Bile and Jaundice Flashcards
what hormone is responsible for the release of bile?
cholecystokinin (CKK)
what are the principle functions of bile?
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
what is bilirubin?
it is a natural degradation product of haem in erythrocytes
what percent of bilirubin is derived from RBCs?
75%
what is haptoglobin used for?
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
what is haemopexin used for physiologically?
it binds free hame - makes a haem-hemopexin complex which is taken up by the liver
iron is then stored bound to ferritin
describe haem degradation and processing
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
what is responsible for the green color of bruising?
biliverdin - an unconjugated form of bilirubin
how does bilirubin enter hepatocyte cells?
via carrier mediated facilitated diffusion with a Z protein
what prevents the efflux of bilirubin back into the blood after it has entered the liver?
binding to cytoplasmic proteins prevents back tracking
what makes bilirubin water soluble?
bilirubin is conjugated with glucuronic acid - catalyzed by UDP-glucuronyl transferase
what prevents the bilirubin from being reabsorbed in the gut?
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
what is jaundice?
it is hyperbilirubinemia- external sign = yellow discolouration of skin and sclera
what are the three classifications of jaundice?
prehepatic
intrahepatic
and
posthepatic jaundice
what is the cause of pre-hepatic jaundice (aka. haemolytic jaundice)?
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
what is the cause of intra-hepatic jaundice generally
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
what generally causes post-hepatic jaundice (obstructive jaundice or choleostatic jaundice)
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
what type of jaundice is characterised by pale stools and dark urine?
post - hepatic jaundice
absence of faecal bilirubin/stercobilin causes pale stools
increased conjugated bilirubin causes dark urine
practice diagnosing the following cases
what is newborn jaundice?
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 -
what is the treatment for newborn jaundice?
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
what is Gilbert’s Syndrome?
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
what is Crigler-Najjar syndrome?
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
