Theme 1: Lecture 6 - Secretions of the intestine, liver, gall bladder and pancreas

Question 1

What are the 3 primary secretions into the small intestine

Answer 1

• intestinal juice (mucus/HCO3-)
• pancreatic juice (digestive enzymes/HCO3-, pH 8)
• bile (bile salts)

Question 2

Brunner’s glands

Answer 2

• located in the submucosa of the duodenum.

- Secrete mucus and HCO3-

Question 3

What are the key endocrine hormones involved with the small intestine

Answer 3

secretin, cholecystokinin (CCK), glucose dependent insulinotrophic peptide, GIP (AKA gastric inhibitory peptide) regulate bile and pancreatic secretions

Question 4

What cells are located in villi of the small intestine

Answer 4

• Absorptive enterocytes

- Goblet cells

Question 5

What cells are located in the intestinal glands AKA crypts of Lieberkuhn

Answer 5

• Enteroendocrine cells

- Paneth cells

Question 6

What do absorptive cells in the small intestine do

Answer 6

Digest and absorb nutrients

Question 7

What do Goblet cells in the small intestine do

Answer 7

Secrete mucus

Question 8

What do enteroendocrine cells in the small intestine do

Answer 8

Secrete secretin, cholecystokinin (CCK) and glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP)

Question 9

What do paneth cells in the small intestine do

Answer 9

Secretes lysozyme and is capable of phagocytosis

Question 10

Describe stem cell renewal of epithelial cells in the small intestine

Answer 10

• rapid turnover of epithelial cells every 3-6 days

- vulnerable to radiation, chemotherapy

Question 11

Describe intestinal juice

Answer 11

fluid containing electrolytes and water (secretory enterocytes), lysozyme (Paneth cells), mucus (goblet cells), alkaline mucus containing fluid (submucosal duodenal Brunner’s glands)

Question 12

Where is cholecystokinin (CCK) secreted from

Answer 12

I cells

Question 13

What does cholecystokinin do

Answer 13

stimulate pancreatic and gallbladder secretion

Question 14

Where is secretin secreted from

Answer 14

S cells

Question 15

What does secretin do

Answer 15

stimulate pancreatic and biliary bicarbonate secretion

Question 16

Where is glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP) secreted from

Answer 16

K cells

Question 17

What does glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP) do

Answer 17

may inhibit acid secretion/stimulate insulin release

Question 18

Describe the structure of the pancreas

Answer 18

• The pancreas consists of glandular epithelial clusters
• 99% exocrine acinar clusters secreting pancreatic juice (water, electrolytes, sodium bicarbonate and pro-enzymes)
• 1% endocrine pancreatic islets (Islets of Langerhans) of 4 types

Question 19

What are the 4 types of islets of Langerhans cells in the pancrea

Answer 19

• Alpha
• Beta
• Delta
• F cell

Question 20

What do the alpha cells of islets of Langerhans cells in the pancreas secrete

Answer 20

Glucagon

Question 21

What do the beta cells of islets of Langerhans cells in the pancreas secrete

Answer 21

Insulin

Question 22

What do the delta cells of islets of Langerhans cells in the pancreas secrete

Answer 22

somatostatin

Question 23

What do the F cells of islets of Langerhans cells in the pancreas secrete

Answer 23

Pancreatic polypeptide

Question 24

Describe secretion from acinar cells in the pancreas

Answer 24

• Stimulated by Acetyl choline released via the parasympathetic vagus stimulation
• Stimulated by CCK - trigger is chyme containing fat and protein products
• Produces lower volume enzyme rich pancreatic juice

Question 25

Describe secretion from ductal cells in the pancreas

Answer 25

- Stimulated by secretin - trigger is H+ in highly acidic chyme - Produces copious HCO3- rich, low enzyme pancreatic juice

Question 26

What enzymes are secreted by the pancreas

Answer 26

- Proteolytic enzymes enzymes secreted in inactive form, convert proteins to peptides - Amylase hydrolyses starch, glycogen and other carbohydrates other than cellulose to form di and trisaccharides - Lipases hydrolyse fat into fatty acids and monogylcerides - Nucleases digest RNA and DNA to nucleic acids

Question 27

What other protein excluding enzymes is secreted by the pancreas

Answer 27

Trypsin inhibitor - prevents activation of trypsin to prevent pancreatic digestion

Question 28

Describe the activation of proteolytic enzymes

Answer 28

- Proteolytic enzymes are produced as inactive precursors called zymogens - Small intestinal brush border enterokinase enzyme cleaves hexapeptide to form active trypsin from trypsinogen - Trypsin cleaves and activates other proteolytic enzymes - Process prevents pancreatic autodigestion (+trypsin inhibitor)

Question 29

Describe duct secretion of HCO3- in the pancreas

Answer 29

- Secretin stimulates high volume HCO3− rich pancreatic juice - HCO3− secretion out of cell into the duct lumen is via Cl−/HCO3− exchange at the apical cell membrane - Cl− is recycled out of the cell via the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel under secretin stimulation via cAMP - Na+ is secreted transcellularly into the duct lumen following HCO3− secretion down electrochemical gradient, water follows by osmosis

Question 30

What does the ionic composition of pancreatic juice depend on

Answer 30

Secretory rate

Question 31

Describe ionic composition of pancreatic juice when it is unstimulated

Answer 31

Low secretion rate - electrolyte content is similar to that of plasma

Question 32

Describe ionic composition of pancreatic juice when it is stimulated

Answer 32

Higher secretion rate and rise in HCO3- from ductal cells inversely related to reduced concentration of Cl- in pancreatic juice

Question 33

Describe dysfunction of the ductal CFTR Cl- channel

Answer 33

- Patients with cystic fibrosis lack a functional Cl− CFTR channel in the luminal membrane, which results in defective ductal fluid secretion - The ducts become blocked with precipitated enzymes and mucus and the pancreas undergoes fibrosis (hence the name of the disease) - Blocked ducts impair secretion of needed pancreatic enzymes for digestion of nutrients, resulting in malabsorption - Treatment of this type of malabsorption includes oral pancreatic enzyme supplements taken with each meal

Question 34

Pancreatitis

Answer 34

an inflammatory disease where pancreatic enzymes are activated within the pancreas (and surrounding tissues), resulting in autodigestion of the tissues

Question 35

What causes pancreatitis

Answer 35

The most common causes of pancreatitis include gallstones and alcohol abuse where obstruction of the pancreatic duct occurs

Question 36

What is the role of bile in digestion

Answer 36

- Required for digestion and absorption of fats from the small intestine - Bile salts (amphipathic with hydrophobic/hydrophilic regions) emulsify fats for digestion by pancreatic lipase, solubilise fat digestion products into micelles for absorption across the mucosa - elimination of waste products (bile pigment bilirubin from heme in red blood cell degradation, Cholesterol, drugs)

Question 37

Where is bile synthesised

Answer 37

Bile is constantly synthesised by hepatocytes lining sinusoidal blood vessels in the liver acinus

Question 38

What are hepatocytes

Answer 38

The key functional cell of the liver forming 80% of the liver mass

Question 39

Where does bile drain into once it has been synthesised by hepatocytes

Answer 39

Bile drains into the blind ended canaliculi and into the bile duct for storage in the gall bladder or direct drainage into duodenum

Question 40

What do liver duct epithelial cells do in response to secretin

Answer 40

add water, Na+, HCO3− to increase bile volume

Question 41

What does the gall bladder do to bile

Answer 41

- Concentrates it - Water and electrolytes (Na+, Cl-, HCO3-) are reabsorbed across the gall bladder mucosa to concentrate bile salts, bilirubin and cholesterol

Question 42

Describe how bile pigment is excreted

Answer 42

- Haem from old/faulty RBC is converted to bilirubin (orange) and oxidised form biliverdin (green) in the spleen/ liver kupffer cells. - Bilirubin is hydrophobic so is transported to liver bound to albumin in unconjugated form - Bilirubin is conjugated (made hydrophilic) with glucuronic acid to form bilirubin diglucuronide by hepatocytes, excreted in bile - Gut bacterial hydrolysis (b glucuronidase) deconjugates bilirubin to form urobilinogen - Urobilinogen is reduced to stercobilin, excreted in faeces (brown colour) - Enterohepatic reabsorption of urobilinogen can occur, most re-secreted in bile (small amount excreted in urine)

Question 43

What is jaundice

Answer 43

The build up of bilirubin (serum bilirubin >30-60 mmol.L-1) (yellow discoloration of skin in severe jaundice)

Question 44

What are the 3 groups that jaundice tends to be divided into

Answer 44

- Pre hepatic - Hepatocellular/congenital - Post hepatic

Question 45

Pre hepatic jaundice

Answer 45

excessive RBC breakdown, build up of unconjugated bilirubin due to overload of processing mechanisms eg haemolytic anaemia

Question 46

Hepatocellular/congenital jaundice

Answer 46

altered hepatocyte function eg Crigler-Najjar syndrome (inborn error of metabolism - absence of hepatocyte bilirubin conjugating enzyme glucuronyl transferase results in increased unconjugated bilirubin)

Question 47

Post hepatic bilirubin

Answer 47

obstruction to normal bile drainage, build up of conjugated bilirubin eg gallstone obstruction of bile flow

Question 48

The role of CCK in relation to bile secretion

Answer 48

- Released in response to fat content of duodenum - Causes gall bladder contraction - Also causes sphincter of hepatopancreatic ampulla (Sphincter of Oddi) relaxation

Question 49

The role of secretin in relation to bile secretion

Answer 49

- Released in response to acidic chyme | - Liver ductal secretion of HCO3− , H20

Question 50

The role of vagal and enteric ACh stimulation in relation to bile secretion

Answer 50

- Minor role | - Causes bile flow and gall bladder contraction

Question 51

Describe enterohepatic circulation of bile salts

Answer 51

bile salts secreted by hepatocytes into bile and continuously recycled through active reabsorption from the ileum and then re-secretion into bile

Question 52

Describe gall bladder disease

Answer 52

Occurs in several forms, ranging from asymptomatic cholelithiasis (gallstones) to biliary colic (blockage of the cystic duct) affecting different areas of the biliary tract

Question 53

What is gallstones commonly caused by

Answer 53

- Excessive water and bile salt reabsorption from bile - Excessive cholesterol in bile causing precipitation (high fat diet) - Inflammation of epithelium (low grade chronic infection)