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Gastro > Physiology and Pharmacology of the Liver > Flashcards

Physiology and Pharmacology of the Liver Flashcards

1
Q

Describe the blood supply to the liver

A

Dual supply in and single supply out

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2
Q

What are all hepatocytes in contact with?

A

Blood from both the hepatic portal vein and the hepatic artery

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3
Q

Where does arterial and venous blood mix

A

In the liver sinusoids

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4
Q

What shape is a cross section of each lobule

A

Hexagonal

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5
Q

What is found in the centre of each lobule

A

a branch of the hepatic vein (central vein)

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6
Q

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

A

A triad (portal triad)

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7
Q

What is in each portal triad

A

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

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8
Q

What is arranged as hepatic plates?

A

Cords of hepatocytes

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9
Q

Blood flows inwardly through what to the central vein

A

Sinusoids

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10
Q

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

A

Canaliculi

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11
Q

What are hepatocytes arranged in between

A

Sinusoids in plates two cells thick

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12
Q

What does the basolateral membrane face

A

The space of Disse

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13
Q

What is the space of Disse

A

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

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14
Q

What forms the canaliculi

A

The apical membrane of adjacent hepatocytes

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15
Q

Sinusoidla spaces contain which 3 types of cells

A

Endothelial cells
Kuppfer cells
Stellate (lto) cells

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16
Q

What do endothelial cells allow the movement of?

A

Solutes but not cells

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17
Q

What type of cells remove particulate matter (bacteria)

A

Kuppfer cellls

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18
Q

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

A

Within the space of Disse

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

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19
Q

Describe the sequence of the intraheaptic bile system

A 
Canaliculi 
Terminal bile ductules
Perilobar ducts
Interlobar ducts
Septal ducts
Lobar ducts
2 hepatic ducts
The common hepatic duct
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20
Q

How much bile is produced per day

A

0.6-1.2 litres per day

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21
Q

Where is bile between meals

A

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

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22
Q

What happens to bile during a meal

A

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

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23
Q

What is the role of bile

A

It participates in the digestion and absorption of fats

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24
Q

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

A

Plasma

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25
Q

Why does the flow rate of bile increase during meals

A

In response to secretin released from duodenal S cells

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26
Q

What does the slightly alkaline pH of bile contribute to?

A

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

27
Q

What do hepatocytes secrete and where?

A

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

28
Q

What is hepatic bile composed of

A 
Primary bile acids mainly cholic and chenodeoxycholic acids
Water and electrolytes
Lipids and phospholipids
Cholesterol
IgA
Bilirubin
29
Q

What is bilirubin a product of

A

The porphyrin component of haemoglobin

30
Q

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

A

Much smaller

31
Q

Where are most bile salts reabsorbed and how?

A

In the terminal ileum and by active transport

32
Q

What do bile salts undergo?

A

Enterohepatic recycling

33
Q

What prevent reabsorption and lower plasma cholesterol?

A

Resins that bind bile salts eg colestyramine and colestipol

34
Q

How much bile salt is lost in the faeces

A

about 5%

35
Q

How is bile salt synthesised?

A

From cholesterol in a series of 14 reactions

36
Q

What first mediates the synthesis of bile salts

A

Cholesterol 7 alpha hydroxylase

37
Q

The rate of bile salt synthesis is dependent upon what?

A

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

38
Q

Secretion across the apical membrane is by what mechanism?

A

Active transport

39
Q

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

A

Cholecystokinin

40
Q

What does secretin cause?

A

Aqueous alkaline bile secretion

41
Q

What is the role of vagal activity

A

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

42
Q

What is the most common pathology of the biliary tract

A

Cholelithiasis (formation of gallstones)

43
Q

What are the options for gall stones

A

Surgery or the use of ursodeoxycholic acid

44
Q

What is the most common analgesic used for biliary pain

A

Morphine

45
Q

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

A

It constricts the sphincter of Oddi

46
Q

What drugs can be used for the relief of biliary spasm

A

Atropine or GTN

47
Q

What alternative analgesics can be used for biliary pain

A

Buprenorphine

Pethidine

48
Q

What is the main organ of drug metabolism

A

Liver

GI tract, lungs and plasma also have an activity

49
Q

Drug metabolism acts to convert parent drugs to what?

A

More polar metabolites that are not readily reabsorbed by the kidney

50
Q

How does drug metabolism often proceed

A

In 2 sequential phases

51
Q

What happens in phase 1 of drug metabolism

A

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

52
Q

What happens in phase 2 of drug metabolism

A

The liver adds an endogenous compound increasing polarity

53
Q

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

A

Aspirin

54
Q

What are the 2 phases of metabolism of aspriin

A

Catabolic - drug in converted to the derivative

Anabolic - The derivative is converted to the conjugate

55
Q

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

A

Haem proteins

56
Q

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

A

CYP1, CYP2 and CYP3

57
Q

What does the drug enter the monooxygenase P450 cycle as

A

As a drug substrate, RH

58
Q

What is essential for this cycle

A

Molecular Oxygen to provide 2 Oxygen atoms

59
Q

What happens to the oxygen atoms

A

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
Q

What do phase 2 reactions usually result in

A

Inactive products

61
Q

Where do phase 2 reactions usually ocur

A

Liver

62
Q

What does phase 2 reactions involve

A

The conjugation of chemically reactive groups

63
Q

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

A

Glucuronidation

64
Q

Name 2 substances which are subject to glucuronidation

A

Bilirubin and adrenal corticosteroids

Gastro (67 decks)

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