5. Hepato-biliary Pathology Flashcards
Liver:
- T/F: has a dual blood supply.
- What is the function of liver?
- True. Hepatic artery and portal vein.
- Protein synthesis
> Metabolism of fat and carbohydrate
> Detoxification of drugs and toxins including alcohol
What it liver failure complication of?
- Acute liver injury
- Hepatitis (Viruses, Alcohol, Drugs)
- Bile duct obstruction - Chronic liver injury i.e. cirrhosis
What causes viral hepatitis?
Hepatitis A Hepatitis B Hepatitis C Hepatitis E Other viruses
Outline pathology of viral hepatitis.
Inflammation of liver
Liver cell damage and death of individual liver cells
What is the outcome of acute inflammation caused by viral hepatitis?
- Resolution: liver returns to normal (Hepatitis A, E)
- Liver failure if severe damage to liver (Hepatitis A, B, E)
- Progression to chronic hepatitis and cirrhosis (Hepatitis B, C)
What is alcoholic liver disease?
- Response of liver to excess alcohol
- Fatty change
- Alcoholic hepatitis
> Acute inflammation
> Liver cell death
> Liver failure - Progress to cirrhosis
- What causes jaundice?
- What are the pathways of bilirubin metabolism?
- What are the classification of causes of jaundice?
- Increased circulating bilirubin caused by altered metabolism of bilirubin
- Pre-hepatic, Hepatic, Post-hepatic
- Pre-hepatic, Hepatic, Post-hepatic
Outline pre-hepatic metabolism of bilirubin.
- Breakdown of haemoglobin in spleen to form haem and globin
- Haem converted to bilirubin
- Release of bilirubin into circulation
What are pre-hepatic causes of jaundice?
Increased release of haemoglobin from red cells (haemolysis). Investigations show haemolysis and elevated unconjugated bilirubin, but normal serum ALP, transferases and albumin. Serum haptoglobulins are low.
Outline hepatic metabolism of bilirubin.
Uptake of bilirubin by hepatocytes
Conjugation of bilirubin (to glucuronic acid) in hepatocytes
Excretion of conjugated bilirubin into biliary system
What are hepatic causes of jaundice?
- Cholestasis
2. Intra-hepatic bile duct obstruction
Define cholestasis.
Accumulation of bile within hepatocytes or bile canaliculi.
What causes cholestasis?
Viral hepatitis
Alcoholic hepatitis
Liver failure
Drugs (Therapeutic, Recreational): Predictable (dose related) vs unpredictable (not dose related).
What causes intra-hepatic bile duct obstruction?
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Tumours of liver
- Hepatocellular carcinoma: Malignant tumour of hepatocytes
- Tumours of intra-hepatic bile ducts e.g. Cholangiocarcinoma (Malignant tumour of bile duct epithelium)
- Metastatic tumours: Common site of metastases
- What is primary biliary cholangitis?
2. How do you diagnose it?
- Organ specific auto-immune disease (mainly affects females)
- Blood test: look for anti-mitochondrial auto-antibodies in serum. Look for raised serum alkaline phosphatase (ALP).
ALP is present in hepatic canalicular and sinusoidal membranes, and also in bone, intestine and placenta.
Serum ALP is raised in both intrahepatic and extrahepatic cholestatic disease of any cause, due to increased synthesis.
Outline pathology of primary biliary cholangitis.
Granulomatous inflammation involving bile ducts
Loss of intra-hepatic bile ducts
Progression to cirrhosis
- Outline pathology of primary sclerosing cholangitis.
- What is it associated with?
- What does primary sclerosing cholangitis increases risk of?
- Chronic inflammation and fibrous obliteration of bile ducts. Loss of intra-hepatic bile ducts. Progression to cirrhosis.
- Associated with inflammatory bowel disease
- Increases risk of development of cholangiocarcinoma
Outline post-hepatic metabolism of bilirubin.
- Transport of conjugated bilirubin in biliary system
- Breakdown of bilirubin conjugate in intestine (ileum)
- Re-absorption of bilirubin: Entero-hepatic circulation of bilirubin
What are post-hepatic causes of jaundice?
Cholelithiasis (gallstones)
Diseases of gall bladder
Extra-hepatic duct obstruction
What are the risk factors for gallstones?
Obesity
Diabetes
Outline pathology of gallstones in the gall bladder.
Due to inflammation which can be:
1. Acute Cholecystitis - acute inflammation of gall bladder: Empyema (perforation of gall bladder, biliary peritonitis). Progression to chronic inflammation.
- Chronic Cholecystitis: Chronic inflammation and fibrosis of gall bladder
What are the causes of common bile duct obstruction?
Gallstones
Bile duct tumours
Benign stricture
External compression (Tumours)
What are the effects of common bile duct obstruction?
- Jaundice
- No bile excreted into duodenum
- Infection of bile proximal to obstruction (Ascending cholangitis)
- Secondary biliary cirrhosis if obstruction prolonged
What is hepatic cirrhosis?
End stage chronic liver disease - Response of liver to chronic injury
What causes cirrhosis?
- Alcohol
- Hepatitis B, C
- Immune mediated liver disease
> Auto-immune hepatitis
> Primary biliary cholangitis - Metabolic disorders
> Excess iron (Primary haemochromatosis)
> Excess copper (Wilson’s disease) - Obesity (Diabetes mellitus)
Outline pathology of cirrhosis.
Diffuse process involving whole liver
Loss of normal liver structure
Replaced by nodules of hepatocytes and fibrous tissue
What are the complications of cirrhosis?
- Altered liver function - Liver failure
- Abnormal blood flow - Portal hypertension
- Increased risk of hepatocellular carcinoma
