Physiology and Pharmacology of the Liver Flashcards Preview

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Flashcards in Physiology and Pharmacology of the Liver Deck (39)
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What is the liver's blood supply?

75% hepatic portal vein
25% hepatic artery


Describe the passage of blood through the liver

Enters via the hepatic portal vein and the hepatic artery. Goes through venules and arterioles, then mixes in the liver sinusoids (fenestrated capillaries).
It then drains to the central vein of the liver lobule, then into branches of hepatic veins, then drains into a hepatic vein.


What shape is each liver lobule?

Hexagonal in cross section


What is at the centre of each liver lobule?

A branch of hepatic vein at its centre (central vein)


What is at each corner of the lover lobules?

A portal triad:
A branch of hepatic portal vein
A branch of hepatic artery
A bile duct


How are hepatocytes arranged in the lobules?

In cords, arranged as hepatic plates


Which direction does blood flow through the sinusoid?

Inwardly, towards the central vein


What does bile flow through? Which direction does it flow in?

It flows outwardly to the bile duct through canaliculi


How are hepatocytes arranged between the sinusoids?
What do the basolateral membranes of these cells face?

In plates, 2 cells thick.
The basolateral membranes face a pericellular space between these cells and the endothelial cells that line the sinusoids, called the space of Disse.


What does the apical membrane of the hepatocytes between the sinusoids create?

The apical membrane is grooved
Forms the canaliculi for bile


What do sinusoidal spaces contain?

Endothelial cells that form a fenestrated structure
Kuppfer cells: macrophages resident to the sinusoidal vascular space- these removed particulate matter and senescent erythrocytes
Stellate (Ito) cells within the space of Disse: important for storage of Vitamin A, may play a role in fibrosis and cirrhosis


How much bile is produced per day?

It is produced continuously, 0.6-1.2 litres per day


Where is bile between meals?

It is stored and concentrated in the gall bladder


What happens to bile during a meal?

Chyme in the duodenum stimulates gall bladder smooth muscle to contract via CCK and vagal impulses.
The sphincter of oddi opens (via CCK)
Bile spurts into the duodenum via cystic and common bile ducts (mixed with bile from the liver)


What secretions make up bile?

Secretion of hepatocytes
Secretion of cholangiocytes
The secretions mix in the ducts


What does hepatic bile consist of?

Primary bile acids: mainly cholic and chenodeoxycolic acids.
These form bile salts with Na+ and K+. Many are conjugated to glycine or taurine. Some are conjugated to sulphate or glucuonate.

Water and electrolytes including Na, K, Ca, Cl and HCO3 ions.

Lipids and phospholipids e.g. lecithin





What may excess cholesterol relative to bile acids and lecithin precipitate into?

Microcrystals that aggregate into gallstone (cholithiasis)


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

Ursodeoxycholic acid


What percentage of the volume of bile does secretion from bile duct cells (cholangiocytes) contribute to?



What does the secretion from cholangiocytes comprise of?

Similar composition to alkaline pancreatic juice
aqueous, alkaline, Na+, K+, Cl-, HCO3-rich


What happens to the flow rate of secretion from cholangiocytes during meals?

During meals flow rate increases in response to secretin released from duodenal S cells

HCO3-/Cl- exchange occurs across the duct cell apical membrane – reduced at high flow rate - therefore HCO3- content increases


What proportion of the bile salts that enter the duodenum is lost in the faeces?
What happens to the rest?

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


Name 2 resins that bind bile salts to prevent reabsorption of cholesterol and lower plasma cholesterol?



How are bile salts transported from the ileum to the into the enterocytes?

The Na+/bile salt transporter ASBT


What mediates the basolateral transport of bile salts into the portal circulation from the enterocytes?

Organic solute transporter ost-alpha/ost-beta


Which transporter transports bile salts back into the liver from the portal circulation?

mainly NTPC, Na-taurocholate cotransporting polypeptide


What is the starting point for bile salt synthesis?
How many reactions are involved in the pathway?
Which enzyme mediates it first?

Synthesis is from cholesterol in a series of 14 reactions, first mediated by cholesterol 7-alpha-hydroxylase (CYP7alpha1) to form the primary bile salts.


What is the rate of synthesis of bile salts dependent on?

the hepatic portal blood concentration of the salts:
Low concentrate stimulates synthesis
High concentration inhibits synthesis


What does CCK cause to happen?

causes gall bladder contraction and relaxation of the sphincter of Oddi


What does secretin cause to happen?

causes aqueous alkaline bile secretion

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