Liver Disease Flashcards
What are the roles of the liver?
Protein synthesis (clotting factors, albumin)
Glucose and fat metabolism
Detoxification and excretion
Defence against infection (Kupffer cells art of reticuloendothelial system)
Acute liver injury results in damage and loss of cells through necrosis or a____
apoptosis
Chronic liver damage leads to _____
fibrosis
Severe forms of chronic liver damage is termed _____ where wide fibrous septa join the portal tracts and central veins
cirrhosis
Name some causes of acute liver injury
Viral (A,B EBC)
Drug
Alcohol
Vascular
Obstruction
Congestion
Name some causes of chronic liver injury
Alcohol
Viral (B, C)
Autoimmune
Metabolic (iron, copper)
What is the presentation of acute liver injury?
Malaise, nausea, anorexia, jaundice
Can also have:
confusion, bleeding, liver pain, hypoglycaemia
What is the presentation of chronic liver injury?
Ascites/oedema, haematemesis (varices causing vomiting blood), malaise, anorexia, wasting, easy bruising, itching, hepatomegaly, abnormal LFTs
Can also have:
jaundice, confusion
What are other conditions to consider when there are symptoms of acute liver injury?
Is there an obstruction?
Is there a malignancy?
What tests give some index of liver function?
Serum bilirubin, albumin, prothrombin time.
Not serum liver enzymes (they indicate whether there is damage)
Cholestatic enzymes are those found in the bloodstream when there is an accumulation of ____ components in liver due to impaired flow of ____.
bile
Name 2 cholestatic liver enzymes
Alkaline phosphatase
Gamma-GT
H__________ enzymes are made in the liver involved in various metabolic processes but may leak into the blood if there is damage or inflammation of the liver.
Hepatocellular
Name some hepatocellular liver enzymes
transaminases (ALT and AST)
What is jaundice?
Raised serum bilirubin
What is an indicator of pre-hepatic jaundice?
Unconjugated bilirubin
What is Gilbert’s syndrome?
Mild deficiency of UDP-glucuronosyltransferase so lack of conjugation of bilirubin. Is generally benign.
True or false: non-conjugated bilirubin is water soluble
False
Therefore, less easily excreted
Other than Gilbert’s syndrome, what is another cause of pre-hepatic jaundice?
Haemolysis (liver’s ability to conjugate bilirubin becomes overwhelmed so more unconjugated bilirubin in bloodstream)
Bilirubin is a product of…
haemoglobin breakdown
The normal serum bilirubin in adults is…
1.2 mg/dl
What organs are involved in the reticuloendothelial system which contain macrophages to break down RBCs?
Spleen, liver and bone marrow
What does unconjugated bilirubin bind to in order to travel to the liver?
Albumin
True of false: unconjugated bilirubin can cross the BBB?
True, it is lipophilic and neurotoxic which is why it needs to be conjugated
The enzyme UDP-glucuronosyltransferase adds a g_____ a___ to make conjugated bilirubin.
glucuronic acid
The conjugated bilirubin travels into the g_____ and mixes with bile before being squirted into the intestines.
gallbladder
In the large intestines, the conjugated bilirubin is metabolised by the gut flora and converted into…
urobilinogen
The urobilinogen either is excreted in the faeces of enters the bloodstream and travels to…
Either the kidneys and urinated out
or
Returns to liver.
What is the recycling of bilirubin to the liver called?
Enterohepatic circulation
What causes intra-hepatic jaundice?
Conditions that damage the liver ie. liver disease
eg Viral hepatitis, non-alcoholic or alcoholic fatty liver disease, tumours, drugs, metabolic disease, autoimmune conditions)
What would tests show in intra-hepatic jaundice?
Increased unconjugated bilirubin due to less conjugation occurring.
Also high transaminases (ALT, AST and APT) which are released when the liver is damaged
What causes post-hepatic jaundice
Bile duct obstruction (cholestasis) due to:
Strictures, gallstones, tumours.
Slows flow of bile, conjugated bilirubin backs up into liver and accumulates. Damages liver so increased transaminases.
Often no urobilinogen made so low levels in urine.
What is pale stool a signs of?
No conjugated bilirubin can reach the intestine, suggesting cholestasis
Other than pale stool, what is another sign of cholestasis?
Dark urine
Reflux of conjugated bilirubin into blood is then excreted in the urine.
True or false: there may be itching with pre-hepatic jaundice?
False
There may be with cholestatic jaundice (intra-hepatic of post-hepatic)
With biliary obstruction, 90% have dilated intrahepatic b____ d____ on ultrasound
bile ducts
What imaging can you do for jaundice?
Ultrasound
Magnetic resonance cholangiogram
Endoscopic retrograde cholangiogram
Where do most gallstones form?
Gallbladder
What are gallstones made of?
Cholesterol, pigment and calcium
What are risk factors of gallstones?
Being female, fat, fertile (also liver disease, ileal disease, TPN, clofibrate)
True or false: most patients with gallstones are asymptomatic
True
Intrahepatic bile duct stones (hepatolithiasis) contain mostly ____ pigment and cholesterol stones
brown
Gallbladder stones (cholecystolithiasis) contain c_____ stones
cholesterol (black pigment)
True or false: cholangitis and pancreatitis are present with gallstones in the bile duct but not gallbladder
True
How do you manage gallbladder stones?
Laparoscopic cholecystectomy
Bile acid dissolution therapy (not very successful)
How do you manage bile duct stones?
ERCP (Endoscopic retrograde cholangiopancreatography) with sphincterotomy and:
removal, crushing or stent placement.
or for large stones, surgery
Weight loss and jaundice could be caused by gallstones or a….
malignancy
30% of acute hepatitis is due to…
drug-induced liver injury (DILI)
What drug causes half of drug-induced liver injury?
Paracetamol
What are common sources of drug-induced liver injury
Antibiotics
CNS drugs
Immunosuppressants
Analgesics
GI drugs (eg PPIs)
Dietary supplements
Multiple drugs
How do you manage paracetamol induce fulminant hepatic failure?
N acetyl cysteine (NAC)
Supportive to correct
coagulation defects, fluid electrolyte and acid base balance, renal failure, hypoglycaemia, encephalopathy
What are causes of ascites?
Chronic liver disease
Portal vein thrombosis
Hepatoma
TB
Neoplasia
Pancreatitis
Cardiac causes
How do you manage ascites?
Fluid and salt restriction
Diuretics
large-volume paracentesis and albumin
Trans-jugular intrahepatic portosystemic shunt (TIPS)
Acute alcohol-related injury causes hepatocyte b_____ and is mediated by neutrophils
ballooning
Alcohol changes the way that hepatocytes metabolise and produce ___
fat
Fat accumulation in hepatocytes is called s_____
steatosis
What is the main cause of liver death in the UK?
alcoholic liver disease (ALD)
Why can cirrhosis cause varices?
Cirrhosis causes fibrosis and increased hepatic resistance so increased splanchnic blood flow which can varices
Why are liver patients vulnerable to infection?
Impaired reticuloendothelial function
reduced opsonic activity (proteins that activate phagocytosis)
What do you give for encephalopathy?
Lactulose
Autoimmune hepatitis usually requires what for diagnosis?
Liver biopsy (usually lymphocytes and plasma cells in portal tracts and lobular parrenchyma. Damage causes apoptosis or necrosis.
Primary sclerosing cholangitis (autoimmune condition of bile ducts) can lead to s____ and gallstones
strictures
What may cause iron deposition in the heart?
Haemochromatosis
Also may deposit in heart and pancreas.
Autosomal recessive.
Raised ferritin and transferrin saturation.
Causes of chronic liver disease
Alcohol
Non-alcoholic steatohepatitis (NASH)
Viral hepatitis (B,C)
Immune (autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis)
Metabolic (haemochromatosis, Wilsons, a1 antitrypsin deficiency)
Vascular (Budd-Chiari)
