GI/Liver Flashcards
List the layers of the bowel wall
4 layers
Mucosa
> Epithelium
> Lamina propria
> Muscularis mucosae
Submucosa
Muscularis propria (or externa)
> Inner circular layer
> Outer longitudinal layer
Subserosa
> Loose, fatty connective tissue
Describe the histological features of ulcerative colitis
Diffuse involvement of lower GIT
Predominantly affects left side of colon in a confluence pattern (diffuse)
Terminal ileum can be involved but generally only in severe cases where the whole bowel is involved (pancolitis)
No transmural changes, focused in mucosa
Crypt architectural changes are very marked
Little / no fibrosis
No granulomas
Describe the treatments for ulcerative colitis
Mesalazine
> Targets inflammation in GI tract
> 4.8g > 2.4g daily for induction of remission in moderate UC
> 2.4g daily as a maintenance dose
> Reduces frequency of flare ups and severity
Escalation of treatment
> Azathioprine (or mercaptopurine)
» With severe relapse / frequently relapsing disease
» Requiring 2 or more corticosteroid courses in a 12 month period
» Risks
»> Intolerance
»> Lymphoma, NMSC
Biologics
Surgery: cure
> Sub-total colectomy
Describe the complications associated with ulcerative colitis
Local
> Haemorrhage
> Toxic dilation aka toxic megacolon
Systemic
> Skin
>Erythema nodosum
> Pyoderma gangrenosum
> Liver
> Sclerosing cholangitis
> Cholangiocarcinoma
> Eyes
> Iritis
> Uveitis
> Episcleritis
> Ankylosing spondilitis
> Malignancy
> Colorectal cancer
» Screening colonoscopy after 10y of disease
» Intervals determined by risk – extent of disease
Describe the features of Crohn’s disease
Chronic inflammatory condition affecting anywhere from mouth to anus
Risk factors
> Smoking
» Stopping reduces relapse rate, need for immunosuppression and surgery
Peak incidence 15-25y
Features
> Abdominal pain
> Diarrhoea (watery > bloody)
> Commonly affects ileum and right sided colon
> Weight loss
> Fistulae, abscesses, oropharyngeal, gastroduodenal
Extra-intestinal symptoms
> Eyes – episcleritis, uveitis
> Joints – sacroilitis, inflammatory arthropathy
> Skin – erythema nodosum
Describe the pathological and histological features of Crohn’s disease
Granulomas – hallmark of Crohn’s
Differences between UC & Crohn’s
> Distribution of inflammation
> Small and large bowel inflammation
> Tends to involve proximal large bowel
> Patchy inflammation resulting in macroscopic “skip lesions”
Type of inflammation
> Transmural process
> Deep ulcerating inflammation
Perianal disease e.g. fistulas / sinus tracts
Macroscopic
> Small bowel strictures
> Narrowed areas with mucosal ulceration
Which investigations are used in the diagnosis of IBD?
Abdominal X-ray
> Exclude small bowel obstruction
Ileocolonoscopy
> Apthous ulcers in terminal ileum
> Active illeitis on biopsy
Faecal calprotectin
> Calcium-binding protein, predominantly derived from neutrophils
> Single 20g sample, stable for 5 days
> Useful test to differentiate between IBD / IBS and assess activity in IBD
> Sensitive but not disease specific
Stool cultures
MR / CT enterography
> Show ulceration and inflammation in terminal ileum
> Mucosal enhancement and luminal narrowing
Describe the staging of IBD
Montreal classification – staging of disease
What are risk factors for severe disease in IBD?
Risk factors for severe disease
Young onset
Smoking
Perianal disease
Stricturing SB disease
Describe the treatment of Crohn’s disease
Thiopurines
> Azathioprine and 6-mercaptourine
Biologics
> TNF-alpha antagonists
> Infliximab / adalimumab
Anti-integrins (alpha-4,beta-7)
> Vedolizumab
Anti-interleukin 12/23
> Ustekinumab
Methotrexate
Surgery
> 70% lifetime risk
> Aimed at removing the minimal amount of GI tract (fistulae, strictures, severe inflammation)
> Recurrence common – 50% further surgery
Describe the pathological changes associated with Crohn’s disease
Acute
> Acute inflammation
> Ulceration
> Loss of goblet cells
> Crypt abscess formation (neutrophils present)
Chronic
> Architectural changes
> Paneth cell metaplasia
> Chronic inflammatory infiltrates in lamina propria
> Neuronal hyperplasia
> Fibrosis
Describe the presentation, investigations, risk factors and treatment associated with infective colitis
Presentation
> Short history of diarrhoea and vomiting
> Abrupt onset and resolution of symptoms
> Systemic upset and fevers prominent
Risk factors
> Travel
> Unwell contacts
> Immunocompromised
Investigations
> Stool sample / CDT
» Need 4 for 90% sensitivity
Treatment
> Conservative if immunocompetent
> Even if bacterial gastroenteritis is confirmed
Describe the presentation and treatment of ischaemic colitis
Presentation
> Abrupt onset pain and bloody diarrhoea +/- SIRS
> Hypoperfusion > embolic
Risk factors
> Elderly
> CV disease
> Heart failure
> Constipation
> Female sex
> Smoker
More severe than IBD
Treatment
> Conservative
> IV fluids +/- antibiotics
Describe the assessment, investigations and treatment of severe ulcerative colitis
Assessment: Truelove and Witts’ classification
Stool frequency
>8/day
>3 & CRP >45 on day 3 predicts need for colectomy in 85%
Treatment
> IV steroids
> Methylprednisolone
> Hydrocortisone
> If non-responsive to steroids
> Surgery: colectomy
> Rescue medical treatment with
» Cyclosporin
» Infliximab (monoclonal antibody to TNF-alpha)
Investigations
> Stool culture
> Bloods
> Abdominal X-ray
» Essential in severe colitis
» Helps assess disease extent and severity
> > > Megacolon
> Transverse diameter of the colon (usually transverse colon >5.5cm or caecum >9cm)
> > > Toxic megacolon
> Megacolon and signs of systemic toxicity
> Emergency colectomy
> Risk of perforation and peritonitis
Other inpatient investigations
> Endoscopy
> Flexible sigmoidoscopy
> Colonoscopy
> CT scan
» Exclude signs of subclinical perforation
Describe the diagnosis and treatment of coeliac disease
Diagnosis
> Serology
> IgA anti-endomysial (immunofluorescence)
> > Anti tTG IgA (quantitative ELISA)
> Duodenal biopsy (second and first part of duodenum)
> Histology: crypt hyperplasia and villous atrophy
Treatments
> Gluten free diet
> Nutritional assessment
> Bone health (FRAX score/DEXA)
> Screen for osteoporosis due to malabsorption of calcium
> If anaemia (iron deficiency or B12/folate), supplementation
> Vaccination (due to increased risk of hyposplenism)
> Pneumococcus
> Meningococcus
Describe the complications associated with coeliac disease
Functional hyposplenism
Microcytic anaemia
Osteoporosis
Low BMI
Calcium/ vitamin D deficient
Dermatitis herpetiformis
Increased risk of cancer, specifically lymphoma (T cell) and small bowel adenocarcinoma
IgA deficiency
List the causes of acute hepatitis
Infections
> Hepatitis A, B, C, D, E
> EBV, CMV, toxoplasmosis
> Leptospirosis
> Q fever
> Syphilis
> Malaria
> Viral haemorrhagic fever
Toxins
Drugs
Alcohol
Autoimmune
Wilson’s: caeruloplasmin test
Haemochromatosis: assess ferritin & transferrin saturation
Describe the clinical features, diagnosis and treatment of hepatitis A
RNA virus
Transmission
> Faeco-oral
> Human reservoir
Virus can survive for months in contaminated water
Virus shed biliary tree into gut
No chronic carriage
Good immunity after infection or vaccination
Clinical features
> Incubation period 2-4 weeks
> Age is main determinant of severity
> Mostly asymptomatic in children <5 years
> Mortality rate 1.5% if >50 year
Diagnosis
> Acute hepatitis A – IgM positive or HAV RNA in blood or stool
> Previous Hep A or vaccinated – IgM positive
Treatments
> No specific treatments
> Maintain hydration, avoid alcohol
> Self-limiting illness
> No role for vaccine or immunoglobulin as treatment
Vaccination
> Hepatitis A vaccine
» Inactivated virus
» 95% efficacy after 4 weeks – 2nd dose gives life protection
» Pre-exposure: travellers, homosexual men, IVDU, chronic liver disease patients
» Post-exposure: outbreak cancer
Describe the clinical features and treatment of hepatitis E
RNA virus
Transmission
> Faeco-oral
> Pork products
> Minimal person-to-person
Incubation period - 40 days
Clinical features
> Similar to hepatitis A plus rare reports of neurological effects
> Guillain-Barré syndrome
> Encephalitis
> Ataxia
> Myopathy
> Case fatality rate 1-3%
Treatment – supportive
> No vaccine
Chronic hepatitis E is seen in very immunosuppressed patient e.g. bone marrow transplants
> Treatment – ribavirin
Describe the clinical features and treatments of hepatitis B
DNA virus
HBV vaccination in most countries
Transmission
> Vertical transmission (most common) - at birth
> Sexual contact
> Blood transfusions
> Blood, semen
> Incubation: 2-6 months
Acute case fatality rate: 0.5-1%
> Age at time of infection determines severity of acute illness and risk of chronic HBV infection (CHB)
> Infection at birth / young child is usually asymptomatic but leads to chronic infection
> Infection as an adult is usually symptomatic but cleared
Chronic HBV
> Development of chronic liver disease in 25%
Results in
> Cirrhosis
> Decompensation
> Hepatocellular carcinoma (HCC)
> Death
Treatment
Acute HBV
> No treatment
> Usually resolves and infection is cleared
Chronic HBV
> Only treat those with liver inflammation
> Increased ALT or biopsy or fibrosis (on fibroscan or biopsy)
2 types
> Immunomodulatory – interferon
> Suppress viral replication – tenofovir or entecavir
Describe the diagnosis of hepatitis B
Lab tests – HBV DNA
Histology - cytoplasmic inclusion – ground glass cytoplasm in hepatocytes
Acute
> SAg – surface antigen
» Marker of infection
> SAb – surface antibody
> Marker of immunity
> Core IgM & IgG – recent infection
> E antigen (eAg) - suggests high infectivity
E antibody (eAb) - suggests low infectivity
Chronic HBV: sAg detectable for >6/12
> Carriers are broadly divided into 2 groups
> > eAg +ve (early disease)
> High viral load
> High risk of CLD and HCC
> Highly infectious
> > eAg –ve (late disease)
> Low viral load
> Lower risk of CLD and HCC
> Less infectious
Describe the clinical features and treatment of hepatitis D
ss RNA virus
> Requires HBV to replicate
Transmission same as hep B
Vertical transmission rare
Acquired by
> Co-infection with HBV
> Super-infection of chronic HBV carriers
> Infection only possible in persons who are HBV sAg+
Increases risk of chronic liver disease
Treatment
>Interferon only
> Bulevirtide – suppressive treatment
Describe the clinical features, diagnosis and treatment of hepatitis C
RNA virus
Incubation period 6-7 weeks
> 25% of newly infected are symptomatic
30% clear infection
70% chronic hep C
> Cirrhosis
> HCC
Diagnosis
> Screening of high risk groups
» Drug users
» Immigrant from high prevalence countries
> Anti HCV IgG positive = chronic or cleared infection
> PCR or antigen positive = current infection / viraemia
Transmission
> Injecting drugs
> Transfusion + transplant
> Sexual / vertical rare
No vaccine, no post exposure prophylaxis
No reliable immunity after infection
Treatment
> Directly acting antivirals (DAAs)
> Inhibit different stages of the replication cycle
> Cure rates >95% with 8-12 weeks of oral treatment
Describe the causes and histology of chronic biliary disease
Causes
> Primary biliary cirrhosis (PBC): anti mitochondrial antibody
> Primary sclerosing cholangitis (PSC): anti-neutrophil cytoplasmic antibody
Histology
Focal, portal predominant inflammation and fibrosis with bile duct injury
Granulomas in PBC
List the clinical features, investigations and treatments associated with autoimmune hepatitis
Clinical presentation
> Asymptomatic
> Non-specific symptoms
» Fatigue
» General ill health
» Lethargy
» Weight loss
>Mild right upper quadrant pain
> Acute jaundice arthralgia
> Unexplained fever
Chronic liver disease
Acute or even fulminant hepatic failure
Investigations
> Elevated AST and ALT
> Anti-nuclear antibody (ANA)
> Anti-smooth muscle antibody (SMA)
> Anti-liver kidney microsomal antibody (LKM)
> Raised IgG
Treatment
> Immunosuppressants
» Corticosteroids: prednisolone, budesonide
» Azathioprine / mycophenolate
Describe the clinical features and treatment of primary biliary cirrhosis
Most common chronic cholestatic liver disease
9:1 female to male
90% have anti-mitochondrial antibodies against pyruvate dehydrogenase complex (PDC-E2) in mitochondria
LFTs
> Elevated GGT & ALP in early disease
> Elevated bilirubin in advanced disease
Symptoms
> Tiredness
> Itching
> Jaundice
Treatment
> Ursodeoxycholic acid
Describe the clinical features, cause and treatment of haemochromatosis
Iron accumulation in tissues and organs including liver, adrenal glands, heart, skin, gonads, joints, pancreas
Presentation
> Abnormal LFTs
> Chronic liver disease
> Polyarthropathy
> Adrenal insufficiency
> Heart failure
> Diabetes
> Skin pigmentation – bronzed diabetes
Cause
> Mutation in HFE gene: autosomal recessive
> Homozygous for C282Y mutation
> Compound heterozygote for C282Y and H63D
Investigations
> Raised ferritin and transferrin saturation
> Not all hyperferritinaemia is iron (infection)
> Liver MRI for iron – liver biopsy
Treated with venesection
Describe the cause, presentation and treatment of Wilson’s disease
Mutation in ATP7B gene: autosomal recessive
Failure to transport excess copper into bile leading to copper accumulation
Presentation
Chronic liver disease <55 years old
5% develop fulminant acute liver failure (often with low ALP and haemolysis)
Neurological or psychiatric symptoms
Parkinsonism with or without hand tremor
Masked facial expressions
Slurred speech, ataxia or dystonia
Low caeruloplasmin
High copper levels
Kayser Fleischer rings
Treatment
Copper chelation – penicillamine or trientine
Oral zinc – reduces copper absorption
Which enzyme deficiency can result in liver disease?
Alpha 1 antitrypsin
Describe the clinical features of alcohol-related liver disease
Alcoholic hepatitis
> Excess alcohol within 2 months
> Bilirubin >80 micromol/L for less than 2 months
> Exclusion of other liver disease
> Treatment of sepsis / GI bleeding
> AST < 500 (AST:ALT ratio >1.5)
Features
> Hepatomegaly
> Fever
> Leucocytosis
> Hepatic bruit
Glasgow Alcoholic Hepatitis Score (GAHS)
Spectrum of alcohol-related liver disease
> Hepatitis: liver cell necrosis, inflammation, Mallory bodies, fatty changes
> Cirrhosis: fibrosis, hyperplastic nodules
> Steatosis: fatty change, perivenular fibrosis
Describe the associations of non-alcoholic fatty liver disease and the investigations used
Main associations
> Obesity
> Type 2 diabetes
> Hyperlipidaemia
Non-invasive tests of liver fibrosis
> APRI
> FIB-4
NAFLD Fibrosis score
> Takes into account age, BMI, IFG/diabetes, AST/ALT ratio, platelet
Fibroscan: transient elastography
> F0-F4
Blood tests
> Enhances liver fibrosis (ELF) test
> FibroTest
Describe the main features of liver cirrhosis
End-stage liver disease characterised by
Diffuse process
> Changes throughout the whole liver
Nodule formation
> Changes from smoothness to lumps of various sizes
Fibrosis
> White tissue
> Result of chronic inflammation (hepatitis) over many years
Persistence of injury-causing agent
Fibrous scarring and hepatocyte regeneration
Eventually irreversible and cirrhosis develops
Describe the consequences of liver failure
Altered intermediary metabolism
Impaired synthesis of urea and glycogen (higher risk of hypoglycaemia)
Reduced albumin and other transport proteins
Coagulation disorders
Reduced complement so prone to infection
Jaundice
Altered xenobiotic metabolism e.g. drugs
Circulatory and endocrine disturbances
Describe the complications associated with liver cirrhosis
Portal hypertension
> Cirrhosis increases resistance to blood flow through liver
> Increases pressure in portal circulation causing:
> > Portal-systemic shunts and varices
> There is a junction where portal and systemic circulation meet
> If pressure is high, portal circulation blood can go back to systemic circulation
> Varices (vein enlargement) may rupture to give massive haematemesis and precipitate hepatic failure and encephalopathy
> > Ascites
> Increased fluid in abdominal cavity
> > Splenomegaly
> Back pressure is exerted on spleen through portal circulation
> Spleen is distensible so can accumulate more blood and become enlarged
Hepatocellular cancer
Describe the pathogenesis of ascites in liver disease
Portal hypertension leads to pressure in splanchnic capillaries and fluid into the peritoneum
Portal hypertension also leads to an increase in nitric oxide
Results in hypovolaemia and renal artery vasoconstriction, resulting in the activation of RAAS and sodium and water retention
List LFTs and what they indicate
- AST: aspartate transaminase; hepatocyte enzyme
- ALT: alanine transaminase; hepatocyte enzyme
- ALP: alkaline phosphatase: bile duct enzyme (may also be elevated in bone pathology or pregnancy)
- GGT: gamma glutamyl transfer: bile duct enzyme
- Albumin: decreased albumin indicates chronic liver disease & reduced synthetic function
- INR: increased INR indicates decreased synthetic ability of the liver, which produces clotting factors
- Bilirubin
CRP also indicates inflammation
Describe the algorithm used in the diagnosis of liver disease when ALP is elevated
Increased ALP
> Increased GGT: perform US or CT
> > Dilated ducts: possible stones, strictures or space-occupying lesion; perform percutaneous cholangiography to diagnose sclerosing cholangitis, stricture or stones
> > Non-dilated ducts: measure anti-mitochondrial antibody
> > > Positive anti-mitochondrial antibody: primary biliary cirrhosis
> > > Negative anti-mitochondrial antibody: perform percutaneous cholangiography to diagnose sclerosing cholangitis, stricture or stones
> normal GGT: bone disease?
Describe the investigations which follow the presence of hepatocyte damage (elevated transaminases)
Serology
> Viral serology for hepatitis
> Autoantibodies for autoimmune hepatitis
Ferritin/iron studies
Copper, caeruloplasmin
Alpha-1-antitrypsin
Describe signs of obstructive jaundice
- Dark urine: conjugated bilirubin
- Pale offensive stools (steatorrhoea): lack of conjugated bilirubin products
- Pruritus (itchy skin) and excoriation marks: bile salt deposition
- Yellow sclerae
List causes of prehepatic jaundice
- Elevated haemolysis:
> sickle cell anaemia
thalassaemia major
malaria
quinine-based anti-malaria drugs…
neonatal jaundice
haemolytic disease of the newborn
List causes of hepatic jaundice
> Gilberts’ syndrome: impaired conjugation of bilirubin
> Primary biliary cirrhosis: impaired transport of conjugated bilirubin into bile canaliculi
> Cirrhosis
> Hepatotoxic drugs e.g. paracetamol overdose
> Viral hepatitis
> Autoimmune hepatitis
> Non-alcoholic fatty liver disease
List causes of post-hepatic / obstructive jaundice
Biliary obstruction leads to cholestasis
- Gallstones
- Biliary strictures
- Pancreatitis
- Pancreatic or bile duct tumours
List risk factors for gallstone formation
5 F’s: female, fair, fertile, forty, fat
Other risk factors: low fibre diet, IBD, family history, Caucasian
Describe complications of gallstones
- Biliary colic
> no jaundice or fever, LFTs normal
> pain epigastrium, RUQ, worse on eating, vomiting is common - Acute cholecystitis
> Pain, nausea, vomiting, fever, RUQ tenderness (Murphy’s sign)
> Raised inflammatory markers, may be abnormal LFTs or jaundice - Empyema
- Mucocoele
- Cancer
Describe Curvoisier’s Law
“In the presence of a palpable enlarged gallbladder which is non-tender and accompanied with mild painless jaundice, cause is unlikely to be gallstones”
Gallstones cause pain
Troublesome gallstones cause chronic inflammation and fibrosis, GB does not distend
List stigmata of chronic liver disease
Palmar erythema
Fingernail clubbing
Gynaecomastia
Testicular atrophy
Dupuytren’s contracture
Caput medusae
Foetor hepaticus
Flapping tremor (hepatic encephalopathy)
Lab features
> Thrombocytopaenia (pancytopaenia)
> Prolonged prothrombin time
> Hypoalbuminaemia
Describe the assessment of the severity of liver disease
Childs-Turcotte-Pugh score
- Considers encephalopathy, ascites, bilirubin, albumin & prothrombin time prolongation
- Grade A: 5-6, mild
- Grade B: 7-9, moderate
- Grade C: 10-15, severe
Models for End-stage Liver Disease (MELD) uses bilirubin, INR and creatinine
Describe the investigations used in ascites
Diagnostic tap
- Cell count
> >500 WBC/cm3 and >250 neutrophils/cm3 suggests spontaneous bacterial peritonitis (SBP)
> Lymphocytosis suggests TB or peritoneal carcinomatosis
- Albumin
> Serum ascites albumin gradient (SAAG) = serum albumin MINUS ascites albumin
» SAAG >11g/l = portal hypertension
Describe the treatment of ascites
Low salt diet
Diuretics
> Spironolactone
» Side-effects e.g. gynaecomastia, hyperkalaemia, hyponatraemia, impotence
> Furosemide
> Side effects e.g. hyponatraemia
Large volume paracentesis
Define hepatic encephalopathy, including precipitating factors
Disease caused by the failure of the cirrhotic liver to remove toxins from the blood, which ultimately negatively affects the brain’s function
Precipitating factors
- GI bleeding
- Infections
- Constipations
- Electrolyte imbalance
- Excess dietary (especially animal) protein
Avoid regular sedation, caution with opiates & avoid hyponatraemia
Precipitating factors negatively affect the patient by
> Further reducing hepatic or cerebral function
> Increasing ammonia levels
> Stimulating an inflammatory response
Describe the clinical signs and treatment of hepatic encephalopathy
Clinical signs: flapping tremor or asterixis
Treatment
> Non-absorbable
> Disaccharides i.e. lactulose
> Aim for 2-3 soft stools/day
> Non (minimally)-absorbable antibiotics: rifaximin
> Gut decontamination: reduces urease and protease activity
Describe non-neoplastic focal liver disease
Developmental / degenerative e.g. cysts
> Commonest is the Von Meyenberg complex = simple biliary hamartoma
> Can resemble metastases by naked eye at operation
> No treatment required
Inflammatory e.g. abscess
Describe the clinical features of hepatic adenoma
Rare
Mainly young women, often associated with hormonal therapy
Risk of bleeding and rupture so excision if large
Describe the clinical features of hepatocellular carcinoma including screening, diagnosis and treatment
Most common primary liver tumour
Usually arises in cirrhosis
Can occur in pre-cirrhotic liver disease (Hepatitis B)
Associated with elevated serum AFP (alpha feto-protein)
Screening: 6 monthly US and plasma AFP
Diagnosis : 2 cross-sectional scans: CT and MRI with typical features
Treatment
> Multiple kinase inhibitors: sorafanib, lenvatanib
> Radiofrequency / microwave ablation
> Transarterial chemoembolisation (TACE)
> Resection
> Liver transplantation
Summarise pharmacokinetic changes in liver disease
Absorption
> Decreased absorption and first-pass effect resulting in higher bioavailability
Distribution
> Reduced plasma protein binding so large fraction of unbound drug
Metabolism
> reduced activity of phase I & II & CYP enzymes
> Delayed clearance by drug metabolising enzymes
Excretion
> Biliary excretion reduced & reduced renal elimination
Describe paracetamol and opioid prescribing in liver disease
Glutathione tissue stores needed to block formation of acetaminophen’s toxic metabolite NAPQI
> reduced stores in cirrhosis, active alcohol consumption also reduces glutathione stores
half-life of paracetamol may be prolonged up to 2x
All opioids can worsen hepatic encephalopathy and should be used cautiously or avoided
Describe the composition, diagnosis and management of gallstones
Types
Pure
> Cholesterol
> Bile pigment
> Mixed
Diagnosis
> Abdominal US
» Visualise gallbladder
» Not able to visualise common bile duct due to air in duodenum
> X-ray (if sufficient calcium)
Management
> Conservative
> Surgical - cholecystectomy
Describe the composition of bile
Composition
> 97% water
> Cholesterol
> Kept in solution by micelles containing bile acids and phospholipid
> Bilirubin pigment
> 500mls secreted by liver daily
Lithogenic (stone-forming)
> Excessive secretion of cholesterol
> Decreased secretion of bile salts
> Excessive secretion of bilirubin e.g. haemolytic anaemia
List causes of acute pancreatitis
Idiopathic
Gallstones
Ethanol
Trauma
Steroid use
Mumps
Autoimmune
Scorpion sting
Hyperglycaemia and hypertriglyceridaemia
ERCP
Drugs e.g. azathioprine
List complications of pancreatitis
- Fat necrosis - autodigestion
- Acute haemorrhagic pancreatitis
- Pancreatitic abscess
> infected pancreatic necrosis
> avascular haemorrhagic pancreas is a good culture medium
> drainage or necrosectomy + antibiotics
Describe the different types of pancreatic cysts
Intraductal papillary mucinous neoplasm
> In continuity with main pancreatic duct or side branch duct
> Dysplastic papillary lining secreting mucin
Mucinous cystic neoplasm
> Mucinous lining, ovarian-type stroma
Serous cystadenoma
> No mucin production
> Almost always benign
Describe pancreatic carcinoma including signs and symptoms, and management
Very poor prognosis
Stent at ERCP for jaundice
Subtypes: ductal adenocarcinoma, most common
> Perineural invasion
> Pre-malignant PanIN asymptomatic (pancreatic intraepithelial neoplasia)
Risk factors: smoking, germline mutations e.g. BRCA
Signs and symptoms
> Painless obstructive jaundice
> New onset diabetes (type 3c)
> Abdominal pain due to pancreatic insufficiency or nerve invasion
> Tumours in head may obstruct pancreatic duct and bile duct
> Double duct sign on radiology
Whipple’s resection
> Only for tumours of head of pancreas
> Remove
» Head of pancreas
» Duodenum immediately adjacent to pancreas
» Bile duct
» Gallbladder
Neoadjuvant therapy
> Folfirinox chemotherapy
Describe pancreatic neuroendocrine tumours
Rare
May secrete hormones – functional
Commonest functional tumour – insulinoma
> Presents with hypoglycaemia
> 90% are benign
Malignant endocrine tumours have a much better prognosis than pancreatic cancer
Describe carcinoma of the ampulla of Vater
Presents earlier and smaller than carcinoma of pancreas (causes obstruction)
May arise from pre-existing adenoma
25% 5 year survival following Whipple’s resection
Describe cholangiocarcinoma
Classified as
> Intrahepatic
> Needs to be distinguished from metastatic adenocarcinoma (similar histology) and hepatocellular carcinoma
> Extrahepatic
> Similar morphology and prognosis to pancreatic carcinoma
Treatment
> Whipple’s resection to remove common bile duct and involve pancreas/duodenum
Describe carcinoma of the gallbladder
Rare
Gallstones present in 80% of cases
Adenocarcinoma
Dismal prognosis unless found incidentally in a gallbladder removed for chronic cholecystitis
Local infiltration may make gallbladder seem abnormally stuck down at theatre
List conditions affecting the oesophagus
- Reflux oesophagitis aka GORD
- Infections
> Candida albicans - fungus
> Herpes simplex virus (immunocompromised) - Inflammation - chemicals
> NaOH, caustic soda, iron, bisphosphonates, teracyclines - Oesophageal erosion: viral nuclear inclusions from HSV oesophagitis
- Eosinophilic oesophagitis: allergic aetiology, causes dysphagia and food bolus obstruction
- Barrett’s oesophagus
- Oesophageal cancer
- Diverticula
- Achalasia
- Schatzki ring
- Systemic sclerosis
- Hiatus hernia
Describe Barrett’s oesophagus including its complications
Metaplastic response to mucosal injury e.g. from long-term GORD
Squamous epithelium becomes glandular, usually intestinal with goblet cells
Dysplastic epithelium is architecturally and cytologically abnormal
> Low grade: cells polarised, nuclei stratified
> High grade: polarity lost, nuclei rounder, prominent nucleoli, abnormal mitoses, necrosis
Associated with the development of benign strictures but also with oesophageal adenocarcinoma
Describe causes of acute gastritis
Alcohol, NSAIDs, severe trauma
Burns (Curling’s ulcers), surgery
Describe autoimmune gastritis including complications
Autoimmune destruction of parietal cells due to auto-antibodies against intrinsic factor and parietal cell antibodies in blood
Leads to
> Complete loss of parietal cells with pyloric and intestinal metaplasia
> Achlorhydria > bacterial overgrowth
> Hypergastrinaemia > endocrine cell hyperplasia / carcinoids
> Persistent inflammation which can lead to epithelial dysplasia and may lead to cancer
Describe the patterns of H pylori infection and how this is treated
Histology
> Lamina propria full of plasma cells and lymphocytes
> Surface erosion and active inflammation
> Helicobacter pylori colonises gastric mucosa causing active chronic inflammation
IL-8 from epithelial cells attracts neutrophils
Higher IL-8: pangastritis
> Hypochlorhydria
> Multifocal atrophic gastritis
> Intestinal metaplasia
> Cancer
Lower IL-8: antral gastritis
> Hypergastrinaemia
> Duodenal ulceration
Host/microbe interface
> Impaired mucosal defence
> NSAIDs interfering with mucosal prostaglandin synthesis
> Bile reflux
Microbe factors
> CagA variants associated with more severe inflammation
Treatment: triple therapy, PPI + 2 antibiotics (amoxicillin, clarithromycin)
Describe chemical / reactive gastropathy
Morphology
> Few inflammatory cells
> Foveolar hyperplasia – corkscrew glands
> Ectatic mucosal capillaries
> Muscle spurs in lamina propria
Antrum more than corpus
Causes
> Bile reflux
> NSAIDs
> Ethanol
> Oral iron
Describe intestinal gastric cancer
Strongly associated with chronic gastritis
> H pylori
> Autoimmune
Background atrophic mucosa
Chronic inflammation
Intestinal metaplasia
Dysplasia
Various classification schemes
> Lauren
» Intestinal or diffuse
> WHO
> Papillary
> Tubular
> Poorly cohesive
Describe diffuse gastric cancer
Individual malignant cells with mucin vacuoles
> Signet ring cells
May invade extensively without being endoscopically obvious
> Linitis plastica – leather bottle stomach
Weaker link with gastritis
Metastasis to ovaries - Krukenberg tumour
Supraclavicular lymph node – Virchow’s node
Sister Joseph’s nodule – umbilical metastasis
Describe hereditary diffuse gastric cancer
CDH1 mutation
Penetrance 70-80%
Small intramucosal foci of diffuse gastric cancer may be numerous
Prophylactic gastrectomy likely to be considered
Increased risk lobular carcinoma of breast
Describe the presentation and causes of upper GI bleeding
Presentation
> Haematemesis
> Coffee ground vomiting
> Melaena
Causes
> Peptic ulcer
» Due to acid, H. pylori, NSAIDs
> Oesophagitis
> Gastritis
> Duodenitis
> Varices: large high pressure vessels anastomosed with abdominal vessels
> Malignancy: ulcerated lesion, rolled edge
> Mallory-Weiss tear: tear in oesophageal lining
Describe the management of upper GI bleeding
Resuscitation as required
> Pulse & BP
> IV access for fluids/bloods
> > > Check bloods – especially Hb & urea;High urea due to breakdown of blood into protein in GI tract
> > > Lie flat and give oxygen
Risk assessment and timing of endoscopy
High risk – emergency endoscopy
Moderate risk – admit & next day endoscopy
Low risk – out-patient management
Drug therapy & transfusion
Describe the risk scores used in the assessment of upper GI bleeding
Rockall Score
> Predicts mortality
> Age
> Shock – pulse & BP
> Comorbidity
> Diagnosis
> Stigmata of recent haemorrhage
Describe the Glasgow Blatchford Score (GBS)
Uses
> Blood urea and haemoglobin
> BP, pulse, melaena or syncope
> Background hepatic disease or cardiac failure
GBS <=1
> Low risk of poor outcome
> Can be discharged for outpatient endoscopy
Describe the different options for endoscopic management of an upper GI bleed
Adrenaline injection
> Constricts blood vessels and limits blood flow
Heater probe
> Burn smaller blood vessels
> Not suitable for varices
Endoscopic clips
Haemostatic powders
Thrombin, laser
Radiological embolisation of bleeding vessel uncontrolled by endoscopy
Describe the treatment of upper GI bleeding caused by varices
Resuscitation
> Restore circulating volume
> Transfuse once Hb <7g/dL
Procedures
> Endoscopic band ligation
> Transjugular intrahepatic portosystemic shunt (TIPS) procedure
> Rescue procedure
> Sengstaken tube – balloon tamponade
> Uncontrolled variceal bleeding
> Last minute temporary control of bleeding
> Beta blockers e.g. propranolol
> Primary prophylaxis
> Cirrhotic patients
> > Prophylactic antibiotics early (high risk of sepsis)
> > Vasopressors (Terlipressin) early
> Constrict splanchnic flow and reduce blood entering collateral circulation
> Surgical shunt / transection
> Very rarely used, high mortality
Prevention of rebleeding
> Beta-blocker + repeated band ligation
What is the characteristic feature of a hepatocellular carcinoma on a CT scan?
Hypervascularity followed by washout (waiting after contrast has passed) is characteristic of HCC
Describe the characteristic features of primary sclerosing cholangitis
Inflammatory condition causing irregularity, narrowing and dilatation of biliary tree
Associated with IBD
Describe the features associated with Crohn’s on MRI enterography
Irregular, thick wall in terminal ileum with ulceration & prominence of fat (hypertrophy), pushing other bowel away
Skip lesion with narrowed lumen; abscess in small bowel (T1 W)
Describe the prep required for CT colonography
Bowel cleansing and tagging with iodine
Bowel distension with CO2
Supine +/- prone CT scans with IV contrast
Conventional 2D CT read
CGI images for 3D read – virtual colonoscopy
Describe the different subtypes of colorectal cancer
Epithelial tumours
> Adenocarcinomas
> Neuroendocrine neoplasms
> Squamous cell carcinoma
> Metastatic carcinoma
> Adenosquamous carcinoma
Non-epithelial tumours
> Gastrointestinal stromal tumours (GISTs)
> Melanoma
> Lymphomas
Describe the pathogenesis of colorectal cancer
- Adenoma – carcinoma sequence
> Aka chromosomal instability pathway
> Mutation in APC (adenoma polyposis gene – dual function tumour suppressor genes)
> Followed by mutation in KRAS
> Later mutations in TP53, PIK3CA, loss of 18q
> Issues with cell survival, DNA repair, apoptosis - Microsatellite instability pathway
> Dysfunction in DNA mismatch repair genes (MMR genes) leading to genetic hypermutability
> Seen in Lynch syndrome but also some sporadic cancers - Aberrant hypermethylation
> Epigenetic modification leading to silencing of gene function
List risk factors for colorectal carcinoma
Adenomas
> Size, number, villous
History of IBD – especially ulcerative colitis
Increasing age
Obesity
Sedentary lifestyle
High fat / low fibre diet
Smoking and alcohol use
Family history – polyposis syndromes
> Familial adenomatous polyposis – APC gene
> Lynch syndrome (HNCC) - mismatch repair defects
Describe colorectal polyps giving examples
Polyp – exophytic protuberant growth
Examples of bowel polyps
> Hamartomatous polyps
> Inflammatory polyps
> Hyperplastic polyps
> Adenomas
All colorectal adenomas are dysplastic
Adenomatous dysplasia
> High grade
> Low grade
Architecture of adenoma
> Villous
> Tubulovillous
> Tubular
Describe the histology of colorectal carcinoma
> Loss of normal architecture
Haphazard arrangement of glands
Tumour invasion through muscularis mucosae – invasive carcinoma
Desmoplastic stroma: pink and spindly
> Confirms invasive carcinoma
Vascular invasion (ENVI – extra-neural vascular invasion)
> Vein elastic fibres are stretched around the deposit of colorectal cancer
Colon cancer blood marker: carcinoembryonic antigen (CEA)
Describe the TNM 8 staging of colorectal carcinoma
T1: enter submucosa
T2: invades into muscularis propria
T3: invasion through muscularis propria into subserosa
T4: invasion of visceral peritoneum and other organs
N0: no regional lymph node mets
N1: 1-3 regional LN mets
N2: 4+ regional LN mets
M0: no distant mets
M1: distant mets
Describe the bowel cancer screening programme
qFIT testing of >50-74 year olds every 2 years
If positive refer for colonoscopy
Patient education of symptoms
- PR bleeding
- Change in bowel habit
