Liver System + Disease

Question 1

What are the functions of liver?

Answer 1

Detoxification
Bile
Cholesterol production
Protein synthesis

Question 2

What proteins does the liver produce?

Answer 2

Albumin
Coagulation

Question 3

Describe alanine aminotransferase (ALT) liver function test

Answer 3

Increased when cells of the liver are inflamed or undergo cell death
Rises dramatically in acute liver damage, such as viral hepatitis

Question 3

Describe aspartate aminotransferase (AST) liver function test

Answer 3

Raised in acute liver damage; less specific for liver disease

Question 4

Describe alkaline phosphatase (ALP) liver function test

Answer 4

Raised in biliary tract damage and inflammation

Question 5

Describe gamma-glutamyl transferase (GGT) liver function test

Answer 5

Produced by the bile duct (sensitive marker for cholestatic damage)
Raised in alcohol toxicity

Question 6

Describe bilirubin liver function test

Answer 6

Plasma total and direct (=conjugated);
Urine urobilinogen and bilirubin

Question 7

What is jaundice?

Answer 7

Symptom of underlying disease
Elevation of serum bilirubin

Question 8

What are the 3 types of jaundice?

Answer 8

Haemolytic
Hepatocellular
Posthepatic

Question 9

What is the cause of haemolytic?

Answer 9

RBC haemolysis

Question 10

What are the causes of hepatocellular?

Answer 10

Infection
Drug
Genetic error
Autoimmune
Neonatal

Question 11

What are the causes of posthepatic?

Answer 11

Intrahepatic bile ducts
Extrahepatic bile ducts

Question 12

What happens in bilirubin metabolism in circulation?

Answer 12

Erythrocytes broken down + haemoglobin released
Globin metabolised
Haem converted to bilirubin
Bound to albumin

Question 13

What happens to bilirubin metabolism in liver?

Answer 13

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

Question 14

What is neonatal jaundice?

Answer 14

Bilirubin transferase low at birth
Unconjugated bilirubin increased in blood

Question 15

How is natal jaundice treated?

Answer 15

Exposure of blue florescent light to skin
= converts bilirubin to H2O soluble isomers

Question 16

What is haemolytic jaundice?

Answer 16

Excessive RBC lysis
= bilirubin produced faster than rate of conjugation by liver

Question 17

What does haemolytic jaundice look like in blood?

Answer 17

Increased unconjugated bilirubin

Question 18

What does haemolytic jaundice look like in urine?

Answer 18

Urobilinogen increased
No bilirubin in urine
Urine normal colour

Question 19

What is hepatocellular jaundice?

Answer 19

Liver damage by hepatitis
= low conjugation efficiency = bilirubin not secreted into bile

Question 20

What does hepatocellular jaundice look like in the blood?

Answer 20

Increased BOTH unconjugated (indirect) &
conjugated (direct) bilirubin.
ALT & AST levels are markedly elevated = HEPATIC DAMAGE

Question 21

What does hepatocellular jaundice look like in the urine?

Answer 21

Bilirubin is present in urine
= urine colour is yellowish brown

Question 22

What does hepatocellular jaundice look like in the stool?

Answer 22

Normal to pale

Question 23

What is obstructive (post-hepatic) jaundice?

Answer 23

Bile duct obstruction
= conjugated bilirubin prevented from passing to intestine
= passes to blood

Question 24

What does obstructive jaundice look like in the blood?

Answer 24

Increased conjugated (direct) bilirubin. γGT & ALP are markedly elevated = BILIARY SYSTEM DAMAGED

Question 25

What does obstructive jaundice look like in the urine?

Answer 25

Bilirubin in urine. Urobilinogen reduced. Complete obstruction, urobilinogen absent Urine yellowish brown colour

Question 26

What does obstructive jaundice look like in the stool?

Answer 26

Pale

Question 27

What is hepatitis?

Answer 27

Inflammation of liver

Question 28

Describe acute hepatitis

Answer 28

Develops quickly Last short period of time Patient recovers normally

Question 29

Describe chronic hepatitis

Answer 29

Develop over number of years Leads to fibrosis + cirrhosis

Question 30

Describe viral hepatitis

Answer 30

Acute/chronic liver injury

Question 31

How is hepatitis A spread?

Answer 31

Faecal-oral spread

Question 32

Describe hepatitis A

Answer 32

Short incubation period Acute Asymptomatic Mild illness RNA virus

Question 33

How is hepatitis A treated?

Answer 33

No specific treatment Prophylactic anti-HAV immunisation - eg. travellers

Question 34

Describe hepatitis E

Answer 34

Acute More severe liver damage than HepA

Question 35

How is HepE treated?

Answer 35

No treatment In extreme conditions = antiviral ribavirin

Question 36

How is HepB spread?

Answer 36

Blood Blood products Sexually

Question 37

Describe HepB

Answer 37

DNA virus Long incubation Liver damage by antiviral immune response

Question 38

What is the treatment for HepB?

Answer 38

Interferon alpha Nucleoside analogues

Question 39

How is HepC spread?

Answer 39

Blood Blood products

Question 40

Describe HepC

Answer 40

RNA virus Short incubation Asymptomatic

Question 41

What is the treatment for HepC?

Answer 41

Treatment depends on strain + stage Lats 24-48 weeks

Question 42

How does sofosbuvir treat HepC?

Answer 42

Uridine nucleotide analogue inhibits HCV polymerase = prevents viral replication

Question 43

What is autoimmune hepatitis?

Answer 43

Autoantibodies against hepatocytes

Question 44

What does autoimmune hepatitis present as?

Answer 44

Jaundice RUQ pain

Question 45

How do you investigate autoimmune Hep?

Answer 45

Type 1 = smooth muscle Abs (80%), anti-nuclear Abs (10%) Type 2 (children) = anti-liver microsomal type 1 Abs

Question 46

How do you treat autoimmune Hep?

Answer 46

Immunosuppressants

Question 47

What is alcohol-induced hepatocellular steatosis?

Answer 47

Fatty change = increased lipid biosynthesis = impaired secretion of lipoproteins = increased catabolism of fat

Question 48

Is hepatic steatosis reversible?

Answer 48

YES = if abstention to alcohol

Question 49

What are the clinical features of alcoholic hepatitis?

Answer 49

Hepatocyte swelling = accumulation of fat + H2O Cellular necrosis Fibrosis Increase in serum bilirubin + ALP

Question 50

What are the clinical features of hepatic steatosis?

Answer 50

Mild increase in serum bilirubin + ALP Asymptomatic

Question 51

What does cirrhosis do?

Answer 51

Hepatocytes replaced by non-functional connective tissue Portal vein hypertension + shunting blood around liver

Question 52

What does cirrhosis not do?

Answer 52

Increase susceptibility to idiosyncratic reactions Increase likelihood of autoimmune-mediated drug reactions

Question 53

What causes cirrhosis?

Answer 53

Alcohol = most common Drugs Chronic viral hepatitis Autoimmune hepatitis

Question 54

What does alcohol-mediated hepatic cirrhosis look like?

Answer 54

Initially liver yellow, large + fatty = reversible stage Brown, shrunken + non-fatty

Question 55

What are the signs of cirrhosis?

Answer 55

Fluid retention + oedema in legs Gallstones Coagulation defects Reduced mental functions Jaundice

Question 56

How is oedema treated?

Answer 56

Salt restriction + treatment with diuretic

Question 57

What are the 3 hepatocyte zones?

Answer 57

Centrilobular = lowest oxygenation Mid-zone Periportal = highest oxygenation

Question 58

What is periportal most susceptible to?

Answer 58

Viral hepatitis

Question 59

What is centrilobular most susceptible to?

Answer 59

Ischaemia

Question 60

Describe paracetamol toxicity

Answer 60

Alcohol induces CYP2E1 expression Accelerates paracetamol hepatoxicity