Hepatobiliary system and pancreas : medical liver disease (Liver pathology) Flashcards
What is jaundice?
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?
What is the concentration of bilirubin that makes jaundice visible?
> 40 umol/l of bilirubin in blood shows signs of jaundice
What are the causes of Jaundice?
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.
What is the pathway of bilirubin metabolism?
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
Give examples of liver function test
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.
What are the histopathological signs in the liver of obstructive jaundice?
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»_space;> bile salts in skin causes itchyness.
What are the investigations done in jaundice?
1) Ultrasound (dilated ducts in obstruction)
2) No dilation»_space;»then biopsy
What is the usual cause of non obstructive jaundice?
Acute hepatitis
What is hepatitis?
Inflammation of the liver
non-neoplastic
What is acute hepatitis?
acute liver injury caused by something that goes away. the liver will return to normal
What is chronic hepatitis?
The cause persists and causes permenant injury to liver
What is the cause short term hepatocyte damage ?
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
What are the causes of chronic hepatitis?
1) immunological = virus, autoimmune, drugs
2) Toxic / metab e.g fatty liver disease = alcohol
3) genetic metabolism disorders (iron, copper)
How does chronic liver disease progress?
- fibrosis around vasculature
- Scarring starts to link vascular structures (bridging fibrosis)
- transforms liver into separate nodules (cirrhosis)
Give examples of hepatotrophic viruses?
1) Hepatitis A,B,C,D,E
* EBV, CMV, HSV cause injury as part of a systemic infection
Which hepatitis virus is lethal in pregnancy?
Hep E
Which hep virus is waterborne, and recently transferred by pigs?
Hep E
Which hep virus can only affect those already infected with hep b?
Hep D
Which hep virus has >70% risk of progressing into chronic hepatitis?
Hep C
What is the affect of alcohol on the liver?
1) fatty change
2) Alcoholic steatohepatitis ( inflammation can lead to acute liver failure)
3) Cirrhosis
What is non-alcoholic fatty liver disease? and what causes it?
Steatosis, steatohepatitis, cirrhosis and hepatocellular carcinoma (HCC) associated with obesity, type 2 diabetes, hyperlipidaemia (not alcohol)
What is the difference between Instrinsic and Idiosyncratic hepatotoxicity?
Intrinsic can be caused by drugs such as paracetamol - it is predictable.
Idiosyncratic is rare and unpredictable
What is the mechanism of paracetamol toxicity?
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.
What is the treatment for paracetamol toxicity?
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
what is cirrhosis?
Cirrhosis is irreversible fibrosis of the liver and conversion of normal liver architecture into nodules
How does cirrhosis prevent normal liver function?
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.
What causes cirrhosis?
Cirrhosis develops over months to decades
1) alcohol
2) Non alcoholic steatohepatitis
3) chronic viral hepatitis
4) Autoimmune liver disease
5) metabolic malfunction
What are the complications of cirrhosis?
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»_space;»death)
2) Liver Cell Failure caused by:
- fewer hepatocytes
- blood bypassing sinusoids
3) Ascities
what causes itchy skin in cirrhosis?
Accumulation /deposition of bile salts in skin
What is alpha 1 antitrypsin deficiency?
- 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
What inherited condition causes insufficient activation of neutrophil enzymes in blood leading to emphysema.
(*also the accumulation in the liver causes cirrhosis)
Alpha 1 antitrypsin deficiency
What is haemochromatosis?
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)
What is wilson’s disease?
Inherited condition that affecting the metabolism of copper. Copper accumulated in the liver (cirrhosis), eyes and brain.
What are the physical signs of cirrhosis?
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)
What are the caused of portal hypertension?
1) PRE-SINUSOIDAL
- e.g. thrombus , fibrosis causes hypertension
2) SINUSOUDAL
- cirrhosis
3) POST SINUSOIDAL
- hepatic vein thrombosis
