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Gastrointestinal > Physiology and pharmacology of the liver > Flashcards

Physiology and pharmacology of the liver Flashcards

1
Q

What are the 10 main functions of the liver?

A 
Metabolic processing 
Detoxification and degradation
Synthesis of plasma proteins
Storage 
Activation of vitamin D
Removal of bacteria and old erythrocytes
Secretion of hormones
Production of acute phase proteins
Excretion of cholesterol and bilirubin
Production of hepatic bile
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2
Q

What is the blood supply to the liver?

A

Dual blood supply
75% of the total blood in the liver comes from the portal vein
25% comes from the hepatic artery

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3
Q

Where does arterial and venous blood mix in the liver?

A

In liver sinusoids

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4
Q

What are sinusoids?

A

Fenestrated (leaky) capillaries

allow direct access between hepatocytes and the blood

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5
Q

What is the passage of blood through the liver?

A

Hepatic artery & portal vein –> arterioles & venules–> sinusoids –> central vein of liver lobule –> branches of hepatic vein –> hepatic vein

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6
Q

What are liver lobules?

A

Functional units of the liver

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7
Q

How are hepatocytes arranged?

A

Hepatocytes are arranged in plates lining the blood-filled sinusoids

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8
Q

What does the basolateral membrane of hepatocytes face?

A

Pericellular space/space of Disse

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9
Q

What is the space of Disse?

A

The space between the hepatocytes and a sinusoid
Contain blood plasma
Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components fro the sinusoids to be absorbed by the hepatocytes

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10
Q

What do the apical membrane of adjacent hepatocytes form?

A

Canaliculi

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11
Q

What does the sinusoidal space contain?

A

Endothelial cells
Kuppfer cells
Stellate cells

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12
Q

What do the endothelial cells form?

A

A fenestrated structure that allows for free movement of solutes but not cells

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13
Q

What are Kupffer cells and where are they found?

A

Kuppfer cells are macrophages resident to sinusoidal vascular space (found on the sinusoidal endothelaial wall)
They remove particulate matter and are involved in the breakdown of red blood cells

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14
Q

What are stellate cells?

A

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

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15
Q

What is the intrahepatic bile system, in sequence (starting small)?

A

Canaliculi, terminal bile ductules, perilobular ducts, interlobular ducts, septal ducts, lobar ducts, two hepatic ducts and the common bile duct

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16
Q

What is the name of the sphincter that controls the entrance of bile to the duodenum?

A

Sphincter of Oddi

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17
Q

How much bile is produced per day?

A

0.6-1.2 liters

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18
Q

Where is bile stored and concentrated?

A

Gallbladder

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19
Q

What triggers the sphincter of Oddi to open?

A

Chyme is the duodenum stimulates gallbladder smooth muscle to contract

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20
Q

What impulses cause the gallblader smooth muscle to contract?

A

CCK and vagal impulses

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21
Q

What secretions is bile made up of?

A

Secretion of hepatocytes and secretion of bile duct cells (25%) that mixes in the ducts

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22
Q

What are bile duct cells called?

A

Cholangiocytes

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23
Q

What process is bile important for?

A

Emulsification of lipids

24
Q

What is the secretion from cholangiocytes composed of?

A

Aqueous, alkaline, Na+, K+, Cl- and HCO3- rich

25
Q

What substance triggers secretion from bile duct cells?

A

Secretin is released from duodenal S cells. Exchange occurs across the duct cells apical membrane = HCO3- moves out of the cell and Cl- move in
This makes the gut lumen more alkali

26
Q

What is the benefit of alkanisation in the gut lumen?

A

Enhances the pancreatic solution to neutralise chyme coming form the stomach - optimum pH for the pancreatic enzyme and helps protect the mucosa from erosion

27
Q

Where do hepatocytes secrete their primary juice?

A

Into canaliculi which drain into terminal biliary ductules

28
Q

What is hepatic bile composed of?

A

Primary bile acids, water, electrolytes, lipids, phospholipids, bilirubin and IgA

29
Q

What are the two main bile acids?

A

Cholic and chenodeoxycholic acid

30
Q

How are bile salts formed?

A

Binding of the bile acids to Na+ and K+

31
Q

How are gallstones formed?

A

If there is excess cholesterol relative to bile acids it may precipitate and form microcrystals that aggregate into gallstones

32
Q

What is the proper medical term for gallstones?

A

Cholelithiasis

33
Q

What can be given to dissolve non-calcified cholesterol gallstones?

A

Ursodeoxycholic acid

34
Q

What is bilirubin?

A

Breakdown product of porphyry a component of haemoglobin

Pigmented (gives urine and faces their colour)

35
Q

What tissue does un-metabolised bilirubin that has not been excreted, often built up in?

A

Fatty tissue

36
Q

What happens to the majority of bile salts that enter the duodenum?

A

The majority is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling

37
Q

What happens do faeces if there is an absence of bile salts?

A

Steatorrhoea

38
Q

What happens to bile salts that are reabsorbed by the liver?

A

Used again or made into cholesterol for the production of more bile

39
Q

How is bile salt synthesised?

A

Series of 14 reactions starting with cholesterol

40
Q

What controls the rate of synthesis of bile salts?

A

The hepatic portal blood concentration of bile salts

low concentration stimulates synthesis

41
Q

By what type of transport does bile salt move across the apical membrane for secretion?

A

Active transport

42
Q

How is the rate of secretion of bile salts controlled?

A

Most powerful stimulus is the bile salt returning to the liver by enterohepatic recirculation during and shorty after a meal - matched rate of secretion to need

43
Q

What is the effect of cholecystokinin (CCK) on the gallbladder and the sphincter of Oddi?

A

Causes the gallbladder to contract and sphincter of Oddi to relax

44
Q

What does secretin trigger?

A

Causes aqueous alkaline bile secretion

45
Q

What treatment can be given fro cholelithiasis?

A

Ursodeoxycholic acid (non-calcified) or surgery

46
Q

What medication can be given to patients with cholelithiasis for analgesia?

A

Morphine (but constricts sphincter of Oddi)
Buprenorphine
Pethidine

47
Q

What medication can be given for relief of biliary spasm?

A

Atropine or glyceryltrinitrate (GTN)

48
Q

How does GTN relieve pain?

A

Nitrates cause muscle relaxation

49
Q

What is a xenobiotic substance?

A

A substance (usually a synthetic chemical) that is foreign to the body

50
Q

What is the liver’s role in drug metabolism?

A

Convert parent drug –> more polar metabolites to facilitate excretion by the kidney
Convert drug –> metabolites

51
Q

How can drug metabolites differ from the parent drug that entered the liver?

A

Usually pharmacologically less active than parent
May convert inactive prodrugs to active compounds
Gain activity
Have unchanged activity
Posses a different type/spectrum of action

52
Q

Give an example of a drug that is activated in by metabolism

A

Enalapril –> enalaprilate

53
Q

Give an example of a drug that has greater activity after metabolism

A

Codine –> morphine

54
Q

What is the difference in the action of aspirin and it’s metabolites?

A

Aspirin - anti-inflammatory and anti-platelet activity

Metabolite (salicylic acid) - anti-inflammatory not anti-platlet activity

55
Q

What happens in phase I of metabolism?

A

Drug is made more polar, chemical reactive (‘handle’) group is added - oxidation, reduction and hydrolysis

56
Q

What happens in phase II of metabolism?

A

Conjugation - endogenous compound is added increasing polarity (usually results in inactive products)

Gastrointestinal (11 decks)

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