Diseases of the hepatobiliary system Flashcards
What are the 3 types of jaundice? And what is meant by this?
Pre hepatic - Too much bilirubin
Hepatic - too few functioning liver cells
Post hepatic - bile duct obstruction
Give an example of a disease that causes pre hepatic jaundice
Haemolytic anaemia
Give 3 examples of a disease that causes hepatic jaundice
Acute diffuse liver cell injury
End stage chronic liver disease
Inborn errors
Give 3 examples of a disease that causes post hepatic jaundice
Stones, strictures or tumour in the bile duct of pancreas
At what level should bilirubin reach before jaundice occurs?
40umol/l
Explain bilirubin metabolism
1) Conjugated billirubin comes from the breakdown of haem
2) Unconjugated bilirubin (lipid soluble) is bound to albumin to be transported through the blood to the liver
3) Liver converts to conjugated bilirubin = water soluble
4) Conjugated bilirubin + bile salts (and other stuff) forms bile = goes to the small intestine
5) Conjugated bilirubin converted by gut bacteria into Urobilinogen
6) Urobilinogen then converted to stercobilin = brown
OR
6) Urobilinogen goes back to the liver and then the kidney
7) Kidney converts to urobilin = yellow
What are the signs of each of the types of jaundice?
Pre hepatic = yellow eyes/skin only
Hepatic = Yellow eyes/dark urine
Post hepatic = yelow eyes/pale stools/dark urine
What is the first sign of a liver with obstructive jaundice?
Jaundice in the skin
What are later signs of a liver with obstructive jaundice?
Oedema
Itchy skin - bile salts on the skin
How does a liver with obstructive jaundice present histologically?
Ductal reaction = proliferation of ductules around the edge
Portal tract enlarged - fibrous tissue
Bile plugs in canaliculae
What are the 4 main causes of acute hepatitis?
Viruses
Alcohol
Hepatotoxic drugs
Autoimmine
How does acute hepatitis present?
From asymptomatic/malaise to encepalopathy/death
Explain the cell/structural changes that occur in hepatitis
Hepatocytes vary in size
Necrosis
What are the causes of viral hepatitis?
Hepatotropic viruses: A, B, C, D (can only get if affected with Hep B), E
Systemic diseases: Epstein-Barr virus, Cytomegalovirus, Herpes simplex virus
What viral causes of hepatits causes acute jaundice?
Hep A and B
How can affects of alcohol on the liver present?
Fatty changes
Alcoholic steatohepatitis - inflammation of the liver with fat accumulation
Cirrhosis
What are Mallory bodies?
Found in the cytoplasm of liver cells
Damaged intermediate filaments within the hepatocytes
What is non alcoholic fatty liver disease?
Same pathology as alcoholic liver disease
Associated with metabolic syndromes e.g. type 2 diabetes, obesity
Cirrhotic liver is a predisposing disease to what?
Hepatocellular carcinoma
What is the criteria for diagnosing drug induced liver injury?
1) Abnormal LFTs after taking drugs
2) Improvement in LFTs after stopping the drug
3) Alternative causes excluded by detailed investigation
4) Increase in LFTs when rechallanged
Explain the mechanism of normal paracetamol metabolism
Normally metabolised via 3 different pathways:
1) Conjugated into glucuronyl transferase = safe
2) Conjugated into sulphotransferase = safe
3i) Converted into N-acetyl p-benzoquinone-imine (toxic) via P450 enzyme
3ii) NAPQI binds to glutathione = safe
Explain the mechanism of paracetamol toxicity
When overdosed there is an increase in NAPQI
Takes alternative route of binding to tissue membrane proteins = Necrosis of liver cells
What is the treatment for paracetamol toxicity and how does it work?
Treatment: N-acetyl cystein
Restores glutathione so more likely to follow the safe pathway of metabolising NAPQI
What is the definition of cirrhosis?
Diffuse hepatic process
Fibrosis
Structurally abnormal nodules
Liver cells still present but portal vein blood bypasses the sinusoids - first pass metabolism does not occue
Cirrhosis causes what to occur due to increase pressure in the liver?
Portal hypertension
Liver has to work harder as blood has to travel through it more times
What are the 5 main causes of cirrhosis?
Alcohol Non alcoholic steatohepatitis Chronic viral infections e.g. Hep B, C Autoimmune liver disease e.g. primary biliary sclerosis Metabolic e.g. alpha 1 antitrypsin
Apart from portal hypertension what are the other signs, symptoms and complications of cirrhosis?
Synthesis of albumin: Oedema, Bruising, Muscle wasting
Ascites - swollen abdomen
Hormone fluid retention = gynacomastia
Spider navi
Oesophageal varices
Caput medusa - varices from umbilical vein collaterals
Excretion: Itching - accumulation of bile salts, Jaundice
Vulnerable to infection
Drug doses will need lowering
What is alpha 1 antitrypsin deficiency?
Alpha 1 antitrypsin protects tissues from enzymes of inflammatory cells
Deficiency = accumulation of proteins causes uncontrolled breakdown of cells
How does alpha 1 antitrypsin deficiency affect the liver and lungs?
Liver = cirrhosis Liver = Emphysema
What is haemochromatosis?
Inborn error of metabolism Iron accumulation in many organs of the body including the liver = cirrhosis Pancreas = diabetes Skin = pigmented Joints = arthritis Heart = cardiomyopathy
What is Wilson’s disease?
Inborn error of copper metabolism Accumulates in: Liver = cirrhosis Eyes = Kayser-Fleischer rings Brain = ataxia
What are the 3 types of portal hypertension with examples
Pre-sinusoidal - Portal fibrosis, Non cirrhotic potal hypertention
Sinusoidal - cirrhosis
Post sinusoidal - Hepatic vein thrombosis
What are the complications of portal hypertension?
Splenomagaly - low platelets due to liver decompesation
Oesophageal varices
Piles
Ascites
