Overview

Volume≈0.6–1 L/day

pH (hepatic bile)≈7.5–8

Bile salt pool≈3 g, recycled ≈4–12×/day

Hepatic bile is isotonic with a pH of about 7.5–8. Gallbladder bile is concentrated and slightly more acidic. Bile is mostly water, and its solids are organised into mixed micelles.

Bile salts make up about two-thirds of the solids. Primary bile acids (cholic and chenodeoxycholic acid) are made from cholesterol in hepatocytes. The rate-limiting enzyme is cholesterol 7α-hydroxylase (CYP7A1). They are then conjugated with glycine or taurine, which lowers their pKa so they stay ionised (as salts) in the intestinal lumen. Colonic bacteria deconjugate and 7α-dehydroxylate them into secondary bile acids (deoxycholic and lithocholic acid). Bile salts are amphipathic, with a hydrophobic and a hydrophilic face, so they coat fat droplets and, above a critical concentration, form micelles that carry lipids to the brush border.

The other solids are phospholipid (mainly lecithin), cholesterol, conjugated bilirubin, electrolytes with HCO₃⁻ added in the ducts, IgA, and excreted drugs and metals such as copper. Cholesterol is insoluble in water and stays dissolved only within bile salt–lecithin micelles. When cholesterol is in excess relative to these, bile becomes supersaturated and stones can form.

Bilirubin pathway: haem from senescent red cells is converted by macrophages to biliverdin and then unconjugated bilirubin, which travels in blood bound to albumin. Hepatocytes conjugate it with glucuronic acid (UGT1A1) and secrete it into bile. In the colon, bacteria convert it to urobilinogen. Some urobilinogen is reabsorbed and excreted in urine as urobilin, which colours urine yellow. The rest becomes stercobilin, which colours faeces brown.

Parts & subdivisions

Bile salts
Conjugated bile acids; emulsify fat and form micelles; about 95% are recycled by the enterohepatic circulation.
Phospholipid (lecithin)
Forms mixed micelles with bile salts and keeps cholesterol in solution.
Cholesterol
Excreted in bile, the body's main route of cholesterol elimination.
Conjugated bilirubin
Bilirubin diglucuronide; the main bile pigment.
Bicarbonate-rich ductular fluid
Added by cholangiocytes under secretin; helps neutralise duodenal acid.

Function

Emulsifies dietary fat and forms micelles, enabling absorption of lipids and fat-soluble vitamins A, D, E and K.
Excretes cholesterol, bilirubin, drugs, toxins and copper.
Helps neutralise gastric acid in the duodenum.
Antimicrobial action and endocrine signalling (FXR/FGF19, TGR5).

Secretions: About 0.6–1 L/day. Bile-salt-dependent flow comes from hepatocytes, bile-salt-independent flow from hepatocytes (glutathione, HCO₃⁻), and ductular flow from cholangiocytes (secretin-stimulated).
Regulation: Bile salts returning to the liver stimulate their own secretion (choleretic effect). Secretin increases ductular bicarbonate and water. CCK empties the gallbladder (cholagogue) and relaxes the sphincter of Oddi. Vagal activity increases flow.

Clinical significance

Classification of jaundice

Pre-hepatic jaundice (haemolysis) gives unconjugated bilirubin and no bilirubin in the urine. Hepatic jaundice (hepatitis, cirrhosis, Gilbert syndrome) gives a mixed picture. Post-hepatic (obstructive) jaundice gives conjugated hyperbilirubinaemia, dark urine (conjugated bilirubin is water-soluble), pale stools, pruritus and a raised ALP. Clinical jaundice appears when serum bilirubin exceeds about 40–50 µmol/L (≈2.5–3 mg/dL).

Bile salt deficiency

Cholestasis, ileal disease or resection, or bacterial deconjugation (SIBO) reduce micelle formation. The results are steatorrhoea and deficiency of vitamins A, D, E and K; for example, vitamin K deficiency prolongs the prothrombin time.

Test yourself

Gallbladder contraction and relaxation of the sphincter of Oddi after a fatty meal are mainly caused by:

Secretin
Gastrin
Cholecystokinin
Somatostatin

Answer: Cholecystokinin

Fatty acids and amino acids in the duodenum release CCK from I cells. CCK contracts the gallbladder, relaxes the sphincter of Oddi and stimulates pancreatic enzyme secretion. Somatostatin inhibits gallbladder emptying.