Physiology and Pharmacology of the Liver Flashcards Preview

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Flashcards in Physiology and Pharmacology of the Liver Deck (64):
1

Describe the blood supply to the liver

Dual supply in and single supply out

2

What are all hepatocytes in contact with?

Blood from both the hepatic portal vein and the hepatic artery

3

Where does arterial and venous blood mix

In the liver sinusoids

4

What shape is a cross section of each lobule

Hexagonal

5

What is found in the centre of each lobule

a branch of the hepatic vein (central vein)

6

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

A triad (portal triad)

7

What is in each portal triad

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

8

What is arranged as hepatic plates?

Cords of hepatocytes

9

Blood flows inwardly through what to the central vein

Sinusoids

10

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

Canaliculi

11

What are hepatocytes arranged in between

Sinusoids in plates two cells thick

12

What does the basolateral membrane face

The space of Disse

13

What is the space of Disse

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

14

What forms the canaliculi

The apical membrane of adjacent hepatocytes

15

Sinusoidla spaces contain which 3 types of cells

Endothelial cells
Kuppfer cells
Stellate (lto) cells

16

What do endothelial cells allow the movement of?

Solutes but not cells

17

What type of cells remove particulate matter (bacteria)

Kuppfer cellls

18

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

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

19

Describe the sequence of the intraheaptic bile system

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

20

How much bile is produced per day

0.6-1.2 litres per day

21

Where is bile between meals

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

22

What happens to bile during a meal

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

23

What is the role of bile

It participates in the digestion and absorption of fats

24

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

Plasma

25

Why does the flow rate of bile increase during meals

In response to secretin released from duodenal S cells

26

What does the slightly alkaline pH of bile contribute to?

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

27

What do hepatocytes secrete and where?

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

28

What is hepatic bile composed of

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

29

What is bilirubin a product of

The porphyrin component of haemoglobin

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

Much smaller

31

Where are most bile salts reabsorbed and how?

In the terminal ileum and by active transport

32

What do bile salts undergo?

Enterohepatic recycling

33

What prevent reabsorption and lower plasma cholesterol?

Resins that bind bile salts eg colestyramine and colestipol

34

How much bile salt is lost in the faeces

about 5%

35

How is bile salt synthesised?

From cholesterol in a series of 14 reactions

36

What first mediates the synthesis of bile salts

Cholesterol 7 alpha hydroxylase

37

The rate of bile salt synthesis is dependent upon what?

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

38

Secretion across the apical membrane is by what mechanism?

Active transport

39

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

Cholecystokinin

40

What does secretin cause?

Aqueous alkaline bile secretion

41

What is the role of vagal activity

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

42

What is the most common pathology of the biliary tract

Cholelithiasis (formation of gallstones)

43

What are the options for gall stones

Surgery or the use of ursodeoxycholic acid

44

What is the most common analgesic used for biliary pain

Morphine

45

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

It constricts the sphincter of Oddi

46

What drugs can be used for the relief of biliary spasm

Atropine or GTN

47

What alternative analgesics can be used for biliary pain

Buprenorphine
Pethidine

48

What is the main organ of drug metabolism

Liver
GI tract, lungs and plasma also have an activity

49

Drug metabolism acts to convert parent drugs to what?

More polar metabolites that are not readily reabsorbed by the kidney

50

How does drug metabolism often proceed

In 2 sequential phases

51

What happens in phase 1 of drug metabolism

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

52

What happens in phase 2 of drug metabolism

The liver adds an endogenous compound increasing polarity

53

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

Aspirin

54

What are the 2 phases of metabolism of aspriin

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

55

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

Haem proteins

56

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

CYP1, CYP2 and CYP3

57

What does the drug enter the monooxygenase P450 cycle as

As a drug substrate, RH

58

What is essential for this cycle

Molecular Oxygen to provide 2 Oxygen atoms

59

What happens to the oxygen atoms

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

60

What do phase 2 reactions usually result in

Inactive products

61

Where do phase 2 reactions usually ocur

Liver

62

What does phase 2 reactions involve

The conjugation of chemically reactive groups

63

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

Glucuronidation

64

Name 2 substances which are subject to glucuronidation

Bilirubin and adrenal corticosteroids

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