Lecture 4.B. - Liver and Gallbladder Secretions

Question 1

Bile secretions from Hepatocytes are _____ (hypo-, hyper-, or isotonic?) with plasma, and as they travel through bile ducts, ______ stimulates duct cells to secrete _____, making bile alkaline.

Answer 1

Isotonic

Secretin

HCO3-

Question 2

Secretion of HCO3 and transport of Cl- in bile duct cells is very similar to that in Pancreatic duct cells. Which channel is mainly responsible in these cells for recycling of Cl- back into the Lumen?

Answer 2

CFTR

Question 3

Bile acid synthesis starts with synthesis of ____ acids by hepatocytes –> these are then
conjugated to ______ acids, specifically _____ or ______ –> These are considered primary bile acids that are secreted and are ______ at neutral pH of small intestine lumen. Secondary bile acids are generated when an _____ group is removed by _____ in the gut.

Answer 3

Steroid acids

Amino Acids

Taurine or Glycine

Ionized

OH

Bacteria

Question 4

Bile facilitates lipid breakdown and absorption in 2 ways:

1. Emulsification of lipids –> greater surface area for lipolytic enzymes to work on
2. ______ formation, essential for lipid absorption.

Answer 4

Micelle

Question 5

Hepatocytes can secrete _____ as part of bile salts or freely/ not bound or modified.

Keep in mind gallstones can form when the concentration of ____ or ______ in bile is too high, bile salt levels are too LOW, or when gallbladder contraction is weak.

Answer 5

Cholesterol

Cholesterol

Bilirubin

Question 6

In the intestinal lumen, cholesterol dissolves in hydrophobic areas of _______.

Answer 6

Micelles

Question 7

Some ________ are also secreted by hepatocytes –> they move into the gallbladder and are secreted into the intestine with the bile –> there, they help to solubilize _____ and integrate into micelles.

Answer 7

Phospholipids

Cholesterol

Question 8

______ and _____ are transporters that move bile acids into bile canaliculi from hepatocytes.

Which one is clinically important as a regulator of hydrophobic waste and drugs? In what types of cells are these transporters of particular clinical relevance and why?

Answer 8

BSEP (Bile salt export protein)

MDR1

MDR1 is

Cancer cells use MDR1 to export chemotherapeutics out of the cells –> evade treatment

Question 9

The gallbladder needs to concentrate bile by about 10x bc it is too small to hold enough bile to digest a normal meal. To do this, it absorbs ____ and ____ via ion channels, creates ______ (hypo-, hyper-, or isotonic?) environment between its cells, which draws water out from the lumen and pushes it via a pressure gradient into the blood.

Answer 9

Na+ and Cl-

Hypertonic

Question 10

______ is the strongest stimulus for gallbladder contraction –> it’s released from ____-cells in the duodenum in response to presence of fatty and amino acids –> it acts via endocrine mech to directly cause contraction of gallbladder and ALSO via _____ nerve which stimulates gallbladder contraction and simultaneous relaxation of the Sphincter of _____ via _____ and NO. Keep in mind ____ containing nerves inhibit gallbladder contraction between meals.

Answer 10

CCK

I-cells

Vagus nerve

Sphincter of Oddi

VIP and NO

VIP

Question 11

________ circulation allows for recycling of bile acids such that the same bile acids used to digest fats at the beginning of a meal can be used to digest fats later in the same meal. Keep in mind this process bypasses the _______.

Conjugated bile acids are absorbed in the distal _____ via secondary active transport via ASBT (aka IBAT) –> they bind to a protein intracellularly, and are transported into circulation to make their way back to the liver –> they are transported into the liver via _____ transporter –> then back into the bile via ______.

Absence of _____ causes Primary Bile Acid malabsorption, while absence of _____ causes Hypercholanemia.

Answer 11

Enterohepatic

Gallbladder

Ileum

NTCP

BSEP

ASBT

NTCP

Question 12

Bilirubin created in the spleen via Hb breakdown binds to _____ in the blood and is transported into hepatocytes. In hepatocytes it is linked to ____ acid via UDP ______ transferase and becomes Bilirubin-_______ –> this end product is secreted into hepatic canaliculi and makes its way into the GI lumen.

Answer 12

Albumin

Glucoronic acid

UDP Glucoronyl transferase

Bilirubin-glucoronide

Question 13

Bacteria in the GI convert Bilirubin-glucoronide into ______ –> most of this is then converted to brown colored _____ and passed in the feces. Some ______ is absorbed into circulation and is passed in urine as yellow colored _____.

Answer 13

Urobilinogen

Stercobilin

Urobilinogen

Urobilin