5.1 Liver and Pancreas

Question 1

The stomach empties chyme __ bursts per/minute into the duodenum

Give 3 features of this chyme

Answer 1

The stomach empties chyme, 3 bursts per/min, into duodenum

Chyme is:
• Acid (lots of HCl)
• Hypertonic
• Partly digested

Question 2

Once chyme enters the duodenum what 2 things must be corrected and how?

Why are enzymes and co-factors required and where do these come from?

Answer 2

1) Acidity corrected by: HCO3 secreted from pancreas, liver and duodenal mucosa
2) Hypertonicity corrected by osmotic movement of water from ECF across duodenal wall

Enzymes and co-factors are required to digest fat. They come from pancreas, intestinal wall and liver, contained in bile acids

Question 3

Explain how the pancreas functions as both an exocrine and endocrine gland + examples

Answer 3

Endocrine component: located in the islets of Langerhans ➞ cells secrete insulin, glucagon and somatostatin

Exocrine component: made up of blind ended acini and ducts ➞ cells secrete enzymes and alkali

Question 4

Give 3 general enzymes that are secreted from the exocrine pancreas

Give 4 specific enzymes within one of these catagories

Answer 4

1) Proteases (secreted as inactive pre-cursors)

• Trypsin(ogen)
• Chymotrypsin
• Elastase
• carboxypeptidase

2) Amylases
3) Lipases

Question 5

What are the 2 hormones responsible for neutralisation of chyme in the duodenum?

What is the overall target of each of these in the exocrine pancrease

Answer 5

1) CCK: acts on acinar cells to secrete somatostatin
2) Secretin: acts on duct cells to secrete HCO3

Question 6

Describe the formation and activation of Acinar secretions at a cellular level

Answer 6

1) enzymes synthesised on ribosomes as inactive precursors
2) packaged into condensing vacuoles by Golgi to form zymogen granules
3) zymogen granules secreted by exocytosis
4) activated in intestine by enzymatic cleavage (by Trypsin)

Question 7

What would amylase in the blood indicate and why may this be caused?

Answer 7

Pancreas is damaged, these enzymes should not be in the blood!!

eg. Pancreatitis ➞ when pancreas is damaged enzymes (amylase) leak out hence and appear in blood

Question 8

What are the 2 ways in which acinar secretion is stimulated?

During which phase is each secreted?

Answer 8

1) CCK from duodenal APUD cells (Intestinal phase)
2) ACh from PNS post-ganglionic neurones via the vagus nerve (Cephalic phase)

Question 9

Where is cholecystokinin secreted from and what is it secreted in response to?

Answer 9

CCK is secreted from endocrine APUD cells in the duodenum in response to:

• hypertonicity
• fats
• gastrin

Question 10

Once CCK has been stimulated what does it do and why?

Answer 10

CCK acts on D cells of the pancreas to secrete somatostatin (+ other enzymes) at the right time during the ‘Intestinal phase’

Somatostatin is a potent antagonist of gastrin, hence acts to turn off acid secretion

Question 11

What stimulates duct secretion of HCO3?

Explain its release, function and negative feedback mechanism

Answer 11

Stimulated by secretin

1) low pH (acid) in duodenum stimulates release of secretin from S cells in the jejunum
2) secretin stimulates HCO3 secretion from duct cells of the pancreas
3) HCO3- neutralises acid in the duodenum

Controlled by negative feedback: more acid into duodenum ➞ more secretin release ➞ more HCO3

Question 12

The action of secretin is facilitated by what other hormone?

Answer 12

CCK

Question 13

How do ductal cells in the pancreas drive secretion of HCO3- into the lumen?

Answer 13

1) [HCO3-] is elevated in the blood due to acid formation
2) Na-/K+ ATPase creates low [Na+] and high [K+] inside the cell ➞ this allows the Na+/H+ antiporter to pump Na+ into cell and H+ out into ECF
3) H+ out combines with HCO3- to form H20 + CO2 ➞ which then moves back into cell and reform H+ and HCO3-
4) The H+ is then recycled back out into the ECF to cont process and the HCO3- is pumped through luminal membrane into blood

Question 14

What are the 2 broad functions of the liver and 3 sub-functions within each

Answer 14

Exocrine function:

1. secretion of bile containing alkaline juice to neutralise stomach acid
2. critical for capacity to digest and absorb fat
3. excretion of bile pigments and biliruben

Metabolism and endocrinology:

1. major contributor for energy metabolism
2. detoxification
3. makes plasma proteins (Albumin) and clotting factors

Question 15

Answer the following questions and label the diagram below:

1) How many lobes does the liver consist of and how are these furthur divided?
2) What is the functional unit of a liver called?
3) What does each lobule drain into and then where does this go?
4) What is located at the peripheries of each lobule and what drains these into the central structure
5) Bile is formed in what?

Answer 15

1) The liver consists of 2 main lobes, both made up of 8 segments that consist of 1,000s lobules (R lobe > L lobe)
2) Lobule
3) Central vein ➞ Hepatic veins ➞ IVC
4) Portal triad (hepatic a + portal v + 1-2 bile ducts), drains via sinusoids into the central vein
5) Hepatocytes

Question 16

Describe the flow of bile from liver into gallbladder

Answer 16

1) Bile is formed in hepatocytes and secreted into canaliculi
2) canaliculi ➞ bile duct
3) bile ducts merge ➞ R and L Hepatic duct
4) R and L Hepatic duct merge ➞ common hepatic duct
5) common hepatic duct ➞ cystic duct ➞ gallbladder

Question 17

What are the 2 distinct sources that supply blood to the liver and where does each come from?

Where do these enter the liver?

Answer 17

1) Hepatic artery (25%): supplies O2 rich blood from heart
2) Hepatic Portal vein (75%): supplies nutrient rich blood from the GI tract (all blood leaving stomach + intestines passes through liver)

Both enter at the “Porta Hepatis” and then branch around the peripheries of the lobules

Question 18

Describe the flow of blood through the liver

Answer 18

Terminal branches of the portal vein and hepatic artery empty and mix as they enter sinusoids in the liver. As blood flows through the sinusoids plasma is filtered into the space between hepatocytes and endothelia to become lymph. Blood then flows into the central vein ➞ hepatic veins ➞ IVC

Question 19

Describe the bile acid ‘dependent’ and ‘independent’ components of bile, where is each component secreted from?

Answer 19

Bile acid dependent:

• secreted into canaliculi by hepatocytes
• contains bile acids and pigments

Bile acid independent

• secreted by duct cells (lining bile ducts)
• contains alkaline juice (HCO3) also controlled by secretin

Question 20

What are the two main bile acids (salts) and what are they derivatived from?

How are they transported in bile?

Answer 20

Main bile acids = cholic acid + chenodeoxycholic acid both derived from cholesterol

They are conjugated to amino acids and travel in bile as micelles that contain bile acids, cholesterol and phospholipids ➞ critical for digestion and absorption of fat

Question 21

Why is digestion of fats in the stomach difficult?

Answer 21

Lipids/Fats are insoluble in water (hydrophobic) ➞ tend to aggregate into large globules as stomach acid breaks down natural emulsions

This makes action of digestive enzymes difficult because it lowers the surface area

Question 22

How does the body overcome digestion of fats? (Include an enzyme that helps)

Answer 22

Bile acids!!!

These act to emulsify fats into smaller globules. This increases the surface area for lipases to cleave FA and glycerol.

Co-lipase is an enzyme which links bile acids and lipases to spread them over surface and aid their function

Question 23

Once broken down how are the free fatty acids carried to the epithelial cells and then how are they transported into them?

What happens to the bile?

Answer 23

Micelles: these act as vehicles to carry hydrophobic molecules through aqueous luminal contents into the ‘unstirred layer’ next to epithelial cells

FA are then released slowly and enter cells by diffusion

The bile acids also contained in micelles remain in the gut to be recycled ➞ but a small proportion are deconjugated by bacteria

Question 24

What happens to the FFA once inside the epithelial cells?

Describe the structure you have mentioned

Answer 24

Once inside FAs are re-synthesised into TAGS and coated with proteins (from the SER) to form chylomicrons

• Chylomicrons: lipids with polar protein and phospholipid coat

These are then exported to lymphatics for transport in blood to tissues

Question 25

What happens to the bile acids that remain in the gut after fatty acids are absorbed?

Answer 25

Bile acids continue to the terminal ileum where they are activly absorbed by epithelium of ileum

They return in hepatic portal blood to hepatic sinusoids and are activley taken up by hepatocytes and re-secreted into canaliculi

Question 26

What happens if neonate is unable to conjugate cholesterol for transport?

Answer 26

The result is unconjugated bilirubin that leads to neonatal jaundice

Question 27

What also stimulates the CCK receptor (other than CCK) and why?

Answer 27

Gastrin, as CCK and gastrin are very similar in structure

Question 28

What is meant by the “entero-hepatic circulation” and what is its significance?

Answer 28

The flow of bile acids from the liver ➞ duodenum ➞ terminal ileum ➞ entry into the hepatic portal blood ➞ to travel back to the liver ➞ REPEAT

This entero-hepatic circulation preserves a pool of bile acids

Question 29

If bile acids are constantly circulating and we have a “bile acid pool” at the ready, why must hepatocytes synthesize more?

Answer 29

Not all bile acids are recovered as some are unconjugated by bacterial action in the gut and lost. Hence, losses are replaced by hepatic synthesis

Question 30

When do bile acids return to the liver and from here where do they travel to be stored?

Answer 30

Bile acids return to liver in between meals and are secreted by canalicular cells well before they are needed next

They are stored in the gall bladder

Question 31

How does the gall bladder accommodate to store large amounts of bile?

What is the potential danger?

Answer 31

Volume stored is reduced in the gallbladder by concentration

It does this by transporting salt and water across gall bladder epithelium (out) thus concentrating the “bile acids” remaining

DANGER: concentration process causes an increases risks of precipitation which may lead to gall stone formation

Question 32

What stimulates the gall bladder to contract and release bile into the duodenum?

What else is released at the same time and why?

Answer 32

CCK

Bile acids are released into duodenum along with enzymes from pancreas AND alkali from pancreas and liver (in response to secretin)

Question 33

What is steatorrhoea and why does it occur?

Provide 3 descriptive characteristics of what the faeces would look like

Answer 33

Steatorrhoea = presence of undigested fat in feces

Occurs when bile acids or pancreatic enzymes are not secreted in adequate amounts causing fat to remain undigested and excreted in feces

Characteristics:

• Pale
• Floating
• Foul smelling

Question 34

Bilirubin is a breakdown product of ______. It is ______ in the liver, then secreted into ______ and excreted in faeces

Answer 34

haemoglobin, conjugated, bile

Question 35

What happens if metabolism of bilirubin goes wrong?

Answer 35

If bilirubin cannot be secreted into the bile it will accumulate in blood leading to Jaundice

Question 36

Describe the process of Haemoglobin break down

Answer 36

Haemoglobin is broken down into Heme and globin. Heme is transferred to the bone marrow, leaving behind biliverdin which is reduced to bilirubin (a yellow compound).

Bilirubin goes to the liver as a substrate for bile production and once bile has done its job the pigment is excreted as

1. stercobilin in feces (brown)
2. urrobilin in urine (straw-coloured)

Question 37

What are the 3 types of jaundice and very briefly explain what the the problem in each is

Answer 37

1) Hemolytic Jaundice (RBC): increased degredations of RBCs ➞ increased bilirubin
2) Hepatocellular Jaundice (LIVER): unable to form conjugated bilirubin
3) Obstructive Jaundice (BILE DUCT): unables to excrete conjugated bilirubin

Question 38

What are Kupffer cells and list 3 of their functions

Answer 38

Specialized macrophages in the walls of hepatic sinusoids:

1) Promote normal liver physiology
2) Release inflammatory mediators in response to toxic compounds
3) Role in the reticuloendothelial system