Intro to liver

Question 1

What are major aspects of liver structure which influence function?

Answer 1

vascular system
biliary tree
3D arrangement of liver cells with vascular or biliary systems

Question 2

Describe the blood supply to liver?

Answer 2

~75% of blood supply from portal vein i.e. blood returning from GI tract
~25% from hepatic artery

Question 3

What are 2 primary cells of liver?

Answer 3

Hepatocytes(60%) - perform most metabolic functions
Kupffer cells (30%)- type of tissue macrophage

Question 4

What is functional unit of liver?

Answer 4

Hepatic lobule

Question 5

Describe the structure of functional unit of liver?

Answer 5

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

Question 6

Describe the biliary system?

Answer 6

Bile secreted by hepatocytes -> series of channels between cells (canalinculi) -> small ducts -> large ducts -> anastomose onto common bile duct

Question 7

How does liver’s microstructure support its roles?

Answer 7

Massive SA for exchange of molecules
sophisticated seperation of blood from bile
specific positioning of pumps to achieve specific localisation of materials

Question 8

What are kupffer cells?

Answer 8

phagocytic macrophages

Question 9

What is function of kupffer cells?

Answer 9

protective barrier

removes senescent cells and gut bacteria/antigens

Question 10

Where do Kupffer reside?

Answer 10

reside in sinusoid

Question 11

What is bile?

Answer 11

complex fluid= water, electrolytes + mix of organic molecules e.g. bile acids, cholesterol, bilirubin and phospholipids

Question 12

What is function of bile?

Answer 12

essential for fat digestion + absorption via emulsification

elimination of waste products from blood in particular bilirubin + cholesterol

Question 13

How is bile concentrated and stored?

Answer 13

Bile from hepatic ducts -> common bile ducts -> duodenum or diverted via cystic duct -> gall bladder -> concentrated + stored

Question 14

What is bilirubin?

Answer 14

Yellow pigment formed from breakdown of haemoglobin

useless + toxic but made in large quantities -> must be eliminated

Question 15

What happens to aged red blood cells?

Answer 15

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

Question 16

How is biliruin formed?

Answer 16

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

Question 17

What is major metabolite in faeces?

Answer 17

Stercobilin -> brown colour

Question 18

In urine, conjugated bilirubin is further metabolised to form what?

Answer 18

yellow urobilin + urobilinogen

Question 19

What is cause of jaundice?

Answer 19

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

Question 20

What are 3 types of jaundice?

Answer 20

pre-hepatic (haemolytic) jaundice
Hepatic jaundice
Post-hepatic (obstructive) jaundice

Question 21

What is pre-hepatic jaundice?

give example

Answer 21

excessive breakdown RBC e.g. neonatal jaundice

Question 22

What is hepatic jaundice?

give example

Answer 22

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

Question 23

What is post-hepatic jaundice?

give example

Answer 23

excess conjugated bilirubin
obstruction to passage into duodenum
enters circulation + into urine (very dark), pruritus (itching)
e.g. gallstones, carcinoma of pancreas/ bile ducts

Question 24

Liver is vital in metabolism + excretion of various substances that can be toxic to body. Give examples of these substances

Answer 24

bilirubin
ammonia
hormones e.g. all steroid hormones inactivated by conjugation + excretion
drugs + exogenous toxins e.g. aspirin, paracetamol, ethanol

Question 25

Liver metabolises drugs + hormones in 2 phases. What are 2 phases? What happens in these phases?

Answer 25

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

Question 26

What are 3 pathways in which paracetamol is metabolised?

Answer 26

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

Question 27

Describe ethanol metabolism?

Answer 27

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

Question 28

What does liver store?

Answer 28

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)