Physiology and Pharmacology of the Liver

Question 1

Describe the blood supply to the liver

Answer 1

Dual supply in and single supply out

Question 2

What are all hepatocytes in contact with?

Answer 2

Blood from both the hepatic portal vein and the hepatic artery

Question 3

Where does arterial and venous blood mix

Answer 3

In the liver sinusoids

Question 4

What shape is a cross section of each lobule

Answer 4

Hexagonal

Question 5

What is found in the centre of each lobule

Answer 5

a branch of the hepatic vein (central vein)

Question 6

What is found in each of the 6 corners of each lobule

Answer 6

A triad (portal triad)

Question 7

What is in each portal triad

Answer 7

A branch of the hepatic portal vein
A branch of the hepatic artery and
A bile duct

Question 8

What is arranged as hepatic plates?

Answer 8

Cords of hepatocytes

Question 9

Blood flows inwardly through what to the central vein

Answer 9

Sinusoids

Question 10

Bile secreted by hepatocytes flows outwardly through what to the bile duct

Answer 10

Canaliculi

Question 11

What are hepatocytes arranged in between

Answer 11

Sinusoids in plates two cells thick

Question 12

What does the basolateral membrane face

Answer 12

The space of Disse

Question 13

What is the space of Disse

Answer 13

An extracellular gap between the pericellular space and the endothelial cells that line the fenestrated sinusoids

Question 14

What forms the canaliculi

Answer 14

The apical membrane of adjacent hepatocytes

Question 15

Sinusoidla spaces contain which 3 types of cells

Answer 15

Endothelial cells
Kuppfer cells
Stellate (lto) cells

Question 16

What do endothelial cells allow the movement of?

Answer 16

Solutes but not cells

Question 17

What type of cells remove particulate matter (bacteria)

Answer 17

Kuppfer cellls

Question 18

Where do the Stellate cells lie and what is their role?

Answer 18

Within the space of Disse

Important for the storage of vitamin A and may play a role in fibrosis and cirrhosis in liver injury

Question 19

Describe the sequence of the intraheaptic bile system

Answer 19

Canaliculi 
Terminal bile ductules
Perilobar ducts
Interlobar ducts
Septal ducts
Lobar ducts
2 hepatic ducts
The common hepatic duct

Question 20

How much bile is produced per day

Answer 20

0.6-1.2 litres per day

Question 21

Where is bile between meals

Answer 21

Stored and concentrated in the gall bladder - the sphincter of Oddi is closed

Question 22

What happens to bile during a meal

Answer 22

Chyme in the duodenum stimulates gall bladder smooth muscle to contract and bile spurts into the duodenum via the cystic and common bile ducts

Question 23

What is the role of bile

Answer 23

It participates in the digestion and absorption of fats

Question 24

During meals, what is the ionic composition of bile similar to

Answer 24

Plasma

Question 25

Why does the flow rate of bile increase during meals

Answer 25

In response to secretin released from duodenal S cells

Question 26

What does the slightly alkaline pH of bile contribute to?

Answer 26

Micelle formation Neutralization of chyme pH adjustment for digestive enzyme action Protection of the mucosa

Question 27

What do hepatocytes secrete and where?

Answer 27

Primary juice in the canaliculi which drain in the the biliary ductules

Question 28

What is hepatic bile composed of

Answer 28

``` Primary bile acids mainly cholic and chenodeoxycholic acids Water and electrolytes Lipids and phospholipids Cholesterol IgA Bilirubin ```

Question 29

What is bilirubin a product of

Answer 29

The porphyrin component of haemoglobin

Question 30

Is the total amount of bile salts in the body smaller or larger than the total amount of bile salts emptied into the duodenum during digestive activity

Answer 30

Much smaller

Question 31

Where are most bile salts reabsorbed and how?

Answer 31

In the terminal ileum and by active transport

Question 32

What do bile salts undergo?

Answer 32

Enterohepatic recycling

Question 33

What prevent reabsorption and lower plasma cholesterol?

Answer 33

Resins that bind bile salts eg colestyramine and colestipol

Question 34

How much bile salt is lost in the faeces

Answer 34

about 5%

Question 35

How is bile salt synthesised?

Answer 35

From cholesterol in a series of 14 reactions

Question 36

What first mediates the synthesis of bile salts

Answer 36

Cholesterol 7 alpha hydroxylase

Question 37

The rate of bile salt synthesis is dependent upon what?

Answer 37

The hepatic portal blood concentration of the salts - low concentration - stimulation and high concentration inhibits synthesis

Question 38

Secretion across the apical membrane is by what mechanism?

Answer 38

Active transport

Question 39

What causes gall bladder contraction and relaxation of the sphincter of Oddi

Answer 39

Cholecystokinin

Question 40

What does secretin cause?

Answer 40

Aqueous alkaline bile secretion

Question 41

What is the role of vagal activity

Answer 41

This produces a mild secretory response in the cephalic phase of digestion

Question 42

What is the most common pathology of the biliary tract

Answer 42

Cholelithiasis (formation of gallstones)

Question 43

What are the options for gall stones

Answer 43

Surgery or the use of ursodeoxycholic acid

Question 44

What is the most common analgesic used for biliary pain

Answer 44

Morphine

Question 45

What is the side effect of using morphine n terms of GI

Answer 45

It constricts the sphincter of Oddi

Question 46

What drugs can be used for the relief of biliary spasm

Answer 46

Atropine or GTN

Question 47

What alternative analgesics can be used for biliary pain

Answer 47

Buprenorphine | Pethidine

Question 48

What is the main organ of drug metabolism

Answer 48

Liver | GI tract, lungs and plasma also have an activity

Question 49

Drug metabolism acts to convert parent drugs to what?

Answer 49

More polar metabolites that are not readily reabsorbed by the kidney

Question 50

How does drug metabolism often proceed

Answer 50

In 2 sequential phases

Question 51

What happens in phase 1 of drug metabolism

Answer 51

The liver makes the drug more polar and adds a chemically reactive group to permit the conjugation

Question 52

What happens in phase 2 of drug metabolism

Answer 52

The liver adds an endogenous compound increasing polarity

Question 53

What is an example of a drug which undergoes the two phases of drug metabolism

Answer 53

Aspirin

Question 54

What are the 2 phases of metabolism of aspriin

Answer 54

Catabolic - drug in converted to the derivative | Anabolic - The derivative is converted to the conjugate

Question 55

What mediates the oxidation reactions of many lipid soluble drugs in the liber

Answer 55

Haem proteins

Question 56

What are some of hte main gene families in the human liver?

Answer 56

CYP1, CYP2 and CYP3

Question 57

What does the drug enter the monooxygenase P450 cycle as

Answer 57

As a drug substrate, RH

Question 58

What is essential for this cycle

Answer 58

Molecular Oxygen to provide 2 Oxygen atoms

Question 59

What happens to the oxygen atoms

Answer 59

One is added to the drug to yield the hydroxyl product ROH which leaves the cycle The other combine with protons to form water

Question 60

What do phase 2 reactions usually result in

Answer 60

Inactive products

Question 61

Where do phase 2 reactions usually ocur

Answer 61

Liver

Question 62

What does phase 2 reactions involve

Answer 62

The conjugation of chemically reactive groups

Question 63

What is a common reaction involving the transfer of glucuronic acid to electron rich atoms of the substrate

Answer 63

Glucuronidation

Question 64

Name 2 substances which are subject to glucuronidation

Answer 64

Bilirubin and adrenal corticosteroids