Intro to Liver and Gallbladder Function

Question 1

What are the 6 main functions of the liver?

Answer 1

Question 2

What is the function of the gallbladder?

Answer 2

Question 3

What is meant by saying that the liver has a dual circulation occurring?

Answer 3

Question 4

The GI system is […] resistance

Answer 4

Low

Question 5

All blood that enters the GI tract and picks up nutrients from GI absorption drains into the […]

Answer 5

Portal vein

Question 6

What happens to the flow of blood into the liver after a meal?

Answer 6

Question 7

What is the first pass effect of the liver?

Answer 7

• Utilize nutrients –> liver carries out a lot of functions, so its very useful for it to have first dibs on nutrients
• Detoxify –> important to have any potential toxins entering body go first to a place where they could be detoxified before reaching heart and brain
• Modify drugs –> important to have drugs modified here so they can exert effects in systemic system without damage

Question 8

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Question 9

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Question 10

Answer 10

Sinusoid = area where hepatic artery blood and portal vein blood mix before draining into central vein

Question 11

Let’s consider a single layer of hepatocytes sandwiched between two sinusoids (see image). Describe the general possibilities for what enters these hepatocytes and what exits and how.

Answer 11

Question 12

Answer 12

Question 13

What is the role of liver endothelial cells?

Answer 13

Fenestrated border to allow flow of material from blood to space of disse

Question 14

What is the role of liver stellate (ito) cells?

Answer 14

Vitamin A and lipid storage, release cytokines, involved in immune/inflammation/fibrosis

Question 15

What is the role of liver Kupfer cells?

Answer 15

Macrophages (APCs) innate immune response, phagocytes for bacteria

Question 16

What is the role of liver dendritic cells?

Answer 16

APCs

Question 17

What is the role of liver Cholangiocytes (biliary endothelium)?

Answer 17

Secrete electrolytes into bile, regulated by secretin and Ach

Question 18

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Question 19

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Question 20

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Question 21

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Question 22

• What is bile?
• Where is it made?
• What are its roles?

Answer 22

Question 23

How does bile aid in lipid digestion?

Answer 23

Question 24

What are the 4 steps in bile synthesis and circulation?

Answer 24

Question 25

Describe the synthesis of **_cannilicular_** bile formation

Answer 25

Digestive contents from absorption in GI tract enter liver via portal vein --\> mix with blood from hepatic artery via sinusoid --\> hepatocytes absorb cholesterol --\> modify it to make either cholic acid or chenodeoxycholic acid --\> these are **_unconjugated_** bile acids that cannot cross canalicular membrane and they cannot be secreted as such --\> hepatocytes conjugate to glycine or taurine to make conjugated bile acids which increases solubility and lowers pKa --\> secreted actively into canaliculus

Question 26

Describe what happens to canalicular bile after it is produced by hepatocytes.

Answer 26

1/ Active membrane pump action is required for canalicular bile secretion 2/ Secretin stimulates cholangiocytes to actively secrete fluid, bicarb and ions into bile. (Somatostatin inhibits it). 3/ This dilutes out the canalicular bile and ductal bile it drains into the biliary tree. Along its path it is modified by the epithelial cells (cholangiocytes) lining it. 4/ Bile then drains into the proximal small bowel, that is, duodenum, and is metabolized by enteric bacteria. Secondary bile acids are formed. 5/ Most bile is recycled via enterohepatic circulation, but some is lost with feces.

Question 27

Once bile mixes with contents of duodenum, it continues through the GI tract. Much of it is reabsorbed by portal vein. Some of it makes its way to colon where it interacts with gut bacteria. What do the bacteria do to the bile?

Answer 27

They conjugate it again making it more hydrophilic. In order to prevent loss of this bile, the body has to deconjugate it in the colon to make it more lipophilic and thus able to be absorbed across intestinal wall into portal circulation.

Question 28

What is enterohepatic circulation of bile?

Answer 28

Question 29

Fatty acids arriving in duodenum triggers [...] and this impacts gallbladder and pancreas by causing [...]

Answer 29

CCK secretion into blood by intestinal I cells Causes GB contraction, pancreatic enzyme release, relaxation sphincter of Oddi

Question 30

Acidic chyme arriving in duodenum triggers [...] and this impacts liver and pancreas by causing [...]

Answer 30

Secretin secretion into blood by intestinal s cells Liver duct cells secrete bicarb into bile, pancreatic ducts secrete bicarb into pancreatic enzyme secretions

Question 31

What effect does vagus stimulation have on gallbladder?

Answer 31

weak contraction

Question 32

Describe how RBCs are metabolized by the liver and how this leads to bilirubin in bile.

Answer 32

Question 33

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Question 34

What is the role of ito cells in the pathogenesis of cirrhosis?

Answer 34

* Stellate cells normally store Vitamin A and lipids and make hepatocyte growth factors. * Following chronic stresses (↑biliary pressure, fatty change, alcohol, viral or other inflammation) eventually stellate cells transform into myofibroblasts. * Fibrosis is caused by these abnormally activated stellate cells making large quantities of collagen filling first the space of Disse, then the sinusoids.