Week 13 - GI/Liver Flashcards
Describe the vasculature of the liver?
- Incoming portal vein and hepatic artery
- Outgoing hepatic vein
How is the normal liver structure arranged?
Portal tracts & parenchyma
List the 7 broad causes of injury to the liver?
- Drugs or toxins incl. alcohol
- Abnormal nutrition/metabolism
- Infection
- Obstruction to bile or blood flow
- Autoimmune liver disease
- Genetic/deposition disease
- Neoplasia
What is inflammation generally?
Body’s response to injury
What is acute inflammation?
Agent causes injury but is the removed (days to weeks)
What is fulminant inflammation?
Severe acute, rapidly progressing towards liver failure
What is chronic inflammation?
Agent causes injury then persists (months to years)
What is acute-on-chronic inflammation?
Chronic liver disease often presents with acute exacerbation plus evidence of underlying chronicity e.g. fibrosis
What does the injurious agent cause?
Cell damage and sometimes death, often with inflammatory cell infiltrate
What is the main location of liver injury?
Parenchyma (hepatocytes) or bile ducts
What 4 structures are interdependent in the liver?
- Parenchyma
- Bile ducts
- Blood vessels
- Connective tissue
What is cirrhosis equal to?
End-stage liver disease
What is the 3-fold definition of cirrhosis?
Diffuse process with Fibrosis + Nodule formation
What is the main aim of diagnosing and treating chronic hepatitis?
Avoid progression to cirrhosis
What are the 2 types of investigations for liver disease?
- Blood tests: LFTs, haematology, viral and autoimmune serology, metabolic tests
- Radiology: at least ultrasound
List the 7 brand patterns/types of liver disease?
- Acute hepatitis
- Acute cholestasis
- Fatty liver disease
- Chronic hepatitis
- Chronic biliary disease
- Hepatic vascular disease
- Deposition/genetic disease
What 2 patterns/types of liver disease may progress to cirrhosis?
Fatty & chronic liver disease
Describe the histological appearance of acute hepatitis of autoimmune cause?
- Diffuse hepatocyte injury seen as swelling
- A few have died, described as “spotty necrosis”
- There is an inflammatory cell infiltrate in all areas: portal tracts, interface and parenchyma
What are dying hepatocytes called?
Acidophil body
What are the 2 causes of acute cholestasis/cholestatic hepatitis?
- Extrahepatic biliary obstruction
2. Drug injury e.g. antibiotics
Describe the histological appearance of acute cholestasis/cholestatic hepatitis?
Brown bile (bilirubin) pigment +/- acute hepatitis
What are 2 causes of chronic biliary/cholestatic disease?
- Primary biliary cirrhosis (PBC)
2. Primary sclerosing cholangitis (PSC)
Describe the histological appearance of chronic biliary/cholestatic disease?
Focal, portal-predominant inflammation and fibrosis with bile duct injury; granulomas (arrow) in PBC
Give 3 examples of Genetic/deposition liver disease?
- Haemochromatosis (iron)
- Wilson’s disease (copper)
- Alpha-1-antitrypsin deficiency
What are the 3 causes of acute hepatitis liver disease?
- Hepatitis viruses A-E
- Drug injury
- Autoimmune liver disease
What are the 3 causes of acute cholestasis or cholestatic hepatitis liver disease?
- Hepatitis virus esp. A & E
- Drug injury
- Extrahepatic biliary obstruction
What are the 3 causes of Fatty liver disease (steatosis and steatohepatitis)?
- Drug injury
- Alcohol
- Metabolic syndrome ie. obesity
What are the 3 causes of chronic hepatitis?
- Hepatitis viruses esp B & C (& D)
- Autoimmune liver disease
- Genetic/deposition e.g. haemochromatosis, Wilson’s
What are the 3 causes of Chronic biliary/cholestatic disease?
- Extrahepatic biliary obstruction
- Chronic biliary disease e.g. PBC
- Genetic/deposition e.g. haemochromatosis, Wilson’s
What are the 2 causes of hepatic vascular disease?
- Drug injury
2. Vascular disease e.g. venous obstruction
What are the 4 aims of investigation of diffuse liver disease?
- Establish DIAGNOSIS in terms of pattern (morphology) of disease
- Establish CAUSE, if possible
- If appropriate, establish GRADE of disease (severity = activity of inflammation)
- If chronic liver disease, establish STAGE (severity of fibrosis i.e. how far towards cirrhosis)
What are the 2 types of treatment for diffuse liver disease?
- Specific treatment against cause: removal of alcohol or drug, weight loss, optimal diabetic control, specific antivirals or immunosuppression, AND/OR
- Supportive treatment for severe acute hepatitis or for cirrhosis in general
What is a common type of liver disease?
Drug induced
What are most drug hepatotoxicities?
Idiosyncratic (rare but usually single clinical pattern) thus difficult to investigate
What are the 2 types of drug-induced liver disease causes?
- Predictable liver damage: paracetamol, methotrexate
2. Non-prescribed drugs: over internet or herbal
What may Augmentin (co-amoxiclav) cause?
Acute cholestatic hepatitis
What is the main differential diagnoses for liver masses (space occupying lesions or focal lesions)?
Inflammatory and other benign lesions and cancer
What is a focal liver disease equal to?
Space occupying lesions (SOLs)
What are the 2 types of liver space occupying lesions (SOLs)?
- Non-neoplastic: Developmental/ degenerative (cysts), Inflammatory (abscess)
- Neoplastic: benign, malignant
What are the 2 usual origins of liver cysts?
- Developmental
2. Degenerative
What is the commonest liver cyst?
Von Meyenberg complex (= simple biliary hamartoma)
Why are Von Meyenberg complexes important?
Can resemble metastases by naked eye at operation
What is the treatment for Von Meyenberg complexes?
No treatment required
Give 3 examples of benign (5%) liver neoplasms?
- Hepatocellular adenoma
- Bile duct adenoma (rare)
- Haemangioma
Give 4 malignant liver neoplasms?
- Hepatocellular carcinoma (HCC)
- Cholangiocarcinoma
- Angiosarcoma
- Metastases
Why is haemangioma and hepatic adenoma’s important?
Differential diagnosis with metastases
Describe a Haemangioma?
- Benign blood vessel tumour
- Biopsy avoided because of risk of bleeding
Describe a hepatic adenoma?
- Rare
- Mainly young women, often associated with hormonal therapy
- Risk of bleeding and rupture so excision if large
What is the most common primary liver tumour?
Hepatocellular carcinoma (HCC)
Describe how Hepatocellular carcinoma (HCC) usually arises?
In cirrhosis and associated with elevated serum AFP (alpha feto-protein)
What are the 6 normal functions of the liver?
- Protein, carbohydrate and fat metabolism
- Plasma protein and enzyme synthesis
- Production of bile
- Detoxification
- Storage of proteins, glycogen, vitamins and metals
- Immune functions
What makes at least 70% of liver disease in the West population?
Fatty liver due to alcohol or obesity
List the 4 signs & symptoms of liver disease?
- From liver itself: hepatomegaly
- From portal hypertension: ascites
- From chronic liver dysfunction: pruritis, spider naevi
- Non-specific: nausea, falls, tremor
What are the 2 symptoms & signs of an abnormal biliary system?
- Accumulation of bilirubin (esp. acute cholestasis): jaundice
- Accumulation of bile acids (esp. chronic cholestasis): pruritis
What are the 3 symptoms of abnormal parenchyma?
- RUQ pain
- In chronic disease: hormonal changes
- Liver failure only once <25% function
What is the sign of abnormal connective tissue matrix in the liver?
Portal hypertension
List 5 liver function tests (biochemistry)?
- Transaminases: AST, ALT
- Alkaline phosphatase (Alk P)
- Gamma glutamyl transferase (GGT)
- Bilirubin (Bil)
- Albumin (Alb)
What is a liver-related haematology test?
Prothrombin time (PTT)
Give 5 examples of liver investigations?
- Viral serology
- Autoimmune serology
- Tests for liver metabolic/genetic disease
- Radiology (imaging): especially masses
- Biopsy (in only few cases)
Give 3 examples of tests for liver metabolic/genetic disease?
- Iron
- Copper
- Alpha-1-antitrypsin
Give 3 examples of radiology tests for liver disease?
- Ultrasound of abdomen
- CT scan of abdomen
- ERCP/MRCP
Describe the presentation of acute hepatitis?
- Short history of RUQ tenderness, malaise etc
- Elevated AST/ALT (and often Bil)
Describe the clinical presentation of fatty liver disease?
- Acute OR chronic “hepatitis”, or
- Asymptomatic abnormal LFTs
What are the 3 causes of fatty liver disease (steatosis and steatohepatitis)?
- Alcohol
- Non-alcoholic or so-called metabolic syndrome, including Type II diabetes, obesity and hyperlipidaemia
- Drugs: methotrexate, amiodarone, steroids
Describe hepatitis C pathology?
Mainly in portal tracts, as chronic inflammation with lymphoid aggregates
What is the clinical definition of chronic hepatitis?
Liver inflammation (abnormal LFTs) for at least 6 months
Describe the clinical presentation of chronic biliary/cholestatic disease?
- Chronic liver disease: itch (symptoms more of excess bile acids than excess bilirubin), OR
- Abnormal LFTs: mainly AlkP and GGT, often relatively mild, persisting for >6 months
Describe the histology of chronic biliary/cholestatic disease?
Focal, portal-predominant inflammation and fibrosis with bile duct injury; granulomas (arrow) in PBC
Describe Primary biliary cirrhosis?
- Auto-immune disease with serum anti-mitochondrial antibodies (AMA) and high IgM
- NOT cirrhotic from outset, but progresses to fibrosis then cirrhosis
- No cure but ursodeoxycholic acid eases symptoms and slows progression
- Liver transplantation, if available, at end-stage
Describe Primary sclerosing cholangitis (PSC)?
- Rare, associated with ulcerative colitis
- Risk of progression to cholangiocarcinoma
Describe the relevance of primary hepatic vascular disease?
Rare (by comparison with cirrhosis) but serious
What is the main form of primary hepatic vascular disease?
Hepatic vein outflow obstruction (Budd-Chiari syndrome) which is often fatal
Describe symptomatic focal liver disease presentation?
Hepatomegaly, RUQ pain or jaundice
What investigations would you perform for focal liver disease?
Imaging by ultrasound and/or CT scan +/- biopsy
Where may a liver abscess arise from?
- Ascending cholangitis
- Hydatid and other parasitic disease
What is Cholangiocarcinoma?
Adenocarcinoma of bile ducts, either intra- or extra-hepatic i.e. also primary liver tumour
How do you diagnose a Cholangiocarcinoma?
Imaging & cytology
What is the prognosis & treatment for Cholangiocarcinoma?
- Prognosis: poor
- Treatment: curative surgery or palliation
What are liver metastases mainly?
Metastatic carcinoma esp adenocarcinoma from gastro-intestinal tract (portal blood supply)
Other than the liver, what may cause a raised ALP?
Bone pathologies
Other than the liver, what may cause a raised AST?
Muscle pathologies
Other than the liver, what may cause a raised isolated bilirubin?
Haemolysis
Advanced cirrhosis may have ________?
Normal blood tests
What 3 tests is liver function indicated by?
- Albumin
- Bilirubin
- Prothrombin time
What 3 investigations would you do for chronic viral hepatitis (Chronic)?
- Ultrasound
2, HBV - HCV
What 4 investigations would you do for autoimmune liver disease (Chronic)
- ANA / SMA / LKM (AIH)
- AMA (PBC)
- Immunoglogulins
- Ultrasound
What 4 investigations would you do for metabolic liver disease (Chronic)?
- Ferritin (haemochromatosis)
- Caeruloplasmin (Wilson’s Disease)
- Alpha 1 anti-trypsin deficiency
- Ultrasound
What 6 investigations would you do for acute viral hepatitis?
- HAV
- HBV
- HCV
- HEV
- CMV
- Ultrasound
What level would you investigate for acute liver injury?
Paracetamol levels
What are the 4 most common causes of abnormal liver blood tests?
- Fatty liver
- Chronic viral hepatitis (Chronic HCV)
- Autoimmune liver disease
- Haemochromatosis
Describe the 3 steps in alcoholic fatty liver disease?
Alcoholic steatosis –> Alcoholic hepatitis –> Alcoholic cirrhosis
Describe the 3 steps in non-alcoholic fatty liver disease?
Steatosis –> Nonalcoholic steatohepatitis (NASH) –> NAFLD cirrhosis
Describe the histological appearance of the steatosis stage of fatty liver disease?
Macrovesicular steatosis with lipid vacuole filling the hepatocyte cytoplasm
Describe the histological appearance of the steatohepatitis stage of fatty liver disease?
Neutrophils and lymphocytes surrounding hepatocytes with Mallory hyaline
Describe the histological appearance of the cirrhotic stage of fatty liver disease?
Pericellular fibrosis as well as bands of fibrous tracts between portal tracts
What are the 3 main associations of Non-alcoholic fatty liver disease (NAFLD)?
- Obesity
- Type 2 Diabetes
- Hyperlipidaemia
What 2 things increase the severity of Non-alcoholic Fatty Liver Disease (NAFLD)?
- Type 2 Diabetes
2. Hypertension
List the blood result features of non-alcoholic fatty liver disease (NAFLD)?
- Fasting plasma glucose or HbA1c: Often Elevated
- ALT: Elevated or normal
- AST: Normal
- AST/ALT ratio: <0.8
- GGT: Elevated or normal
- Triglycerides: Elevated
- HDL-cholesterol: Low
- Mean corpuscular volume: Normal
List the blood result features of alcoholic fatty liver disease (ALD)?
- Fasting plasma glucose or HbA1c: usually normal
- ALT: Elevated or normal
- AST: elevated
- AST/ALT ratio: >1.5
- GGT: Markedly Elevated
- Triglycerides: Variable, may be elevated
- HDL-cholesterol: Elevated
- Mean corpuscular volume: Elevated
List the 10 clinical features of alcoholic fatty liver disease (ALD) from mild to severe?
- Malaise
- Nausea
- Hepatomegaly
- Fever
- Jaundice
- Sepsis
- Encephalopathy
- Ascites
- Renal Failure
- Death
List the 5 essential features of the newly jaundiced ALD patient (alcoholic hepatitis)?
- Excess alcohol within 2 months
- Bilirubin > 80mmol/l for less than 2 months
- Exclusion of other liver disease
- Treatment of Sepsis/ GI Bleeding
- AST < 500 (AST: ALT ratio >1.5)
What are the 4 characteristic features of the newly jaundiced ALD patient (alcoholic hepatitis)?
Hepatomegaly +/- fever +/- leucocytosis +/- hepatic bruit
What is GAHS?
The Glasgow Alcoholic Hepatitis Score (GAHS)
- Ranges from 1-3
What 3 features is the rate of Hepatitis C progression related to?
- Male sex
- Age >40 at time of acquisition
- Alcohol >50g/week
List the 5 risk factors for hepatitis C virus?
- Intravenous drug use (80% of users)
- Blood transfusions
- Sexual transmission
- Vertical transmission (~3%)
- Needle-stick transmission (~5-10%)
What are the 5 stages of liver fibrosis?
- None
- Portal fibrosis
- Portal fibrosis with septa
- Bridging fibrosis
- Cirrhosis
Machine is used as a non-invasive test of liver fibrosis?
FibroScan®
What are 2 commercially available blood tests?
- Enhanced Liver Fibrosis Test (ELF)
2. FibroTest
List 5 signs of chronic liver disease?
- Spiders
- Fœtor
- Encephalpathy
- Prolonged prothrombin time
- Hypoalbuminaemia
List 3 signs of portal hypertension?
- Caput medusa
- Hypersplenism
- Thrombocytopenia (pancytopenia)
What score assessed the severity of liver fibrosis?
Childs-Turcotte-Pugh Score
- Grade A: 5-6 (mild)
- Grade B: 7-9 (moderate)
- Grade C: 10-15 (severe)
What is the model for end-stage liver disease (MELD) used for now?
Allocate donor organs in USA for liver transplant
- Mild: <10
- Moderate: 10-15
- Severe >15
What causes hypersplenism (thrombocytopenia) in chronic liver disease?
Raised portal pressure
What causes oesophago-gastric varices in chronic liver disease?
Porto-systemic shunting from raised portal hypertension
What causes encephalopathy in chronic liver disease?
Porto-systemic shunting from raised portal hypertension
What causes hyperdynamic circulation in chronic liver disease?
Reduced effective circulating volume from vasodilation (nitric oxide) and splanchnic vasodilatation
What causes ascites in chronic liver disease?
Sodium retention from compensatory vasopressors (RAAS, catecholamines)
What causes hepato-renal syndrome in chronic liver disease?
Renal vasoconstriction from compensatory vasopressors (RAAS, catecholamines)
What are the 2 tests in the diagnostic tap for assessing ascites?
- Cell count
2. Albumin
What cell count suggests spontaneous bacterial peritonitis (SBP)?
> 500 WBC/ cm3 and/ or >250 neutrophils/cm3
What does lymphocytosis suggest?
TB or peritoneal carcinomatosis
What is the serum ascites albumin gradient (SAAG) equal to?
Serum albumin MINUS ascitic albumin g/l
What SAAG = portal hypertension?
SAAG >11g/l
What are the 5 ways to manage ascites?
- Low salt diet
- Diuretics
- Paracentesis
- Transjugular intrahepatic portosystemic shunt (TIPSS)
- Liver transplant
Give 2 examples of diuretics used for ascites?
- Spironolactone
2. Furosemide
What should patients with ascites aim for?
Weight loss of 0.5-1 kg/day
What 2 things should be monitored when managing ascites?
- Renal function
2. Electrolytes
List the 4 side effects of Spironolactone diuretic?
- Gynaecomastia
- Hyperkalaemia
- Hyponatraemia
- Impotence
What is the main side effect of Frusemide (Furosemide) diuretic?
Hyponatraemia
What are the 5 common precipitating factors for hepatic encephalopathy?
- Gastrointestinal bleeding
- Infections
- Constipation
- Electrolyte imbalance
- Excess dietary (esp. animal) protein
What 3 things do the 5 precipitating factors for hepatic encephalopathy lead to?
- Reduction of hepatic or cerebral function
- Stimulation of an inflammatory response
- Increasing ammonia levels
What are the 3 exacerbating factors to avoid with hepatic encephalopathy?
- Regular sedation
- Caution with opiates
- Avoid hyponatraemia
What scoring system is used to grade mental state in hepatic encephalopathy?
Conn Score (West Haven classification) - Grade 0-4
What should you aim for when prescribed a Non-absorbable Disaccharides (ie lactulose)?
2-3 soft stool/day
What does gut ‘decontamination’ reduce?
Urease and protease activity
List the 5 non-specific symptoms for hepatitis?
- Malaise, fever, headaches
- Anorexia, nausea and vomiting
- Right upper quadrant abdominal pain
- Dark urine
- Jaundice
Describe the 2 lab results for hepatitis?
- Raised ALT / AST / Bilirubin
2. Clotting Derangement
Describe chronic hepatitis?
- Hepatitis virus present for more than 6 months
- Usually asymptomatic by this stage
What are the 2 routes of transmission for hepatitis?
- Faecal oral
2. Blood Borne- contact with body fluids
List the 7 causes of acute hepatitis?
- Infections
- Toxins
- Drugs
- Alcohol
- Autoimmune
- Wilsons
- Haemochromatosis
List 7 infections which can cause acute hepatitis?
- Hep A, B, C, D, E
- EBV, CMV, Toxo
- Leptospirosis
- Q Fever
- Syphilis
- Malaria
- Viral hemorrhagic fevers (VHFs)
What are the 2 ways to diagnose viral hepatitis via laboratory tests?
- Detection of specific immune response (IgM or IgG)
2. Viral nucleic acid detection (RNA or DNA), or Antigen detection (HBV and HCV)
Describe the features of Hepatitis A?
- RNA virus
- Virus can survive for months in contaminated water
- Virus shed via bilary tree into gut
- Good Immunity after infection or vaccination
What is the unique feature of hepatitis A virus?
No Chronic Carriage
What are the 2 routes of transmission for hepatitis A?
- Faeco-oral
2. Human reservoir
What determines the severity of Hepatitis A virus?
Age:
- Mostly asymptomatic in children < 5 yrs
- Mortality rate 1.5% if > 50 year
Describe the management/prognosis of hepatitis A virus?
- No specific treatments
- Maintain hydration, avoid alcohol
- Usually self-limiting illness
- No role for Vaccine or IgG
How do you diagnose acute hepatitis A?
IgM Positive or RNA in blood or stool
How do you diagnose previous hepatitis A or vaccinated?
IgG Positive
Describe the hepatitis A vaccine?
- Inactivated virus
- 95% efficacy after 4 weeks
- 2nd dose gives life protection
In what 4 people would you give pre-exposure hepatitis A vaccine?
- Travellers
- Homosexual men
- IVDU
- Chronic liver disease patients
When would you give pre-exposure Hepatitis A Immune Globulin?
- Vaccine allergic
- <4 wks to travel
- Confers 3-6 months immunity
Describe the features of hepatitis E virus?
- RNA virus
- More common than Hep A in the UK
- 4 genotypes
What are the 3 modes of transmission for hepatitis E virus?
- Faeco-oral
- Pork products
- Minimal person-to-person transmission
Describe the clinical features of hepatitis E virus?
- Similar to Hepatitis A plus rare reports of neurological effects
- Case-fatality rate: 1 - 3%, higher in pregnant women for some genotypes (G1)
Describe the management of hepatitis E virus?
- Treatment: Supportive
- No Vaccine
When would you see chronic hepatitis E virus & how would you treat them?
- Very immunosuppressed patients: bone marrow transplants
- Treatment with ribavirin
List the 4 neurological manifestations which are associated with hepatitis E?
- Guillaine Barre syndrome
- Encephalitis
- Ataxia
- Myopathy
Describe the features of hepatitis B virus?
- DNA virus
- HBV vaccination included in immunisation schedule in most countries
List the 6 routes of transmission for hepatitis B virus?
- Mother to baby- vertical transmission usually at birth
- Contaminated needles & syringes
- Child to child
- Organs and tissue transplantation
- Fluids (blood, semen)
- Transfusion (blood, blood products)
What is the most common worldwide route of transmission for hepatitis B virus?
Vertically at birth
What 2 things does the age at the time of hepatits B infection determine?
- Severity of acute illness
2. Risk of Chronic HBV Infection (CHB)
Describe the difference between hepatitis B infection at birth & as an adult?
- Infection at birth / young child is usually asymptomatic but leads to chronic infection
- Infection as an adults is usually symptomatic but is cleared
List the 6 clinical signs of hepatitis B virus (vague so difficult to diagnose)?
- Weight loss
- Abdo pain
- Fever
- Cachexia
- Mass in abdomen
- Bloody ascites
What blood result suggests hepatitis B virus?
HBsAg +ve
List the 5 problems with chronic hepatitis B virus?
- Development of chronic liver disease in 25%
- Cirrhosis
- Decompensation
- Hepatocellular Carcinoma (HCC)
- Death
List the 6 hepatitis B lab tests that we measure?
- sAg: Surface antigen- marker of infection
- sAb: Surface antibody- marker of immunity
- cAb: Core antibody
- eAg: e antigen- suggests high infectivity
- eAb: e antibody- suggests low infectivity
- HBV DNA
What test results give a diagnosis of hepatitis B virus?
sAg or DNA are detectable
What is the definition of chronic hepatitis B virus?
sAg detectable for >6/12months
What are the 2 groups of chronic hepatitis B carriers?
- 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
What is the treatment for acute hepatitis B virus?
No treatment
What is the treatment for chronic hepatitis B virus?
- Most do not require treatment
- Immuno-modulatory: Inferferon
- Suppress viral replication: Tenofovir or Entecavir
When would you treat chronic hepatitis B patients?
Only treat those with liver inflammation (LFT or Biopsy) or
fibrosis (on Fibroscan or Biopsy)
What are the 3 ways to prevent hepatitis B virus?
- Education (safe sex, injecting etc)
- Immunisation with HBV sAg Vaccine
- HBV vaccination to newborn- 6 doses in first year
- Tenofovir during the last trimester of pregnancy if high Viral Load
Describe the features of hepatitis D virus?
- ss RNA virus
- Requires HBV to replicate
- Transmission same as Hep B
- Vertical transmission is rare
In what 3 ways is hepatitis D acquired?
- Co-infection with HBV
- Super-infection of chronic HBV carriers
- Increases risk of chronic liver disease
How do you treat hepatitis D virus?
Peg IFN only
Describe the aims of hepatitis B treatment?
Not curative, but reduce risk of complications
Describe the features of hepatitis C virus?
- RNA virus
- No vaccine, no post exposure prophylaxis
- No reliable immunity after infection
- Multiple Genotypes of HCV
What are 3 ways to transmit hepatitis C virus?
- Injecting drugs
- Transfusion + Transplant
- Sexual / vertical rare
What are the 2 types of hepatitis C infections?
- Chronic infection (70%)- cirrhosis (25%) or HCC (1-5%)
2. Clear infection (30%)
Describe the clinical signs of hepatitis C virus?
- Mostly asymptomatic
- Multitude of extra-hepatic manifestations
How are most hepatitis C infections diagnosed?
By screening of high risk groups- drug users & immigrants to UK from high prevalence countries
What blood test result indicates chronic hepatitis C infection or cleared infection?
Anti HCV IgG positive
What blood test result indicates current hepatitis C infection/viraemia?
PCR or Antigen positive
What is the aim of hepatitis C treatment?
Cure infection- cure rates of >95% within 8-12 weeks of oral treatment
How do you treat hepatitis C virus?
- Direct Acting Antiviral (DAAs) inhibit different stages of the replication cycle
- The DAA regimen is decided according to Genotype and degree of fibrosis / cirrhosis
What 2 types of hepatitis viruses have an effective treatment?
HBV and HCV
What 3 types of hepatitis viruses can lead to chronic hepatitis?
- HBV
- HCV
- HDV
What 2 things can gallstones be made of?
Cholesterol or Bile pigment (most are mixed)
What do 10% of gallstones have?
Sufficient calcium to be seen on plain X-rays
How are most gallstones diagnosed?
By ultrasound
How much bile does the liver secrete daily?
500mls
Describe the cholesterol in bile?
Not water soluble and is kept in solution by micelles containing bile acids and phospholipid
What causes the colour of bile?
Bile pigment, bilirubin which is a breakdown product of haemoglobin
When does bile become lithogenic (stone forming) for cholesterol?
If there is excessive secretion of cholesterol or decreased secretion of bile salts
What is the 1st indication of the presence of gallstones in a 1/3rd of patients?
Acute Cholecystitis
Describe the presentation of Acute Cholecystitis?
Severe right upper quadrant pain, tenderness and fever
Describe the blood results of Acute Cholecystitis?
Leucocytosis and normal serum amylase
Describe the prognosis of Acute Cholecystitis?
Usually resolves spontaneously but can progress to empyema, gangrene and rupture
What initiates Acute Cholecystitis?
Stone obstruction of cystic duct causing supersaturation of bile and chemical irritation
Describe the cause of chronic cholecystitis?
- May be a sequel to repeated attacks of acute cholecystitis
- Inflammation secondary to chemical damage (supersaturated bile) rather than bacterial infection
What is virtually always present in chronic cholecystitis?
Gallstones
What are the 3 most common causes of acute pancreatitis?
- 50% secondary to alcohol abuse
- 30% secondary to gallstones
- 20% other causes: “GET SMASHED”
Describe the presentation of acute pancreatitis?
Presents with severe upper abdominal pain, fever, leucocytosis and raised serum amylase
What are 2 potential complications of acute pancreatitis?
- Pancreatic Abscess
2. Pseudocyst
Describe a Pancreatic Abscess?
- Infected pancreatic necrosis
- Avascular haemorrhagic pancreas good culture medium
- Drainage or necrosectomy plus antibiotics
What is the cause of 85% of chronic pancreatitis?
Alcohol abuse
Describe the features of chronic pancreatitis?
- Stones and concretions in ducts
- Can be hereditary
- Usually painful
- May present with exocrine or endocrine failure
Describe a pancreatic pseudocyst?
- No epithelial lining
- Commonly in lesser sac
- High concentration of pancreatic enzymes
- May resolve spontaneously
- May be drained into stomach
Describe a pancreatic Intraductal papillary mucinous neoplasm?
In continuity with main pancreatic duct or side branch duct, dysplastic papillary lining secreting mucin
Describe a pancreatic Mucinous cystic neoplasm?
- Mucinous lining
- “Ovarian-type” stroma
Describe a pancreatic Serous cystadenoma?
- No mucin production
- Almost always benign
Describe a carcinoma of the pancreas?
- 5% of cancer deaths
- 66% in head of pancreas
What are 3 types of carcinomas of the pancreas?
- Ductal adenocarcinoma- most common
- Perineural invasion
- Pre-malignant PanIN asymptomatic
What are the 2 risk factors for carcinoma of the pancreas?
- Germline mutations (e.g. BRCA) account for small proportion of patients,
- SMOKING is by far biggest risk factor
List the 3 signs and symptoms of a carcinoma of the pancreas?
- Painless obstructive jaundice
- New onset diabetes
- Abdominal pain due to pancreatic insufficiency or nerve invasion
Describe the “double duct sign” on radiology of a carcinoma of the pancreas?
Tumours in head may obstruct pancreatic duct and bile duct
When would you perform a Whipple’s resection?
- Only for tumours of head of pancreas
- Only about 10% of these patients suitable for operation
What is the average life expectancy following a Whipple’s resection?
20 months
Describe the (Neo)adjuvant therapy for carcinoma of the pancreas?
Folfirinox chemotherapy associated with (limited) improvement in metastatic disease
Describe Pancreatic Neuroendocrine Tumours?
- Rare
- May secret hormones (functional)
- Commonest functional tumour is insulinoma which presents with hypoglycaemia
What % of insulinomas are benign?
90%
What type of pancreatic tumours have the better prognosis?
Malignant endocrine tumours have much better prognosis than pancreatic carcinoma
Describe a carcinoma of the ampulla of vater?
- Presents when smaller than carcinoma of pancreas
- May arise from pre-existing adenoma
What is the 5 year survival rate of a carcinoma of the ampulla of vater?
25% 5 year survival following Whipples’ resection
How is a Cholangiocarcinoma classified?
Intrahepatic / extrahepatic depending on origin
What does a Intrahepatic cholangiocarcinoma need to be distinguished from?
From metastatic adenocarcinoma (which may have similar histology) and hepatocellular carcinoma
Describe Extrahepatic cholangiocarcinoma?
- Similar morphology and prognosis to pancreatic carcinoma
- Treatment is currently Whipple’s operation to remove common bile duct and involved pancreas/duodenum
Describe carcinoma of the gallbladder?
- Rare
- Adenocarcinoma
- Local infiltration may make gallbladder seem abnormally stuck down at theatre
What is the prognosis of carcinoma of the gallbladder?
Dismal prognosis unless found incidentally in a gallbladder removed for chronic cholecystitis
What are the 2 functions of the pancreas?
- Exocrine- Manufacture and secretion of enzymes to digest food
- Endocrine- Glucose control
Describe the 3 parts to diagnosing acute pancreatitis?
- Pain in keeping with pancreatitis
- Amylase 3 times upper limit of normal
- Characteristic CT appearance
Describe mild acute pancreatitis?
Absence of organ failure/ local/ systemic complications
Describe moderately severe acute pancreatitis?
Presence of transient organ failure or presence of local/ systemic complications in absence of organ failure
Describe severe acute pancreatitis?
Persistent organ failure
List the 9 causes of acute pancreatitis?
- Gallstones
- Ethanol
- Trauma
- Steroids
- Mumps
- Autoimmune
- Scorpion sting
- ERCP
- Drugs
Describe the initial treatment of acute pancreatitis?
ABC’s
- Fluids
- Oxygen
- Organ support
- Antibiotics
What is the pro of giving antibioitcs for acute pancreatitis?
Several studies suggested meropenem for 1 week in pancreatitis with necrosis decreases mortality
What is the con for giving antibiotics for acute pancreatitis?
Concern that giving broad spectrum antibiotics in sterile necrosis will select out MRSA or fungal infection with higher mortality
Describe early feeding in acute pancreatitis?
Nasogastric or nasojujenal
List the 3 investigations for acute pancreatitis?
- US to assess for gallstones
- MRCP to assess for CBD stones
- CT if diagnostic doubt or concern about complications
What are 2 differential diagnosis for acute pancreatitis?
- Perforated duodenum
2. Ischaemic bowel
Describe early phase acute pancreatitis?
- Systemic disturbance from host response to local pancreatic injury (usually over by one week).
- SIRS may progress to MODS
Describe late phase acute pancreatitis?
Local and septic complications
What is the % mortality for severe acute pancreatitis?
Up to 25% dependant on age and comorbidities
List 4 further managements of acute pancreatitis to treat the cause?
- ERCP
- Lap Cholecystectomy
- Alcohol addictions advice
- Stop medication
Describe the sequelae of pancreatitis?
- Complete resolution with / without organ dysfunction
- Necrosis with/ without infection
- Fluid collection: peripancreatic fluid collection, pseudocyst, pancreatic fistula
Describe pancreatic necrosis?
Predicts complicated disease but initial management not altered
What is the purpose of serial CT for pancreatic necrosis?
For resolution, or repeat if deterioration in organ function/ increase in organ support
Describe Infected pancreatic necrosis?
- Ongoing sepsis and progression to MODS
- Requires intervention
What are the 3 types of managements for infected pancreatic necrosis?
- Open necrosectomy
- Percutaneous necrosectomy
- Radiological drainage
List the 2 complications of pancreatic necrosis?
- Bleeding- interventional radiology
2. Erosion to surrounding structures- surgery
Describe the Interventional radiology for bleeding?
- Access via groin
- Selective cannulation of coeliac trunk
- Commonly splenic artery aneurysm, may be gasproduodenal artery
- Usually coils placed before and after bleed, can be stunted
Describe the prognosis of a Pancreatic Pseudocyst?
May settle without intervention (almost always by 12 weeks)
What may a pancreatic pseudocyst require if its symptomatic?
Drainage
Describe the drainage of a Pancreatic Pseudocyst?
- Can drain to stomach laparoscopically or endoscopically
- May drain transpapillary
Describe the management of a pancreatic fistula?
- May require period of parenteral nutrition
- Would attempt endoscopic treatment in first instance
- May require salvage distal pancreatectomy
List the 5 after affects of pancreatitis?
- May be diabetic
- May require creon pancreatic enzyme supplements
- May require restorative surgery
- Significant impact on quality of life
- If gallstones- needs gallbladder removed
Describe the spread of head and neck cancer?
May spread to lymph nodes in neck, usually on the same side
What are the 2 risk factors of head & neck cancer?
- Smoking
2. Alcohol
What is a classic presentation of head/neck cancer?
A persistent, non-healing ulcer without definite, identifiable cause
List the 4 layers of the oesophagus?
- Mucosa (non-keratinising stratified squamous)
- Muscularis mucosae
- Submucosa
- Muscularis propria
- Advenitia
Describe the normal oesophageal mucosa?
Lining of non-keratinising stratified squamous epithelium
Describe the histological appearance of reflux oesophagitis (GORD)?
- Acid and digestive enzymes injure squamous epithelium lining oesophagus
- Increased numbers of inflammatory cells and the basal zone of the squamous epithelium is hyperplastic
List 2 potential infections of the oesophagus?
- Candida albicans (fungus)
2. Herpes simplex virus
List 3 chemicals causing inflammatory oesophageal pathology?
- Peptic oesophagitis / GORD: reflux of acid, bile
- Caustics: lye (NaOH, caustic soda)
- Pills: iron, bisphosphonates, tetracycline
Describe the histological appearance of Candida oesophagitis?
Active chronic inflammation with many neutrophils especially near the luminal surface of the epithelium
What stain confirms spores & hyphae of Candida albicans?
PAS stain
Describe the histological appearance of oral herpes simplex infection?
- Atypical squamous cells
- Inflammatory exudate and cells (‘slough’)
What is Barrett’s oesophagus?
A metaplastic response to mucosal injury e.g. from long term GORD
Describe the histological appearance of Barrett’s oesophagus?
Squamous epithelium becomes glandular, usually intestinal with goblet cells
What is Barrett’s oesophagus associated with?
Development of benign strictures but also with adenocarcinoma
What are the 3 types of dysplasia?
- ‘Indefinite for dysplasia‘
- Low grade dysplasia
- High grade dysplasia
What is dysplastic epithelium?
Architecturally & cytologically abnormal
Describe low grade dysplasia?
- Cells polarised
- Nuclei stratified
Describe high grade dysplasia?
- Polarity lost.
- Nuclei rounder, vesicular
- Prominent nucleoli
- Abnormal mitoses
- Necrosis
What is the risk of Barrett’s oesophagus?
Cancer risk ~0.4% per annum due to dysplastic cells
Who is more likely to get Barrett’s oesophagus?
Males > Females (increasing)
Describe the different risks of cancer between low and high grade dysplasia in Barrett’s?
- Increased risk but progression to cancer still slow
- LGD has nearly the same cancer risk as HGD
Describe the role of surveillance/screening in Barrett’s oesophagus?
- 4 biopsies (Seattle Protocol) every 2cm effective at finding dysplasia, but laborious
- Targeted biopsy may eventually replace it with improvements in endoscopy
What endoscopic treatment may avoid the need for radical surgery in Barrett’s oesophagus?
Radiofrequency ablation- reduced cancer risk
What are 2 types of oesophageal cancers?
- Squamous carcinoma
2. Adenocarcinoma
What is oesophageal Squamous carcinoma associated with?
- Smoking
2. Drinking
What is adenocarcinoma of the oesophagus associated with?
- Gastro-oesophageal reflex (GORD)
2. Obesity
List 5 causes of acute gastritis?
- Alcohol
- Medication e.g. NSAIDs
- Severe trauma
- Burns (Curling’s ulcers)
- Surgery
List 3 causes of chronic gastritis?
- Autoimmune
- Bacterial (H pylori)
- Chemical
What is autoimmune gastritis?
Destruction of parietal cells due to auto-antibodies against intrinsic factor & parietal cell antibodies in blood
List 4 things that autoimmune gastritis leads to?
- Complete loss of parietal cells with pyloric & intestinal metaplasia
- Achlorhydria -> bacterial overgrowth
- Hypergastrinaemia -> endocrine cell hyperplasia /carcinoids
- Persistent inflammation which can lead to epithelial dysplasia and may lead to cancer
What effect does H. pylori have?
Colonises gastric mucosa causing active chronic inflammation
What does IL-8 do?
From epithelial cells attracts neutrophils
Describe the 2 patterns of gastritis occurring after exposure to H. pylori?
- Antral-predominant gastritis -> hypergastrinaemia and duodenal ulceration
- Pangastritis -> hypochlorhydria, multifocal atrophic gastritis, intestinal metaplasia, cancer
What is thought to be the reason why two patterns of gastritis occur after exposure to H. pylori?
Microbe-host interface
What type of gastritis do patients with higher IL-8 tend to get?
Pangastritis
What type of gastritis do patients with lower IL-8 tend to get?
Antral gastritis
List the 2 associations of the formation of peptic ulceration?
- Impaired mucosal defense (due to NSAID interfering with mucosal prostaglandin synthesis, bile reflux)
- Microbe factors (CagA + variants associated with more severe inflammation)
List 3 signs of Helicobacter pylori infection?
- Haematemesis
- Melena
- Abdominal pain
List 3 consequences of peptic ulceration?
- Haemorrhage
- Perforation
- Fibrosis (leading to stenosis)
Describe the histological appearance of chemical gastritis?
- Few inflammatory cells
- Surface congestion oedema, elongation of gastric pits, tortuosity, reactive hyperplasia / atypia, ulceration
Where in the stomach is chemical gastritis commonly seen?
Antrum more than corpus
List 4 causes of chemical gastritis?
- Bile reflux
- NSAIDs
- Ethanol
- Oral iron
What is gastric cancer strongly associated with?
Chronic gastritis: H pylori or autoimmune
Describe the histological appearance of gastric cancer?
- Background atrophic mucosa
- Chronic inflammation
- Intestinal metaplasia
- Dysplasia
What is gastric cancer morphologically classified as via the Lauren Classification?
‘Intestinal’ or ‘ diffuse’ types
What is diffuse gastric cancer?
Individual malignant cells with mucin vacuoles (‘signet ring’ cells)
Why is diffuse gastric cancer called linitis plastica (‘leather bottle stomach’)?
May invade extensively without being endoscopically obvious
Describe the 3 clinical signs of diffuse gastric cancer?
- Metastasis to ovaries (‘Krukenberg tumour’)
- Supraclavicular lymph node (‘Virchow’s node’)
- ‘Sister Joseph’s nodule’ (umbilical metastasis)
List 3 presenting features of upper GI bleeding?
- Haematemesis
- “Coffee ground” vomiting
- Melaena
What are the 3 sources of upper GI bleeding?
- Oesophagus
- Stomach
- Duodenum
What is the % mortality & rebreeding of upper GI bleeding (in the UK)?
- Mortality: 10%
- Rebleeding: 13%
List 7 causes of upper GI bleeding & their % occurrence?
- Peptic ulcer- 36%
- Oesophagitis- 24%
- Gastritis- 22%
- Duodenitis- 13%
- Varices- 11%
- Malignancy- 4%
- Mallory-weiss tear- 4%
What are 3 causes of peptic ulcers?
- Acid
- H. pylori
- NSAIDs
Describe the management of upper GI bleeding?
- Resuscitate if required
- Risk assessment & timing of endoscopy
- Drug therapy & transfusion
Describe how to resuscitate in an upper GI bleed?
- Pulse & BP - IV access for fluids/blood (check bloods, esp Hb & urea) - Lie flat & give oxygen
Describe how the risk of an upper GI bleed affects the timing of endoscopy?
- High risk:emergency endoscopy
- Moderate risk: admit & next day endoscopy
- Low risk:out-patient management
What is the endoscopic risk score for upper GI bleeding?
Rockall (predicts mortality)
What are the 3 endoscopic risk scores for upper GI bleeding?
- “Admission” Rockall
- Glasgow Blatchford (predicts need for intervention or death)
- AIMS 65
What does a Glasgow Blatchford score (GBS) of <= 1 mean?
Identifies those at very low risk of poor outcome: can be discharged for out-patient endoscopy
When do most upper GI bleed patients get their endoscopy?
Within 24 hrs (even at weekend)
When do low risk upper GI bleed patients (GBS <= 1) get their endoscopy?
Can be discharged for out-patient endoscopy
When do very high risk upper GI bleed patients (haemodynamic instability or severe ongoing bleeding) get their endoscopy?
Emergency endoscopy
List the 4 things needed for endoscopic therapy?
- AdrenaIine injection
- Heater probe
- Endoscopic clips
- Thrombin, laser
What is the benefit of IV proton pump inhibitors (PPIs) in upper GI bleeding?
- Not beneficial prior to endoscopy
- Reduces rebleeding & mortality if given post-endoscopy to the higher risk patients who required endoscopic therapy
What should you do for upper GI bleed patients on aspirin & NSAIDs?
- Continue low dose aspirin after upper GI bleeding once haemostasis achieved (& add PPI)
- Stop NSAIDs
What should you do for upper GI bleed patents on Clopidogrel, Warfarin & DOACs?
Once haemostasis achieved, discuss risks & benefits with cardiologist/stroke team & patient, but generally try to restart these medications
When would you transfuse blood in an upper GI bleed?
Once Hb <7-8g/dL
When would you transfuse platelets in an upper GI bleed?
If actively bleeding & platelet count <50x109/L
When would you give Fresh frozen plasma in an upper GI bleed?
If INR>1.5
When would you give prothrombin complex concentrate in an upper GI bleed?
If on warfarin & active bleeding
What are 3 ways to treat oesophageal varices?
- Endoscopic banding
- TIPS
- B-Blocker drugs
What is the % mortality rate for variceal bleeding?
30-40%
What is the reason for an increase in variceal bleeding?
Due to the rise in alcohol, hepatitis C & fatty liver disease
How would you resuscitate an acute variceal bleed?
- Restore circulating volume - Transfuse once Hb<7 g/dL - Consider airway protection
How do you diagnose an acute variceal bleed?
Endoscopy
What are the 3 therapies for an acute variceal bleed?
- Antibiotics early
2. Vasopressors (Terlipressin) early - 3. Endoscopic band ligation
What does TIPS stand for?
Trans-jugular intrahepatic stent shunt
What are 3 ways to manage uncontrolled variceal bleeding?
- Sengstaken tube
- TIPS useful “rescue” procedure for failed endoscopy & drug therapy (high mortality)
- Surgical shunt/transection (very rarely used)
What are the 2 primary prophylaxis for Variceal Bleeding?
Beta-blockers or Banding
What are 5 treatments for acute variceal bleeding?
- Antibiotics & Terlipressin (in A&E)
- Banding first line for oesophageal variceal bleeding
- Tissue glue injection for gastric variceal bleeding
- TIPS for uncontrolled variceal bleeding
- Balloon tamponade (as temporary salvage)
What are the 2 treatments for prevention of variceal rebleeding?
Beta-blocker + repeated Banding
What are the 4 key points to optimal management of an upper GI bleed?
- Resuscitate
- Risk assess
- Timing of endoscopy
- Drug therapy & transfusion
List the 5 layers of the intestines?
- Mucosa
- Submucosa
- Muscular propria
- Subserosal fat
- Peritoneal surface
What are the crypts called in the small intestine?
Crypts of Lieberkuhn
List 9 causes of inflammation in the intestines?
- Coeliac Disease (small intestine)
- Idiopathic Chronic Inflammatory Bowel Disease
- Crohns Disease
- Ulcerative Colitis (large intestine)
- Infection
- Ischaemia
- Radiation colitis
- Diversion colitis
- Microscopic colitis
What is the cause of Coeliac disease?
Immunological response to gliadin (gluten derived peptide)
Describe how the immunological response to gliadin in coeliacs disease leads to malabsorption?
Gliadin presented by HLA molecules to helper T cells –> lymphocytic response –> epithelial damage –> flattening of villi –> less surface area for absorption of nutrients –> malabsorption
Describe the inheritance/genetics of coeliacs disease?
- Prevalence in 1st degree relatives is approx 10%
- Strong association between coeliac disease & HLA haplotypes DQ2 & DQ8
What is elevated in classical coeliacs sprue?
Serum TTG elevated
How is coeliacs disease managed?
Removal of gluten-containing foods from diet
What happens to the small intestine structure in coeliacs disease?
Crypt hyperplasia
What are the 3 types of Chronic Inflammatory bowel diseases?
- Crohn’s Disease
- Ulcerative Colitis
- “Indeterminate colitis”
List the 5 intestinal chronic changes in IBD?
- Crypt distortion
- Loss of crypts
- Submucosal fibrosis
- Paneth cell metaplasia
- Neuronal Hyperplasia
List the 4 acute changes seen during active disease of chronic IBD?
- Cryptitis
- Loss of goblet cells
- Crypt abscess formation
- Ulceration
Describe the symptoms of ulcerative colitis?
- Relapsing
- Bloody mucoid diarrhoea (stringy mucus) with pain/cramps relieved by defecation
- Lasts days/months, then remission for months/years
- Initial attack may cause medical emergency for fluid & electrolyte imbalance
What % of UC patients have 1 relapse per 10 year period?
97%
List 9 extra intestinal manifestations of ulcerative colitis?
- Migratory polyarthritis
- Ankylosing spondylitis
- Erythema nodosum
- Clubbing of fingertips
- Primary sclerosing cholangitis
- Pericholangitis
- Cholangiocarcinoma (rare)
- Uveitis
- Sacroiliitis
List the 5 complications of ulcerative colitis?
- Perforation
- Toxic megacolon
- Iliac vein thrombosis
- Carcinoma
- Lymphoma
What % of ulcerative colitis patients require colectomy during first 3 years?
30%
What is recommended in patients with long-standing extensive UC & why?
Regular colonoscopy with biopsy to detect precancerous dysplastic changes
What is Crohn’s disease?
Transmural granulomatous disease affecting oesophagus to anus but discontinuous, usually involves small intestine & colon with rectal sparing, less severe in distal vs. proximal colon (i.e. preferential right-sided involvement)
What is the prevalence of Crohn’s disease in primary western populations?
3 per 100,000, peaks in teens/twenties & ages 50-69
List the 4 symptoms of Crohn’s disease?
- Episodic mild diarrhea
- Fever
- Pain
- May be precipitated by stress: if colon affected, may have anemia
What do 20% of people with Crohn’s disease have?
Abrupt onset, resembling acute appendicitis or bowel perforation
List the 5 complications of Crohn’s disease?
- Fibrosing strictures (common in terminal ileum)
- Fistula
- Malabsorption
- Toxic megacolon
- Carcinoma (but lower risk than in UC)
List the 7 additional histological features of Crohn’s disease (different from UC features)?
- Skip lesions
- Fistulas / sinus tracts
- Malabsorption (if ileum involved)
- Granulomas
- Deep ulcerations
- Marked lymphocytic infiltration
- Serositis
What are the long term risks of IBD?
- Higher risk of colonic carcinoma than general population
- Colonic/rectal adenocarcinoma is the most common intestinal malignancy
What is the lifetime risk of colorectal cancer in the UK?
- 1 in 16 men
- 1 in 20 women
Describe how genetic abnormalities occur?
At the cellular level secondary to damage to DNA of existing stem cells, allowing the cells to survive when they should normally undergo apoptosis
What may abnormalities in response to proliferative stimuli result in?
Increased cell proliferation
Why are numerous abnormalities required for a cancer to develop its malignant potential?
Because of the numerous checks on cells division
What does it mean when a cell is dysplastic?
The abnormal cell morphology has survived as its stayed compatible with the development of some abnormalities
Describe adenomas of the colon?
- Also known as benign glandular neoplasms
- Dysplastic, and the majority are polyps
What are 4 differentials of adenomas?
- Hyperplastic (metaplastic) polyps
- Hamartomatous polyps
- Inflammatory polyps
- Submucosal lesions (lipoma, leiomyoma)
List 5 risk factors for colorectal cancer?
- Adenoma- size, number
- IBD
- Family History
- Other Carcinomas
- Polyposis syndromes- FAP, Lynch syndrome
What size of polyps increase the risk of colorectal cancer?
> 2cm
What histological type of polyp is more likely to turn malignant?
Flat polyps with a villous pattern have a much larger surface area & no stalk
List 2 scoring systems for colorectal cancer?
- Dukes’ staging
2. TNM staging
Describe Dukes’ A & B colorectal cancers?
Fat better prognosis so no need to expose to toxic side effects of chemotherapy
What may individual colorectal tumours be targeted by?
Preoperative neoadjuvant therapy
List 3 ways to detect colorectal cancer early?
- Screening colonoscopy of UC Patients
- Bowel Cancer Screening Programme faecal occult blood of >50 -75 year old (+ve –> colonoscopy)
- Patient education of symptoms
List 3 other primary tumours arising in the small or large intestines?
- Neuroendocrine tumours
- GISTs
- Lymphomas
What is proctitis?
Distal colitis limited to the rectum
What is proctosigmoiditis?
Colitis limited to retum & sigmoid
What is left sided colitis?
UC to the splenic flexure
What is extensive colitis?
UC to the hepatic flexure
What is pan colitis?
Colitis of the whole colon
What is the definition of ulcerative colitis?
Diffuse mucosal inflammation limited to the colon
What 2 factors define Crohn’s disease?
- Location- colonic, terminal ileal, perianal etc
2. Pattern of disease- inflammatory, fistulating, stricturing
What is the definition of Crohn’s disease?
Patchy transmural inflammation affecting any part of GI tract
Is ulcerative colitis or crohn’s more common?
Ulcerative colitis is more common
Slight _____ preponderance in Crohn’s?
Female
Slight ____ preponderance in UC?
Male
Describe the epidemiology of IBD?
- Diseases of young people
- Peak incidence between 10-40 years
- 15% present at 60+
- Approx 240,000 people with IBD in the UK
Describe the pathogenesis of IBD?
- Aetiology unknown
- “Host response to environmental triggers in genetically susceptible individuals”
Describe the relationship between smoking and IBD?
- Increases risk of Crohn’s
- Reduces risk of UC
List the 7 things to ask about when taking an IBD history?
- Stool frequency, consistency, urgency, blood
- Abdo pain, malaise, fever
- Weight loss
- Extraintestinal symptoms (joint, eyes, skin)
- Travel
- Family Hx
- Smoking
List the 6 things to do when performing an examination to diagnose IBD?
- Weight
- Pulse
- Temperature
- Anaemia
- Abdominal tenderness
- Perineal examination
List the 8 investigations to do when diagnosing IBD?
- FBC, ESR, U&E’s, LFTs, CRP
- Stool cultures + C. Difficile toxin
- Faecal Calprotectin
- AXR
- Rigid sigmoidoscopy
- Colonoscopy
- Small bowel radiology
- Labelled WCC scanning
What investigation should you avoid in severe IBD disease?
Endoscopic examination
List the 3 treatments common to UV & Crohn’s?
- Coricosteroids
- Thiopurines
- Biologics
What is the treatment for UC alone?
5ASAs
What are the 2 treatments for Crohn’s disease alone?
- Methotrexate
2. Immune modulating diets
List the 4 glucocorticoids for IBD treatment?
- IV hydrocortisone, methylprednisolone
- Oral Prednisolone
- Budesonide
- Beclometasone
What effect do steroids have on IBD?
- Rapid induction of remission
- Poor evidence for maintaining remission
Describe the slow reducing course of steroids?
- Prednisolone 40mg daily/1 week
- Reduce by 5mg/ week
List the 5 significant side effects of steroids?
- Immunosuppression
- Impaired glucose tolerance
- Osteoporosis
- Weight gain
- Cushingoid appearances
What is the most widely used aminosalicylates?
Mesalazine
List the 3 ways to give Mesalazine (aminosalicylates)?
- pH dependent release/resin coated (Asacol, Salofalk)
- Time controlled release (Pentasa)
- Delivery by carrier molecules (sulphasalazine, osalazine, balsalazide)
What are Aminosalicylates also effective as?
Topical therapy- enemas/suppositries
List 4 brand names for Mesalazine?
- Asacol
- Pentasa
- Octasa (cheapest)
- Ipocol
List the 2 main roles of Aminosalicylates?
- Induction of remission in mild-moderate ulcerative colitis
- Maintenance of remission in UC
What is Aminosalicylates reliant on?
Compliance rather than delivery system
What does a higher dose (4-4.8g day) of Aminosalicylates do?
- Higher remission rates
- Better mucosal healing
What is the pro and con of Aminosalicylates?
- PRO: Maintenance therapy may reduce cancer risk
- CON: Little evidence to support use in Crohn’s
What % of people have adverse effects on Sulphasalazine?
10-45%
What % of people have an intolerance to Mesalazine?
15%
Describe the adverse effects of Aminosalicylates?
Renal impairment (interstial nephritis, nephrotic syndrome) is rare and idiosynchratic
Give 2 examples of Thiopurines unlicensed for IBD therapy?
Azathioprine and mercaptopurine
What are Thiopurines effective for?
Maintenance therapy for UC and Crohn’s
Describe the steroid sparing agent aspect of Thiopurines?
- Those requiring 2+ course steroids in a year
- Relapse on <15mg prednisolone
- Post-op prophylaxis in complicated Crohn’s
Describe Thiopurines?
- Purine anti-metabolites
- Immune modulating drugs
- Essentially prevent T cell clonal expansion in response to antigenic stimuli
- Allow T cell apoptosis
What is the dose of Azathioprine (Thiopurines)?
1.5–2.5mg/kg/day
What is the dose of Mercaptopurine (Thiopurines)?
1–1.5mg/kg/day
What may predict Leucopenia?
Thiopurine methyl transferase (TPMT)
How do you monitor Thiopurines?
Weekly FBC + LFTs for 8/52 then at least every 3/12
Describe how/why we measure thiopurines 6TGN (6-Thioguanine nucleotides) active metabolites?
- Tailored dosing to ensure drug within therapeutic window
- Assessment of compliance
Describe why we measure thiopurines 6MMP (6-methylmercaptopurine) metabolite?
Associated with risk of hepatotoxiciy
List the 7 common side effects of Thiopurines?
- Leucopenia
- Nausea, vomiting
- Arthralgia
- Pancreatitis
- Hepatitis
- Squamous skin cancers
- Haematological malignancy
What is methotrexate?
- Anti-metabolite
- Folate scavenger so need folate supplements
What is the dose for methotrexate?
15-25mg weekly SC
What is methotrexate effective for treating?
- Effective in Crohn’s
- Little evidence in UC
- Widely used in inflammatory disease
List the 5 side effects of methotrexate?
- GI upset
- Hepatotoxicity
- Immunosuppression
- Sepsis
- Pulmonary fibrosis
What is Infliximab?
Murine Anti-TNF alpha monoclonal antibody
What is Infliximab effective for treating?
- Severe or fistulating Crohn’s
- Rescue acute severe UC
- Moderate to severe UC refractory to other treatment
What is Infliximab now available as?
A variety of “biosimilars”
Describe the dose of Infliximab?
- Loading regime at 0/2/6 weeks
- 2 monthly intravenous infusion
What are 3 CONS of Infliximab?
- Loss of efficacy
- Allergic reactions
- Expensive
What is Adalumimab?
Humanised Anti-TNF alpha monoclonal antibody
What is the dose for Adalumimab?
Fortnightly SC injections
What are the 2 CONS of Adalumimab?
- Less reactions
2. Less need for concomitant immunosuppression
What is Golimumab?
Humanised anti-TNF alpha
What is the dose of Golimumab?
2 weekly sc injections
What is Golimumab licensed for?
Moderate to severe Ulcerative colitis (not Crohn’s)
What are the 2 infection risks associated with Anti-TNF biologic drugs?
- Reactivation of TB
2. Reactivation of Hepatitis B
What are the 2 neurological side effects associated with Anti-TNF biologic drugs?
- Incidence of MS
2. Progressive multifocal leucoencephalopathy
What type of malignancy does biologics increase your risk of?
Lymphoma
How does Vedoluzimab work?
Anti-adhesin- binds Integrin α4β7 (lymphocyte adhesion molecule)
What is Vedoluzimab effective for treating?
- Gut specific so few risks of neurotoxicity
- Appears better for UC than Crohn’s
What type of IBD patient warrant hospital admission?
Patients who fail to respond to optimal treatment with 5ASA/prednisolone or with severe disease
What is the management of acute severe colitis?
- Intravenous steroid therapy required
- Liaison with colorectal surgeon
What factors predicts colectomy in 85% of acute severe colitis patients?
Stool frequency >8/day / CRP >45 on day 3
List the 4 investifations for acute severe colitis?
- Daily FBC, ESR, U+Es, CRP
- Stool cultures (including C.Difficile)
- Daily AXR
- Sigmoidoscopy
What is the treatment for acute severe colitis?
- Prophylatic LMW heparin
- IV hydrocortisone 100mg QDS or Methylprednisolone 30mg BD
What are the 2 options for changing the treatment of acute severe colitis after 72 hrs?
- Improving- oral prednisolone 40mg
2. No improvement- rescue therapy
What are the 3 types of rescue therapy for acute severe colitis?
- Ciclosporin 2mg/kg/day IV
- Infliximab 5mg/kg single dose
- Surgery
Describe surgery for ulcerative colitis?
- Surgery “curative”
- Ileo-anal pouch or ileostomy
Describe surgery for Crohn’s disease?
- Indicated for stricturing, perforation, fistulizing disease
- Sparing as will come back
What are the 6 aetiologies of the “acute abdomen”?
- Burst
- Blocked
- Inflamed
- Lost its blood supply
- Combination
- Nothing to do with the abdomen
What 2 conditions, unrelated to the abdomen, can cause an acute abdomen?
- Myocardial infarction
2. Pneumonia
What are 3 reasons why there is an increased use of imaging?
- Increased availability
- Increasing number elderly patients
- Increased accuracy
How useful is lmaging?
- Depends on what’s wrong with the patient
2. Depends on quality of clinical assessment
What are the 3 types of imaging available for the abdomen?
- Plain films (Xray)
- Ultrasound
- CT
What are the 3 different densities of the plain abdominal film?
- Gas
- Soft tissue: fat, muscle, bowel wall, solid organ, blood vessel
- Bone
What does the plain abdominal imagine reaching the X-ray detector depend on?
Densities encountered as X-ray travels through body
Are gallstones usually visible on plain X-ray?
NO
What are 3 normal gals shadows on a plain abdominal X-ray?
- Colon externally
- Small bowel centrally
- Stomach medial LUQ
Describe the movement of different parts of the colon?
- Ascending & descending colon- usually fixed
- Transverse & sigmoid- variable
What is Chilaiditi syndrome?
Rare condition when pain occurs due to transposition of a loop of large intestine (usually transverse colon) in between the diaphragm & liver, visible on plain abdominal X-ray or chest X-ray
What type of inflammatory conditions is an abdominal X-ray useful for?
- Colitis
- Not specific in other inflammatory conditions
What type of inflammatory condition is an abdominal ultrasound useful for?
Cholecystitis (and appendicitis if young and slim)
What is the 1st choice of imaging for abdominal inflammation?
CT
What is a chest X-ray sensitive for?
Free gas (good for perforation)- approx 80% sensitive
What imagine is good/bag for an abdominal perforation?
- GOOD: CT
- BAD: AXR as it’s very subtle
What 2 types of imaging is useful for abdominal obstruction?
- Abdominal X-ray
- CT for cause
What 4 things should you look for when imaging for abdominal obstruction?
- Small &/or large bowel dilatation?
- How much gas in colon?
- Any gas in rectum?
- Any complications- ischaemia, perforation?
What occurs in an incomplete small bowel obstruction?
- Some gas is still seen in the colon
- Small bowel more distended than large
What occur in a complete small bowel obstruction?
- No gas is seen in the colon
- Small bowel more distended than large
What are the 2 types of volvulus in the abdomen?
- Caecum
2. Sigmoid
What abdominal imaging is non-specific for ischaemia?
Abdominal X-ray
What do positive ischaemic signs on an abdominal X-ray suggest?
Advanced ischaemia
WHat is the 1st choice of imaging for ischaemia?
CT but <60% sensitive
What clinical sign can a plain abdominal X-ray show?
Pneumoperitoneum
What is the radiation dose for CXR, AXR & Abdo/pelvis CT?
- CXR: 0.02 mSv
- AXR: 0.5 mSv
- CT abdomen/pelvis: 6-10mSv
What is 10mSv radiation dose equal to?
1:1000 life time risk of fatal cancer (for adult age 30-39)
How common are coincidentalomas due to radiation?
Up to 25% in >70’s
What 2 things are plain radiography’s especially good at detecting?
- CXR- perforation
2. AXR- obstruction
List the 3 main examination findings indicating chronic liver disease?
- Clubbing
- Palmar erythema
- Spider naevi
What are 4 special investigations for liver disease?
- Hepatitis serology
- Ferritin & transferrin sat
- Liver autoantibodies
- Alpha-fetoprotein
What haematology results suggest cirrhosis?
- Raised bilirubin & Prothrombin
- Low albumin & platelets
What are 4 complications of cirrhosis?
- Ascites
- Variceal bleeding
- Encephalopathy
- Hepatocellular carcinoma
What is Diagnostic paracentesis?
Removal of a small quantity of fluid for testing
When would you undertake Diagnostic paracentesis?
All patients with new onset ascites, admission with worsening ascites or clinical condition
What 3 things are tested in a Diagnostic paracentesis?
- PMN count and culture (plain container & blood culture bottles)
- Total ascitic protein & albumin
- Cytology
What is the definition of Spontaneous Bacterial Peritonitis (SBP)?
> 250 neutophils/mm3 in ascites in absence of intra-abdominal source of infection or malignancy (often culture -ve)
What is spontaneous Bacterial Peritonitis?
Frequent, life threatening infection in cirrhotic patients
What is type of bacteria typically causes spontaneous Bacterial Peritonitis?
Usually gram-ve bacteria
What is the % mortality rate of spontaneous bacterial peritonitis?
10-40%
How would you treat spontaneous bacterial peritonitis?
IV antibiotics + IV albumin
How would you manage ascites?
Salt restriction & Diuretics: Oral Spironolactone +/- Frusemide
What 3 things is refractory ascites (fluid overload) unresponsive to in <10% of patients?
- Sodium restriction
- 400mg/day spironolactone
- 160mg/day frusemide
What are the 3 treatments for refractory ascites?
- Large Volume paracentesis (LVP)
- Transjugular Intra-hepatic stent (TIPS)
- Liver transplant (if suitable)
What does genetic haemochromatosis (C282Y mutation) lead to?
Excessive absorption of dietary iron which leads to iron overload in liver, heart, pancreas, joints, skin (“bronze diabetes”)
What are 3 things diagnosing genetic haemochromatosis?
- Raised ferritin & transferrin saturation
- HFE gene
- Liver biopsy rarely needed
How is genetic haemochromatosis treated?
Venesection
What are 4 causes of hyperamylasaemia?
- Pancreatitis, disruption pancreatic duct
- Biliary conditions (gallbladder infection/ perforation, choledocolithiasis, cholangitis)
- Enteric contents to peritoneum/ circulatory system (perforated viscus/ ischaemia)
- Other source of amylase parotid gland (viral infection, stone parotid duct)
What are raised transaminases a sign of?
Destruction of hepatocytes
What is raised all phos a sign of?
Damage to bile ducts
What is the initial management of pancreatitis?
IV fluids, catheter & nil by mouth
List 3 haemostatic therapies?
- Endoscopic: Variceal band ligation
- Balloon Tamponade (temporary)
- Transjugular intrahepatic stent (TIPS)
Describe the surveillance tests for Hepatocellular carcinoma (HCC) in cirrhosis?
6-monthly ultrasound +/- the level of alpha-fetoprotein
List the 3 management techniques for small curable Hepatocellular carcinoma (HCC)?
- Liver transplant if suitable
- Resect tumour
- Radio-frequency ablation (RFA)
List the 3 management techniques for larger incurable Hepatocellular carcinomas (HCC)?
- Trans-arterial Chemoembolisation (TACE)
- Oncology drug therapy (Sorafenib)
- Palliative care
Describe the epithelial surface of a normal oesophagus?
Non-keratinising stratified squamous epithelium
What is the 3 part cancer pathway of Barrett’s oesophagus?
Metaplasia –> Dysplasia –> Adenocarcinoma
What is the prevalence & epidemiology of oesophageal cancer?
- 1700 new patients/year
- Median age 72yrs
- Male > females
When is oesophageal cancer often diagnosed?
Advanced stage
What is the 5 year survival of oesophageal cancer for males & females?
Male: 10%
Female: 16%
What are 5 investigations to stage oesophageal cancer?
- CT scan
- PET-CT scan
- Endoscopic Ultrasound (EUS)
- Laparoscopy
- MRI, bone scan
What are the 3 curative options for oesophageal cancer?
- Surgery: no locally advanced disease, metastases, significant comorbidities
- Oncology: local disease & no metastases
- Endoscopic therapy: if very early disease
What are the 3 Palliative options for oesophageal cancer?
- Oncology
- Endoscopic therapy
- Supportive care
