Medical liver diseases Flashcards
Bilirubin metabolism
Produced by red blood cell breakdown in the spleen
It is then conjugated in the liver with glucuronic acid to make it soluble
It is excreted via bile
Bacteria in the gut make it unconjugated again
It is not absorbed - passed out of faeces
but a small amount is reabsorbed from gut and bile acids are secreted then reabsorbed
Jaundice and bilirubin
Jaundice is visible when bilirubin is >40umol/l
It is the commonest sign of liver disease
Pre-hepatic jaundice
too much bilirubin produced
haemolytic anaemia
hepatic jaundice
too few functioning liver cells
acute diffuse liver cell injury
end stage of chronic liver disease
post hepatic jaundice
bile duct obstruction by a stone, structure or tumour
usually in the bile duct of the pancreas
symptoms and signs of jaundice
Yellowing of skin and eyes for pre-hepatic
Yellow eyes, skin and dark urine for hepatic
Yellow eyes dark urine and pale stool for post hepatic
diagnostic pathway for jaundice
Ultra sound to check for dilation of ducts in obstruction
If no dilation, take a liver biopsy
Liver function tests for jaundice
increase of Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST
Raised conjugated bilirubin without extrahepatic duct obstruction indicates disease of hepatocytes
Histopathology of jaundiced liver
First sign:
Bile in the liver parenchyma
(jaundice in the skin, patient is yellow)
Increasing with time: Portal tract expansion, Oedema Ductular reaction – proliferation of ductules around the edge of portal tracts Bile salts and copper can’t get out Accumulate in hepatocytes Bile salts in skin = itch
How is bile visible histologically?
Bile pigment is visible in the bile plugs which represent the bile that has been excreted by hepatocytes into intracellular canaliculi
Hepatitis - the different causes (8)
Viral Alcohol Obesity Drugs Inherited haemochromatosis Wilson's disease Alpha-1 antitrypsin deficiency Autoimmune
Acute vs chronic hepatitis
Acute and Chronic refer to the time frame – acute hepatitis has a recent onset, and will resolve back to normal as long as the cause does not persist.
Chronic hepatitis has by definition been present for over 6 months, and results in ongoing liver cell injury and progressive structural liver damage of scarring and remodelling.
Causes of acute hepatitis
things that damage hepatocytes, short term Inflammatory injury (hepatitis) – Viral, drugs, autoimmune, unknown (‘seronegative’)
Clinical presentation of acute hepatitis
Asymptomatic, malaise, jaundice, coagulopathy, encephalopathy, death
Causes of chronic hepatitis
Immunological injury – virus, autoimmune, drugs
Toxic/metabolic injury – fatty liver disease,
Alcoholic or non- alcoholic fatty liver disease (NAFLD)
Drugs
Genetic inborn errors – iron, copper, alpha 1 antitrypsin
Biliary disease – autoimmune, duct obstruction, drugs,
Vascular disease – clotting disorders, drugs
progression of chronic liver disease
scarring gradually increases
starts to link vascular structures (bridging)
eventually transforming the liver tissue into separate nodules – end stage = cirrhosis.
A normal
B portal fibrosis
C bridging fibrosos
D cirrhosis
Types of hepatotrophic viruses
A, B, C
D = delta, only in people with B
E waterborne, increasingly recognised in UK in last few years, zoonosis, pigs
What viruses can cause Hepatitis?
EBV, CMV, HSV – usually immunocompromised host
Epstein barr
cytomegalovirus
herpes simplex
Vaccines for Viral Hep
A and B have one but C does not
Hepatitis A
Picorna RNA
Hepatitis B
Hepadna DNA
Hepatitis C
Flavivirus RNA
As hepatitis progresses, the amount of fibrosis…
Increases
Portal areas become short and fibrous
Bridging occurs
Ending in cirrhosis
Alcohol and the liver
1 Fatty change (steatosis)
2 Alcoholic steatohepatitis
3 Cirrhosis
Depends on dose and susceptibility
Significant driver of mortality from liver disease
Histological signs of steatohepatitis
Fatty change
Ballooned hepatocyte with Mallory Body
Inflammatory cells
Fibrosis in portal tracts and around hepatocytes
NAFLD - none fatty acid liver disease
what is it caused by and what is the Tx?
Same pathological spectrum as alcoholic liver disease
Associated with “Metabolic syndrome” – obesity, type 2 diabetes, hyperlipidaemia, also some drugs
Now recognised to be the commonest cause of liver disease
Treatment – address the causes of metabolic syndrome
Steatosis vs. Steatohepatitis
Steat = fatty change Steatohepatitis = fatty change plus hepatocyte injury
Hepato toxic drugs - Iatrogenic
induced inadvertently
by a doctor
or by medical treatment
or diagnostic procedures
Classification of drug induced liver injury (DILI)
Intrinsic
every time, predictable
e.g. paracetamol
Idiosyncratic
- rare, unpredictable
metabolic or immunological
Acute liver failure due to paracetamol
Metabolised in liver
5% toxic intermediary
Conjugated with Glutathione
Overdose:
Run out of glutathione
Antidote n-acetylcysteine if < 8 hours replenishes
0-24h Mild symptoms
Nausea, vomiting , sweating
24-72h Increasing liver cell death
3-5 days Massive necrosis, liver failure and death
Haemochromatosis - what is it?
Inborn error of iron metabolism ‘bronzed diabetes’ Iron accumulates in Liver - cirrhosis Pancreas - diabetes Skin - pigmented Joints – arthritis Heart - cardiomyopathy
What is inherited wilson’s disease?
Inborn error of copper metabolism
Usually presents at a younger age
Copper accumulates in
Liver – Cirrhosis
Eyes – Kayser-Fleischer rings
Brain – Ataxia, etc.
Treated by chelate copper and enhancement of its extraction using 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
Autoimmune liver disease- autoimmune hepatitis
Mostly female patients
Auto-antibodies (anti-nuclear, smooth muscle, etc.), raised IgG, ALT, other autoimmune diseases
Liver biopsy – plasma cells, “interface” hepatitis
Can cause severe acute liver failure (needing transplant) or chronic disease (cirrhosis)
Treatment by immune suppression
Primary biliary cholangitis - how does it present?
Anti-mitochondrial antibodies
Elevated alkaline phosphatase
Bile duct granulomas at early stage,
Then ductopenia (loss) and cirrhosis
Primary sclerosing cholangitis (PSC) - how does it present?
Associated with ulcerative colitis, high alk phos
‘pruned tree’ on biliary imaging
Periductal “onion skin” fibrosis
then ductopenia and cirrhosis
What is cirrhosis?
Diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.
Liver cells still present, but portal vein blood bypasses the sinusoids so the hepatocytes cannot perform their function
And often fewer liver cells (240 billion –> 172 billion)
Pressure inside the liver increases causing portal hypertension.
Causes of cirrhosis
Alcohol
Non-alcoholic steatohepatitis (metabolic syndrome)
Chronic viral hepatitis – B, C
Autoimmune liver disease – autoimmune hepatitis,
primary biliary cirrhosis, primary sclerosing cholangitis
Metabolic – iron, copper, alpha 1 antitrypsin
How does cirrhosis appear microscopically?
Regenerative nodules of hepatocytes
Surrounded by sheets of fibrous tissue
Structural cell changes due to cirrhosis
fibrosis causing portal hypertension:
Increased blood flow, stiff liver
Pressure rises in portal vein
Oesophageal varices / haemorrhoids/ caput medusa
Liver cell failure due to cirrhosis
fewer hepatocytes and blood bypasses sinusoids
Synthetic - oedema, bruising, muscle wasting
Detoxifying – drugs, hormones, encephalopathy
Ascites – low albumin, portal hypertension, hormone fluid retention (aldosterone)
Failure of excretion:
Bile > Jaundice
Bile salts > Itching
What is hepatic failure? How does it present in acute vs. chronic?
acute is just severe rapid liver injury
chronic leads to:
Ascites
Muscle wasting
Bruising
Gynaecomastia
Spider naevi
Varices, Caput medusae =
variceal umbilical vein collaterals
Liver biopsy in chronic liver disease
Can provide Information on: Cause of disease Current activity Stage of disease Response to treatment
