GI and Liver Flashcards
How long does hepatitis persist for to be deemed chronic?
6 months.
Give 3 infective causes of acute hepatitis.
- Hepatitis A to E infection.
- EBV.
- CMV.
- Toxoplasmosis.
Give 3 non-infective causes of acute and chronic hepatitis.
- Alcohol.
- Drugs.
- Toxins.
- Autoimmune.
Give 3 symptoms of acute hepatitis.
- General malaise.
- Myalgia.
- GI upset.
- Abdominal pain.
- Raised AST, ALT.
- +/- jaundice.
Give 3 infective causes of chronic hepatitis.
- Hepatitis B (+/-D).
- Hepatits C.
- Hepatitis E.
What are the potential complications of chronic hepatitis?
Uncontrolled inflammation -> fibrosis -> cirrhosis -> HCC.
Is HAV a RNA or DNA virus?
HAV is a RNA virus.
How is HAV transmitted?
Faeco-oral transmission. E.g. contaminated food/water; shellfish.
Who could be at risk of HAV infection?
Travellers and food handlers.
Is HAV acute or chronic?
Acute! There is 100% immunity after infection.
How might you diagnose someone with HAV infection?
Viral serology: initially anti-HAV IgM and then anti-HAV IgG.
Describe the management of HAV infection.
- Supportive.
- Monitor liver function to ensure no fulminant hepatic failure.
- Manage close contacts.
Describe the primary prevention of HAV.
Vaccination.
Is HEV a RNA or DNA virus?
HEV is a small RNA virus.
How is HEV transmitted?
Faeco-oral transmission.
Is HEV acute or chronic?
Usually acute but there is a risk of chronic disease in the immunocompromised.
How might you diagnose someone with HEV infection?
Viral serology: Initially anti-HEV IgM and then anti-HEV IgG.
Describe the primary prevention of HEV.
- Good food hygiene.
- A vaccine is in development.
Is HBV a RNA or DNA virus?
HBV is a DNA virus! It replicates in hepatocytes.
How is HBV transmitted?
Blood-borne transmission e.g. IVDU, needle-stick, sexual, MTCT.
HBV is highly infectious!
Describe the natural history of HBV in 4 phases.
- Immune tolerance phase: unimpeded viral replication -> high HBV DNA levels.
- Immune clearance phase: the immune system ‘wakes up’. There is liver inflammation and high ALT.
- Inactive HBV carrier phase: HBV DNA levels are low. ALT levels are normal. There is no liver inflammation.
- Reactivation phase: ALT and HBV DNA levels are intermittent and inflammation is seen on the liver -> fibrosis.
What HBV protein triggers the initial immune response?
The core proteins.
How might you diagnose someone with HBV?
Viral serology: HBV surface antigen can be detected from 6w - 3m or anti-HBV core IgM after 3 months.
Describe the management of HBV infection.
- Supportive.
- Monitor liver function.
- Manage contacts.
- Follow up at 6 months to see if HBV surface Ag has cleared. If present -> chronic hepatitis.
How would you know if someone had acute or chronic HBV infection?
You would do a follow up appointment at 6 months to see if HBV surface Ag had cleared. If it was still present then the person would have chronic hepatitis.
What are the potential consequences of chronic HBV infection?
- Cirrhosis.
- HCC.
- Decompensated cirrhosis.
How can HBV infection be prevented?
Vaccination - injecting a small amount of inactivated HbsAg.
Describe two treatment options for HBV infection.
- Alpha interferon - boosts immune system.
- Antivirals e.g. tenofovir. They inhibit viral replications.
HBV treatment: give 3 side effects of alpha interferon treatment.
- Myalgia.
- Malaise.
- Lethargy.
- Thyroiditis.
- Mental health problems.
Is HDV a RNA or DNA virus?
It is a defective RNA virus. It required HBsAG to protect it.
Infection with what virus is needed for HDV to survive?
HDV can’t exist without HBV infection! It needs HBsAg to protect it.
How is HDV transmitted?
Blood-borne transmission, particularly IVDU.
Is HCV a RNA or DNA virus?
HCV is a RNA virus.
How is HCV transmitted?
Blood borne.
Give 4 risk factors for developing HBV/HCV infection.
- IVDU.
- People who have required blood products e.g. blood transfusion.
- Needle-stick injuries.
- Unprotected sexual intercourse.
- Materno-foetal transmission.
How might you diagnose someone with current HCV infection?
Viral serology - HCV RNA tells you if the infection is still present.
You want to find out if someone has previously been infected with HCV. How could you do this?
Viral serology - anti-HCV IgM/IgG indicates that someone has either a current infection or a previous infection.
Describe the treatment for HCV.
Lots of new drugs have been developed recently for HCV infection. Direct acting antivirals (DAA) are currently in use e.g. NS5A and NS5B.
What percentage of people with acute HCV infection will progress onto chronic infection?
Approximately 70%.
What percentage of people with acute HBV infection will progress onto chronic infection?
Approximately 5%.
How can HCV infection be prevented.
- Screen blood products.
- Lifestyle modification.
- Needle exchange.
There is currently no vaccination and previous infection does not confer immunity.
What types of viral hepatitis are capable of causing chronic infection?
Hepatitis B (+/-D); C and E in the immunosuppressed.
What is acute pancreatitis?
An inflammatory process with release of inflammatory cytokines (TNF alpha, IL-6) and pancreatic enzymes (trypsin, lipase).
What are the 3 different types of acute pancreatitis?
- 70% are oedematous; acute fluid collection.
- 25% are necrotising.
- 5% are hemorrhagic.
Give 5 causes of acute pancreatitis.
- Gallstones.
- Alcohol.
- Hyperlipidaemia.
- Direct damage e.g. trauma.
- Idiopathic.
- Toxic e.g. drugs, infection, venom.
Give 4 symptoms of acute pancreatitis.
- Severe epigastric pain that radiates to the back.
- Anorexia.
- Nausea, vomiting.
- Signs of septic shock e.g. fever, dehydration, hypotension, tachycardia.
How can acute pancreatitis be diagnosed?
Pancreatitis is diagnosed on the basis of 2 out of 3 of the following:
1. Characteristic severe epigastric pain radiating to the back.
2. Raised serum amylase.
3. Abdominal CT scan pathology.
Name a scoring system that can be used a prognostic tool in acute pancreatitis.
The abbreviated glasgow scoring system.
What 8 points make up the glasgow scoring system?
PaO2 < 8kPa.
Age > 55 years.
Neutrophils > 15x10^9.
Calcium < 2mmol/L.
Raised urea > 15mmol/L.
Elevated enzymes.
Albumin < 32g/L.
Sugar - serum glucose > 15mmol/L.
Describe the treatment for acute pancreatitis.
- ANALGESIA!
- Catheterise and ABC approach for shock patients.
- Drainage of oedematous fluid collections.
- Antibiotics.
- Nutrition.
- Bowel rest.
Give 2 potential complications of acute pancreatitis.
- Systemic inflammatory response syndrome.
- Multiple organ dysfunction.
What is chronic pancreatitis?
Chronic inflammation of the pancreas leads to irreversible damage.
Describe the pathogenesis of chronic pancreatitis.
The pathogenesis is not fully understood but the current theory is that pancreatic duct obstruction leads to activation of pancreatic enzymes -> necrosis -> fibrosis.
Describe how alcohol can cause chronic pancreatitis.
Alcohol -> proteins precipitate in the ductal structure of the pancreas (obstruction) -> pancreatic fibrosis.
What immunoglobulin might be elevated in someone with autoimmune chronic pancreatitis?
IgG4.
How is autoimmune chronic pancreatitis treated?
It is very steroid responsive.
Give 5 symptoms of chronic pancreatitis.
- Severe abdominal pain.
- Epigastric pain radiating to the back.
- Nausea, vomiting.
- Decreased appetite.
- Exocrine/endocrine dysfunction.
A sign of chronic pancreatitis is exocrine dysfunction. What can be a consequence of this?
- Malabsorption.
- Weight loss.
- Diarrhoea.
- Steatorrhoea.
A sign of chronic pancreatitis is endocrine dysfunction. What can be a consequence of this?
Diabetes mellitus.
What is the treatment for chronic pancreatitis?
Opiates in a controlled environment for severe pain.
Give 4 functions of the liver.
- Glucose and fat metabolism.
- Detoxification and excretion.
- Protein synthesis e.g. albumin, clotting factors.
- Defence against infection.
Name 3 things that liver function tests measure.
- Serum bilirubin.
- Serum albumin.
- Pro-thrombin time.
Name an enzyme that increases in the serum in cholestatic liver disease (duct and obstructive disease).
Alkaline phosphatase.
What enzymes increase in the serum in hepatocellular liver disease?
Transaminases e.g. AST and ALT.
Name two hepatocellular enzymes.
Transaminases e.g. AST and ALT.
Name a cholestatic enzyme.
Alkaline phosphatase.
Give 4 causes of hepatitis.
- Viral e.g. A, B, C, D, E.
- Drug induced.
- Alcohol induced.
- Autoimmune.
Give 2 possible outcomes of acute liver disease.
- Recovery.
- Liver failure.
Give 5 causes of acute liver disease.
- Viral hepatitis.
- Drug induced hepatitis.
- Alcohol induced hepatitis.
- Vascular.
- Obstruction.
Give 3 symptoms of acute liver disease.
- Malaise.
- Lethargy.
- Anorexia.
- Jaundice may develop later on.
Give 2 possible outcomes of chronic liver disease.
- Cirrhosis.
- Liver failure.
Give 5 causes of chronic liver disease.
- Alcohol.
- NAFLD.
- Viral hepatitis (B, C, E).
- Autoimmune diseases.
- Metabolic e.g. haemochromatosis.
- Vascular e.g. Budd-Chiari.
What is Budd-Chiari syndrome?
A vascular disease associated with occlusion of hepatic veins that drain the liver.
Give 5 signs of chronic liver disease.
- Ascites.
- Oedema.
- Malaise.
- Anorexia.
- Bruising.
- Itching.
- Clubbing.
- Palmar erythema.
- Spider naevi.
Drug induced liver injury is common. What question should you remember to ask in a patient history?
Have you started taking any new medication recently?
Name a drug that can cause drug induced liver injury.
- Co-amoxiclav.
- Flucloxacillin.
- Erythromyocin.
- TB drugs.
Name 3 drugs that are not known to cause drug induced liver injury.
- Low dose aspirin.
- NSAIDS.
- Beta blockers.
- HRT.
- CCB.
What enzyme is responsible for ‘mopping up’ reactive intermediates of paracetamol and so prevents toxicity and liver failure?
Glutathione transferase.
What are the potential consequences of hepatocyte regeneration in someone with liver cirrhosis?
Neoplasia and therefore HCC. Hepatocyte regeneration is liable to errors.
Give 3 causes of iron overload.
- Genetic disorders e.g. haemochromatosis.
- Multiple blood transfusions.
- Haemolysis.
- Alcoholic liver disease.
90% of people with haemochromatosis have a mutation in which gene?
HFE.
Haemochromatosis is a genetic disorder. How is it inherited?
Autosomal recessive inheritance.
Describe the pathophysiology of haemochromatosis.
Uncontrolled intestinal iron absorption leads to deposition in the liver, heart and pancreas -> fibrosis -> organ failure.
What protein is responsible for controlling iron absorption?
Hepcidin.
Levels of this protein are decreased in haemochromatosis.
How might you diagnose someone with haemochromatosis?
- Raised ferritin.
- HFE genotyping.
- Liver biopsy.
Name 3 metabolic disorders that can cause liver disease.
- Haemochromatosis - iron overload.
- Alpha 1 anti-trypsin deficiency.
- Wilson’s disease - disorder of copper metabolism.
Describe the mechanism by which alpha 1 anti-trypsin deficiency can lead to chronic liver disease.
Alpha 1 anti-trypsin deficiency results in protein retention in the liver -> eventually cirrhosis.
What is Wilson’s disease?
An autosomal recessive disorder of copper metabolism; there is excessive deposition of copper in the liver. This can lead to fulminant hepatic failure and cirrhosis.
What can cause raised unconjugated bilirubin?
A pre-hepatic problem e.g. haemolysis due to sickle cell disease, spherocytosis, hypersplenism etc.
Describe the urine and stools in someone with pre-hepatic jaundice?
Urine and stools are normal. There is no itching and the LFT’s are normal.
What can cause raised conjugated bilirubin?
Raised conjugated bilirubin indicates a cholestatic problem e.g. liver disease (hepatic) or bile-duct obstruction (post-hepatic).
Describe the urine and stools in someone with cholestatic jaundice?
Dark urine and pale stools. There may be itching and LFT’s are abnormal.
Give 3 causes of duct obstruction.
- Gallstones.
- Stricture (narrowing) e.g. malignant, inflammatory.
- Carcinoma.
- Blocked stent.
Give 4 causes of hepatic jaundice.
- Viral hepatitis.
- Alcoholic hepatitis.
- Drugs.
- Cirrhosis.
Give 3 symptoms of jaundice.
- Biliary pain.
- Rigors - indicate an obstructive cause.
- Abdomen swelling.
- Weight loss.
What is ascites?
An accumulation of fluid in the peritoneal cavity that leads to abdominal distension.
Give 4 pathophysiological causes of ascites and an example for each.
- Local inflammation e.g. peritonitis.
- Leaky vessels e.g. imbalance between hydrostatic and oncotic pressures.
- Low flow e.g. cirrhosis, thrombosis, cardiac failure.
- Low protein e.g. hypoalbuminaemia.
Describe the pathogenesis of ascites.
- Increased intra-hepatic resistance leads to portal hypertension -> ascites.
- Systemic vasodilation leads to secretion of RAAS, NAd and ADH -> fluid retention.
- Low serum albumin also leads to ascites.
What are the 3 phases of alcoholic liver disease.
- Fatty change: hepatocytes contain triglycerides.
- Alcohol hepatitis.
- Alcoholic cirrhosis: destruction of liver architecture and fibrosis.
What might be seen histologically that indicates a diagnosis of alcoholic liver disease?
Neutrophils and fat accumulation within hepatocytes.
What is non alcoholic steato-hepatitis (NASH)?
An advanced form of non-alcoholic fatty liver disease.
Give 3 causes of non-alcoholic fatty liver disease.
- Type 2 diabetes mellitus.
- Hypertension.
- Obesity.
- Hyperlipidaemia.
What is cirrhosis?
A chronic disease of the liver resulting from necrosis of liver cells followed by fibrosis. The end result is impairment of hepatocyte function and distortion of liver architecture.
Give 3 causes of cirrhosis.
- Alcohol!
- Hepatitis B and C.
- Any chronic liver disease e.g. autoimmune, metabolic, vascular etc.
What is the treatment of liver cirrhosis?
- Deal with the underlying cause e.g. stop drinking alcohol.
- Screening for HCC.
- Consider transplant.
Approximately what percentage of blood flow to the liver is provided by the portal vein?
75%.
Portal hypertension can lead to varices. Explain why.
Obstruction to portal blood flow e.g. cirrhosis leads to portal hypertension. Blood is diverted into collaterals e.g. the gastro-oesophageal junction and so causes varices.
Give 3 causes of portal hypertension.
- Cirrhosis and fibrosis (intra-hepatic causes).
- Portal vein thrombosis (pre-hepatic).
- Budd-Chiari (post-hepatic cause).
What are the potential consequences of varices?
If they rupture -> haemorrhage.
What is the primary treatment for varices?
Endoscopic therapy - banding.
What is peritonitis?
Inflammation of the peritoneum often due to infection.
What can cause peritonitis?
- Bacterial infection due to a perforated organ; spontaneous bacterial peritonitis; infection secondary to peritoneal dialysis.
- Non-infective causes e.g. bile leak; blood from ruptured ectopic pregnancy.
What is the commonest serious infection in those with cirrhosis?
Spontaneous bacterial peritonitis.
It can also affect immunocompromised people and those undergoing peritoneal dialysis.
Name a bacteria that can cause spontaneous bacterial peritonitis.
- E.coli.
- S.pneumoniae.
How can spontaneous bacterial peritonitis be diagnosed?
By looking for the presence of neutrophils in ascitic fluid.
Give 3 symptoms of peritonitis.
- Pain.
- Tenderness.
- Systemic symptoms e.g. nausea, chills, rigor.
Name a cause of pelvic inflammatory disease.
A complication of chlamydial infection.
Give 4 reasons why liver patients are vulnerable to infection.
- They have impaired reticulo-endothelial function.
- Reduced opsonic activity.
- Leukocyte function is reduced.
- Permeable gut wall.
What is primary biliary cirrhosis?
An autoimmune disease where there is progressive lymphocyte mediated destruction of intra-hepatic bile ducts -> cholestasis -> cirrhosis.
Describe 2 features of the epidemiology of primary biliary cirrhosis.
- Females affected more than men.
- Familial - 10 fold risk increase.
Describe the pathophysiology of primary biliary cirrhosis.
Lymphocyte mediated attack on bile duct epithelia -> destruction of bile ducts -> cholestasis -> cirrhosis.
Give 3 diseases associated with primary biliary cirrhosis.
- Thyroiditis.
- RA.
- Coeliac disease.
- Lung disease.
(Other autoimmune diseases).
Give 5 symptoms of primary biliary cirrhosis.
- Itching.
- Fatigue.
- Dry eyes,
- Joint pains.
- Variceal bleeding.
What is the treatment for primary biliary cirrhosis?
Ursodeoxycholic acid; improves liver enzymes; reduces inflammation and portal pressure and therefore the rate of variceal development.
Give 3 risk factors for gallstone development.
- Female.
- Obese (fat).
- Fertile.
How can gallstones be removed from the gall bladder?
Laproscopic cholecystectomy.
Give 4 potential complications of gallstones in the bile duct.
- Biliary pain.
- Obstructive jaundice.
- Cholangitis (infection of the biliary tract).
- Pancreatitis.
What is ascending cholangitis?
Obstruction of biliary tract causing bacterial infection. Regarded as a medical emergency.
Name the triad that describes 3 common symptoms of ascending cholangitis.
Charcot’s triad:
1. Fever.
2. RUQ pain.
3. JAUNDICE (cholestatic)!
What is charcot’s triad?
It describes 3 common symptoms of ascending cholangitis:
1. Fever.
2. RUQ pain.
3. Jaundice (cholestatic)!
What investigations might you do in someone who you suspect might have ascending cholangitis?
- Ultrasound.
- Blood tests - LFT’s.
- ERCP - definitive investigation.
Describe the management of ascending cholangitis.
- IV fluid.
- IV antibiotics e.g. cefotaxime and metronidazole.
- ERCP to remove stone.
- Stenting.
What is the difference between ascending cholangitis and acute cholecystitis?
A patient with acute cholecystitis would not have signs of jaundice!
What is acute cholecystitis?
Inflammation of the gall bladder caused by blockage of the bile duct -> obstruction to bile emptying.
Give 3 symptoms of acute cholecystitis.
- RUQ pain.
- Fever.
- Raised inflammatory markers.
- NO JAUNDICE!
Give 2 risk factors for acute cholecystitis.
- Obesity.
- Diabetes.
Describe the pathophysiology of primary sclerosing cholangitis.
Inflammation of the bile duct -> strictures and hardening -> progressive obliterating fibrosis of bile duct branches -> cirrhosis -> liver failure.
Give 3 symptoms of primary sclerorsing cholangitis.
- Itching.
- Rigor.
- Pain.
- Jaundice.
75% also have IBD.
What is biliary colic?
Gallbladder attack - RUQ pain due to a gall stone blocking the bile duct.
What can trigger biliary colic?
Eating a heavy meal especially one that is high in fat.
Give 5 causes of diarrhoeal infection.
- Traveller’s diarrhoea.
- Viral e.g. rotavirus, norovirus.
- Bacterial e.g. E.coli.
- Parasites e.g. helminths.
- Nosocomial e.g. c.diff.
Give 5 causes of non-diarrhoeal infection.
- Gastritis/peptic ulcer disease e.g. h.pylori.
- Acute cholecystitis.
- Peritonitis.
- Typhoid/paratyphoid.
- Amoebic liver disease.
Give 3 ways in which diarrhoea can be prevented.
- Access to clean water.
- Good sanitation.
- Hand hygiene.
What is the diagnostic criteria for traveller’s diarrhoea?
> 3 unformed stools per day and at least one of:
- Abdominal pain.
- Cramps.
- Nausea.
- Vomiting.
It occurs within 3 days of arrival in a new country.
Give 3 causes of traveller’s diarrhoea.
- Enterotoxigenic e.coli (ETEC).
- Campylobacter.
- Norovirus.
Describe the pathophysiology of traveller’s diarrhoea.
Heat labile ETEC modifies Gs and it is in a permanent ‘locked on’ state. Adenylate cyclase is activated and there is increased production of cAMP. This leads to increased secretion of Cl- into the intestinal lumen, H2O follows down as osmotic gradient -> diarrhoea.
Which type of e.coli can cause bloody diarrhoea and has a shiga like toxin?
Enterohaemorrhagic e.coli (EHEC) aka e.coli 0157.
What does EIEC stand for?
Enteroinvasive e.coli.
Which type of e.coli is responsible for causing large volumes of watery diarrhoea?
Enteropathogenic e.coli (EPEC).
What does EAEC stand for?
Enteroaggregative e.coli.
What does DAEC stand for?
Diffusely adherent e.coli.
What is the leading cause of diarrhoeal illness in young children?
Rotavirus.
There is a vaccine - rotarix.