Biliary System

Question 1

Liver functions

Answer 1

1. Metabolic processing of absorbed nutrients – maintains blood glucose homeostasis.
2. Detoxification and/or degradation of body wastes, hormones and other foreign compounds.
3. Storage of iron, fats, vitamins and glycogen.
4. Excretion of cholesterol and bilirubin.
5. Production and secretion of bile.

Question 2

First pass effect

Answer 2

drugs must first pass through the liver before they get

into the systemic circulation.

Question 3

Bile fxs:

Answer 3

digestion and absorption of fats and excretion of water insoluble substances such as cholesterol and bilirubin.

Question 4

Bile formation and secretion

Answer 4

Bile is formed by liver epithelial cells and secreted by a 
transport mechanism (a bile salt carrier that uptakes conjugated bile acids) in the canalicular membrane. It is then secreted into the bile cannaliculi, modified by the intra- and extra-hepatic biliary system, stored in the gallbladder and delivered into the duodenum. In the hepatocytes primary bile acids are synthesized from cholesterol and are converted into bile salts.  Normally the liver secretes 600-1200ml of bile per day.

Question 5

Bile composition

Answer 5

Bile is composed of inorganic substances, primarily electrolytes. Concentrations of Na+, Ca2+, K+, and HCO3- are slightly higher and concentrations of Cl- are lower.

Bile also contains organic substances including bile acids, bile pigments, cholesterol, phospholipids and a small amount of protein.

Bile acids are mostly present as bile salts because their pKa is below the pH of bile.

The major bile salts in man are glycine- and taurine- conjugates of cholate (~40%), chenodeoxycholate (~40%) (which are primary bile salts synthesized by the liver), deoxycholate (~20%) and lithocholate (~1-3%) which are secondary bile salts produced by the bacterial alteration of primary bile salts.

Bilirubin also in bile

Question 6

Bilirubin

Answer 6

Bilirubin, the major bile pigment, is produced from porphyrin, a breakdown product of hemoglobin from old red blood cells.

In the liver it is conjugated with glucuronic acid to produce the water soluble bilirubin glucuronide. Bilirubin glucuronide is then excreted from the liver in bile. It is not well absorbed from the intestine and is excreted in the feces. A small percentage is reduced to urobilinogen by bacteria in the distal small intestine. A significant amount of urobilinogen enters the portal circulation and is returned to the liver where it is either secreted in the bile or, allowed to enter the systemic circulation from which it is removed via the kidneys. High concentrations of bilirubin produce the yellow coloration of jaundice.

Question 7

Enterohepatic circulation

Answer 7

Enterohepatic circulation is the re-circulation of bile salts from the
liver to the small intestine and back again. It is necessary because of
the limited pool of bile salts available for the absorption of fat.

1. ~95% of the bile salts are actively reabsorbed in the terminal ileum;
   the rest are excreted in the feces.
2. The total circulating pool of bile salts (primary and secondary) is
   about 3.6g. About 4-8g of bile salts are needed to digest a meal so the
   bile salt pool circulates about two times per meal and about 6-8 times
   per day.
3. The rate of bile salt synthesis is determined by the rate of return to
   the liver. The normal rate is 0.2 -0.4g/day, which compensates for the
   fecal loss.

Question 8

Gallbladder emptying

Answer 8

Entrance of fat and protein digestion
products into the duodenum stimulates the release of CCK. CCK contracts the gallbladder and relaxes
the sphincter of Oddi, emptying the gallbladder.

Question 9

JAUNDICE

Answer 9

is a yellowing of the skin due to the production of more bilirubin within the tissues and
blood than can be excreted. It has multiple causes:

Question 10

hemolytic jaundice

Answer 10

Excessive breakdown of red blood cells resulting in:

Question 11

hepatic jaundice

Answer 11

Liver disease where the liver cannot deal with even a normal amount of bilirubin resulting in a:

Question 12

obstructive jaundice

Answer 12

Blockage of the bile duct such that bilirubin cannot get to the intestine to be excreted. This results
in an:

Question 13

physiologic hyperbilirubinemia

Answer 13

In neonates the liver does not always function adequately for about the first week of life. Under these conditions all bilirubin being produced by the body cannot be conjugated with glucuronic acid by the liver. This results in an increased plasma concentration of bilirubin and a mild yellowing of the skin and eye whites. This type of jaundice is known as physiologic hyperbilirubinemia and reverses spontaneously as the liver begins to function normally.

Question 14

CHOLESTASIS

Answer 14

is the suppression of bile secretion, which can occur in acute or chronic liver disease. The constituents of bile components (eg. Bile acids, bilirubin) may therefore be retained within the hepatocyte and regurgitated into the systemic circulation which can cause three major effects:

• symptoms of jaundice and pruritus (itching)
• damage to hepatocytes resulting in release of liver enzymes into the plasma
• impairment of lipid digestion and absorption due to decreased bile acids entering the duodenum

Question 15

GALLSTONES

Answer 15

may be caused by excess cholesterol in bile acting as a “seed” or by the elevation of the Ca2+ ion concentration
as water is extracted from bile in the gallbladder. Pigment stones can occur when unconjugated bilirubin co-precipitates with calcium. Often gallstones are asymptomatic, however they can
become lodged into one of the ducts (cystic, bile, or at junction with pancreatic) and cause problems. If this leads to loss of the gallbladder function, diet modification will be necessary because bile is available
only as a dilute continuous stream which does not change in response to lipid in the intestinal lumen.