Secretions of the intestine, liver, gall bladder and pancreas

Question 1

The small intestine

Answer 1

Governs the majority of chemical digestion and absorption of nutrients, electrolytes and water
Primary secretions are intestinal juice (mucus/HCO3-), pancreatic juice (digestive enzymes) and bile (bile salts)
Key endocrine hormones: secretin, cholecystokinin (CCK), glucose dependent insulinotrophic peptide (GIP) (regulate bile and pancreatic secretions)

Question 2

Secretory cells of the small intestine

Answer 2

Villi: absorptive entueroctes and mucus secreting goblet cells
Intestinal glands: enterocytes secreting isotonic fluid, enters-endocrine cells, paneth cells
In the duodenum only: Brunner’s glands secrete mucus and HCO3-

Question 3

Secretions of the small intestine

Answer 3

Intestinal juice (1.2L): fluid containing electrolytes and water (secretory enterocytes), lysozyme (paneth cells), mucus (goblet cells), alkaline mucus containing fluid (submucosal duodenal Brunner’s glands).
Key endocrine hormone secretion into vasculature (by enteroendocrine cells):
CCK (I cells) - stimulate pancreatic and gall bladder secretion
Secretin (S cells) - stimulate pancreatic and biliary bicarbonate secretion
GIP (K cells) - may inhibit acid secretion/stimulate insulin release.
Exocrine pancreatic juice (1.5L): bicarbonate/digestive enzymes.
Bile (0.5-1L): bile salts for lipid emulsification (liver hepatocyte synthesis, gall bladder storage)

Question 4

The Pancreas

Answer 4

Exocrine pancreas secrets pancreatic juice containing bicarbonate rich secretion (pH8) and digestive enzymes essential for normal digestion and absorption
Structure: consists of glandular epithelial clusters - 99% exocrine acing clusters secreting pancreatic juice (water electrolytes, sodium bicarbonate and pro-enzymes) & 1% endocrine pancreatic islets of 4 types secreting glucagon (alpha) insulin (beta) soma statin (delta) pancreatic polypeptide (F cell)

Question 5

Regulation of Exocrine pancreatic secretion

Answer 5

Acinar enzyme production: acetylcholine released via P/S vagus stimulation, CCK (trigger is the chyme containing fat and protein products), produces lower volume enzyme rich pancreatic juice.
Ductal bicarbonate and water: secretin (trigger is H+ in highly acidic chyme), and produces copious, HCO3- rich, low enzyme pancreatic juice

Question 6

Pancreatic Enzymes

Answer 6

Proteolytic 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 monoglycerides
Nucleases digest RNA and DNA to nucleic acids
Trypsin inhibitor prevents activation of trypsin to prevent pancreatic digestion

Question 7

Activation of proteolytic enzymes

Answer 7

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 8

Duct secretion of sodium bicarbonate

Answer 8

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 9

Ionic composition depends on secretory rate

Answer 9

Unstimulated: Low secretion rate – electrolyte content is similar to that of plasma
Stimulated: Higher secretion rate and rise in HCO3- from ductal cells inversely related to reduced concentration of Cl- in pancreatic juice; Al all rates, pancreatic juice is isotonic with plasma

Question 10

Regulation of pancreatic juice secretion

Answer 10

Neurotransmitter acetylcholine (Ach) mediated vago-vagal gastro-pancreatic reflex, hormones gastrin, secretin, cholecystokinin (pancreozymin)

Question 11

Dysfunction in ductal CFTR Cl- channel

Answer 11

• 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 12

Dysfunction in the enzyme activation process

Answer 12

• Pancreatitis is an inflammatory disease where pancreatic enzymes are activated within the pancreas (and surrounding tissues), resulting in autodigestion of the tissues
• The most common causes of pancreatitis include gallstones and alcohol abuse where obstruction of the pancreatic duct occurs

Question 13

Role of bile in digestion

Answer 13

Required for digestion and absorption of fats from the small intestine (up to 1 L secreted /day): 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 (breakdown product stercobilin gives faecal brown colour); Cholesterol; drugs

Question 14

Synthesis and secretion of bile in the liver

Answer 14

Bile is constantly synthesised by hepatocytes lining sinusoidal blood vessels in the liver acinus
Hepatocytes are the key functional cell of the liver forming 80% of the liver mass
Bile drains into the blind ended canaliculi and into the bile duct for storage in the gall bladder or direct drainage into duodenum
Liver duct epithelial cells add water, Na+, HCO3- to increase bile volume response to hormone secretin

Question 15

Gall bladder concentrates bile

Answer 15

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

Question 16

Excretion of bile pigment bilirubin in bile

Answer 16

Haem from old/faulty RBC converted to bilirubin (orange) and oxidised form biliverdin (green) (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)
Enterohepatic reabsorption of urobilinogen, most re-secreted in bile (small amount excreted in urine)

Question 17

Jaundice

Answer 17

The build up of bilirubin (serum bilirubin >30-60 mmol.L-1) (yellow discoloration of skin in severe jaundice)
May occur when underlying disease processes disrupt the production and excretion bilirubin
Jaundice tends to be divided into:
o Pre-hepatic– excessive RBC breakdown, build-up of unconjugated bilirubin due to overload of processing mechanisms eg haemolytic anaemia
o 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)
o Post-hepatic– obstruction to normal bile drainage, build up of conjugated bilirubin eg gallstone obstruction of bile flow

Question 18

Bile secretion and its regulation

Answer 18

CCK released in response to fat content of duodenum - Gall bladder contraction & Sphincter of hepatopancreatic ampulla (Sphincter of Oddi) relaxation
Secretin released in response to acidic chyme - Liver ductal secretion of HCO3− , H20
Minor role for vagal and enteric ACh stimulation - Bile flow, gall bladder contraction

Question 19

Enterohepatic circulation of bile salts

Answer 19

Enterohepatic circulation: bile salts secreted by hepatocytes into bile and continuously recycled through active reabsorption from the ileum and then re-secretion into bile
94% bile salts return via portal vein to drive bile synthesis in the liver
Many hydrophobic drugs (e.g., acetaminophen) are deactivated by the liver and excreted into bile; enterohepatic recycling frequently occurs, slowing the rate of drug elimination

Question 20

Gall bladder disease

Answer 20

Occurs in several forms, ranging from asymptomatic cholelithiasis (gallstones) to biliary colic (blockage of the cystic duct) affecting different areas of the biliary tract
Gallstones commonly caused by: Excessive water and bile salt reabsorption from bile; Excessive cholesterol in bile causing precipitation (high fat diet); Inflammation of epithelium (low grade chronic infection)