Liver failure and jaundince

Question 1

Where is bile made and why?

Answer 1

Bile in made in the liver and passes to 2nd part of duodenum, through papilla. Helps for intake of dietery lipids/Vitamins, removal of xenobiotics, cholesterol homeostasis

Question 2

How much bile is made?

Answer 2

500ml/day-made mostly by hepatocytes (60%)m and 40% by cholangiocytes (biliary epithelium)
Green yellow colour

Question 3

What happens to bile as it goes down the duct?

Answer 3

Altering of pH, fluidity. H20 drawn into it, glucose out, Ig8

Question 4

What transporters excrete bile?

Answer 4

BSEP MDR1,2,3 pump bile acids in and out of hepatocytes, and add stuff to it. It usually depends on bile salt concentrations in the cell and bile
BSEP: Active transport of bile
MDR1: Xenobiotics, MDR3: translocate phospholipids

Question 5

What are bile acids?

Answer 5

Na and K salts of bile acids. Made from cholesterol remenants
4 acids in humans-Cholic acid and chenodeoxychloic acid made by liver (primary acid), but modified by gut biome to deoxycholic acid and lochitic acid (secondary acid)

Question 6

What is the function of bile salts?

Answer 6

Bile salts reduce the surface tension of fats and emulsify (because amphipathic-one side is hydrophilic and one is hydrophobic-surrounds fat)
But potentially cytotoxic

Question 7

Through what structures does bile duct flow?

Answer 7

Right and left hepatic duct goes to common bile duct. Gall bladder also fits in, common hepatic ducts, Then fuse with pancreatic duct then to 2nd duodenum through papilla-sphincter of oddi

Question 8

Where is bile stored when you are not eating?

Answer 8

Bile is constantly produced, but the sphincter of oddi is closed-so bile is stored in the gall bladder

Question 9

What happens when you eat?

Answer 9

Cholecystokinin hormone released as eat releases the sphincter of oddi allowing bile in and makes the gall bladder contract to squeeze the bile out
Mosly released with FA

Question 10

What is enterohepatic circulation?

Answer 10

Phenomenon where some things from the liver enter bile, then to intestine, where it is absorbed again and goes back to liver-a cycle
Some drugs can do that for a long time. But Bile salts are also a big part

Question 11

What happens to bile salts in enteroheptic circulation? Why does that matter clinically?

Answer 11

A lot of bile salts are re-taken up in the terminal illieum. secondary salts (litohaff is 99% excreted) If you have terminal ilium problems, then not absorbed, become cytotoxic and causes problems
Also as bile isn’t absorbed with vitamins, lack of Vit A,D, E, K

Question 12

What are the functions of the gall bladder?

Answer 12

Stored biles (50ml)-acidifies and CONCENTRATES bile-therefore it stores quite a lot
near 20 10x more concentrated (more solids (10%), higher bile salts and lower pH

Question 13

What is cholescystectomy? And what are the concequences?

Answer 13

Surgical removal of gall bladder. But gall bladder only AIDS in digestion-non essential. Normal health can exits, but need to avoid food with high fat content

Question 14

What is bilirubin?

Answer 14

BR-H20 insoluble yellow pigment. Comes from (75%) of haemoglobin breakdown, and other haem proteins. Made in spleen

Question 15

Describe the metabolism of bilirubin

Answer 15

Made in spleen, but binds albumin (liver made) in blood and goes to liver. There it dissociates and enters hepatocytes
Free BR enters, and it gets conjugated to glucuronic acid (using UDPGT enzymes)-makes diglucoronid BR (conjugated BR)-makes it water soluble
Total BR=conjugated+unconjugated
In gut bacteria can make it to urobilinogens

Question 16

What happens to bilirubin during digestion?

Answer 16

In the colon gets acted on by bacteria-made to stercobilinogen-then oxidise stercobilin which is brown-why faeces are

Question 17

What is jaundice?

Answer 17

Just a symptom of high bilirubin in the system-1st thing to go yellow is white of eyes
>34/50 uM/L. Normal is around 25uM/L
Choleostasis-slow/cessation of bile salts
and jaundice can be caused by more than just choleostasis

Question 18

What are the 3 groups of liver related jaundice?

Answer 18

Pre-hepatic, hepatic and post hepatic

Question 19

What is pre-hepatic jaundice?

Answer 19

Problem in bilirubin before arrives to liver-increases production of bilirubin
can be caused by heamolysis (RBC destroyed too fast (drugs, spepsis)), Massive transfusion, reabsorption of heamoatoma, ineffecrive erythropoiesis
Production of bilirubin is too high for the down stream mechanisms to keep up
High UNCONJUGATED BR-can help find with blood test

Question 20

What is hepatic jaundice?

Answer 20

Hepatocellular-Hepatocytes not working. Nomal amout of BR made, but liver disease damaging hepatocytes (not working/dieing)-less conjugation and less BR excretion
can be caused by acute liver failure (paracetamol overdose), chonic liver failure (chronic liver disease-Hep B,C, alcohol, AID) Intraheptaic cholestasis (Sepsis, TPN, drugs)
MOSTLY UNCONJUGATED (that’s why it doesn’t go in bile)-differ from pre-hepatic jaundice because pre-hepatic has normal liver-test liver proteins

Question 21

What is post-hepatic jaundice?

Answer 21

Also called obstructive. BR is produced fine. But obstruction in the bile duct/hepatic duct-bile entering gut is lowered, therefore less BR made in, and more free
Can be causes by Stones, gall bladder cancer, head of pancreas cancer
MOSTLY CONJUGATED BR
Therefore less stercobiligun and stercobilinogen goes down-faeces lose colour
Some gets rid by kidney then-dark pee

Question 22

What is gilberts syndrome?

Answer 22

Commonest cause (up to 5%)-elevated Unconjugated BR in blood
AR-causes reduction of UPDGT (conjugated BR) activity
No serious consequences, mild jaundice may appear, under exerction, stress and more

Question 23

What is liver failure?

Answer 23

Amount of destroyed liver cells overtakes the regeneration potential
Liver has incredible regeneration potential (50% in 6 months)
Often apoptosis-can be caused by paracetamol
Necrossis (ischemia)
Very dangerous