Jaundice & Liver failure Flashcards
What is jaundice?
Symptom of excessm bilirubin
WHy do we make bile?
Cholesterol homeostasis
Lipid and vitamin absorption
Removal of waste products
- xenobiotics
- drugs
- hormones
How much bile is produced daily? Where? Drain?
Half a litre
Hepatocytes - 60pc
Cholangiocytes - line biliary tree - 40pc
Drains from liver through bile ducts into DUODENUM
WHat is the role of the biliary tree?
ALteration of pH and fluidity
- HCO3 added, H2O etc
How is bile modified? Give examples
BIliary excretion of bile salts goverened
bu
BSEP - active transport of bile acids MRP3 MRP2 MDR1 - mediates excretion of xenobiotics MDR3 - phospholipid translocation
What are the two primary bile acids?
Cholic acid
Chenodoxycholic acid
How are secondary acids formed? What are they?
Converted by colonic bacteria
What is the function of bile salts?
Reduce fat’s surface tension
Envelop fat in a micelle
- amphiphilic, so carries it in the hydrophobic core
What are the problems of high bile salts?
Cytotoxic
- detergent-like actions
How is bile flow and secretion regulated? Where and how does it drain?
Bile drains out of right liver from right hepatic duct
Also stored in gall bladder
- drains through cystic duct
Both vessels join above pancreas to form common bile duct, which then enters the duodenum
Regulated by sphincter of Oddi
- closes Ampulli when no food
- when food, cholecystokinin relaxes sphincter, squeezes gall bladder to pump bile. more prevalent if fatty diet
What is enterohepatic circulation? What are the uses ?
Where liver cells transfer substances from plasma to bile
They are then reabsorbed by liver cells
Drugs can utilise this
Bile salts can too
- 95pc of bile salts are reabsorbed in the gut and return to liver via HPV
Where is bile reabsorbed?
Terminal ileum
What is terminal ileum disease?
Terminal ileum disease
- means that bile isnt reabsorbed
- bile salts continue to enter colon
- cause irritation and diarrhoea
What might occur if there is a lack of bile in the gut?
Steatorrhea
Deficiency of Vit ADEK
Give 3 functions of the gall bladder?
Stores
Acidifies
Concentrates bile
Why might the gall bladder concentrate bile?
Store more - it is small but this means that more salts can be retained per unit^3
What are the effects of a cholecystectomy?
Nothing major, healthy
- bile is still made from liver
- no store so constant drip
- however, fatty foods may lead to diarrhoea
What is bilirubin? How is it formed?
Water insoluble, yellow pigment
Hb breakdown
Haem protein catabolism
Ineffective bone marrow erythropoeisis
Where is bilirubin made and how does it get to the liver? Describe uptake
Made in the spleen and bound to albumin to be transported in circulation to travel to liver.
Once in the liver, it disassociates and then enters the hepatocytes.
Binds to cytoplasmic proteins and forms glucoronic acid by UDPGT
Now it is more soluble, and then transported into bile canaliculi
How is BR metabolised and excreted? Why are faeces brown?
Formation of urobilinogen by bacterial action in the intestine
Urobilinogen passes into the stool as stercobilinogen
Oxidation of stercobilinogen to stercobilin
Why does jaundice occur?
Increased plasma bile salts due to incomplete bile removal
What is cholestasis?
Cessation of bile flow, likely cause of jaundice
What causes jaundice? What are the group?
Pre-hepatic
Hepatic
Post-hepatic
Why does pre-hepatic jaundice occur?
Increased BR production
- Increased haemolysis
- Massive transfusion
- Haematoma resorption - lot of dead RBCs
- Ineffective erythropoiesis
Means that too much BR for the liver to deal with
Why does hepatic jaundice occur? Give specific examples
Defective uptake, normal production
- Occurs due to disease of hepatocytes
- less conjugation and hence less BR excretion
- Liver failure
- chronic
- acute
- viral hepatitis
- autoimmune disease
If a patient has pre-hepatic jaundice, will they have high or low conjugated BR levels? Is this the same for hepatic jaundice?
Low, high free BR
Yes
How can pre-hepatic and hepatic jaundice be differentiated?
Liver function
- liver enzymes high as cell death leads to enzyme release
Why does post - hepatic jaundice occur? Give specific examples
Defective transport of BR via biliary duct system
- physical obstruction which reduces bile flow into duodenum
- hence lower bile can flow, amount of plasma BR increases
Obstructions
- gall stones
- cancer - tumour of pancreas head
If a patient has post-hepatic jaundice, will they have high or low conjugated BR levels? What differentiates it from the others?
High
Less enters gut
Hence, less stercobilin in gut
- faeces are less brown
- dark urine by BR excretion
What is Gilbert’s syndrome?
Hereditary cause of increased BR, is AR
- benign
Caused by reduction in action of UDPGT - can’t conjugate BR
Hence, mild jaundice may appear in times of fasting, stress and infection
What is liver failure? Why?
Amount of liver cells being destroyed is much larger than those being made
Ischaemia
Necrosis
Apoptosis
