1. By Jonathan Tsun & Ilona Blee
Liver Physiology
By Jonathan Tsun & Ilona Blee

2. List the SEVEN main functions of the liver.
Metabolism – carbohydrates, proteins & lipids
Excretion – bilirubin
Synthesis – albumin/plasma proteins, cholesterol, bile
Storage – glycogen
Detoxification – drugs
Destruction of RBC’s and bacteria
Immune function - ?Which cells
Kupffer cells!
Think: MESSDDI
Kupffer cells are like the macrophages of the liver

3. The liver is made up of hepatocytes which are arranged into lobules; how are lobules functionally classified?
Zone 1 periportal hepatocytes are the most oxygenated; carry out oxidative metabolism, gluconeogenesis & urea synthesis
Zone 2 = middle
Zone 3 pericentral hepatocytes are the least oxygenated; carry out drug metabolism, glycolysis & lipogenesis
Could think of this like a Bull's-eye where number three is in the middle so it’s the highest number

4. What is the blood supply to the liver?
70% Hepatic portal vein
30% Hepatic artery
What vasculature does the hepatic artery originate from?
Coeliac trunk – can work backwards logically to remember this  the liver is a foregut structure therefore is likely to have a foregut blood supply
What is the venous drainage of the liver?
Hepatic veins
Where do the hepatic veins drain into?
Inferior vena cava
You cannot just say “Portal vein”, as there are other portal veins in the body!
Picture from sketchy medicine

5. What are the FOUR major cell types in the liver?
Hepatocytes
Endothelial cells which line the sinusoid walls
Kupffer cells (modified macrophages)
Lipocytes (or stellate cells) for fat storage
Where is bile produced and stored? How much is produced per day?
Bile is produced in the liver
Bile is stored and concentrated in the gall bladder
litres is produced per day
We’ve only put the how much bile is produced per day question in because in previous formatives they have asked how much gastric juice is produced per day, so they could ask this about bile
But it shouldn’t be top of your revision list
Make sure you go over old formatives because quite often the questions are copied and pasted

6. HORMONES
*SAQ exam style question: Which hormones control the pancreas and biliary tree and what are their physiological effects?
Secretin
Bile production in the liver
Bicarbonate secretion from the pancreas
Cholecystokinin
Gall bladder contraction to release bile
Enzyme secretion from the pancreas
Where are these hormones secreted?
Small intestine (duodenum)
Secretin is released from S cells in the duodenum
Cholecystokinin is synthesized in the mucosal epithelium of the small intestine and secreted in the duodenum
Basically they’re both secreted in the duodenum

7. LIVER FUNCTION TESTS  what FOUR enzymes are included in this?
Aspartate transaminase (AST)
Alanine transaminase (ALT)
*Alkaline phsophatase
Gamma-glutamyl transferase (GGT)
 Transaminases are released by hepatocytes
 Alkaline phosphatase is found on the luminal surface of bile duct cells
TRUE or FALSE: LFT’s measure liver function.
FALSE!
So what does LFT really measure?
It indicates hepatocyte/biliary damage
The transaminases are also called transferases; I like to think of them as transaminases because it keeps them separated from gamma glutamyl transferase
But if just knowing transferase helps you remember them all then that’s fine, just know whatever is written in your lecture
Picture from sketchy medicine

8. TRUE test of liver function – what parameters are measured and why?
Albumin levels
Liver’s ability to synthesise proteins (e.g. albumin)
Prothrombin time (clotting screen)
Liver’s ability to synthesise clotting factors
Urea levels
Liver’s ability to convert ammonia into urea
Bilirubin levels
Liver’s ability to conjugate bilirubin
 Remember this using “A PUB”
Liver function is probably not so good after being at the pub ..

9. What are the SIX components of bile?
Bile salts
Lecithin  phospholipid
HCO3- (Bicarbonate)
Cholesterol
Bile pigments
Trace metals
What are bile acids derived from?
Describe how bile acids are recycled (location/route)
Reabsorbed in the terminal ileum
Go via the enterohepatic circulation
Back to the liver, to be used again or re-conjugated
Some
Little
Hepatocytes
Can’t
Produce
Trace metals

10. What are the FOUR functions of bile salts?
Emulsification of lipids to be broken down by pancreatic lipases
Elimination of cholesterol
Prevents cholesterol precipitation in the gall bladder
Facilitates absorption of fat-soluble vitamins
Vitamins A, D, E & K
Name an example of a bile pigment
Bilirubin
How is bilirubin formed?
Formed from the breakdown of haem in the spleen and bone marrow

11. ON EXAMINATION: What are FIVE signs of chronic liver disease?
This is an example of a question you might be expected to say in an OSCE for an abdominal examination but they can easily ask you about OSCE things in written examinations!
Palmar erythema
Liver/metabolic flap
Leuconychia  think leukocytes/white cells = white nails
Yellowing of the skin or sclera (jaundice)
Dilated umbilical veins  caput medusae
Abdominal distension  ascites
Umbilical herniation
Be careful – if you want to mention a sign, make sure you have an understanding (even a brief one) of what is causing these signs – you may be asked.
For example:
Yellowing of the skin/sclera – hyperbilirubinaemia due to liver’s inability to metabolise bilirubin for excretion
Dilated umbilical veins – built up back-pressure due to hepatic portal vein hypertension  blood travels to the route of least resistance (which is reopening umbilical veins)
Ascites – combination of increased hydrostatic pressure (due to hepatic portal vein hypertension) and reduced oncotic pressure (due to liver’s failure to produce adequate proteins)  fluid escapes into the abdominal cavity

12. Drug metabolism  what are the THREE phases?
Phase I: addition of a functional group to a drug to activate it. This increases the polarity of the drug and makes it able to undergo phase II reactions
Phase II: addition of a large/bulky chemical group to inactivate the drug. This makes the drug more hydrophilic, which will mean it is easier to excrete
Phase III: transport either into circulation for renal elimination or into bile for excretion in feces
Define: Bioavailability
The proportion of a drug that enters the circulation unchanged and is available to go to its site of action.

13. List FIVE factors affecting drug metabolism.
Liver disease
Age
Drug interactions
Genetics
Environmental influences

14. Statins! Can you name an example of a statin? Simvastatin
Atorvastatin  lipitor
What is the mechanism of action of statins?
HMG CoA reductase inhibitors; this enzyme is basically the terminal step in the sequence of cholesterol metabolism so by stopping it you are lowering cholesterol
With cholesterol levels think: keep the lows “low” and the highs “high”  keep low density lipoproteins low and high density lipoproteins high

15. MCQ Which one of these is an example of a phase II metabolism reaction?
Oxidation
Reduction
Conjugation
Hydrolysis
Can you name a conjugation reaction?
Glucuronidation

16. Some drug interactions can inhibit drug metabolism, which one of these listed below is an example of this, a cytochrome P450 inhibitor?
St. John’s Wort
Carbamazepine
Grapefruit juice
Rifampicin
Ritonavir
If you have a patient who strictly must have grapefruit juice as part of her diet, what changes must you make to the doses of her medications?
You must reduce the doses of medications that are cytochrome P450-dependent
Reduced metabolism by cytochrome P450  reduced drug clearance  increased drug levels in body!

17. THANK-YOU!
Any questions?