5- Gallbladder Function and Bile Production

Bile v. Bilirubin

Bile is not bilirubin but bilirubin is one of the many constituents of bile

Bilirubin is the breakdown product of hemoglobin

What’s the main blood supply to the liver?

• Hepatic portal vein (75%)

• Hepatic artery (25%)

What do apical and basolateral surfaces of hepatocytes (liver cells) each face?

• Apical surfaces of hepatocytes face bile canaliculi

• Basolateral surfaces of hepatocytes face sinusoids

What do sinusoids empty into?

Central veins → hepatic veins → IVC

What are sinusoids lined with?

• Kupffer cells

• Fenestrated endothelial cells

Note: no basement membrane between endothelium and hepatocytes

Perisinusoidal Space (Space of Disse)

• Space between hepatocyte and sinusoids

• Blood is cleansed and passed through

Sinusoid

• Space between hepatocytes

Lobules

Functional units of liver, hexagonal arrangements surrounding a central vein.

Bile Canaliculus

Bile carrying channels runs between sinusoids and within each hepatic plate.

Each hepatocyte is in contact with a sinusoid on one side and bile cannaliculus on other side.

Liver Acinus

• Functional unit of hepatic parenchyma

• Hepatocytes in each acinus are arranged in 3 zones

3 Elliptical Zones of Hepatocytes within Liver Acinus

1. Zone 1

   1. cells are the first liver cells affected by viral hepatitis

2. Zone 2

   1. Intermediate

3. Zone 3

   1. Centrilobular

   2. P450

   3. cells are the first liver cells affected by ischemia and alcoholic hepatitis, and are most sensitive to toxic injury

What forms the common bile duct?

Common hepatic and cystic ducts

What forms the ampulla of Vater?

Common bile duct may merge with pancreatic duct

Before entering the duodenum

Common Sphincter/Sphincter of Oddi

Regulates flow out of common bile duct and pancreatic duct.

Prevents bile from entering duodenum

Where is bile actively diverted to between meals?

Gallbladder (from the liver)

Describe the composition of canalicular bile:

Active

Isotonic

Bile salts are actively secreted by:

The Liver

When bile salts become concentrated, they form:

Micelles

What colors bile yellow? What about brown in the stool?

• Bilirubin gives a golden yellow color to bile

• Stercobilin gives a brown color to the stool

Bile Composition Percentages?

• Bile Acid 67%

• Phospholipid 22%

• Cholesterol 4%

• Bilirubin 0.3%

• Protein 4.5%

How much bile is secreted per day? How much can the gallbladder hold?

1000 ml/day

50 ml/day

4 Major Bile Components

1. Bile Salts

2. Cholesterols/Phospholipids

3. Bilirubin

4. Protein/Bicarb

Functions of bile

• Emulsify lipids

• Form micelles using bile salts

• Neutralize pH of gastric chyme

• Natural immunity

• Prevent gallstone formations

When does the gallbladder deliver bile to the duodenum?

During a meal!

Gallbladder Functions

• Concentrate bile

• Store bile

• Decrease alkalinity of bile

• Secrete mucus in bile

Where are most bile salts reabsorbed by active transport?

Terminal Ileum

Cholelithiasis

Formation of stones (calculi) within the gallbladder or biliary duct system.

Can be caused by excess cholesterol in the bile or too much bilirubin (causes pigment stones).

Cholecystitis

Inflammation of gall bladder

Cholangitis

Inflammation of the biliary ducts

Gallstones form due to:

1. Abnormal bile composition

2. Biliary stasis

3. Inflammation of gallbladder

Cholestasis (cause, sx, types(2))

• Bile can’t flow from liver → duodenum

• Sx:

  • Fatigue

  • Pruitus (itching)

  • Jaundice

  • Pale stool

  • Dark Urine

• 2 types:

  • Obstructive

  • Metabolic (issue with bile formation)

2 Categories of Cholestatic Liver Disease

Intra-hepatic (obstruction at the level of hepatocytes/canalicular membrane)

Extra-hepatic (impediment in the biliary tree)

Hyperlipidemia (Eruptive xanthomas) is characteristic of some:

Cholestatic diseases

Risk factors for Cholelithiasis?

• Female

• Fertile

• Fat

• Forty

The 4 F’s!