Theme 1: Lecture 6 - Secretions of the intestine, liver, gall bladder and pancreas Flashcards
What are the 3 primary secretions into the small intestine
- intestinal juice (mucus/HCO3-)
- pancreatic juice (digestive enzymes/HCO3-, pH 8)
- bile (bile salts)
Brunner’s glands
- located in the submucosa of the duodenum.
- Secrete mucus and HCO3-
What are the key endocrine hormones involved with the small intestine
secretin, cholecystokinin (CCK), glucose dependent insulinotrophic peptide, GIP (AKA gastric inhibitory peptide) regulate bile and pancreatic secretions
What cells are located in villi of the small intestine
- Absorptive enterocytes
- Goblet cells
What cells are located in the intestinal glands AKA crypts of Lieberkuhn
- Enteroendocrine cells
- Paneth cells
What do absorptive cells in the small intestine do
Digest and absorb nutrients
What do Goblet cells in the small intestine do
Secrete mucus
What do enteroendocrine cells in the small intestine do
Secrete secretin, cholecystokinin (CCK) and glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP)
What do paneth cells in the small intestine do
Secretes lysozyme and is capable of phagocytosis
Describe stem cell renewal of epithelial cells in the small intestine
- rapid turnover of epithelial cells every 3-6 days
- vulnerable to radiation, chemotherapy
Describe intestinal juice
fluid containing electrolytes and water (secretory enterocytes), lysozyme (Paneth cells), mucus (goblet cells), alkaline mucus containing fluid (submucosal duodenal Brunner’s glands)
Where is cholecystokinin (CCK) secreted from
I cells
What does cholecystokinin do
stimulate pancreatic and gallbladder secretion
Where is secretin secreted from
S cells
What does secretin do
stimulate pancreatic and biliary bicarbonate secretion
Where is glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP) secreted from
K cells
What does glucose dependent insulinotrophic peptide AKA gastric inhibitory peptide (GIP) do
may inhibit acid secretion/stimulate insulin release
Describe the structure of the pancreas
- 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
What are the 4 types of islets of Langerhans cells in the pancrea
- Alpha
- Beta
- Delta
- F cell
What do the alpha cells of islets of Langerhans cells in the pancreas secrete
Glucagon
What do the beta cells of islets of Langerhans cells in the pancreas secrete
Insulin
What do the delta cells of islets of Langerhans cells in the pancreas secrete
somatostatin
What do the F cells of islets of Langerhans cells in the pancreas secrete
Pancreatic polypeptide
Describe secretion from acinar cells in the pancreas
- 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
Describe secretion from ductal cells in the pancreas
- Stimulated by secretin - trigger is H+ in highly acidic chyme
- Produces copious HCO3- rich, low enzyme pancreatic juice
What enzymes are secreted by the pancreas
- 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
What other protein excluding enzymes is secreted by the pancreas
Trypsin inhibitor - prevents activation of trypsin to prevent pancreatic digestion
Describe the activation of proteolytic enzymes
- 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)
Describe duct secretion of HCO3- in the pancreas
- 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
What does the ionic composition of pancreatic juice depend on
Secretory rate
Describe ionic composition of pancreatic juice when it is unstimulated
Low secretion rate - electrolyte content is similar to that of plasma
Describe ionic composition of pancreatic juice when it is stimulated
Higher secretion rate and rise in HCO3- from ductal cells inversely related to reduced concentration of Cl- in pancreatic juice
Describe dysfunction of the ductal CFTR Cl- channel
- 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
Pancreatitis
an inflammatory disease where pancreatic enzymes are activated within the pancreas (and surrounding tissues), resulting in autodigestion of the tissues
What causes pancreatitis
The most common causes of pancreatitis include gallstones and alcohol abuse where obstruction of the pancreatic duct occurs
What is the role of bile in digestion
- 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)
Where is bile synthesised
Bile is constantly synthesised by hepatocytes lining sinusoidal blood vessels in the liver acinus
What are hepatocytes
The key functional cell of the liver forming 80% of the liver mass
Where does bile drain into once it has been synthesised by hepatocytes
Bile drains into the blind ended canaliculi and into the bile duct for storage in the gall bladder or direct drainage into duodenum
What do liver duct epithelial cells do in response to secretin
add water, Na+, HCO3− to increase bile volume
What does the gall bladder do to bile
- Concentrates it
- Water and electrolytes (Na+, Cl-, HCO3-) are reabsorbed across the gall bladder mucosa to concentrate bile salts, bilirubin and cholesterol
Describe how bile pigment is excreted
- 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)
What is jaundice
The build up of bilirubin (serum bilirubin >30-60 mmol.L-1) (yellow discoloration of skin in severe jaundice)
What are the 3 groups that jaundice tends to be divided into
- Pre hepatic
- Hepatocellular/congenital
- Post hepatic
Pre hepatic jaundice
excessive RBC breakdown, build up of unconjugated bilirubin due to overload of processing mechanisms eg haemolytic anaemia
Hepatocellular/congenital jaundice
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 bilirubin
obstruction to normal bile drainage, build up of conjugated bilirubin eg gallstone obstruction of bile flow
The role of CCK in relation to bile secretion
- Released in response to fat content of duodenum
- Causes gall bladder contraction
- Also causes sphincter of hepatopancreatic ampulla (Sphincter of Oddi) relaxation
The role of secretin in relation to bile secretion
- Released in response to acidic chyme
- Liver ductal secretion of HCO3− , H20
The role of vagal and enteric ACh stimulation in relation to bile secretion
- Minor role
- Causes bile flow and gall bladder contraction
Describe enterohepatic circulation of bile salts
bile salts secreted by hepatocytes into bile and continuously recycled through active reabsorption from the ileum and then re-secretion into bile
Describe gall bladder disease
Occurs in several forms, ranging from asymptomatic cholelithiasis (gallstones) to biliary colic (blockage of the cystic duct) affecting different areas of the biliary tract
What is 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)
