Lecture 5: Biliary tree and gallstones

Question 1

Describe the structure of the biliary tree

Answer 1

Hepatocytes produce the bile which gets secreted into the bile canaliculi that originate between the hepatic cells.

The bile flows in the canaliculi toward the interlobular bile ducts and then into progressively larger ducts, septal bile ducts, intrahepatic ducts, left and right hepatic duct, common hepatic duct and finally reaching the common bile duct.

From these ducts the bile either empties directly into the duodenum (ampulla of Vater) or is diverted for minutes up to several hours through the cystic duct into the gallbladder.

Question 2

Common bile duct passes ____ the duodenum where it meets the pancreatic duct

Answer 2

Behind

Question 3

Flow of the bile is regulated by the ?

Answer 3

Sphincter of Oddi (smooth muscle)

Question 4

The initial portion is secreted by the principal functional cells of the liver, the hepatocytes; this initial secretion contains?

Answer 4

• Bile acids
• Cholesterol
• and other organic constituents.

Question 5

In its course through the bile ducts, a second portion of liver secretion is added to the initial bile. What is this additional secretion that is added?

Answer 5

Sodium and bicarbonate ions secreted by epithelial cells that line the ductules and ducts

Question 6

Sodium and bicarbonate ions secreted by epithelial cells that line the ductules and ducts are stimulated by which hormone?

Answer 6

Secretin

Question 7

What is the volume capacity of the gallbladder?

Answer 7

30 to 50 mL

Question 8

What is the epithelium that lines the gallbladder?

Answer 8

Simple columnar epithelium

Question 9

Where anatomically does the gallbladder lie

Answer 9

It lies in the gallbladder fossa on inferior surface of the right lobe of the liver

Question 10

The maximum volume that the gallbladder can hold is only 30 to 60 milliliters. Nevertheless, as much as 12 hours of bile secretion (usually about 450 milliliters) can be stored in the gallbladder because the gallbladder concentrates the bile

Describe how this is done?

Answer 10

• Most of this gallbladder absorption is caused by active transport of sodium through the gallbladder epithelium, and this transport is followed by secondary absorption of chloride ions, water, and most other diffusible constituents.

Question 11

Murphy’s point is the anatomical surface sign for which structure?

Answer 11

The gallbladder

Question 12

What are the components of bile

Answer 12

• Conjugated bilirubin
• Bile acids
• Cholesterol
• Water
• Electrolytes
• Phospholipids

Question 13

Describe how bilirubin is formed

Answer 13

• Old red blood cells break down after 120 days
• Most components are recycled
• Haem from haemoglobin is broken down to biliverdin
• Biliverdin is converted to unconjugated bilirubin

Question 14

Bilirubin is formed by the _____ in the form of ______

Answer 14

A) Spleen

B) Unconjugated bilirubin

Question 15

_____ bilirubin is insoluble in water so is transported in the blood bound to ____.

Answer 15

A) Unconjugated
B) Albumin

Question 16

Describe Gilbert’s syndrome

Answer 16

genetic defect on chromosome 2 for the locus coding for the UGT-1A1 protein.

This enzyme is important in the conjugation of bilirubin (from unconjugated to conjugated bilirubin)

Without it, bilirubin cannot be conjugated and therefore secreted in bile.

Question 17

The precursor of the bile salts is ?

Answer 17

Cholesterol

Question 18

Describe the formation of bile salts

Answer 18

Hepatcytes synthesis the primary bile salts

Cholesterol derivatives are conjugated with the amino acids glycine and taurine to form primary bile acids

Bacterial action in the gut convert primary bile acids to secondary bile acids

Question 19

Which hormone(s) causes the contraction of the gallbladder

Answer 19

Cholecystokinin

Vagal stimulation

Question 20

What does cholecystokinin do in relation to the biliary tree

Answer 20

Causes:

• Gallbladder contraction
• Relaxation of the sphincter of Oddi

Question 21

What hormone causes:

• Gallbladder contraction
• Relaxation of the sphincter of Oddi

Answer 21

Cholecystokinin (CCK)

Question 22

What hormone(s) causes:

• Gallbladder relaxation
• Contraction of the sphincter of Oddi

Answer 22

Sympathetic nerves

Vasoactive intestinal polypeptide (VIP)

Somatostatin

Question 23

Vagal stimulation causes ____ of the gallbladder.

Sympathetic stimulation causes ____ of the gallbladder.

Answer 23

A) Contraction

B) Relaxation

Question 24

About 94 percent of the bile salts are reabsorbed into the blood from the small intestine.

What two mechanisms cause the bile salts to be reabsorbed

Answer 24

• About one half of this by diffusion through the mucosa in the early portions of the small intestine
• The remainder by an active transport process through the intestinal mucosa in the distal ileum.
• They then enter the portal blood and pass back to the liver.

Question 25

•Synthesis of new bile acids in the liver compensates for ___ loss

Answer 25

Faecal

Question 26

Describe the enterohepatic circulation of bile salts

Answer 26

* This recirculation of the bile salts * Bile salts are reabsorbed into the blood from the small intestine * The bile salts enter the portal blood and pass back to the liver. * Upon reaching the liver and during first passage through the venous sinusoids, these salts are absorbed almost entirely back into the hepatic cells * The small quantities of bile salts lost into the feces are replaced by new amounts formed continually by the liver cells.

Question 27

If the terminal ileum does not absorb bile acids then what happens?

Answer 27

The bile salts reach the colon and cause diarrhoea “bile salt diarrhoea”

Question 28

When does "bile salt diarrhoea" occur

Answer 28

* After surgery if the terminal ileum or ileocaecal valve is removed * Disease of the terminal ileum eg Crohn’s disease

Question 29

What are the 5 Fs associated with gallstones?

Answer 29

**Female** **Fair** - more common in Caucasians **Fertile** **Forty** - Increasing incidence with age **Fat** - Diet (low fibre)

Question 30

Approx. 15% of the population has gallstones. What is the treatment for these?

Answer 30

* Approx 80% asymptomatic - these do not require any treatment * Laparoscopic cholecystectomy

Question 31

What are the 3 main types of gallstones

Answer 31

1. **Cholesterol** **stone** 2. **Bile** **pigment** **stone** 3. **Mixed** **stone** - most common (80%)

Question 32

Define Cholecystitis

Answer 32

Inflammation of gallbladder

Question 33

Define Cholelithiasis?

Answer 33

Gallstones (within gallbladder)

Question 34

Define Cholecystectomy

Answer 34

Removal of gallbladder

Question 35

Define Choledocholithiasis

Answer 35

Gallstone within bile duct

Question 36

Define Cholangitis

Answer 36

Infection of bile duct

Question 37

Describe the pathogensis of cholesterol gallstones

Answer 37

The liver produces bile that contains an excess of cholesterol because there is either a relative deficiency of bile salts or a relative excess of cholesterol. Cholesterol is solubilised by bile but high levels of cholesterol lead to supersaturation, typical when levels of oestrogen are high. Additionally, it could be due to biliary stasis or increase in bilirubin production.

Question 38

Describe the pathogenesis of bile pigment gallstones

Answer 38

They are common in the Far East, where infection allows bacterial β-glucuronidase to hydrolyse conjugated bilirubin to its free form, which then precipitates as calcium bilirubinate. The mechanism of black pigment gallstone formation in developed countries is not satisfactorily explained.

Question 39

Name some of the complications that can occur from gallstones in the gallbladder

Answer 39

* Biliary colic * Acute Cholecystitis * Empyema * Mucocoele * Cancer

Question 40

Name some of the complications that can occur from gallstones in the common bile duct

Answer 40

* Obstructive jaundice * Cholangitis * Pancreatitis

Question 41

Name some of the complications that can occur from gallstones in the small intestine

Answer 41

Gallstone ileus

Question 42

Describe biliary colic

Answer 42

* This is when there is a gallstone in the gallbladder that is obstructing bile flow. * Typically right upper quadrant pain following a fatty meal as gallstones obstruct the cystic duct during contraction of the gallbladder. * Does not cause jaundice as the bile can still be secreted from the liver. * Liver function test is commonly normal

Question 43

Describe Acute Cholecystitis

Answer 43

* Impacted gallstone in gallbladder leading to the gallbladder wall oedema/inflammation and development of bacterial infection within the wall. * **Clinical** **symptoms**: Pain, nausea, vomiting, fever, abdominal tenderness * **Investigation**: Raised inflammatory markers, sometimes abnormal LFT +/- jaundice * **Treat**: antibiotics, analgesia, elective cholecystectomy when symptoms settle

Question 44

Connect the correct statements

Answer 44

**AST/ALT** – hepatocyte enzymes (AST also found in cardiac muscle cells) **ALP/GGT** – enzymes associated with bile duct cells but different isoenzyme of ALP also produced in bone **Bilirubin** – conjugated and secreted by liver

Question 45

Aspartate aminotransferase (AST) is found in which cells?

Answer 45

present in cytosol and mitochondria of **hepatocytes**, also in **cardiac** muscle, **skeletal** muscle, **kidneys**, **CNS**

Question 46

Alkaline phosphatase (ALP) is found where?

Answer 46

A canalicular enzyme found in microvilli of cells lining bile tubes and sinusoidal surface hepatocytes. Also found in bone

Question 47

ALP and GGT will be severely raised in which pathology? A) Obstructive (posthepatic) B) Hepatic

Answer 47

A) Obstructive (posthepatic)

Question 48

Define Curvoisier’s Law

Answer 48

“in the presence of a palpable enlarged gallbladder which is non-tender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones”

Question 49

Name some of the extrinsic compression causes that can result in obstructive biliary tree

Answer 49

**Tumours** –Most commonly pancreatic –Lymph nodes **Inflammation** –Esp pancreatitis **Mirizzi Syndrome**

Question 50

Pancreatic cancer symptoms can include painless or painful jaundice? and why?

Answer 50

Painless jaundice Because it can obstruct the common bile duct

Question 51

Name some of the intramural causes that can obstruct the biliary tree

Answer 51

**Tumours** –Cholangiocarcinoma **Inflammation** –Primary Sclerosing Cholangitis (PSC) –IgG4 disease **Scarring / fibrosis** –Post inflammatory –Post surgical

Question 52

Name some of the intraluminal causes that can obstruct the flow of bile

Answer 52

* Stones * Sludge * Polyps