jaundice and liver failure Flashcards
why do we produce bile?
- Cholesterol homeostasis. - Dietary lipid/vitamin absorption - Removal of xenobiotics/drugs/endogenous waste product.
what is bile composed of?
- Bile is 97% water and exists in an alkaline solution. - 500ml produced
what cells secrete bile?
60% by hepatocytes 40% by Cholangiocytes in the biliary tree
what are the roles of the bilary tree?
- Alter pH, fluidity and modifies bile. - Facilitates passage of H2O into the bile via osmosis - Reabsorbs glucose and some organic acids - Secretes HCO3 -and Cl into the bile through CFTR. - contribute IgA antibodies
how is bile transported?
- Apical transporters secrete the bile salts and toxins which also govern flow rate of bile
what happens if the transporters stop?
cholestasis
what are examples of the transporters?
BSEP – Bile Salt Excretory Pump ( active transport of the bile acids into the bile ) - MRP1 MDR related proteins
how many bile acids do we have what are they separated into?
- 4 bile salts 2 primary and 2 secondary - primary is converted into secondary Cholic Acid → Deoxycholic Acid Chenodeoxycholic Acid → Lithocholic Acid
whata re 2 main functions of the bile?
- Reduce surface tension of fats. - Emulsify fats
how do bile salts work?
- they form micelles - due to they hydrophilic and hydrophobic nature
issue with bile salts?
- they can be toxic in high concentrations
** look at the anatomy of the gall bladder and biliary tree :
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what happens at the ampulla of the bile duct?
the sphincter of Oddi controls bile secretion into the 2nd duodenum.
what duct does the cystic duct join?
pancreatic duct before entering the duodenal papilla
what happens when you eat? what hormone is secreted?
Cholecystokinin
what are the functions of Cholecystokinin ?
- Relax the sphincter of Oddi. -Contract the smooth muscle around gall bladder.
what is entrohepatic circulation?
- where the liver cells transfer various substances including drugs from to the plasma to the bile
how does entrohepatic circulation affect drugs?
Can re-activate/prolong drug action - can affect drug dosage
what happens when bile cells undergo entrohepatic circulation?
- 95% of bile salts reabsorbed in the terminal ileum - 5% are converted to secondary bile acids in the colon by colon bacteria - 3g of bile salts at any one time, secreted 2x a meal.
what happens if someone does not have a terminal ileum?
– less resorption = more fatty stool as less bile salt excreted - malabsorption of fat soluble vitamins can cause irritable bowel
what are functions of the gall bladder?
- storage - acidification - concentrates bile bu H2O diffusion
what are the effects of a Cholecystectomy ? ( gall bladder removal )
- Gall Bladder aids digestion but is NOT essential. - they might get bowel problems -so they have to avoid very fatty foods
what is bilirubin?
H2O insoluble, yellow pigment.
what is bilirubin produced from?
- 75% - Hb breakdown – in the spleen - 22% - Catabolism of other haem proteins. - 3% - Ineffective bone marrow erythropoiesis.
how is bilirubin metabolised and excreted?
- BR is bound to albumin - most of it dissociates in the liver - free BR enters the hepatocyte and binds to cytoplasmic proteins - in the hepatocyte it joins to glucoronic acid - Glucuronyl transferase catalyses production of bilirubin diglucuronide
**show a diagram of this process?
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what is total bilirubin?
free BR + conjugated BR
what are Urobilinogens?
H2O-soluble, colourless derivatives of BR formed by gut bacterial action
what happens to the bilirubin in the colon?
- 50% of urobilinogen is passed in the stool as Stercobilinogen. - Faeces are brown as Stercobilinogen is oxidised to stercobilin
what forms urobilinogens?
some unconjugated BR enters enterohepatic circulation and some forms urobilinogens
what happens to the other 50% of urobilinogen?
Half of urobilinogen (UBR) formed is reabsorbed -20% of the 50% reabsorbed into the general circulation is excreted in urine.
what is Cholestasis ?
cessation of bile flow - Can result in jaundice but isn’t a pre-requisite
what is jaundice?
excess BR in the blood - yellow tinge to the skin, whites of eyes and mucous membranes
what are the causes of jaundice?
pre hepatic and hepatic
explain pre hepatic ? what is this characterised by? what investigations are carried out?
Increased quantity of unconjugated BR, due to: - dying of blood cells (haemolysis) - massive transfusion - haematoma - Ineffective erythropoiesis. - Hb drop without overt bleeding - Blood film
what is the hepatic cause of liver?
- when the hepatocytes are not working - due to : - defective uptake - defective conjugation - Defective BR excretion.
what might cause hepatic cause of liver?
- liver failure paracetamol OD - Intrahepatic cholestasis from sepsis,
explain post hepatic jaundice? common causes? what happens to stercobilin?
- defective transport of BR - due to common bile duct stones -gall bladder cancer - Stool pale as there is less stercobilin the urine is dark as the BR is sent to the kidneys
what is a hereditary cause of jaundice?
– GILBERT’S SYNDROME - (autosomal recessive) - 5% of population - raise of UNCONJUGATED bilirubin in the blood stream. - due to 70% - 80% reduction in enzyme activity (Glucuronyl transferase ) which causes the conjugation of BR
define acute liver failure?
- the rate of hepatocyte death > regeneration rate can be two types - apoptotic (NO inflammation) - necrotic INFLAMMATION
how can we subdivide liver failure?
- Fulminant/Acute Hepatic Failure rapid - Sub-fulminant less rapid
what is the cause of liver failure in the far east?
viral hepatitis
**what are the differences between normal liver function and liver failure?
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what are some of the causes of death due to liver failure?
Bacterial/fungal infection
. o Circulatory instability.
o Cerebral oedema.
o Renal and/or respiratory failure.
o Coagulopathy.
what is the only way of treating liver failure?
- Liver transplant the ONLY therapeutic intervention of PROVEN benefit.
