Intro to liver Flashcards
What are major aspects of liver structure which influence function?
vascular system
biliary tree
3D arrangement of liver cells with vascular or biliary systems
Describe the blood supply to liver?
~75% of blood supply from portal vein i.e. blood returning from GI tract
~25% from hepatic artery
What are 2 primary cells of liver?
Hepatocytes(60%) - perform most metabolic functions Kupffer cells (30%)- type of tissue macrophage
What is functional unit of liver?
Hepatic lobule
Describe the structure of functional unit of liver?
Hexagonal plates of hepatocytes around central hepatic vein -> at each of 6 corners is triad of branches of portal vein, hepatic artery and bile duct
Describe the biliary system?
Bile secreted by hepatocytes -> series of channels between cells (canalinculi) -> small ducts -> large ducts -> anastomose onto common bile duct
How does liver’s microstructure support its roles?
Massive SA for exchange of molecules
sophisticated seperation of blood from bile
specific positioning of pumps to achieve specific localisation of materials
What are kupffer cells?
phagocytic macrophages
What is function of kupffer cells?
protective barrier
removes senescent cells and gut bacteria/antigens
Where do Kupffer reside?
reside in sinusoid
What is bile?
complex fluid= water, electrolytes + mix of organic molecules e.g. bile acids, cholesterol, bilirubin and phospholipids
What is function of bile?
essential for fat digestion + absorption via emulsification
elimination of waste products from blood in particular bilirubin + cholesterol
How is bile concentrated and stored?
Bile from hepatic ducts -> common bile ducts -> duodenum or diverted via cystic duct -> gall bladder -> concentrated + stored
What is bilirubin?
Yellow pigment formed from breakdown of haemoglobin
useless + toxic but made in large quantities -> must be eliminated
What happens to aged red blood cells?
remain in circulation for about 120 days
end of lifespan,dead/damaged RBC digested by macrophages throughout body primarily in spleen but also in liver of red bone marrow
Fe is recycled -> Fe goes into iron stores + can be recycled to be made into new RBCs + other aspects
Globin chains are protein ->catabolised down into various aas + can be reused
Haem(porphyrin) -> elimiated by broken down into biliverdin converted into biliruibin ->then taken into liver incorporated into bile -> then removed
How is biliruin formed?
Haem is converted into free bilirubin in series of steps:
released into plasma -> carried around bound to albumin
free bilirubin absorbed by hepatocytes -> conjugated with glucoronic acid
conjugated bilirubin secreted into bile -> metabolised by bacteria intestinal lumen + eliminated into faeces/urine
What is major metabolite in faeces?
Stercobilin -> brown colour
In urine, conjugated bilirubin is further metabolised to form what?
yellow urobilin + urobilinogen
What is cause of jaundice?
excessive quantities of either free or conjugated bilirubin accumulate in extracellular fluid (ECF)
-> yellow discoloration of skin, sclera (white part of eye) + mucous membranes is observed
What are 3 types of jaundice?
pre-hepatic (haemolytic) jaundice
Hepatic jaundice
Post-hepatic (obstructive) jaundice
What is pre-hepatic jaundice?
give example
excessive breakdown RBC e.g. neonatal jaundice
What is hepatic jaundice?
give example
hepatocyte damage
e.g. cirrhosis drugs, hepatitis A,B,C,E , Gilberts syndrome (congenital disorder where there is decrease in conjugating enzyme)
excess conjugated and/or unconjugated bilirubin
What is post-hepatic jaundice?
give example
excess conjugated bilirubin
obstruction to passage into duodenum
enters circulation + into urine (very dark), pruritus (itching)
e.g. gallstones, carcinoma of pancreas/ bile ducts
Liver is vital in metabolism + excretion of various substances that can be toxic to body. Give examples of these substances
bilirubin
ammonia
hormones e.g. all steroid hormones inactivated by conjugation + excretion
drugs + exogenous toxins e.g. aspirin, paracetamol, ethanol
Liver metabolises drugs + hormones in 2 phases. What are 2 phases? What happens in these phases?
Phase 1 (primarily oxidation/reduction) - occurs in smooth ER , catalysed primarily by family of cytochrome P450 enzymes. Makes substrate into polar compound Phase 2 (conjugation) to make it more water soluble
What are 3 pathways in which paracetamol is metabolised?
Glucoronidation -> Phase 2 reaction. Glucuronoyl is conjugated onto paracetamol to then inactivate allowing it to be eliminated
Sulfation -> addition of sulfate molecule to paracetamol + then eliminating it
N hydroxylation + dehydration -> intermediate product NAPQI is toxic -> detoxified by glutathione (GSH) conjugation -> Phase 1 reaction followed by phase 2 reaction
Describe ethanol metabolism?
Ethanol enters liver where it’s metabolised into acetaldehyde by alcohol dehydrogenase (only present in liver). Product of this metabolism is lot of NADH -> removed by liver via hunting it into different metabolic processes already occurring in liver
Acetylaldehyde -> acetate
this conversion is done via acetaldehyde dehydrogenase
What does liver store?
Hepatocytes are important depots for storage of fat soluble vitamins D,K,E,A
store Vit B12 + enough stored to last 2-3 years
Stores folate
Iron is stored as ferritin which can be released when needed (Blood-Fe buffer)
