Exocrine secretory functions and the liver and pancreas 4

Question 1

LEARNING OBJECTIVES:

*Exocrine secretions
*Pancreatic Proteolytic Enzymes
*Pancreatic Amylase
*Pancreatic Lipase
*Pancreatic Acinar Cells
*Ductular Cell Secretions
*Liver Structure
*Gallbladder and Bile

Question 2

Pancreatic secretions: it is a mixed gland what are the endocrine and exocrine secretions?

Answer 2

Exocrine - Enzymes (from acini) (amylase/lipase/protease), Bicarbonate (from duct)
Enzymatic alkaline mix that is drained into a central duct and empties into the duodenum for the food content

Endocrine - Insulin & glucagon from the Islets of Langerhans into circulatory system

Question 3

Pancreatic enzymes:

Answer 3

Proteolytic enzymes
Pancreatic amylase
Pancreatic lipase

Question 4

What do acinar and duct cells make in pancreas?

Answer 4

Acinar cells make enzymes and release from their apical side

Duct cells make sodium bicarbonate: watery solution with bicarbonate: HCO3 mix with enzymes giving us an alkaline enzyme mix

Question 5

What are enzymes packages into in the acinar cells of exocrine pancreas secretion?
What does each enzyme break down?
Where are they released into?

Answer 5

Enzymes are packages into granules called zymogens and within each granule you have proteolytic enzymes to breakdown proteins, amylase for carbohydrates and lipase for fats

Zymogens are released into central lumen
and travel down the duct

Question 6

Protein digestion in duodenum:

Answer 6

Protein digestion: proteins broken into absorable units: a.a.
Role of pancreas proteolytic enzymes they are held in duodenum to back up activity of pepsin to help break down proteins

=> Made in an inactive form in pancreas form and then deposited into duodenum to break down food

Question 7

Trypsinogen must remain inactive within the pancreas, why?
How do they become activated?

Answer 7

So they do not break down proteins here, they only are active in the duodenum for food breakdown of proteins into amino acids

Located in duodenal wall: enteropeptidase/enterokinase where it converts trypsinogen into trypsin which converts inactive enzyme chymotrypsinogen into chymotrypsin and converts precarboxypeptidase into carboxypeptidase
These active enzymes attack different peptide linkeages to break down poly peptide chains into amino acids
Mucous is secreted as well here to protect lining of the wall on the surface

Question 8

Pancreatic amylase?

Answer 8

Key player working with salivary amylase

they work together to breakdown glucose chains into simple chain sugar molecules

Question 9

Pancreatic lipase?

Answer 9

Most complicated
Makes in zymogen granules and deposited into small intestine and acts on emulsified lipids to break them down into monoglycerides and free fatty acids

Question 10

Acinar cells in pancreas?
What way is it located where does it empty its enzymes what are the ducts called - the network of them?

Answer 10

Parametal and orientated so apex points towards centre into central lumen: intercalated duct is what it is called this is where they release their enzymes
These ducts merge together to make intra lobular ducts which merge together to make inter lobular ducts

Question 11

Zymogen granules directed towards?
How do release their contents?

Answer 11

Central lumen with duct
Via exocytosis: fuse with membrane and deposit enzymes in the centre

Question 12

Route from acini to duodenum?

Answer 12

Acini -> intercalated ducts -> interlobular duct
then there are 2 different pathways:

interlobular duct -> main pancreatic duct (Wirsung’s duct) -> common bile duct -> hepatopancreatic ampulla -> sphincter of oddi -> major duodenal papilla

interlobular duct -> accessory pancreatic duct (duct of Santorini) -> minor duodenal papilla

Question 13

Major duodenal papilla what is drained into this?
What does the sphincter of Oddi do?

Answer 13

Enzymatic sodium bicarbonate solution drains into it here
It guards the enzymatic bicarbonate solution coming in

Question 14

Some individuals have duct of santorini but not all
how many?

Answer 14

60-70% of individuals which drains solution into minor duodenal papilla

Question 15

Ductular Cell Secretions:
What is the cellular mechanism by which sodium bicarbonate is made by duct cells within the exocrine pancreas?

Answer 15

Acidic chyme must be neutralised quickly in the duodenal lumen
Sodium bicarbonate rich fluid is secreted by duct cells of the duodenum that neutralises this acidic chyme

Happens in a pancreatic duct cell
Lumenal membrane on right and basal lateral on left hand side
key goal is to make sodium bicarbonate solution
need to deposit sodium ions and bicarbonate ions into the lumen
Duct cells have key enzymes: carbonate anhydrase - ca - same one from parietal cells of stomach
Take CO2 made by cellular metabolism or taken in by diffusion and Ca enzyme combines this with OH^- ions to make HCO3: bicarbonate - 1 source to make bicarbonate intracellularly in duct cells
However most of it actually comes from the plasma: main source via sodium potassium ATP pump
Sodium ions pumped out and potassium pumped in and this lowers the sodium concentration intracellularly which facilitates primary active transport mechanism - this symporter that brings sodium in from the plasma into the duct cell down into electrochemical gradient and that brings bicarbonate ions in with it

The majority of bicarbonate exits via antiporter moving down electrochemical gradient in exchange for chloride ions and some also diffuse through this CFTR (cystic fibrosis transmembrane conductance regulator protein) channel
Now we have bicarbonate in the lumen, what about sodium?
Very simple it passively diffuses between cells in the pancreatic duct cells - there are leaky tight junctions between these cells and this is how sodium gets across and combines with bicarbonate to make sodium bicarbonate

Question 16

Where does pancreas secretion occur?
How is this ductular cell secretions of sodium bicarbonate controlled?
Secretin? and CCK?

Answer 16

Pancreas secretion occurs at the intestinal phase of digestion when chyme is in the small intestine
Secretin and Cholecystokinin (CCK)
Secretin is made by duodenal mucosa and carried in the blood to pancreatic duct cell
Secretin is what induced pancreatic duct cells to make sodium bicarbonate solution
Acid is a stimulus for this secretin release
Feedback mechanism to neutralise the acid

CCK is also made by secretin in duodenal mucosa and stimulates the enzymatic production to breakdown the food contents particularly fat and protein

Question 17

Control of pancreatic aqueous NaHCO3 secretion via pathway?

Answer 17

Acid in the duodenal lumen causes increased secretin release from the duodenal mucosa. This secretin is carried by the blood and has a positive effect on the pancreatic duct cells where it induces an increased secretion of aqueous NaHCO3 solution into the duodenal lumen which then neutralises this acid via this feedback mechanism

Question 18

Control of pancreatic enzyme secretion?

Answer 18

Fat and protein products in the duodenal lumen cause an increase CCK release from the duodenal mucosa and CCK is carried by the blood into the pancreatic acinar cells whee it has a positive effect and induces increased secretion of pancreatic digestive enzymes into the duodenal lumen which then digests the fat and protein products in the duodenal lumen via this feedback mechanism

Question 19

Liver functions? 8

Answer 19

*Secretion of bile salts
*Detoxification
*Plasma proteins
*Storage
*Vitamin D activation- works with the kidneys - key for regulating intake of calcium in the diet
*Secretion of hormones - IGF as an example, key involvement in growth
*Inflammation
*Excreting cholesterol and bilirubin

Question 20

Nutrients absorbed into blood are delivered to
the liver via?

Answer 20

Hepatic portal vein - breaks up into diverse network of capillary beds called liver sinusoids
This allows liver to filter and process what we have taken in
Circuit exits via hepatic vein into circulatory system
Fats are awkward to this - are different they are in chylomicrons which cannot enter so they enter lacteals - lymphatic vessels which joins the thoracic duct and enters venous channel of the neck

Question 21

Function unit of lobular structure of liver?
What do they look like?
Individualised cells of liver?
Hepatocytes continuously secrete?

Answer 21

Lobules
- hexagon shape with 6 sides to it and centre there is a central vein that join together to form hepatic vein, at each corner there is a collection of vessels, so 6 collection of vessels
Edge there is: branch of hepatic artery carrying oxegnated blood to the liver, branch of hepatic portal veins which drains from the digestive ytact
artery and vein join together to make liver sinusoids which are little blood vessels that all drain blood towards central vein
last vessel is a branch of bile duct at periphery and this gives off little vessels the bile canaliculi - arrows at different direction for here
Hepatocytes
Bile

Question 22

1. What do secreted bile salts consist of?
2. How much are reabsorbed and by what?
3. What are these reabsorbed bile salts recycled by?

Answer 22

1. Secreted bile salts consist of 95% old, recycled bile salts and 5% newly synthesis bile salts.
2. 95% of bile salts are reabsorbed by terminal ileum.
3. Reabsorbed bile salts are recycled by enterohepatic circulation.

Question 23

Hepatocytes secrete bile continuously and this is the perfect example of? Explain

Answer 23

Structure function relationship
Hepatocytes are all orientated at a specific position - one side they border a blood vessel: a sinusoid and on opposite side they have a border with this bile canialiculi and this facilitates that each liver cell can take components from the blood that are needed to synthesis bile on one side of the cell and make bile in cell and then deposit cell on other side via canaliculi and go to bile duct
All little bile ducts come together to make big common bile duct

Question 24

Bile is continuous secreted by liver - how much?

Answer 24

250mL - 1L per day
Mainly water and bile salts in its composition
as we store between meals we have reabsorption of fluids particularly water and that concentrates the bile salts in the gall bladder, concentration of bile salts is a lot higher when in gallbladder compared to liver storage and that is how you can get gall stones as there is a high concentration of them here

Question 25

Bile salts primarily are what?
Derived from?
Primary bile acids include?
Secondary bile acids include?
Bile acids primary and secondary secretion?
Bile acid conjugation takes place what does this enhance?

Answer 25

Bile acids
Mainly cholesterol
Cholic acid and chenodeoxycholic acid
Deoxycholic, lithocholic and ursodeoxycholic acids
Primary – secreted by hepatocytes
Secondary – secreted by colonic bacteria
In the liver by addition of glycine or taurine to bile acid, this conjugation enhaces their detergent activity and allows them to emulsify fats

Question 26

Dietary fats are emulsified how?
What are micelles?

Answer 26

*Dietary fat in the form of triglycerides is emulsified by the detergent actions of bile salts

Micelles are water-soluble particles that can carry the end products of fat digestion within their lipid-soluble interiors

Question 27

Enterohepatic circulation

Answer 27

*Most bile salts are recycled
between the liver and small
intestine
*3-4g bile salts in body
*3-15g bile salts may be emptied
into the duodenum

Question 28

Cholestasis

Answer 28

Impaired production and/or excretion of bile
Causes: Primary biliary cirrhosis (autoimmune)
Primary Sclerosing cholangitis (inflammation of ducts). Progressive familial intrahepatic cholestasis
Obstructive jaundice (e.g. gallstones)
Consequences: pruritis, hypercholesterolaemia,
jaundice

Question 29

Gall bladder structure?
Sphincter of Oddi?
Vagal nerve role?
Major mobiliser of bile?

Answer 29

Fundus - base, Body and Neck
Also a cystic duct that comes off it and joins hepatic duct
Once they join it is called the common bile duct
Bile flows down and joins main pancreatic duct and there is a sphincter of Oddi

=> CCK is a real multitasker - its a pancreatic enzyme, secretory regulatiory but it also modulates bile
There is this neural control: via cranial vagus never the dorsal vagal complex
The vagus nerve also mobilises bile and contracts its muscle and shunts the bile out of it and this neural control takes place during cephalic and gastric phase
=> CCK: causes major contraction and mobilisation of bile during intestinal phase

Question 30

Constituent of bile changes as its stored in the gall bladder?

Answer 30

This is how gallstones can occur and then gall bladder is removed but doesn’t affect functioning as common bile duct dilates to accomodate bigger volume

Question 31

What volume is absorbed by the small intestine per day?
Food eaten?
Fluid drunk?
Volume of faeces eliminated from the colon per day?

Answer 31

9000 mL
1250g
1250 mL

1 mL of H20 weighs 1g and a high % of food and faeces is H20, we can roughly equate grams with mililitres of fluid
150g