Wk 2 - Physiology: Pancreas and Biliary Tree

Question 1

Discuss the components of bile formations.

Answer 1

• Bile acid dependent
• Bile acid independent (mainly due to Na+ and associated anions but other substances secreted in bile, including drugs, can cause an increased flow – a choleresis)
• Water follows by osmosis

Question 2

What product forms from the breakdown of haemoglobin?

Answer 2

Bilirubin (haem is broken down via haem oxygenase to biliverdin, which is then broken down to bilirubin via biliverdin reductase).

Question 3

What is ‘free bilirubin’?

Answer 3

Unconjugated bilirubin is not water-soluble and travels in the plasma bound to plasma proteins but, because it is unconjugated, it is called FREE BILIRUBIN

Question 4

What organ takes up free (unconjugated) bilirubin?

Answer 4

The liver

Question 5

List some cases in which plasma free bilirubin concentrations are increased.

Answer 5

• Excess is made e.g. as a result of excessive haemolysis or if the liver fails to take it up.
• Some drugs compete for bilirubin uptake and some individuals have a mild genetically based impaired bilirubin uptake (Gilbert’s Syndrome) and plasma bilirubin may be raised if they take these drugs or if bilirubin uptake mechanisms are stressed

Question 6

What is Gilbert’s Syndrome?

Answer 6

Mild genetically based impaired bilirubin uptake

Question 7

What will excess plasma free bilirubin lead to?

Answer 7

Jaundice

Question 8

Free bilirubin is taken up by the ______, where it is ______ and ______ into the ______.

Answer 8

Free bilirubin is taken up by the liver, where it is conjugated and secreted into the bile.

Question 9

What causes obstructive jaundice occur?

Answer 9

If the bile duct is blocked (for example by gallstones, adhesions or cancer of the head of the pancreas) then as a result of the increased duct concentration and pressure some of this conjugated bilirubin passes back into the blood causing “obstructive jaundice”.

Question 10

Give an example where there is intrahepatic obstructive jaundice.

Answer 10

In the case of alcohol-induced liver disease the cells lining the bile duct in the liver may swell and obstruct bile secretion this causes “intrahepatic obstructive jaundice”

Question 11

What happens to bilirubin when there is obstructive jaundice?

Answer 11

• Conjugated bilirubin goes out into the bloodstream/plasma
• This plasma conjugated bilirubin passes through the glomerular capillaries into the urine (hence the urine is very dark)

Question 12

What causes the darker coloured urine in individuals with jaundice?

Answer 12

Conjugated plasma bilirubin passes thru the glomeruli into the urine –> causing darker coloured urine.

Question 13

In the intestine, the ______ bilirubin is converted to _______ as a result of bacterial action and this is then in turn converted to _______ and then ______ which is oxidised to ______ giving the faeces its characteristic brown colour.

Answer 13

In the intestine, the conjugated bilirubin is converted to urobilinogen as a result of bacterial action and this is then in turn converted to urobilin and then stercobilinogen which is oxidised to stercobilin giving the faeces its characteristic brown colour.

Question 14

What gives faeces its characteristic brown colour?

Answer 14

Metabolism of bilirubin in the intestines into the final product of stercobilin.

Question 15

Describe the breakdown/metabolism pathway of bilirubin (intestines and urine). Use a diagram to illustrate that.

Answer 15

1. Creation of Bilirubin
   
   1. Reticuloendothelial cells are macrophages which are responsible for the maintenance of the blood, through the destruction of old or abnormal cells. They take up red blood cells and metabolise the haemoglobin present into its individual components; haem and globin. Globin is further broken down into amino acids which are subsequently recycled.
   2. Meanwhile, haem is broken down into iron and biliverdin, a process which is catalysed by haem oxygenase. The iron gets recycled, while biliverdin is reduced to create unconjugated bilirubin.
2. Bilirubin Conjugation
   
   1. In the bloodstream, unconjugated bilirubin binds to albumin to facilitate its transport to the liver. Once in the liver, glucuronic acid is added to unconjugated bilirubin by the enzyme glucuronyl transferase. This forms conjugated bilirubin, which is soluble. This allows conjugated bilirubin to be excreted into the duodenum in bile.
3. Bilirubin Excretion
   
   1. Once in the colon, colonic bacteria deconjugate bilirubin and convert it into urobilinogen. Around 80% of this urobilinogen is further oxidised by intestinal bacteria and converted to stercobilin and then excreted through faeces. It is stercobilin which gives faeces their colour.
   2. Around 20% of the urobilinogen is reabsorbed into the bloodstream as part of the enterohepatic circulation. It is carried to the liver where some is recycled for bile production, while a small percentage reaches the kidneys. Here, it is oxidised further into urobilin and then excreted into the urine.

Question 16

What does excessive haemolysis lead to?

Answer 16

1. Pre hepatic jaundice (plasma pigments enter the skin)
2. Normal yellow urine (urobilin in plasma)
3. Dark faeces (stercobilin formed in gut)

Question 17

What would biliary obstruction cause?

Answer 17

1. Obstructive jaundice (plasma pigments enter the skin)
2. Dark urine (water-soluble pigments in plasma)
3. Pale faeces (bile pigments not reaching lower GI tract)

Question 18

What would liver failure lead to?

Answer 18

1. Intra hepatic jaundice (plasma pigments enter the skin)
2. Possibly pale urine (less urobilin in plasma)
3. Pale faeces (stercobilin not formed in the gut - this requires the liver failure to be quite severe)

Question 19

Where is bile primarily secreted from?

Answer 19

The liver

Question 20

Where is bile modified?

Answer 20

Gallbladder and bile ducts

Question 21

What leads to stone formation from bile?

Answer 21

• Na+, Cl-, HCO3- and H2O are absorbed in the gall bladder
• This concentrates the bile and may result in stone formation
• Micelles form containing the bile salts and cholesterol. Stones may be cholesterol, pigment or mineral (Ca++) based

Question 22

Describe the mechanism of bile flow into the duodenum.

Answer 22

1. Controlled by the reciprocal activity of the gall bladder and the sphincter at the base of the duct (sphincter of Oddi)
2. Between meals the sphincter is contracted and the flow of bile is diverted into the gall bladder. There is a receptive relaxation in the gall bladder such that the pressure does not increase greatly.
3. Gallbladder volume falls as water is reabsorbed
4. Food (esp fatty foods) in the duodenum initiates CCK secretion this causes the gall bladder to contract
5. The duct sphincter opens as the early part of the peristaltic wave driving the food passes it and bile is secreted into the duodenum

Question 23

What initiates bile secretion into duodenum?

Answer 23

Presence of food (esp fatty food) in the duodenum

Question 24

List some of the main functions of bile acids.

Answer 24

1. They inhibit 7α-hydroxylase in liver which provides a control on their rate of synthesis by negative feedback
2. They promote choleresis – bile flow
3. They stimulate phospholipid secretion
4. They help to solubilise cholesterol in the bile duct and gallbladder by forming micelles
5. They emulsify fats, fatty acids, monoglycerides and phospholipids in the jejunum
6. They aid absorption of the fat soluble vitamins A,D,E &K
7. They inhibit salt and water reabsorption in the colon
8. They stimulate colonic motility

Question 25

Where are bile acids usually reabsorbed?

Answer 25

Bile acids are very irritant to the colon but they do not normally get this far because they are powerfully reabsorbed in the terminal ileum

Question 26

What is the pancreas?

Answer 26

• Exocrine structure that produces digestive enzymes
• There is also an endocrine component α, β and δ cells

Question 27

What controls pancreatic secretion?

Answer 27

• The pancreas is controlled by hormones and nerves
• Secretin stimulates salt and water secretion
• CCK stimulates enzyme secretion
• Gastrin shares a terminal tetrapeptide with CCK and has some CCK like activity
• Vagus causes a powerful vasodilation
• Vagus –
  
  • ACh fibres cause enzyme secretion
  • VIP fibres cause salt and water secretion

Question 28

Where is secretin produced?

Answer 28

Produced by cells in the crypts of Lieberkühn between the villi of the duodenum and jejunum

Question 29

What stimulates secretin release?

Answer 29

Low pH in gut lumen

Question 30

List the two functions of secretin.

Answer 30

1. Stimulates the production of salt and water by the pancreas
2. Inhibits stomach acid secretion and motility to control food entry into duodenum

Question 31

Where is CCK produced?

Answer 31

In cells in “pear-shaped” glands which are situated in the intestinal mucosa and have apical processes which reach into the lumen (similar to G cells in stomach)

Question 32

What stimulates CCK release?

Answer 32

Stimulus to release is food in the duodenum/jejunum especially fat

Question 33

What are the functions of CCK?

Answer 33

1. Stimulates gall bladder contraction
2. Stimulates pancreatic enzyme secretion
3. Has gastrin like activity
4. Inhibits gastric emptying

Question 34

Describe the different phases of pancreatic secretion.

Answer 34

• Cephalic phase mainly via the vagus from the nucleus tractus solitarius and the dorsal vagal nucleus
• Gastric Phase – distension of the stomach via vago vagal reflexes. Gastrin has some CCK like activity
• Intestinal – secretin, CCK and vagus