Secretions of the intestine, liver, gallbladder and pancreas Flashcards
What is the role of the small intestine?
Governs the majority of chemical digestion and absorption of nutrients, electrolytes and water
What are the primary secretions of the intestine?
- intestinal juice (mucus/HCO3-)
- pancreatic juice ( digestive enzymes)
- bile (bile salts)
How are bile and pancreatic secretions regulated?
Key endocrine hormones secretin, cholecystokinin (CCK), glucose dependent insulinotrophic peptide * (GIP) regulate bile and pancreatic secretions
What are the secretory cells of the small intestine?
Villi: absorptive enterocytes and mucus secreting goblet cells
Intestinal glands: Enterocytes secreting isotonic fluid, entero-endocrine cells, paneth cells
In the duodenum only: Brunner’s glands secrete mucus and HCO3-
How doe stem cell renewal of epithelial cells work?
Derive from daughter cells at bottom of crypt
Start at bottom and move up during differentiation
What is the turnover of epithelial cells and what is the consequence of this?
- rapid turnover of epithelial cells every 3-6 days
- vulnerable to radiation, chemotherapy
Summarise the secretions of the small intestine
- Intestinal juice (1.2 L):
- 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 (by enteroendocrine cells) into vasculature
- CCK (I cells)– stimulate pancreatic and gallbladder secretion
- Secretin (S cells)–stimulate pancreatic and biliary bicarbonate secretion
- GIP (K cells) – may inhibit acid secretion/ stimulate insulin release
- Exocrine pancreatic juice (1.5 L): bicarbonate / digestive enzymes
- Bile (0.5-1 L) : bile salts for lipid emulsification (liver hepatocyte synthesis, gall bladder storage)
What does the pancreas secrete?
•Exocrine pancreas secretes pancreatic juice containing bicarbonate rich secretion (pH 8) and digestive enzymes essential for normal digestion and absorption
What is the structure of the pancreas?
•The pancreas consists of glandular epithelial clusters
What are the 2 types of glandular epithelial clusters found in the pancreas?
- 99% exocrine acinar clusters secreting pancreatic juice (water, electrolytes, sodium bicarbonate and pro-enzymes)
- 1% endocrine pancreatic islets (Islets of Langerhans) of 4 types secreting glucagon (alpha), insulin (beta), somatostatin (delta), pancreatic polypeptide (F cell)
Complete the diagram on the exocrine acinar cluster
Complete the diagram on acinar and ductular secretion
What is acinar and ductular secretions made of?
Ductular - NaHCO3, fluid
Acinar - enzymes, NaCl, fluid
How is acinar enzyme production regulated?
- Acetylcholine released via P/S vagus stimulation
- CCK – trigger is chyme containing fat and protein products
- Produces lower volume enzyme rich pancreatic juice
How is ductal bicarbonate and water secretions regulated?
- Secretin - trigger is H+ in highly acidic chyme
- Produces copious, HCO3- rich, low enzyme pancreatic juice
What are the 5 pancreatic enzymes?
- 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 monogylcerides
- Nucleases digest RNA and DNA to nucleic acids
- Trypsin inhibitor prevents activation of trypsin to prevent pancreatic digestion
How are proteolytic enzymes activated?
- 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
Why are proteolytic enzymes produced in the inactive form?
•Process prevents pancreatic autodigestion (+trypsin inhibitor)
What does secretin stimulate?
•Secretin stimulates high volume HCO3− rich pancreatic juice
Which cells are involved in duct secretion of sodium bicarbonate?
•HCO3− secretion out of cell into the duct lumen is via Cl−/HCO3− exchange at the apical cell membrane
How does duct secretion of sodium bicarbonate occur?
- 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 this diagram show?
•HCO3− secretion out of cell into the duct lumen is via Cl−/HCO3− exchange at the apical cell membrane
Complete the diagram with which ions each line represents
How does ionic composition of pancreatic juice depends on secretory rate when it is unstimulated and stimulated?
- 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
At all rates pancreatic juice is ____tonic with plasma
Isotonic
How is pancreatic juice secretion regulated?
Neurotransmitter acetylcholine (Ach) mediated vago-vagal gastro-pancreatic reflex, hormones gastrin, secretin, cholecystokinin (pancreozymin)
Complete the diagram on pancreatic juice regulation
What goes wrong with cystic fibrosis?
- 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
How is malnutrition caused by cystic fibrosis treated?
•Treatment of this type of malabsorption includes oral pancreatic enzyme supplements taken with each meal
What is pancreatitis?
•Pancreatitis is an inflammatory disease where pancreatic enzymes are activated within the pancreas (and surrounding tissues), resulting in autodigestion of the tissues
What is pancreatitis caused by?
•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 ( 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
How is bile synthesised?
- Bile is constantly synthesised by hepatocytes lining sinusoidal blood vessels in the liver acinus
- Bile drains into the blind ended canaliculi and into the bile duct for storage in the gall bladder or direct drainage into duodenum
What are hepatocytes?
•Hepatocytes are the key functional cell of the liver forming 80% of the liver mass
Where is bile stored?
Bile is stored in the gall bladder
What effect does secretin have on bile?
Liver duct epithelial cells add water, Na+, HCO3− to increase bile volume in response to hormone secretin
How does the gallbladder concentrate bile?
Water and electrolytes (Na+, Cl-, HCO3-) are reabsorbed across the gall bladder mucosa to concentrate bile salts, bilirubin and cholesterol
How is unconjugated bilirubin formed?
•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
How is bilirubin excreted?
- 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)
How is bilirubin reabsorbed?
•Enterohepatic reabsorption of urobilinogen, most re-secreted in bile (small amount excreted in urine)
Complete the diagram on bilirubin
What causes jaundice?
- 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
What are the 3 types of jaundice?
- 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 to normal bile drainage, build up of conjugated bilirubin eg gallstone obstruction of bile flow
How is bile secretion regulated?
- 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
What is 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 _______ to drive _________
•94% bile salts return via portal vein to drive bile synthesis in the liver
What is the effect of enterohepatic circulation on drugs?
•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
Name an asymptomatic and symptomatic gallbladder 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 are gallstones 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)
