Exam #5: Liver & Gallbladder Flashcards Preview

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Flashcards in Exam #5: Liver & Gallbladder Deck (26):
1

Describe the directional flow of blood through the liver.

- Grossly, deoxygenated blood flows from the GI organs to the liver via the portal vein, which is located in the "corner" of each liver lobule--at the portal triad
- Oxygenated blood flows from the aorta/ hepatic artery to the portal triad
- From the portal vein/ hepatic artery in the corner of the lobule, blood flows to the central vein in the middle of the liver lobule
- Central vein dumps into hepatic veins, which ultimately return blood to the heart via the SVC

2

Describe the directional flow of bile.

Bile is produced by liver hepatocytes & moves in the OPPOSITE direction of blood i.e. away from the central vein to the bile duct in the corner of the liver lobule, part of the portal triad

3

How do hepatocytes "handle" chemical compounds i.e. what are the four key steps in hepatocyte biotransformation of compounds?

1) Uptake
2) Transport
3) Biotransformation
4) Secretion

4

Describe the uptake process of hepatocyte biotransformation.

Uptake occurs across the basolateral membrane of the hepatocyte via two general mechanisms:
1) Free diffusion
2) Transporters

5

How are compounds transported through the cell to the site of biotransformation?

Compounds taken up by liver hepatocytes bind proteins & are carried to the site of chemical modification.

*****Note, these proteins serve an important function: prevention of damage to the liver by harmful compounds

6

How are substances transported back into the blood for excretion by the kidneys or into the bile for fecal elimination, after biotransformation has occurred?

Water-soluble
- After biotransformation, compounds are transported back into the blood if they're water soluble-->kidney-->excreted in urine

Lipid-soluble
-If the compound is still lipophillic-->bile-->feces

*These processes are mediated by a number of different transporters with a differential expression

7

What is Phase I biotransformation? What is the end result of Phase I biostranformation?

*****Remember that the end goal of biotransformation is to make a substance more hydrophilic

Phase I= step taken to make the molecular more polar by exposing a functional group (better substrate for phase II). Specific reactions that occur include:
- Oxidation
- Reduction
- Hydrolysis

****Note that not all molecules undergo Phase I

8

What is Phase II biotransformation? What is the end result of Phase I biostranformation?

*****Remember that the end goal of biotransformation is to make a substance more hydrophilic

Phase II= conjugation of a large bulky molecule to the functional group exposed in phase I. Specific reactions include:
- Glucuronidation
- Sulfation
- Acetylation

9

How are bile salts synthesized?

Remember that hepatocytes produce bile that moves from the central vein to the bile duct in the portal traid. The steps involved in this process include:

1) Cholesterol is transformed into the bile acids
2) The main bile acid is "cholic acid"
3) Bile acids undergo Phase I & II biotransformation, to produce the more hydrophilic bile salt

10

Where is bile produced? Where is bile stored? Where is bile secreted? What happens to secreted bile salts?

- Bile produced & secreted by the liver
- 1/2 of the bile produced is secreted into the gallbladder & concentrated
- 1/2 is secreted directly into the duodenum

*****95% of the secreted bile is recycled via the portal vein carrying bile back to the liver from the intestines

11

What are the key stimuli that promote the secretion of bile into the duodenum?

There are two key stimuli regulating the secretion of bile:
1) Fat in the duodenum= CCK release
2) Vagal stimulation in response to sight, taste, smell, & intestinal distention cause ACh release

*****BOTH CCK & ACh lead to:
- Gallbaldder contraction & secretion of bile into the bile duct
- Relaxation of the sphincter of Oddi for release into the duodenum

12

What key stimulus inhibits the secretion of bile into the duodenum?

Somatostatin

13

What is enterochepatic circulation? Outline the pathway of enterohepatic circulation.

The is the circulation the recycles bile acids i.e.:
1) Bile from the liver & gallbladder travels to the duodenum via the bile duct
2) Bile is reabsorbed into the portal vein from the distal ileum & carried back to the liver for recycling

14

What is portal hypertension?

This is a sign of liver dysfunction; there is high blood pressure in the portal venous system

15

Describe the pathophysiology of portal hypertension.

- Portal HTN is high blood pressure in the portal vein i.e. the vein that carries blood to the liver from the GI tract
- This high blood pressure is caused by impedance of blood flow

16

What are the symptoms of portal hypertension?

1) Varices--distention of collateral veins of the esophagus, rectum, & stomach
2) Splenomegaly
3) Ascites
4) Hepatic ecephalopathy

17

Describe the symptoms and pathophysiology of jaundice.

- Jaundice/ icterus, is a yellowing of the skin from accumulation of bilirubin in the blood
- Bilirubin is a product of heme breakdown that is normally excreted by the liver
- Impaired liver function= bilirubin accumulation

18

Describe the symptoms and pathophysiology of cirrhosis.

- Cirrhosis of the liver refers to scarring/fibrosis of hepatic tissue that results in altered hepatic blood flow. Causes include:
1) Alcoholism
2) Biliary obstruction
3) Autoimmune disease

Symptoms include: portal HTN & jaundice

19

Describe the symptoms and pathophysiology of cholelithiasis.

Cholelithiasis is the formation of gallstones in the gallbladder from:
1) Cholesterol-- overproduction of cholesterol, or impaired production of bile salts
2) Pigment--calcium bilirubinate

****Can lead to cholestasis, or impaired bile flow

20

Describe the symptoms and pathophysiology of cholecystitis.

Cholecystitis is the inflammation of the gallbladder from a gallstone lodged in the cystic duct

****Can lead to cholestasis, or impaired bile flow

21

What is the first-pass effect?

This is the concept in pharmacology referring to the manner in which compounds are transported to the liver after being

22

What are the different cells of the liver, and what are their functions?

Hepatocytes=
- Functional cells of liver
- Polarized epithelial cell
- Interface w/ blood & bile

Kupffer= phagocytic macrophages that are exposed to portal blood

Endothelial= large pores between cells
- minimal basement membrane

Stellate= regulate blood flow between the fenestrae & across the Space of Disse to the hepatocytes

23

What is the difference between a primary and a secondary bile acid?

Primary= no modification

Secondary= modified by the bacteria in the gut (duodenum)

24

How do the production and secretion of bile acid/ salts in the liver compare?

The liver secretes far greater amounts of bile salts than are produced; thus, the liver is recycling bile acids

25

What organ facilitates the enterohepatic circulation of bile acids & bile salts?

Ileum

26

What happens when the Ileum is removed & these bile acids are NOT recycled?

Malnutriation

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