Liver: Medical Flashcards
How many lobes does the liver have?
3
Right left and caudate
How many blood supplies does liver have?
2
Hepatic arterial and portal venous (65% from portal vein)
What drains blood from the liver?
Hepatic vein
What drains bile from liver?
Biliary tract
What is in the portal triads/tracts?
Hepatic artery, portal vein, bile duct
What is the anatomical unit of the liver? Which direction does the blood flow?
Hepatic lobule
Hexagonal structure, at the apical points are the portal tracts and in the centre is the hepatic vein.
Blood flows form portal tracts to the centre of the lobule
Difference between liver lobules and acini?
Lobules= structural unit, hexagonal unit with central vein at the centre
Acini= functional, centred on the dual blood supply with the central veins at the periphery. Divided into zones 1-3 of oxygenation
Functions of hepatocytes
Synthesis:
- Bilirubin
- Albumin
- Clotting factors
Metabolise:
-Drugs
Contain:
-Enzymes (ALT/AST/GGT)
Which is a better marker of acute severe liver injury, albumin or coagulation factors?
Coagulation factors as albumin has a much longer half life
Where is ALP normally found?
In bile
Can b raised due to muscle or bone damage
Which viruses can affect the liver?
Hepatitis A,B,C,E
Rarely EBV or CMV
Imiaging investigations for any suspected liver disease? (4)
USS/CT for bile duct dilation
ERCP/MRCP to further assess bile duct dilatation
Endoluminal USS to look for mass in pancreatic head
Fibroscan for cirrhosis
CT/MRI liver
Liver biopsy
Does the liver produce immunoglobulins?
No
Causes of acute liver injury?
Viral hepatitis Alcohol Drugs Autoimmune Biliary disease
What is chronic hepatitis?
Hepatitis > 6 months
At what bilirubin level is there clinical jaundice?
> 30 micromol/L
Hyperbilirubinaemia is >22
Most common cause of pre-hepatic jaundice?
Haemolytic anaemia (sickle cell, thalassaemia, drugs, infections)
Causes of hepatic jaundice
Viral hepatitis Alcoholic hepatitis Drug induced liver disease Autoimmune liver disease PSC, PBC
**End stage cirrhosis (decompensation)
What causes cholestasis in liver?
Damage to hepatocytes or intra- or extrahepatic obstruction
What pattern of necrosis is seen with paracetamol toxicity?
Confluent (Centrizonal) necrosis
What pattern of necrosis is seen with individual hepatocyte death?
Spotty necrosis
What patterns of liver injury can be caused by drugs?
Fatty change Centrilobular necrosis Massive necrosis Hepatitis Fibrosis Granulomatous reaction Cholestasis
Causes of chronic liver disease
Viral hepatitis Autoimmune hepatitis Drug induced Alcohol NAFLD PSC/PBC **Metabolic: Haemochromatosis, Wilson's, anti alpha trypsin 1
What is secondary biliary cirrhosis?
Chronic biliary obstruction leading to liver cirrhosis
Causes of extrahepatic biliary obstruction
Stones
Benign stricture from PSC
Tumour
Symptoms of PBC
Middle aged females
Itch
Jaundice
What markers are raised in PBC?
*AMA (anti mitochondrial antibodies)
ALP and cholesterol
Histology: Portal tract lymphocytic infiltrate which destroys bile ducts +/- granulomas
PBC
What is ductopaenia?
Bile duct destruction
What is PBC?
Autoimmune ductopaenia
What is PSC?
Chronic inflammation involving intra and extra hepatic bile ducts
What bowel disease is linked to PSC?
UC
Diagnosis of PSC?
MRCP will show beading
Histology: periductal ‘onion skinning’ concentric fibrosis, ductopaenia
PSC
How is bilirubin conjugated in the liver?
Made water soluble by binding to glucuronic acid by the enzyme GLUCURONYL TRANSFERASE
Which viruses increase risk of HCC?
Hep B and C
Which hepatitis has the most risk for chronic hepatitis?
C
What type of virus is hepatitis?
RNA
Transmission route of hep A?
Faecal oral
Benign and self limiting, no chronic infection or risk of chronic hepatitis
Which hepatitis viruses have a carrier state?
B,C,D
Which hepatitis viruses are spread though IV use?
BCD
Two phases of Hep B viral growth?
Proliferative
Intergrative
3 patterns of Hep B disease?
Acute disease and recovery
Asymptomatic carrier
Chronic infection and cirrhosis
Important marker in hep B infection?
HBsAg
What % of people with hep C are asymptomatic?
75% but much higher percentage develop chronic infection and cirrhosis
What histological pattern of liver damage is cause by chronic hepatitis?
Interface hepatitis where inflammatory cells spill into adjacent hepatocytes
Also called piecemeal necrosis
Example of a drug which can cause chronic hepatitis?
Methotrexate
Which autoantibodies are present with autoimmune hepatitis
ASMA (anti smooth muscle)
ANA (anti nuclear)
How is hepatitis graded and staged?
grade: necroinflammatory disease activity
stage 0-6: degree of fibrosis and nodularity
True/false: Hep D infection is limited to persons already infected with Heb B
True
Characteristics of liver cirrhosis? (Don’t learn off)
- Diffuse irreversible disruption of liver architecture
- Structurally abnormal REGENERATIVE nodules of hepatocytes
- Separated by bridging bands of fibrous tissue
Features of decompensated liver failure
Jaundice Coagulopathy Encephalopathy Hypoproteinaemia Hyperaldosteronism
What causes portal hypertension?
Increased portal blood flow
Hepatic vascular resistance
A-V shunting
Causes ascites, splenomegaly, oesophageal varices, haemorrhoids, caput medusae
What cancer are people with cirrhosis at risk of?
Hepatocellular carcinoma
Where do oesophageal varcies commonly form?
At lower oesophagus at a site of portal-systemic anastomosis
Most common cause of liver cirrhosis?
Alcoholic liver disease 60-70%
Also: NASH Viral hepatitis Biliary disease Hereditary Haemochromatosis Autoimmune hep. Wilsons Alpha 1 anti trypsin deficiency Idiopathic
Histology of alcoholic liver disease: 3 overlapping patterns. Simple ____ or fatty change (80% of cases). ______ (10-20%). Cirrohosis (10%)
Steatosis (reversible fatty change)
Steatohepatitis
Why does alcohol damage the liver? (3 factors)
Cellular energy diverted to alcohol metabolism instead of eg fat metabolism
Toxic acetaldehyde accumulation
Direct stimulation of collagen synthesis by alcohol
Histology features of steatohepatitis
CHICKEN WIRE
Hepatocyte ballooning
Fat vacuoles
Mallory bodies (eosinophilic globules)
Neutrophil reaction
Fibrosis
Examples of metabolic causes of chronic liver disease?
Haemochromatosis
WIlson’s
a1 anti trypsin deficiency
Which gene is associated with haemochromatosis?
HFE gene mutation (C282Y)
Pathogenesis of haemochromatosis?
Autosomal recessive
HFE gene mutation results in excessive iron absorption in small intestine
Complications of haemochromatosis?
Iron deposits in liver, heart, pancreas etc.
Bronze pigmentation DM (pancreas involvement) Cardiac arrhythmias Infertility High risk of cirrhosis and HCC
Diagnosis of hameachromatosis?
iron studies (transferrin and ferritin)
Histology
Genetic testing for C282Y mutation
Histology of haemochromatosis: ____ _____ blue stain demonstrates granular distribution of iron in hepatocytes.
Perl’s Prussian blue stain
Treatment of haemochromatosis
Venesection and iron chelating agents
Inheritance pattern of WIlson’s
Autosomal recessive
Pathology of WIlson’s disease
Accumulation of copper in hepatocytes due to mutation in Cu-transporting ATPase
Usually presents with brain/eye involvement
Histology of WIlson’s
Non specific
May detect Copper in liver with stains but it is very patchy
Diagnosis of WIlson’s
Confirmed by biochemistry (serum/urine.liver tissue Cu studies)
Treatment for WIlson’s
Penicillamine (chelating agent)
What characteristic Wilson’s sign appears on the peripheral iris?
Kayser-Fleischer RIng
WHat is alpha 1 anti trypsin? How does deficiency cause disease?
It is a serum protease inhibitor, produced in the liver. (PiMM is normal phenotype, PiZZ is abnormal).
Causes cirrhosis of the liver and emphysema in the lung (because elastase activity is increased)
What stain is used to diagnosis a1AT globules?
PAS
