Physiology of the Liver Flashcards
1
Q
Describe blood supply to the liver.
A
- Around 250-500 ml/min of oxygenated, nutrient-poor blood flows via hepatic artery
- Majority is oxygen-poor and nutrient-rich via hepatic portal vein (1000-1300 ml/min)
- Hepatic portal system - low pressure system (around 9 mmHg)
- Venous system pools and drains into hepatic vein and eventually IVC - pressure in hepatic vein is 0 mmHg
2
Q
Why does the liver act as a blood reservoir?
A
Liver is expandable
- Normal volume around 450 ml (around 10% of total blood volume)
3
Q
What can cause build up of blood in the liver?
A
- Anything causing pressure to rise in right atrium of heart
4
Q
Describe the liver lobules.
A
- Hexagonal functional units of liver
- Central vein at centre of lobule
- At each corner of lobule is portal triad - branch of hepatic portal vein, hepatic artery and bile duct
- Blood exits portal vein and hepatic artery into sinusoid and drains into central vein
5
Q
Describe the sinusoids.
A
- Fenestrations found in the linings - some around 1um in diameter - large enough for proteins to pass through
- Some substances pass into hepatocytes lining sinusoid
6
Q
Describe the relationship between the hepatic vein and the central vein.
A
- Hepatocytes produce substances e.g albumin - pass into sinusoid and into central vein
- Each central vein coalesces to form hepatic vein
7
Q
Describe the role of the hepatocytes.
A
- Metabolise substances from sinusoids and secrete products/synthesise substances and secrete back into sinusoid - drains back into central vein
- Bile synthesis - secrete into biliary caniculi - drain in opposite direction
8
Q
Describe stellate cells
A
- Found in space underneath endothelial cells
- Functions as store for vitamin A
- May act as APCs
9
Q
How do stellate cells change during liver diseases?
A
- Loss of lipid droplets
- More prominent RER and Golgi apparatus
- Migrate out of space of Disse and increase metalloprotease production - remodel ECM and increase fibrosis
10
Q
Describe detoxification
A
- PHASE 1 - Involves enzymes involved in oxidation, reduction and hydrolysis e.g cytochrome P450 enzymes and dehydrogenases.
- Most metabolites from Phase 1 are highly active
- PHASE 2 - Conjugation to other molecules - become more water soluble - cannot cross membranes. More easily excreted
11
Q
Define xenobiotics
A
Any substance foreign to the body
12
Q
Describe paracetamol detoxification.
A
- Doesn’t undergo Phase 1 Metabolism
- 45-55% metabolised by glucuronosyltransferase
- 20-30% by sulfotransferase
- Less than 15% - hydrolysis by cytochrome P450 - produces hepatotoxic product NAPQI - conjugated by gultathione S-transferase
13
Q
Why do paracetamol overdoses cause liver damage?
A
- NAPQI concentrations saturate glutathione S-transferase
14
Q
Describe protein metabolism.
A
- Deamination - catalysed by deaminases. Requires addition of water. Formation of ammonia.
- Ammonia enters urea cycle and converts to urea for excretion, or transamination where amine group produces non-essential amino acids
- Remaining product - gluconeogenesis
15
Q
Describe plasma protein production and a factor that affects them.
A
- 90% of production occurs in hepatocytes e.g clotting factors, carrier proteins, hormones
- LIVER DISEASE e.g cirrhosis
16
Q
Describe red blood cell breakdown.
A
- Done by macrophages called Kupffer cells - broken down into globin and haem groups
- Globin broken down by peptidases into amino acids
- Haem groups broken down into iron - transferred to bone marrow via transferring to make new RBCs
- Rest broken down into biliverdin, then unconjugated bilirubin and then conjugated
17
Q
Describe conjugated bilirubin.
A
- Excreted into bile ducts and through intestines
- If built up, results in jaundice and results from increased RBC breakdown, bile duct blockage and liver cell damage
18
Q
Describe glucose metabolism. PART 1
A
- In liver, enters through GLUT2 channel (not insulin dependent)
- Insulin potentiates inward flow of glucose - activates hepatic glucokinase - glucose phosphorylated to G6P
- Enters glycolysis to produce ATP
19
Q
Describe glucose metabolism. PART 2
A
- Insulin activates glycogen synthase - stimulates glycogenesis, and stimulates glycerol and fatty acid production - triglyceride formation
- Glucagon binds to glucagon receptor (GPCR) - activates intracellular glycogen phosphorylase - glycogen broken down into G1P and then G6P
20
Q
Describe glucose metabolism. PART 3
A
- Glucagon prevents FFAs becoming triglycerides and direct them to beta-oxidation - enter mitochondria and form ketone bodies
- Ketone bodies only used as energy in muscle, brain and heart
21
Q
Describe bile formation. PART 1
A
- Bile acids made from conversion of cholesterol to cholic and chenodeoxycholic acid (primary bile acids)
- These travel down biliary tree. Half stored in gall bladder - remainder enters small intestine and travels to ileum
- In ileum - bacteria breaks these down into deoxycholic and lithocholic acid (secondary bile acids)
22
Q
Describe bile formation. PART 2
A
- In liver, secondary bile acids conjugated with glycine or taurine to produce bile salts - aids in digestion of lipids
- Bile salts stored in gallbladder and released in response to fatty meal or enter small intestine
- In small intestine, bacteria can remove glycine and taurine - turned back into secondary bile acids for reabsorption
-
23
Q
Describe the fate of the bile acids.
A
- 5% lost in faeces
- Majority reabsorbed in hepatic portal vein - secretion and reabsorption circuit known as enterohepatic circulation
24
Q
Describe liver regeneration
A
- Removal of around 70% of liver results in regeneration to original size
- Considered in liver transplants
