Hepatobiliary system and pancreas : medical liver disease (Liver pathology)

Question 1

What is jaundice?

Answer 1

Jaundice is the yellow colouring of the skin and eyes caused by high levels of bilirubin in the blood. It is the commonest sign of bilirubin?

Question 2

What is the concentration of bilirubin that makes jaundice visible?

Answer 2

> 40 umol/l of bilirubin in blood shows signs of jaundice

Question 3

What are the causes of Jaundice?

Answer 3

1) PRE HEPATIC:
- too much bilirubin produced e.g. in haemolytic anaemia. unconjugated bilirubin from the break down of heme (from RBCs) increased in blood

2) HEPATIC:
- too few functioning liver cells decreases ability to metabolize and excrete bilirubin leading to build up of unconjugated bilirubin in blood (e.g. in acute diffuse liver cell injury, end stage chronic liver disease)

3) POST HEPATIC:
- Bile obstruction e.g caused by stone, tumour, stricture in bile duct. so conjugated bilirubin in bile cannot enter the gut. Key features : pale stool and dark urine.

Question 4

What is the pathway of bilirubin metabolism?

Answer 4

1) Unconjugated bilirubin is formed by the breakdown of RBCs
2) Unconjugated bilirubin is metabolised and conjugated in the liver and excreted in bile.
3) Bile salts and some bilirubin is absorbed by the gut.

***Bile helps to emulsify lipids for digestion

Question 5

Give examples of liver function test

Answer 5

1) Liver enzymes :
Liver enzymes leak out from hepatocytes in liver disease. So more enzymes the more severe the disease. An increase in ezymes over some time = chronic. Rapid/very high levels = severe acute.

2) Alkaline Phosphotase : (bile duct problem)
Alk Phos leaks from bile ducts it is high in obstructive jaundice and chronic biliary disease.

3) Albumin is produced by the liver. will be low in chronic liver disease.
4) Clotting factors are produced by the liver. Will be low in acute liver disease and liver failure.

Question 6

What are the histopathological signs in the liver of obstructive jaundice?

Answer 6

1) Bile in the liver parenchyma (jaundice»yellow)
2) portal tract expansion (blockage of bile duct causes dilation upstream)
3) Oedema
4) Bile salts and copper cant get out so accumulates in hepatocytes and in skin&raquo_space;> bile salts in skin causes itchyness.

Question 7

What are the investigations done in jaundice?

Answer 7

1) Ultrasound (dilated ducts in obstruction)

2) No dilation&raquo_space;»then biopsy

Question 8

What is the usual cause of non obstructive jaundice?

Answer 8

Acute hepatitis

Question 9

What is hepatitis?

Answer 9

Inflammation of the liver

non-neoplastic

Question 10

What is acute hepatitis?

Answer 10

acute liver injury caused by something that goes away. the liver will return to normal

Question 11

What is chronic hepatitis?

Answer 11

The cause persists and causes permenant injury to liver

Question 12

What is the cause short term hepatocyte damage ?

Answer 12

Inflammatory:

1) virus (specifically attack liver (hepatotrophic) or systemic e.g. CMV)
2) drugs
3) autoimmune
4) unknown (more than half of sever hepatitis is unknown)

toxic / metabolic injury:

1) alcohol
2) drugs e.g.paracetamol

Question 13

What are the causes of chronic hepatitis?

Answer 13

1) immunological = virus, autoimmune, drugs
2) Toxic / metab e.g fatty liver disease = alcohol
3) genetic metabolism disorders (iron, copper)

Question 14

How does chronic liver disease progress?

Answer 14

• fibrosis around vasculature
• Scarring starts to link vascular structures (bridging fibrosis)
• transforms liver into separate nodules (cirrhosis)

Question 15

Give examples of hepatotrophic viruses?

Answer 15

1) Hepatitis A,B,C,D,E

* EBV, CMV, HSV cause injury as part of a systemic infection

Question 16

Which hepatitis virus is lethal in pregnancy?

Answer 16

Hep E

Question 17

Which hep virus is waterborne, and recently transferred by pigs?

Answer 17

Hep E

Question 18

Which hep virus can only affect those already infected with hep b?

Answer 18

Hep D

Question 19

Which hep virus has >70% risk of progressing into chronic hepatitis?

Answer 19

Hep C

Question 20

What is the affect of alcohol on the liver?

Answer 20

1) fatty change
2) Alcoholic steatohepatitis ( inflammation can lead to acute liver failure)
3) Cirrhosis

Question 21

What is non-alcoholic fatty liver disease? and what causes it?

Answer 21

Steatosis, steatohepatitis, cirrhosis and hepatocellular carcinoma (HCC) associated with obesity, type 2 diabetes, hyperlipidaemia (not alcohol)

Question 22

What is the difference between Instrinsic and Idiosyncratic hepatotoxicity?

Answer 22

Intrinsic can be caused by drugs such as paracetamol - it is predictable.

Idiosyncratic is rare and unpredictable

Question 23

What is the mechanism of paracetamol toxicity?

Answer 23

NAPQI is a compund in paracetamol.
Normally it removed by enzymes or bound to glutathione. However when levels get too high it binds co-valently to tissue membrane proteins causing necrosis.

Question 24

What is the treatment for paracetamol toxicity?

Answer 24

N-acetyl cystein (restores glutathione and avoids liver cell damage)

*Glutathione is the liver’s natural antioxidant. It prevents NAPQI (paracetamol compound) from binding to the tissue membrane and causing necrosis

Question 25

what is cirrhosis?

Answer 25

Cirrhosis is irreversible fibrosis of the liver and conversion of normal liver architecture into nodules

Question 26

How does cirrhosis prevent normal liver function?

Answer 26

Although the hepatocytes are still present, portal vein blood bypasses the sinusoids so that the liver cells cannot perform their functions.

Pressure inside the liver increases due to stiffness this causes portal hypertension.

Question 27

What causes cirrhosis?

Answer 27

Cirrhosis develops over months to decades

1) alcohol
2) Non alcoholic steatohepatitis
3) chronic viral hepatitis
4) Autoimmune liver disease
5) metabolic malfunction

Question 28

What are the complications of cirrhosis?

Answer 28

1) Structural changes due to fibrosis causes:
- portal hypertension (caused by increased blood flow and stiffness in liver)
- Oesophageal varices (if rupture, high pressure internal bleeding&raquo_space;»death)

2) Liver Cell Failure caused by:
- fewer hepatocytes
- blood bypassing sinusoids

3) Ascities

Question 29

what causes itchy skin in cirrhosis?

Answer 29

Accumulation /deposition of bile salts in skin

Question 30

What is alpha 1 antitrypsin deficiency?

Answer 30

• rare, inherited
• abnormal anti-protease which cannot be exported from the hepatocyte.
• It accumulates in the liver cells and injures them leading to cirrhosis.
• The protein becomes insufficient in blood, leading to the failure to inactivate neutrophil enzymes.»»can cause emphysema

Question 31

What inherited condition causes insufficient activation of neutrophil enzymes in blood leading to emphysema.

(*also the accumulation in the liver causes cirrhosis)

Answer 31

Alpha 1 antitrypsin deficiency

Question 32

What is haemochromatosis?

Answer 32

Inherited condition that causes excess absorption of iron into the blood. The excess iron is then deposited in the Liver causing cirrhosis. It is also deposited in the pancreas (diabetes), joints (arthritis), skin (pigmented) and heart (cardiomyopathy)

Question 33

What is wilson’s disease?

Answer 33

Inherited condition that affecting the metabolism of copper. Copper accumulated in the liver (cirrhosis), eyes and brain.

Question 34

What are the physical signs of cirrhosis?

Answer 34

1) Ascites (caused by portal hypertension)
2) Muscle wasting (inability of liver to metabolize proteins)
3) Bruising (insufficient clotting factors produced)
4) Gynaecomastia (oestrogen is metabolised in liver. increased oestrogen : testosterone)
5) Spider naevi (red spider like - skin)

Question 35

What are the caused of portal hypertension?

Answer 35

1) PRE-SINUSOIDAL
- e.g. thrombus , fibrosis causes hypertension

2) SINUSOUDAL
- cirrhosis

3) POST SINUSOIDAL
- hepatic vein thrombosis