Theme 11 L7: Medical liver diseases Flashcards
What are the functions of the liver?
- Produce bile
- Protein production e.g clotting factors
- Cholesterol production
- Store excess glucose as glycogen
- Convert ammonia to urea for renal excretion
- Vitamin metabolism/ storage
- Metabolise drugs/ toxins
- Regulate clotting
- Create immune factors & filter bacteria from blood
- Clearance of billirubin
Explain bilirubin metabolism
- bilirubin is produced by red blood cell breakdown in the spleen (“unconjugated”)
- then “conjugated” in liver with glucuronic acid to make it soluble and excreted
What is enterohepatic circulation?
some bilirubin is re-absorbed from gut; bile acids secreted with it are reabsorbed
What is the intermediate compound before heme breaks down into bilirubin?
biliverdin
When is jaundice visible?
when bilirubin > 40 umol/l
What is the cause of pre-hepatic jaundice?
too much bilirubin produced
Which conditions is pre-hepatic jaundice associated with?
- haemolytic anaemia
- Gilbert’s syndrome - harmless deficient conjugation of billirubin
What is the cause of hepatic jaundice?
too few functioning liver cells –> fails to break down bilirubin
Which conditions is hepatic jaundice associated with?
- acute diffuse liver cell injury
- end stage chronic liver disease
- inborn errors of metabolism
What is the cause of post-hepatic jaundice?
bile duct obstruction by a stone, stricture, tumour
How is bilirubin transported to the liver?
it is insoluble so it is transported in the plasma bound to albumin
Which type of bilirubin accumulates in pre-hepatic jaundice?
unconjugated bilirubin - bound to albumin, insoluble, not excreted
What is the symptoms of pre-hepatic jaundice?
yellow eyes and skin
Which type of bilirubin accumulates in hepatic jaundice?
Mostly conjugated, water soluble
What is the symptoms of hepatic jaundice?
yellow skin/ eyes and dark urine
Which type of bilirubin accumulates in post-hepatic jaundice?
conjugated - soluble, excreted but cant get into gut
What is the symptoms of post- hepatic jaundice?
yellow eyes, dark urine, pale stool
What is included in LFTs?
- bilirubin (conjugated and unconjugated)
- liver enzymes: ALT, AST aminotransferases
What is raised in obstructive jaundice and chronic biliary disease?
raised alk phos
What are most non-obstructive cases of jaundice caused by?
acute hepatitis
What is the first histopathological sign in liver with obstructive jaundice?
bile in the liver parenchyma
Very high levels of liver enzymes suggests what?
acute liver disease / hepatitis
What are the symptoms of acute hepatitis?
asymptomatic malaise jaundice coagulopathy (failure of clotting) encephalopathy deayh
What is confluent panacinar necrosis of the liver?
all hepatocytes have died
What are some causes of chronic hepatitis?
- immunological injury - viral, autoimmune, drugs
- toxic/metabolic injury - fatty liver disease, alcoholic or non-alcoholic fatty liver, drugs
- genetic inborn errors - iron, copper, alpha 1 antitrypsin accumulate in liver and damage it
- biliary disease - autoimmune, duct obstruction, drugs
- vascular disease - clotting disorders, drugs
Explain the pathology of cirrhosis?
During any chronic liver disease, scarring (fibrosis) gradually increases and starts to link vascular structures (bridging) eventually transforming the liver tissue into separate nodules – end stage
What are the hepatotrophic viruses?
- Hep A, B, C, D (only in patients with hepB), E
- other viruses: EBV, CMV, HSV (usually in immunocompromised host)
Which hepatitis is most likely to progress to chronic hepatitis?
hepC
How do we assess the severity of chronic hepatitis?
grade = how inflamed stage = how much fibrosis/ scarring
Is liver fibrosis reversible?
yes - the liver can regenerate
Explain the 3 stages that alcohol abuse has on the liver
- Fatty change (steatosis)
- Alcohol steatohepatitis
- Cirrhosis
What is a common cause of non-alcoholic fatty liver disease (NAFLD)?
Obesity
What is the pathogenesis of NAFLD?
Same as alcoholic liver disease:
- steatosis
- steatohepatitis
- cirrhosis
- HCC
What is the commonest cause of acute liver injury?
Drug induced liver injury (DILI)
When do you overdose on paracetamol?
when you run out of glutathione
What is the antidote for paracetemol overdose?
n-acetylcysteine
What happens in paracetmol overdose over the course of:
0-24 hours
24-72 hours
3-5 days
0-24 hrs mild symptoms - nausea, vomiting, sweating
24-72 hrs: increasing liver cell death
3-5 days: massive necrosis, liver failure and death
What is haemochromatosis?
inherited inborn error of iron metabolism -
Which locations does iron accumulate in in haemochromatosis and what are the effects of this?
liver causing cirrhosis pancreas causing diabetes skin causing pigmentation joints causing arthritis heart causing cardiomyopathy
How do you treat haemochromatosis?
venesection - to deplete iron stores to normal
What is Wilson’s disease?
inherited inborn error of iron metabolism - usually presents at a younger age
In wilson’s disease, copper accumulates where and what are the effects of this?
- in liver causing cirrhosis
- in eyes causing kayser-fleischer rings
- in brain causing ataxia
How do you diagnose Wilson’s disease?
serum copper & caeruloplasmin, urinary copper, slit lamp, liver biopsy
How do we treat wilson’s disease?
drugs that chelate copper and enhance its excretion e.g penicillamine
What is alpha 1 antitrypsin deficiency?
- abnormal anti-protease which cannot be exported from hepatocyte
- accumulates in liver cells and injures them - cirrhosis
- insufficient in blood, failure to inactivate neutrophil enzymes - emphysema
What is PBC?
Primary biliary cholangitis:
- autoimmune
- anti mitochondrial anti bodies
- bile duct granulomas at early stage
- then ductopenia (loss) and cirrhosis
Which LFT will you expect to be elevated in PBC?
Alkaline phosphatase
What is PSC?
Primary sclerosing cholangitis:
- autoimmune
- pruned tree on biliary imaging
- peri ductal “onion skin” fibrosis
- then ductopenia and cirrhosis
What condition is PSC associated with?
ulcerative colitis, high alk phos
What are the complications of cirrhosis?
- increased blood flow - portal hypertension
- pressure rises in portal vein
- oesophageal varices/ haemorrhoids
- blood by passes sinusoids so there is liver cell failure
What are the signs of chronic liver failure?
- ascites
- muscle wasting
- bruising
- gynecomastia
- spider naevi
- viruses, caput medusae
