Diseases of the Hepatobiliary System 1 Flashcards
At what level of bilirubin is jaundice visible?
> 40micromol/l
What is the commonest sign of liver disease?
Jaundice
What is the cause of pre-hepatic jaundice?
Haemolytic uraemia
What is the general principle cause of hepatic jaundice?
Too few functioning liver cells
Give 3 causes of hepatic jaundice?
1) Acute diffuse liver cell injury
2) End stage chronic liver disease
3) Inborn errors
What is the cause of post hepatic jaundice?
Bile duct obstruction - eg. stone stricture or tumour (nb. could be in liver or pancreas)
What kind of bilirubin is produced by red cell breakdown?
Unconjugated
Where is bilirubin conjugated?
In the liver
Pre-hepatic jaundice is raised levels of what kind of bilirubin?
Unconjugated, bound to albumin, not exctreted
What are the 2 symptoms a patient notices with pre hepatic jaundice?
Yellow sclera
Yellow skin
ie. doesnt reach anywhere else as it is in soluble and cant be excreted
What kind of bilirubin is raised in hepatic jaundice, is it soluble?
Mainly conjugated, soluble
What are the 2 main symptoms that a patient notices with hepatic jaundice?
1) yellow eyes
2) dark urine
(Soluble so can get in urine)
What kind of bilirubin is raised in post hepatic jaundice?
Conjugated - it is soluble but cant be excreted
What 3 symptoms does a patient notice with post hepatic jaundice?
1) Pale stool
2) Yellow eyes
3) Dark urine
What 2 liver enzymes leak from hepatocytes, how would there levels in acute and chronic liver disease differ?
AST and ALT
Chronic - mild increase over time
Acute - severe acute liver disease
What enzyme leaks from bile ducts?
Alkaline Phosphate
Is albumin raised or lowered in chronic liver disease?
Lowered
Does albumin have a long or short half life?
Long half life
Are clotting factors raised or reduced in liver disease?
Low in liver disease
Do clotting factors have a long or short half life?
Short
What is the first histopathological sign of obstructive jaundice?
Bile in the liver parenchyma (hence patient is yellow)
As time goes on what are the 4 other histopathological signs of obstructive jaundice?
1) Portal tract expansion
2) Oedema
3) Ductular reaction - proloferation of duictules aroudn the edge
4) Bile salts and copper cant get out - accumulated in hepatocytes and patient gets itchy as bile salts accumulate in skin
What are most non obstructive cases of jaundice due to?
Hepatitis
What is the process of investigation of jaundice?
USS to check for dilated ducts in obstruction
Only in no dilated ducts then do a liver biopsy to look for cause of jaundice
What is hepatitis?
Inflammation of the liver - essentially any liver disease that is non neoplastic
What happens to liver enzymes in hepatitis?
Raised
What is the broad difference between causes of acute hepatitis and chronic hepatitis?
Acute - caused by something which goes away
Chronic - caused by something which doesnt go away
Doe hepatitis always have symptoms?
No - its commonly asymptomatic
What are the 2 milder symptoms of hepatitis?
1) Malaise
2) Jaundice
What can be the haematological effect of hepatitis?
Coagulopathy
What are the 2 most serious presentations of hepatitis?
1) Encephalopathy
2) death
What 2 things does the severity of the symptoms of hepatitis depend on?
1) The number of liver cells damaged
2) How good the liver regeneration is
What are the 2 broad classes of causes of acute hepatitis?
1) Inflammatory - viral, drugs, autoimmune, unknown (sero negative)
2) Toxic/metabolic injury - alcohol, drugs, paracetemol
Why can lobular disarray be seen in an acute hepatitis biopsy?
Lobular disarray = disordered appearance of the liver cell plates
Due to the injury and death of individual liver cells
What are the 5 causes of chronic hepatitis?
1) Immunological injury
2) Toxic/metabolic injury - fatty liver disease, alcohol, NAFLD, drugs
3) Genetic inborn errors - iron, copper, alpha 1 anti-trypsin
4) Biliary disease
5) Vascular disease - clotting disorders, drugs
What is the basic pathology of chronic liver disease?
1) Injury to liver cells
2) inflammation
3) Formation of scar tissue and regeneration of hepatocytes
What are the 2 uses of biopsy in diagnosis of liver disease?
1) To determine the cause of damage - some causes have specific pathological features
2) To assess the stage of the disease - ie. how much scarring and where does it lie on the spectrum from normal to cirrhosis
What is the pattern of scarring from normal liver to cirrhosis?
1) Scarring starts around portal tracts - this is portal fibrosis
2) Scarring then links portal tracts - bridging fibrosis
3) Scarring then links all vascular structures (portal tracts and central veins) - cirrhosis
In addition to viruses hepatitis A, B and C, in which people is hepatitis D seen in?
Only people with heaptitis B
How is hepatitis E transmitted, is it seen in the uk?
Waterborne - increasingly seen in the UK, zoonosis
In addition to the hepatitis viruses what 3 other viruses can cause hepatitis as part of systemic disease?
1) EBV
2) CMV
3) HSV
What is the route, of transmission, treatment and vaccine for Hep A?
Faecal-oral
No treatment
Ig Vaccine
Can Hep A infection ever cause chronic hepatitis?
No
What is the route, of transmission, treatment and vaccine for Hep b?
Parenteral
IFN and IV Iamivudine
Ig Vaccine
What is the route, of transmission, treatment and vaccine for Hep C?
Parenteral
IFN and IV ribavirin
No vaccine
Can hep b evolve to chronic hepatitis?
Yes in 10% of adults
Can hep c evolve to chronic hepatitis?
Yes in over 70% of adults
What are the 3 steps of the spectrum of alcoholic liver disease?
1) Fatty change
2) Steatohepatitis
3) Cirrhosis
(depends on dose and susceptibility)
What is steatohepatitis?
Get fatty change (steatosis) = fatty deposits in the liver
Get inflammatory cells and ballooned hepatocytes with mallory bodies
Get fibrosis in portal tracts and around hepatocytes (pericellular fibrosis)
What is non-alcoholic fatty liver disease?
Same spectrum as fatty liver disease but is associated not with alcohol but metabollic syndrome (type 2 DM, hyperlipidaemia and also some drugs)
What is the commonest cause of liver disease?
NAFLD
What is the treatment for NAFLD?
Address the cause of metabolic syndrome
What is DILI?
Drug induced liver injury
What is the broad causes of DILI?
iatrogenic
In which 2 ways is DILI classified?
1) Intrinsic - anyone taking this drug is likely to get it
2) Idiosyncratic - depends on individual susceptibility, rare
What ratio is used to classify the type of acute liver injury in DILI into hepatic, cholestatic or mixed?
Ratio of ALT:alk phos
What is the most common symptoms of DILI?
Jaundice
Does DILI tend to cause acute or chronic liver disease?
Acute as improves on stopping the drug but can sometimes cause chronic
What are the 3 standard criteria for diagnosing DILI?
1) Onset of LFTs after intake of drugs
2) Improvement (reduction of 50%) in LFTs after stopping the drug
3) Alternative causes excluded, including by biopsy
What is the basic mechanism of paracetemol toxicity?
1) Too much paracetemol exceeds the safe metabolic pathways (glucuronyl transferase and sulphotransferase)
2) Paracetemol then gets metabolised by P53 to a taxc metabollite NAPQ1
3) NAPQ1 binds covalently to heptocytes membrane proteins and causes necrosis
What chemical can bind NAPQ1 to make it safe and stop it causing hepatocyte damage?
Glutathione
What is the treatment for paracetemol toxicity, how does it work?
IV N acetyl-cysteine - restores glutathione
how is cirrhosis defined?
Diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules - liver cells still present but cant perform function due to loss of hepatic lobules
Why does portal hypertension occur in cirrhosis?
Increased blood flow to a stiff liver, pressure within the liver increases and in the portal vein - nb this can also lead to oesophageal varices
What is the end point of chronic liver disease?
Cirrhosis
What are the 5 common causes of cirrhosis?
1) Alcohol
2) NAFLD
3) Chronic viral hepatitis - C and B
4) Autoimmune liver disease - autoimmune hepatitis
5) Metabolic - iron, copper, alpha 1 antitrypsin
Why are patients with cirrhosis vulnerable to infection?
Because the liver is an important sight of the immune response
Cirrhosis can cause symptoms due to fewer hepatocytes through what 4 mechanisms?
1) Lack of synthesis - oedema, bruising, muscle wasting
2) Lack of detoxification - encephalopathy
3) Ascites - due to low albumin, portal hypertension, hormone fluid retention (aldosterone)
4) Lack of excretion - bilirubin = jaundice, bile salts = itching
Alpha 1 anti trypsin deficiency is a metabolic disorder which can cause liver disease, how does it do so?
Abnormal anti protease made in the liver which cannot be exported from the hepatocyte - accumulates in the liver and injures them causing cirrhosis
In alpha 1 anti trypsin deficiency the low levels of alpha 1 anti trypsin in the serum make patients vulnerable to which lung disease?
Emphysema
In haemachromatosis, iron accumulates in what 5 organs, causing what conditions?
1) Liver - cirrhosis
2) Pancreas - diabetes
3) Skin - pigmented
4) Joints - arthritis
5) Heart - cardiomyopathy
What is Wilson’s disease?
An inborn error of copper metabolism
What 3 organs does copper accumulate in Wilson’s disease?
1) Liver -cirrhosis
2) Eyes - Kayser-Faisher rings
3) Brain - ataxia
What is the treatment for Wilsons disease?
Chelate copper and enhance its excretion
What is the therapy for haemachromatosis?
Venesection - to deplete iron stores to normal
What are the 6 physical signs of cirrhosis?
1) Ascites
2) Muscle wasting
3) Bruising
4) Gynaecomastia
5) Spider Naevi
6) Caput medusae - varices from umbilical vein collaterals
What is the definition of portal hypertension?
increased pressure of blood in the portal veins >12mmHg
What are the 4 main complications of portal hypertension?
1) Splenomegaly - low platelets
2) Oesophageal varices - haemorrhage
3) Piles - perianal vairces but nb. most arent to do with portal hypertension
4) Part of cause of ascites
Into which 3 categories can the causes of portal hypertension be classified?
1) Post sinusoidal - hepatic vein thrombosis
2) Sinusoidal - cirrhosis
3) Pre sinusoidal - portal fibrosis in cirrhosis and non cirrhotic portal hypertension such as sarcoid, schistosomiasis, portal vein thrombus
