Bile and Jaundice

Question 1

what hormone is responsible for the release of bile?

Answer 1

cholecystokinin (CKK)

Question 2

what are the principle functions of bile?

Answer 2

excretory= excretes bile pigments, degradation of haem, cholesterol, bile acids/salts, drugs and their metabolites, paticulate matter

Digestive- digests fats via alkaline secretion, bile salts and phsopholipids emulsify fats into small droplets - bile salts activate pancreatic hydrolyase precursors

Question 3

what is bilirubin?

Answer 3

it is a natural degradation product of haem in erythrocytes

Question 4

what percent of bilirubin is derived from RBCs?

Answer 4

75%

Question 5

what is haptoglobin used for?

Answer 5

it forms a complex with haemoglobin and is metabolized by the liver and spleen forming iron-globin complex and bilirubin - it prevents loss of iron in urine

Question 6

what is haemopexin used for physiologically?

Answer 6

it binds free hame - makes a haem-hemopexin complex which is taken up by the liver

iron is then stored bound to ferritin

Question 7

describe haem degradation and processing

Answer 7

haem is breaksdown to bilirubin - it is then transported into the bloodstream bound to albumin - it is taken up by the liver- the liver conjugates the bilirubin with glucuronic acid (for water solubility)- it is excreted in bile - urobilinogens formed in intestinal tract by gut flora - some urobilinogen is reabsorbed in the kidney to give urobilin (yellow color of urine) - some urobilinogen is conjugated further in the gut to make sterocobilin which is the brown color in feces

Question 8

what is responsible for the green color of bruising?

Answer 8

biliverdin - an unconjugated form of bilirubin

Question 9

how does bilirubin enter hepatocyte cells?

Answer 9

via carrier mediated facilitated diffusion with a Z protein

Question 10

what prevents the efflux of bilirubin back into the blood after it has entered the liver?

Answer 10

binding to cytoplasmic proteins prevents back tracking

Question 11

what makes bilirubin water soluble?

Answer 11

bilirubin is conjugated with glucuronic acid - catalyzed by UDP-glucuronyl transferase

Question 12

what prevents the bilirubin from being reabsorbed in the gut?

Answer 12

it is deconjugated by the gut flora and then oxidised to urobilinogen so it is fat soluble once again - though some of hte urobilirubin is reabsorbed into the kidney (and oxidized again to urobilin) and excreted via urine

the rest of the urobilinogen is metabolised to brown stercobilin and excreted into faeces

Question 13

what is jaundice?

Answer 13

it is hyperbilirubinemia- external sign = yellow discolouration of skin and sclera

Question 14

what are the three classifications of jaundice?

Answer 14

prehepatic

intrahepatic

and

posthepatic jaundice

Question 15

what is the cause of pre-hepatic jaundice (aka. haemolytic jaundice)?

Answer 15

when bilirubin production exceeds uptake capacity of liver - too much RBcell breakdown

often times, excess RBC lysis is commonly due to autoimmune disease

• clinically we would see high plasma levels of unconjugated bilirubin

Question 16

what is the cause of intra-hepatic jaundice generally

Answer 16

when the bilirubin cannot be conjugated and/or excreted by damaged hepatocytes - so liver damage generally

here you would see impaired uptake, conjugation, or secretion of bilirubin - it reflects generalized liver dysfunction

*clinically this is usually accompanied by other abnormal biochemical markers of liver function

Question 17

what generally causes post-hepatic jaundice (obstructive jaundice or choleostatic jaundice)

Answer 17

obstruction to biliary flow - in this case conjugated bilirubin is regurgitated into the blood

clinically you would see high levels of conjugated plasma bilirubin - as well as other biliary metabolites

Question 18

what type of jaundice is characterised by pale stools and dark urine?

Answer 18

post - hepatic jaundice

absence of faecal bilirubin/stercobilin causes pale stools

increased conjugated bilirubin causes dark urine

Question 19

practice diagnosing the following cases

Answer 19

Question 20

what is newborn jaundice?

Answer 20

it is a form of unconjugated hyprbilirubinaemia - physiological jaundice

-causes: immature/impaired hepatic uptake, or red cell destruction

complication - free unbound unconjugated bilirubin may be deposited in brain can cause kernicterus - rare form of brain damage -

Question 21

what is the treatment for newborn jaundice?

Answer 21

most cases will resolve on their own within first 10 days of life - many times we use UV therapy (bili lamp ) which takes the place of conjugation allowing the bilirubin to become water soluble and excretable. COOL

otherwise we can exchange blood transfusion to remove excess bilirubin

or give maternal phenobarbitone prior to induction of labour of premature infant which crosses the placenta and induces synthesis of UDP-glucuronyl transferase

Question 22

what is Gilbert’s Syndrome?

Answer 22

characterized by mild, fluctuating unconjugated hyperbilirubinaemia - often correlates with fasting or illness

50% of affected cases are inherited

causes: - reduced activity of UDP - glucuronyl transferase
- defect in bilirubin uptake

onset of symptoms in teens

can be treated with small doses of phenobarbitone to stimulate UDP-glucuronyl transferase activity

Question 23

what is Crigler-Najjar syndrome?

Answer 23

it is a rare disorder presenting with severe unconjugated hyperbilirubinaemia

caused by mutation in gene coding for UDP- glucuronyl transferase

type 1= complete absense

type 2= marked reduction in enzyme activity

treatment is liver transplant for type 1, or phenobarbitone for type 2

Question 25

what is Dubin-Johnson and Rotor’s syndrome?

Answer 25

benign autosomal recessive disorder presenting with conjugated hyperbilirubinaemia - characterized by impaired biliary secretion of conjugated bilirubin

Question 26

Case study:

10 day old premature infant, born at 34 weeks gestational age, was

clinically jaundiced.

Answer 26

newborn jaundice - which is hepatic jaundice

Question 27

Case study :

43-year-old woman presented with three week history of jaundice and

upper abdominal pain. Her urine was dark and stools pale. On

examination she was jaundiced; there was hepatomegaly.

Answer 27

high bilirubin, high ALP, high AST and ALT - indicates liver damage

no urobilinogen and bilirubin present in the urine = complete obstruction of the biliary tract

Question 28

Case study

53-year-old women presented to her GP with a generalised itchy rash. On examination, GP noticed that she was clinically jaundiced.

Answer 28

high ALP, high AST and high ALT, high gamma GT

ALP is very high so this is obstructive jaundice