Secretions of the intestine, liver, gallbladder and pancreas

Question 1

what are the. primary secretions of the small intestine

Answer 1

intestinal juice (mucus/HCO3-)
pancreatic juice (digestive enzymes)
bile (bile salts)

Question 2

what are key endocrine hormones involved

Answer 2

secretin
CKK
GIP
regulate bile and pancreatic secretions

Question 3

what are the secretory cells of the SI

Answer 3

villi (absorptive enterocytes and mucus secreting goblet cells)
intestinal glands (enterocytes secreting isotonic fluid, enteroendocrine cells, panted cells)
in duodenum only (Brunner's lands secrete mucus and HCO3-)

Question 4

Stem cell renewal of epithelial cells

Answer 4

Rapid turnover of epithelial cells every 3-6 days
differentiate and migrate moving to top of villi
Vulnerable to radiation and chemo

Question 5

Secretions of SI

Answer 5

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

Question 6

Key endocrine hormone secretion (by enteroendocrine cells) into vasculature

Answer 6

CCK (I cells) – stimulate pancreatic and gallbladder secretion
Secretin (S cells) 0 stimulate pancreatic and biliary bicarbonate secretion
GIP (K cells) – may inhibit acid secretion/stimulate insulin release

Question 7

Exocrine/pancreatic juice

Answer 7

bicarbonate/digestive enzymes

Question 8

Bile

Answer 8

bile salts for lipid emulsification (liver hepatocyte synthesis, gall bladder storage)

Question 9

The pancreas’ secretions

Answer 9

Exocrine pancreas secretes pancreatic juice containing bicarbonate rich secretion (pH 8) and digestive enzymes essential for normal digestion and absorption

Question 10

Pancreatic structure

Answer 10

Clusters of glandular epithelial clusters
99% exocrine acinar clusters secreting pancreatic juice (water, electrolytes, sodium bicarbonate, pro-enzymes)
1% endocrine pancreatic islets (islets of Langerhans) of 4 types secreting glucagon (a), insulin (B), somatostatin (delta), pancreatic polypeptide (F cell)

Question 11

Exocrine acinar clusters

Answer 11

like grapes 
main duct to interlobular ducts with lobule with acinar 
acinar cell (cck, ach) enzyme and cl- rich secretion
duct cell (secretin) HCO3- rich secretion

Question 12

Acinar and ductular secretions

Answer 12

acinar enzymes NaCl fluid

ductular NaHCO3 fluid

Question 13

Regulation of Acinar enzyme production

Answer 13

Ach released via ps vagus stimulation
CCK – trigger is chyme containing fat and protein products
Produces lower volume enzyme rich pancreatic juice

Question 14

regulation of ductal bicarbonate and water

Answer 14

Secretin – trigger is H+ in highly acidic chyme

Produces copious HCO3- rich low enzyme pancreatic juice

Question 15

Pancreatic enzymes

Answer 15

Proteolytic enzymes secreted in inactive form, proteins to peptides
Amylase hydrolyses starch, glycogen and other carbs (other than cellulose) to form di and trisaccharides
Lipases hydrolyse fat into fatty acids and monoglycerides
Nucleases digest RNA and DNA to nucleic acids
Trypsin inhibitor prevents activation to trypsin to prevent pancreatic digestion

Question 16

Activation of proteolytic enzymes

Answer 16

Produced as inactive precursors called zymogens
SI 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 17

Duct secretion of sodium bicarbonate

Answer 17

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

Question 18

Ionic composition depends on secretory rate

Answer 18

Unstimulated – low secretion rate, electrolyte content similar to plasma
Stimulated – high secretion rate, rise in HCO3- from ductal cells inversely related to reduced concentration of Cl- in pancreatic juice

Question 19

Dysfunction in ductal CFTR Cl- channel

Answer 19

CF patients lack functioning channel in luminal membrane leads to defective ductal secretion
Duct blocked with precipitated enzymes and mucus, pancreas undergoes fibrosis
Blocked ducts impair secretion of pancreatic enzymes for digestion, malabsorption
Treated by taking oral pancreatic enzyme supplements with each meal

Question 20

Dysfunction in enzyme activation process

Answer 20

Pancreatitis – inflammatory disease when pancreatic enzymes are activated in pancreas (and surrounding tissues) resulting in autodigestion of tissues
Most common cause is gallstone and alcohol abuse where obstruction of duct occurs

Question 21

Role of bile in digestion

Answer 21

Digestion and absorption of fats
Bile salts (amphipathic) emulsify fats for digestion by pancreatic lipase, solubilise fat digestion products into micelles for absorption across mucosa

Question 22

role of bile in elimination of waste products

Answer 22

Bile pigment bilirubin from haem in RBC degradation (breakdown product stercobilin gives faecal brown colour)
Cholesterol
Drugs

Question 23

Synthesis and secretion of bile in liver

Answer 23

Bile constantly secreted by hepatocytes lining sinusoidal blood vessels in liver acinus
Hepatocytes are key functional cell of liver, 80% mass
Bile drains into blind ended canaliculi and into bile duct for storage in gallbladder or direct drainage into duodenum

Question 24

how does bile reach the gall bladder

Answer 24

Gallbladder via R and L hepatic ducts of liver, to cystic duct, bile duct and sphincter
Liver duct epithelial cells add water Na HCO3- to increase bile volume in response to secretin

Question 25

Gallbladder concentrates bile

Answer 25

Water and electrolytes (Na, Cl, HCO3) reabsorbed across gallbladder mucosa to concentrate bile salts, bilirubin and cholesterol

Question 26

Excretion of bile pigment bilirubin in bile

Answer 26

Haem from old/faulty RBC converted to bilirubin and oxidised to biliverdin (spleen, liver Kupffer cells), transported to liver bound to albumin in unconjugated form
Conjugated (made hydrophilic) with glucuronic acid to bilirubin diglucuronide by hepatocytes, excreted in bile
Gut bacterial hydrolysis (B glucuronidase) deconjugates bilirubin to form urobilinogen
Urobilinogen reduced to stercobilin, excreted in faeces (brown colour)

Question 27

Jaundice

Answer 27

Build up of bilirubin in blood

May occur when underlying disease process disrupts production and excretion of bilirubin

Question 28

Jaundice divided into

Answer 28

Pre-hepatic – excessive RBC breakdown, build up of unconjugated bilirubin due to overload of processing mechanisms eg haemolytic anaemia
Hepatocellular/congenital – altered hepatocyte function eg Crigler-Najjar syndrome (inborn error of metabolism – absence of hepatocyte bilirubin conjugating enzyme glucuronyl transferase, results in increased unconjugated bilirubin)
Post-hepatic – obstruction of normal bile drainage, build up of conjugated bilirubin eg gallstone obstruction of flow

Question 29

Bile secretion

Answer 29

CCK release in response to fat content of duodenum
Gall bladder contraction, sphincter of hepatopancreatic ampulla (sphincter of oddi) relaxes
Secretion released in response to acidic chyme – liver ductal secretion of HCO3- and H20
Minor role for vagal and enteric Ach stimulation, bile flow and gallbladder contraction

Question 30

Enterohepatic circulation of bile salts

Answer 30

Biles salts secreted by hepatocytes into bile and continuously recycled through active reabsorption from ileum and then reabsorbed into bile
94% bile salts return via portal vein to drive bile synthesis in liver

Question 31

what happens to hydrophobic drugs

Answer 31

Many hydrophobic drugs are deactivated by liver and excreted into bile
Enterohepatic recycling frequent, slowing the rate of drug elimination

Question 32

Gallbladder disease

Answer 32

Occurs in several forms, ranging from asymptomatic chlolelithiasis (gallstones) to biliary colic (blockage of cystic duct) affecting different areas of biliary tract
Gallstones commonly caused by excessive water and bile salt reabsorption from bile, excessive cholesterol in bile causing precipitation, inflammation of epithelium (low grade chronic infection),