficiencies
• Anaemia
• Osteoporosis
• Hyposplenism (with immunodeficiency, particularly to encapsulated bacteria such as Streptococcus pneumoniae)
• Ulcerative jejunitis
• Enteropathy-associated T-cell lymphoma (EATL)
• Non-Hodgkin lymphoma
• Small bowel adenocarcinoma
Describe Crohn’s disease
Crohn’s Disease
• Chronic inflammatory disorder characterised by patchy, transmural inflammation of intestinal mucosa
• Can affect any part of the gastrointestinal tract from mouth to anus
• Skip lesions are the main identifier
• Inflammation is found in all layers from mucosa to serosa, with increased goblet cells and granulomas
C - Cobblestone appearance
R - Rosethorn ulcers
O - Obstruction
H - Hyperplasia of lymph nodes
N - Narrowing of lumen
S - Skip lesions
N – No blood or mucus (less common)
E – Entire GI tract
S – “Skip lesions” on endoscopy
T – Terminal ileum most affected and Transmural (full thickness) inflammation
S – Smoking is a risk factor (don’t set the nest on fire)
What tests (microscopic/macroscopic findings) confirm Crohn’s disease?
Macroscopic = seen on endoscopy
• Cobblestone appearance - caused by superficial ulcers which become deep and sepiginous (wavy margin)
• Bowel wall thickening
• Lumen narrowing
• Deep ulcers
• Fistulae
• Fissures
Microscopic = seen on histology
• Inflammatory infiltration:
○ Hyperplasia of lymph nodes
○ Granulomas
• Skip lesions
• Transmural ulceration (from mucosa to serosa)
• Increased goblet cells
Complications of Crohn’s disease.
Complications
• Bowel obstruction (stricture)
○ Thickened wall of intestines causes narrowing of the bowel
○ This is more common in Crohn’s than UC
• Fistula
○ Inflammation goes through the wall and creates tunnels
○ Abnormal passage between 2 organs or an organ and the outside of your body
○ Can become infected
• Abscesses
○ Swollen, pus-filled pockets of infection in intestinal walls
• Anal fissures
○ Small tears in the anus that may cause itching, pain or bleeding
• Ulcers
• Malnutrition
• Inflammation in other areas of the body
• Colorectal cancer
Presentation of Crohn’s disease.
Presentation
Symptoms
Nausea & vomiting
Fatigue
Low-grade fever
Weight loss
Abdominal pain
Diarrhoea (+/- blood)
Rectal bleeding
Perianal disease
Signs
Pyrexia
Dehydration
Angular stomatitis
Aphthous ulcers
Pallor
Tachycardia
Hypotension
Abdominal pain, mass and distension
Inducing remission in Crohn’s disease
Inducing Remission
• First line: Steroids (e.g. oral prednisolone or IV hydrocortisone)
• If steroids alone don’t work, consider adding immunosuppressant medication under specialist guidance:
○ Azathioprine
○ Mercaptopurine
○ Methotrexate
○ Infliximab
○ Adalimumab
• Apply nutritional alterations
○ Exclusive enteral nutrition (EEN) is a liquid diet that excludes all food + drink expect water.
○ Supplement drink at 25kcal/kg/day
○ 1g/kg/day of protein
Maintaining remission in Crohn’s disease
Maintaining Remission
• Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well. • First line = thiopurines: ○ Work through purine synthesis inhibition in lymphocytes -> immunosuppressive properties ○ E.g.Mercaptopurine + Azathioprine ○ SE: pancreatitis + hepatotoxicty • Alternatives: ○ Methotrexate ▪ Inhibits dihydrofolate reductase ▪ Immunomodulatory + anti-inflammatory properties ▪ SE: bone marrow suppression, hepatotoxicity + pulmonary toxicity ○ Monoclonal antibodies ▪ E.g. Infliximab + Adalimumab ▪ SE: numbness/tingling, vision problems, leg weakness, chest pain, SOB, new joint pain, hives/itching
What surgery can be done for Crohn’s disease?
Surgery
• Ileocaecal resection = when the disease only affects the distal ileum it is possible to surgically resect this area and prevent further flares of the disease.
○ Often recurs within 10 years
• Stoma
○ May be needed after an operation to remove part of the bowel
○ Colostomy = created with loop of large intestine, solid waste
○ Ileostomy = created with end of small intestine, liquid waste + undigested food
• Surgery can also be used to treat strictures and fistulas secondary to Crohns disease.
What is ulcerative colitis?
UC is a disease of the colonic mucosa, which has a relapsing-remitting course. It is characterised by inflammation of the mucosa, affecting the rectum (rectal sparing occurs but is rare) and may progress proximally through the colon. The terminal ileum may be affected (‘backwash ileitis’) in those with extensive colitis.
Diagnosing ulcerative colitis
Diagnosis is based on macroscopic assessment (e.g. endoscopy) and histological evidence (e.g. biopsy) of colonic inflammation.
Imaging
Abdominal X-rays are useful for looking at dilatation of the bowel and perforations. Dilatation is said to be present if:
• Small bowel: diameter > 3cm
• Large bowel: diameter > 6cm
• Caecum: diameter > 9cm
Computed tomography may be organised where there is concern regarding complications (e.g. toxic megacolon) and prior to surgery.
Endoscopy
Colonoscopy is considered the diagnostic investigation of choice as it allows assessment of the whole colon. Biopsies can be taken for histological assessment of the mucosa. Caution should be taken during acute flares due to the increased risk of perforation. Sigmoidoscopy may be used as an alternative endoscopic test.
Presentation of ulcerative colitis
Presentation:
The hallmark of UC is bloody diarrhoea / rectal bleeding.
Patients with UC may become acutely unwell with features of hypovolaemic shock, so it is important to resuscitate patients with respect to airway, breathing and circulation.
Symptoms
• Weight loss
• Fatigue
• Abdominal pain
• Loose stools
• Rectal bleeding
• Tenesmus (incomplete emptying)
• Urgency
Signs
• Febrile
• Pale
• Dehydrated
• Abdominal tenderness
• Abdominal distension/mass
• Tachycardic, hypotensive
Additional symptoms of ulcerative colitis
Extra-colonic manifestations
Approximately 25% of patients will develop extra-colonic manifestations during their lifetime.
Musculoskeletal
Arthritis is the most common extracolonic manifestation, which may be a simple peripheral arthritis or more complex spondyloarthropathy (e.g. ankylosing spondylitis).
Eyes, mouth & skin
Uveitis (inflammation of the uvea) is strongly associated with UC.
Extracolonic manifestations of the mouth commonly include aphthous ulcers. The skin is another organ widely affected by UC, leading to erythema nodosum, which is a type of panniculitis that classically results in multiple, painful, purple nodules on the anterior aspect of the shins.
Hepatobiliary
Numerous hepatobiliary pathologies are associated with UC including fatty liver disease and autoimmune liver disease.
Haematological
Two common haematological problems associated with UC are anaemia and thromboembolism.
Gastroenteritis
Acute gastritis is inflammation of the stomach and presents with nausea and vomiting. Enteritis is inflammation of the intestines and presents with diarrhoea. Gastroenteritis is inflammation all the way from the stomach to the intestines and presents with nausea, vomiting and diarrhoea.
Gastroenteritis management
A sample of the faeces can be tested with microscopy, culture and sensitivities to establish the causative organism and antibiotic sensitivities.
Assess patients for dehydration. Attempt a fluid challenge and if they are able to tolerate oral fluid and are adequately hydrated consider outpatient management. If not vomiting and tolerated then rehydration solutions (e.g. dioralyte) can be used. If dehydrated then intravenous fluids can be used to rehydrate them and prevent dehydration until oral intake is adequate again.
Slowly introduce a light diet in small quantities once oral intake is tolerated again. Advise them to stay off work or school for 48 hours after symptoms have completely resolved.
Antidiarrhoeal medication such as loperamide and antiemetic medication such as metoclopramide are generally not recommended but may be useful for mild to moderate symptoms. Antidiarrhoeals should be avoided in e. coli 0157 and shigella infections and where there is bloody diarrhoea or high fever.
Antibiotics should only be given in patients that are at risk of complications and once the causative organism is confirmed.
Post gastroenteritis complications
Post-Gastroenteritis Complications
There are possible post-gastroenteritis complications:
• Lactose intolerance
• Irritable bowel syndrome
• Reactive arthritis
• Guillain–Barré syndrome
What viruses generally cause gastroenteritis?
Viral Gastroenteritis
Viral gastroenteritis is the most common. Viral gastroenteritis is highly contagious.
• Rotavirus
• Norovirus
• Adenovirus is a less common cause and presents with a more subacute diarrhoea
e coli and gastroenteritis
E. coli
Escherichia coli (E. coli) is a normal intestinal bacteria. Only certain strains cause gastroenteritis. It is spread through contact with infected faeces, unwashed salads or water.
E. coli 0157 produces the Shiga toxin. This causes abdominal cramps, bloody diarrhoea and vomiting. The Shiga toxin destroys blood cells and leads to haemolytic uraemic syndrome(HUS).
The use of antibiotics increases the risk of haemolytic uraemic syndrome therefore antibiotics should be avoided if E. coli gastroenteritis is considered.
Campylobacter Jejuni and gastroenteritis
Campylobacter Jejuni
Campylobacter is a common cause of travellers diarrhoea. It is the most common bacterial cause of gastroenteritis worldwide. Campylobacter means “curved bacteria”. It is a gram negative bacteria that is curved or spiral shaped. It is spread by:
○ Raw or improperly cooked poultry
○ Untreated water
○ Unpasteurised milk
Incubation is usually 2-5 days. Symptoms resolve after 3-6 days. Symptoms are: § Abdominal cramps § Diarrhoea often with blood § Vomiting § Fever Antibiotics can be considered after isolating the organism where patients have severe symptoms or other risk factors such as HIV or heart failure. Popular antibiotic choices are azithromycin or ciprofloxacin.
Shigella and gastroenteritis
Shigella
Shigella is spread by faeces contaminating drinking water, swimming pools and food. The incubation period is 1-2 days and symptoms usually resolve within 1 week without treatment. It causes bloody diarrhoea, abdominal cramps and fever. Shigella can produce the Shiga toxin and cause haemolytic uraemic syndrome. Treatment of severe cases is with azithromycin or ciprofloxacin.
