T11-L7: Medical Liver Diseases Flashcards
What is bilirubin combined with in the liver to become conjugated?
Glucuronic acid
- Once conjugated it is excreted in bile and bacteria act on the bilirubin to conjugate it again so that it cannot be absorbed and so excreted into bile. Some however a small amount is not unconjugated again and along with bile acids forming part of the enterohepatic circulation.
Give prehepatic causes of jaundice.
In this case these is a rise in unconjugated bilirubin
- Haemeolysis
- Gilbert’s syndromes- this is a harmless deficiency that leads to the build up of bilirubin in times of stress
Give hepatic causes of jaundice.
This leads to a build up of The kidneys can excrete it leading to dark urine and yellow eyes/skin. Causes include:
Few functioning hepatocytes e.g. in acute liver injury, end stage liver disease and inborn errors of metabolism.
Give post-hepatic causes of jaundice.
This leads to a build up of conjugated bilirubin leading to dark urine (as it is soluble), yellow eyes/skin and pale stools (as bilirubin is not passed into faeces).
Give liver function tests.
- Albumin levels - low in liver disease
- Clotting factor levels through INR
- Aminotransferases - ALT and AST
- Blood tests
In addition to the LFTs we can also use ultrasound and biopsy to test for the cause of liver damage.
What effects do we see in the liver as bile accumulates?
- Portal Tract Expansion
- Oedema
- Ductular reaction - proliferation of the ductules around the portal tracts
- Bile salts which are toxic build up (cause itchy skin). The copper cannot get out. These accumulate in the liver and skin.
What is the aetiology of acute hepatitis?
- Viruses
- Drugs
- Autoimmune
- Unknown (seronegative)
What do we see histologically on acute hepatitis?
Loss of hepatocytes. All that remains is collagen and vascular stature - known as pan acing encores,
What is the comment cause of hepatitis in the UK? Give their modes of transmission.
Viral hepatitis A, B and C
Hepatitis A - food and water borne
Hepatitis B and C - parenteral rout - most common is maternal and through IVDU (and through blood products)
These a can progress to chronic infection - 70% in Hepatitis C and 10% in Hepatitis B.
Other causes include EBV and CMV in the immunocompromised.
What does Hepatitis D require to survive?
Hepatitis B
What is alcoholic steatohepatitis?
Fat deposition and inflammation. When cells cannot cope with the oxidative stress due to the fat accumulation they undergo cell damage with ballooning - breakdown of the cytoskeleton and hydronic enlargement. Mallory bodies are also seen - these are pink condense cytoplasm with an inflammatory infiltrate.
What is the fastest growing case fo liver disease in the Western World?
Non-Alcoholic Fatty Liver Disease (NAFLD)
What is the type of liver injury that occurs when you overdose in a drug?
Intrinsic
What is the antidote for paracetamol overdose?
N-acteylcysteine
Which hepatocytes are destroyed first in instrinc hepatic injury?
Those furthest from the portal tracts. They produce the toxic metabolite and are first to undergo necrosis.
What is Haemochromatosis?
An inborn error of metabolism that leads to an accumulation of iron. This leads to cirrhosis, diabetes, pigmented skin, arthritis and cardiomyopathy. The treatment is venesection to deplete iron stores.
What is Wilson’s disease?
An inborn error of metabolism that leads to the accumulation of Copper. This leads to cirrhosis, Kayser-Fleischer rings (dark rings that surround the iris) in the eye and ataxia.
What is Alpha-1-AntiTripsin disorder?
Anti-trypsin is an abnormal and so cannot be exported from hepatocytes and others cells of the body. The protease therefore accumulates in the liver and injures them causing cirrhosis. It is also therefore insufficient in blood and so failures to inactivate neutrophil enzymes leading to emphysema
Give examples of autoimmune liver disease.
- Autoimmune hepatitis
- Primary Sclerosing Cholangitis
- Primary Biliary Cholangitis
What is Primary biliary cholangitis?
Definition: This is an autoimmune inflammation of the biliary tree.
Epidemiology: It mainly effects middle aged women.
Aetiology: Autoimme
Pathogenesis: Characterised by anti-mitochondrial antibodies. Bile duct granulomas are produced at an early stage and surrounded by Kupffer cells.
Clinical features: This leads to an elevated phosphate. The destruction of the cells can lead to ductopenia (loss of the bile duct) and cirrhosis.
What is Primary Sclerosing Cholangitis?
Definition: A long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts which normally allow bile to drain from the gallbladder.
It presents with high ALP and biliary features such as a ‘pruned tree - a narrowing in biliary untagging. There is periductal “onion skin” fibrosis seen around the duct.
It is associated with ulcerative colitis.
Long term, it can lead to ductopenia and cirrhosis.
Give causes of cirrhosis.
- Alchohol
- Drugs
- Virus - Hepatitis B and C
- Autoimmune
- Metabolic - e.g. iron, copper and A1AT deficiency
What are complications of cirrhosis?
In cirrhosis there is widespread fibrosis and scarring. there is loss of the architecture leading to nodal repair. The liver cells are bypassed as the blood travels to the portal vein.
Consequences include:
- Loss of detoxification of drugs and hormone - can lead to encephalopathy
- Clotting problems and so bruising
- Malnutrition due to vitamin loss
- Oedema due to lack of albumin
- Ascites
- Muscle wasting
- Susceptibility to infection - antibodies not produced
- Failure to excrete bile and bile salts leading to jaundice and itchy skin respectively
- Portal hypertension (oesophageal varies)
How does a patient with chronic liver disease present?
- Ascites
- Muscle wasting
- Bruising
- Gynaecomastia
- Spider naevi
- Varices, Caput medusae = variceal umbilical vein collaterals
