L4: Liver Disease and Cirrhosis Flashcards
What tests/investigations are done to identify if there is steatosis in the liver?
- ultrasound
- liver blood tests (transaminases)
What stain can be used to highlight fat droplets and visualize fatty change?
Oil Red O Stain
What is Mallory’s Hyaline suggestive of?
alcohol-related steatohepatitis
What is the pathogenesis of liver injury due to alcohol metabolism (liver injury in alcoholics)?
- fat synthesis stimulated
- free radicals generated via MEOS pathway
- acetaldehyde is toxic
- altered intracellular metabolism
What is the MEOS pathway? When is it activated?
- induced in heavy drinkers
- produces more reactive/toxic intermediates
What is the treatment for alcohol-related liver damage?
ABSTINENCE
- if really severe, steroids
NAFLD is typically a/w with metabolic syndrome. What does metabolic syndrome entail?
obesity, T2DM, insulin resistance, high triglycerides, low HDL cholesterol
What is the treatment for NAFLD?
- weight loss
- exercise
- treat underlying risk factors in metabolic syndrome
A genetic defect in the HFE gene can lead to disease?
Hereditary (Primary) Haemochromatosis
Which chromosome is the HFE gene located on?
chromosome 6p
A mutation in HFE gene can lead to hereditary haemochromatosis. What are 2 mutations that may be present? What mutations are the most common
C282Y
H63D
most cases are C282Y/C282Y homozygotes
Iron is transported in the blood by what?
Transferrin
What will give the % saturation of iron which then will indicate the iron storage status?
Transferrin
Iron has 2 storage forms which are:
Ferritin and Haemosiderin
What is the function of Hepcidin?
- it blocks iron entry into the blood circulation from GIT
- inhibitory target = Ferroportin
if there is lack of hepcidin there will be lots of iron in the blood
What does the HFE gene code for?
Hepcidin
What is the treatment of haemochromatosis?
Venepuncture/Phlebotomy
What stain is used to identify haemochromatosis? What does it typically stain for?
Perl’s Stain (Prussian Blue)
- stains for haemosiderin (iron storage form)
What is the Kayser-Fleischer ring indicative of?
Wilson’s Disease - increase in copper in body
What are the test values for Type 1 AIH?
ANA/SMA Positive
AMA Negative
What are the test values for Type 2 AIH?
Anti-LKM Positive
What is the treatment for AIH?
Immunosuppression (steroids, azathioprine)
What are the test values for Primary Biliary Cirrhosis (PBC)?
- high Alk Phos
- elevated IgM
- AMA positive
- SMA negative
What is the treatment for Primary Biliary Cirrhosis (PBC)?
- Ursodeoxycholic Acid (UDCA)
- symptomatic treatment
- OLT
not steroids!
If PSC is intra-hepatic mainly what would it lead to?
progressive cholestasis going to cirrhosis
If PSC is extra-hepatic mainly what would it lead to?
stricture with CBD obstruction, risk ascending cholangitis
PSC has a strong associated with IBD and what in particular?
Ulcerative Colitis
note: there is an increased risk of cholangiocarcinoma
In advanced liver disease, there may be a failure of oestrogen inactivation and this may lead to:
- spider naevi
- palmar erythema
- gynaecomastia
- testicular atrophy
What criteria does the Child-Pugh score contain? What is it used for?
albumin, PT, bilirubin, ascites, HE
used as a prognosis of cirrhosis
What criteria does the MELD score contain? What is it used for?
PT, bilirubin, creatinine
it rates the severity of liver disease to see how much the patient needs a liver transplant
What is steatosis?
fatty change of the liver
Is steatosis typically macrovesicular or microvesicular?
Macrovesicular
What is steatohepatitis?
fatty change a/w inflammation
What condition does MACROvesicular fatty change of the liver usually cause?
alcoholic syndrome and metabolic syndrome (NAFLD)
What condition does MICROvesicular fatty change of the liver usually cause?
acute liver failure
List some of the histological features of steatohepatitis
- lobular inflammation/necrosis (centered in zone 3 around hepatic vein)
- neutrophils in inflammatory infiltrate
- Mallory’s hyaline (w/in hepatocytes)
- perivenular fibrosis (around hepatic vein)
Mallory’s Hyaline may be suggestive of alcohol-related damage in the liver. How does it look like in histology?
- dense pink intracytoplasmic inclusions
- altered intracellular proteins
Primary Sclerosing Cholangitis (PSC) on its own, increases the risk for which type of cancer?
Cholangiocarcinoma
PSC which occurs in IBD patients, increases the risk for which type of cancer?
Colorectal Cancer
