Gallbladder & Bile

Question 0

How is chyme conditioned as it enters the duodenum?

Answer 0

Hypertonicity corrected by osmotic movement of water across the duodenal wall into the lumen (therefore can cause reduced BP if gastric emptying is too fast)

Acidity corrected by HCO3- secreted by the pancreas, liver, and duodenal mucosa

Digestion completed by enzymes from pancreas & small intestinal mucosa + bile acids from liver

Question 1

Define chyme.

Answer 1

Semi-liquid acid mass of food (produced by actions of gastric juices & churning movements of the stomach)

Question 2

What does the exocrine component of the pancreas secrete? How are these enzymes synthesised and stored?

Answer 2

Alkaline juice from ducts (water, ions, HCO3-)

Enzymes from acini

• amylases
• lipases
• proteases e.g. trypsinogen, chymotrypsinogen, elastase, carboxypeptidase

Synthesised by ribosomes, packaged into condensing vacuoles, form zymogen granules, secreted by exocytosis, activated in intestine by enzymatic cleavage

Question 3

What factors stimulate acinar secretion of enzymes from the pancreas?

Answer 3

Cephalic phase of digestion (pancreas synthesises enzymes ahead of time) via the vagus nerve (ACh)

Cholecystokinin (CCK) (duodenal APUD cells) which itself is stimulated by hypertonicity & fats in chyme (i.e. digestion is required)

note: gastrin is a competitive inhibitor of CCK (similar structure)

Question 4

How do pancreatic ducts secrete alkaline juice?

Answer 4

HCO3- taken from blood (alkaline tide) and reintroduced into the gut via duct cells

Stimulated by secretin, which is released from jejunal cells in response to reduced pH (despite increased pH in duodenum)

CCK makes duct cells more sensitive to secretin

Question 5

How are bile acids transported in the blood?

Answer 5

Conjugated to amino acids

Question 6

Outline the function of bile acids and where they travel within the enterohepatic circulation.

Answer 6

Travel down common bile duct into the duodenum

Conjugated with amino acids (increases solubility) & converted into secondary bile acids by intestinal bacteria

Re-emulsifies fat into small globules to increase s.a. for lipases (+ colipases link bile acids and lipases)

Sequester cholesterol, fat-soluble vitamins, and phospholipids

Travel as micelles (carries fat into unstirred layer so fatty acids can diffuse into the blood) - bile acids + cholesterol + phospholipids

Lipids resynthesised in epithelial cells and exported to lymphatics as chylomicrons

Bile acids released back into lumen and actively reabsorbed in the terminal ileum

Return to sinusoids via hepatic portal vein & re-secreted into canaliculi by hepatocytes

95% of bile acids recycled (some bile acids are unconjugated from amino acids by bacteria and are lost, therefore hepatocytes need to synthesise new bile acids)

Question 7

How are bile acids stored?

Answer 7

Bile acids are not continuously secreted (sphincter in biliary tree shuts so bile acids move back up the cystic duct into the gallbladder)

Volume stored reduced by transporting salt and water across the gallbladder epithelium, concentrating the bile (increases risk of precipitation and formation of gallstones)

CCK stimulates contraction of gallbladder muscle in response to gastric emptying

Question 8

How can the appearance of the gallbladder give a clue to diagnosis?

Answer 8

Shrunken, fibrotic gallbladder indicates gallstones formed over a long period of time

Enlarged gallbladder indicates a short period of biliary obstruction e.g. malignancy

Tender gallbladder indicates acute cholecystitis

Tender and distended gallbladder indicates mucocele/empyema related to gallstones

Question 9

What are the components of bile?

Answer 9

Water
Electrolytes (inc. HCO3-) - bile acid independent (secreted by duct cells)

Bile acid dependent (secreted into canaliculi by hepatocytes)

• bile acids e.g. cholic acid, chenodeoxycholic acid
• conjugated bilirubin

Cholesterol + phospholipids

Question 10

What is Charcot’s triad?

Answer 10

Triad of symptoms associated with ascending cholangitis (infection of obstructed biliary system)

• RUQ pain
• jaundice
• fever

Question 11

Give some examples of pathology associated with gallstones.

Answer 11

Cholecystitis: stones -> oedema -> mucosal ulceration -> fibropurulent exudate -> pain, systemic inflammatory response syndrome, pyrexia, sepsis

Biliary colic: impaction of stone + gallbladder contraction causes intermittent pain

Mucocoele = space/organ distended by mucus
Empyema = mucocele + infection
Obstructive jaundice
Ascending cholangitis = infection of obstructed biliary system

Question 12

What is the term for the formation of stones in the gallbladder? What is the aetiology associated?

Answer 12

Cholelithiasis

“fat, fair, forty, fertile, female”

• female, increasing age, obesity
• diet: fats & cholesterol?
• oral contraceptive pill
• ileal disease/resection e.g. Crohn’s
• haemolytic disease

80% mixed stones (cholesterol + calcium + bile pigments)
10 % pure cholesterol
10% pigment stones (calcium bilirubinate)