Liver System + Disease Flashcards
What are the functions of liver?
Detoxification
Bile
Cholesterol production
Protein synthesis
What proteins does the liver produce?
Albumin
Coagulation
Describe alanine aminotransferase (ALT) liver function test
Increased when cells of the liver are inflamed or undergo cell death
Rises dramatically in acute liver damage, such as viral hepatitis
Describe aspartate aminotransferase (AST) liver function test
Raised in acute liver damage; less specific for liver disease
Describe alkaline phosphatase (ALP) liver function test
Raised in biliary tract damage and inflammation
Describe gamma-glutamyl transferase (GGT) liver function test
Produced by the bile duct (sensitive marker for cholestatic damage)
Raised in alcohol toxicity
Describe bilirubin liver function test
Plasma total and direct (=conjugated);
Urine urobilinogen and bilirubin
What is jaundice?
Symptom of underlying disease
Elevation of serum bilirubin
What are the 3 types of jaundice?
Haemolytic
Hepatocellular
Posthepatic
What is the cause of haemolytic?
RBC haemolysis
What are the causes of hepatocellular?
Infection
Drug
Genetic error
Autoimmune
Neonatal
What are the causes of posthepatic?
Intrahepatic bile ducts
Extrahepatic bile ducts
What happens in bilirubin metabolism in circulation?
Erythrocytes broken down + haemoglobin released
Globin metabolised
Haem converted to bilirubin
Bound to albumin
What happens to bilirubin metabolism in liver?
Dissociates from albumin
Enters hepatocytes
Conjugated with 2 glucuronic acids
Conjugated secreted by hepatocytes
into bile
Bile secreted
Intestinal bacteria degrade bilirubin to urobilinogen
80% oxidised + secreted in faeces
20% secreted in urine
What is neonatal jaundice?
Bilirubin transferase low at birth
Unconjugated bilirubin increased in blood
How is natal jaundice treated?
Exposure of blue florescent light to skin
= converts bilirubin to H2O soluble isomers
What is haemolytic jaundice?
Excessive RBC lysis
= bilirubin produced faster than rate of conjugation by liver
What does haemolytic jaundice look like in blood?
Increased unconjugated bilirubin
What does haemolytic jaundice look like in urine?
Urobilinogen increased
No bilirubin in urine
Urine normal colour
What is hepatocellular jaundice?
Liver damage by hepatitis
= low conjugation efficiency = bilirubin not secreted into bile
What does hepatocellular jaundice look like in the blood?
Increased BOTH unconjugated (indirect) &
conjugated (direct) bilirubin.
ALT & AST levels are markedly elevated = HEPATIC DAMAGE
What does hepatocellular jaundice look like in the urine?
Bilirubin is present in urine
= urine colour is yellowish brown
What does hepatocellular jaundice look like in the stool?
Normal to pale
What is obstructive (post-hepatic) jaundice?
Bile duct obstruction
= conjugated bilirubin prevented from passing to intestine
= passes to blood
What does obstructive jaundice look like in the blood?
Increased conjugated (direct) bilirubin.
γGT & ALP are markedly elevated = BILIARY SYSTEM DAMAGED
What does obstructive jaundice look like in the urine?
Bilirubin in urine.
Urobilinogen reduced.
Complete obstruction, urobilinogen absent
Urine yellowish brown colour
What does obstructive jaundice look like in the stool?
Pale
What is hepatitis?
Inflammation of liver
Describe acute hepatitis
Develops quickly
Last short period of time
Patient recovers normally
Describe chronic hepatitis
Develop over number of years
Leads to fibrosis + cirrhosis
Describe viral hepatitis
Acute/chronic liver injury
How is hepatitis A spread?
Faecal-oral spread
Describe hepatitis A
Short incubation period
Acute
Asymptomatic
Mild illness
RNA virus
How is hepatitis A treated?
No specific treatment
Prophylactic anti-HAV immunisation - eg. travellers
Describe hepatitis E
Acute
More severe liver damage than HepA
How is HepE treated?
No treatment
In extreme conditions = antiviral ribavirin
How is HepB spread?
Blood
Blood products
Sexually
Describe HepB
DNA virus
Long incubation
Liver damage by antiviral immune response
What is the treatment for HepB?
Interferon alpha
Nucleoside analogues
How is HepC spread?
Blood
Blood products
Describe HepC
RNA virus
Short incubation
Asymptomatic
What is the treatment for HepC?
Treatment depends on strain + stage
Lats 24-48 weeks
How does sofosbuvir treat HepC?
Uridine nucleotide analogue inhibits HCV polymerase
= prevents viral replication
What is autoimmune hepatitis?
Autoantibodies against hepatocytes
What does autoimmune hepatitis present as?
Jaundice
RUQ pain
How do you investigate autoimmune Hep?
Type 1 = smooth muscle Abs (80%), anti-nuclear Abs (10%)
Type 2 (children) = anti-liver microsomal type 1 Abs
How do you treat autoimmune Hep?
Immunosuppressants
What is alcohol-induced hepatocellular steatosis?
Fatty change
= increased lipid biosynthesis
= impaired secretion of lipoproteins
= increased catabolism of fat
Is hepatic steatosis reversible?
YES
= if abstention to alcohol
What are the clinical features of alcoholic hepatitis?
Hepatocyte swelling = accumulation of fat + H2O
Cellular necrosis
Fibrosis
Increase in serum bilirubin + ALP
What are the clinical features of hepatic steatosis?
Mild increase in serum bilirubin + ALP
Asymptomatic
What does cirrhosis do?
Hepatocytes replaced by non-functional connective tissue
Portal vein hypertension + shunting blood around liver
What does cirrhosis not do?
Increase susceptibility to idiosyncratic reactions
Increase likelihood of autoimmune-mediated drug reactions
What causes cirrhosis?
Alcohol = most common
Drugs
Chronic viral hepatitis
Autoimmune hepatitis
What does alcohol-mediated hepatic cirrhosis look like?
Initially liver yellow, large + fatty = reversible stage
Brown, shrunken + non-fatty
What are the signs of cirrhosis?
Fluid retention + oedema in legs
Gallstones
Coagulation defects
Reduced mental functions
Jaundice
How is oedema treated?
Salt restriction + treatment with diuretic
What are the 3 hepatocyte zones?
Centrilobular = lowest oxygenation
Mid-zone
Periportal = highest oxygenation
What is periportal most susceptible to?
Viral hepatitis
What is centrilobular most susceptible to?
Ischaemia
Describe paracetamol toxicity
Alcohol induces CYP2E1 expression
Accelerates paracetamol hepatoxicity
