Medical liver diseases

Question 1

Bilirubin metabolism

Answer 1

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

Question 2

Jaundice and bilirubin

Answer 2

Jaundice is visible when bilirubin is >40umol/l

It is the commonest sign of liver disease

Question 3

Pre-hepatic jaundice

Answer 3

too much bilirubin produced

haemolytic anaemia

Question 4

hepatic jaundice

Answer 4

too few functioning liver cells

acute diffuse liver cell injury

end stage of chronic liver disease

Question 5

post hepatic jaundice

Answer 5

bile duct obstruction by a stone, structure or tumour

usually in the bile duct of the pancreas

Question 6

symptoms and signs of jaundice

Answer 6

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

Question 7

diagnostic pathway for jaundice

Answer 7

Ultra sound to check for dilation of ducts in obstruction

If no dilation, take a liver biopsy

Question 8

Liver function tests for jaundice

Answer 8

increase of Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST

Raised conjugated bilirubin without extrahepatic duct obstruction indicates disease of hepatocytes

Question 9

Histopathology of jaundiced liver

Answer 9

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

Question 10

How is bile visible histologically?

Answer 10

Bile pigment is visible in the bile plugs which represent the bile that has been excreted by hepatocytes into intracellular canaliculi

Question 11

Hepatitis - the different causes (8)

Answer 11

Viral
Alcohol
Obesity
Drugs
Inherited haemochromatosis 
Wilson's disease
Alpha-1 antitrypsin deficiency
Autoimmune

Question 12

Acute vs chronic hepatitis

Answer 12

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.

Question 13

Causes of acute hepatitis

Answer 13

things that damage hepatocytes, short term
Inflammatory injury (hepatitis) –
Viral, drugs, autoimmune, unknown (‘seronegative’)

Question 14

Clinical presentation of acute hepatitis

Answer 14

Asymptomatic, 
malaise, 
jaundice, 
coagulopathy, encephalopathy, 
death

Question 15

Causes of chronic hepatitis

Answer 15

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

Question 16

progression of chronic liver disease

Answer 16

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

Question 17

Types of hepatotrophic viruses

Answer 17

A, B, C
D = delta, only in people with B
E waterborne, increasingly recognised in UK in last few years, zoonosis, pigs

Question 18

What viruses can cause Hepatitis?

Answer 18

EBV, CMV, HSV – usually immunocompromised host

Epstein barr
cytomegalovirus
herpes simplex

Question 19

Vaccines for Viral Hep

Answer 19

A and B have one but C does not

Question 20

Hepatitis A

Answer 20

Picorna RNA

Question 21

Hepatitis B

Answer 21

Hepadna DNA

Question 22

Hepatitis C

Answer 22

Flavivirus RNA

Question 23

As hepatitis progresses, the amount of fibrosis…

Answer 23

Increases
Portal areas become short and fibrous
Bridging occurs
Ending in cirrhosis

Question 24

Alcohol and the liver

Answer 24

1 Fatty change (steatosis)
2 Alcoholic steatohepatitis
3 Cirrhosis

Depends on dose and susceptibility

Significant driver of mortality from liver disease

Question 25

Histological signs of steatohepatitis

Answer 25

Fatty change Ballooned hepatocyte with Mallory Body Inflammatory cells Fibrosis in portal tracts and around hepatocytes

Question 26

NAFLD - none fatty acid liver disease what is it caused by and what is the Tx?

Answer 26

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

Question 27

Steatosis vs. Steatohepatitis

Answer 27

``` Steat = fatty change Steatohepatitis = fatty change plus hepatocyte injury ```

Question 28

Hepato toxic drugs - Iatrogenic

Answer 28

induced inadvertently by a doctor or by medical treatment or diagnostic procedures

Question 29

Classification of drug induced liver injury (DILI)

Answer 29

Intrinsic every time, predictable e.g. paracetamol Idiosyncratic - rare, unpredictable metabolic or immunological

Question 30

Acute liver failure due to paracetamol

Answer 30

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

Question 31

Haemochromatosis - what is it?

Answer 31

``` Inborn error of iron metabolism ‘bronzed diabetes’ Iron accumulates in Liver - cirrhosis Pancreas - diabetes Skin - pigmented Joints – arthritis Heart - cardiomyopathy ```

Question 32

What is inherited wilson's disease?

Answer 32

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

Question 33

What is alpha 1 antitrypsin deficiency?

Answer 33

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

Question 34

Autoimmune liver disease- autoimmune hepatitis

Answer 34

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

Question 35

Primary biliary cholangitis - how does it present?

Answer 35

Anti-mitochondrial antibodies Elevated alkaline phosphatase Bile duct granulomas at early stage, Then ductopenia (loss) and cirrhosis

Question 36

Primary sclerosing cholangitis (PSC) - how does it present?

Answer 36

Associated with ulcerative colitis, high alk phos ‘pruned tree’ on biliary imaging Periductal “onion skin” fibrosis then ductopenia and cirrhosis

Question 37

What is cirrhosis?

Answer 37

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.

Question 38

Causes of cirrhosis

Answer 38

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

Question 39

How does cirrhosis appear microscopically?

Answer 39

Regenerative nodules of hepatocytes Surrounded by sheets of fibrous tissue

Question 40

Structural cell changes due to cirrhosis

Answer 40

fibrosis causing portal hypertension: Increased blood flow, stiff liver Pressure rises in portal vein Oesophageal varices / haemorrhoids/ caput medusa

Question 41

Liver cell failure due to cirrhosis

Answer 41

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

Question 42

What is hepatic failure? How does it present in acute vs. chronic?

Answer 42

acute is just severe rapid liver injury chronic leads to: Ascites Muscle wasting Bruising Gynaecomastia Spider naevi Varices, Caput medusae = variceal umbilical vein collaterals

Question 43

Liver biopsy in chronic liver disease

Answer 43

``` Can provide Information on: Cause of disease Current activity Stage of disease Response to treatment ```