Secretions of the Intestine, Gall bladder and Pancreas. (FT: Physiology)

Secretin - this causes an increase in the production of HCO3- and water (high volume, HCO3- rich and low enzyme pancreatic juice) when there is an increase in H+ (highly acidic chyme).

Bicarbonate and water produced by the pancreatic ductal cells is controlled by?

Bile is constantly synthesised by hepatocytes lining sinusoidal blood vessels in the liver. 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 left and right hepatic ducts of the liver. In healthy individuals, bile is stored in the gall bladder.

Bile is constantly synthesised by _____ lining sinusoidal blood vessels in the liver. _____ are the key functional cell of the liver forming _____ of the liver mass. Bile drains into the blind-ended canaliculi and into the _____ and _____ _____ ducts of the liver. In healthy individuals, bile is stored in the _____ _____.

Gall bladder contraction and the relaxation of the sphincter of Oddi (hepatopancreatic sphincter).

CCK is released in response to the fat content of the duodenum and leads to what?

Liver --> Right and Left hepatic ducts --> Common hepatic duct --> cystic duct --> Gall bladder Gall bladder --> Cystic duct --> Common bile duct (pancreatic duct joins to the common bile duct) --> duodenum (when the hepatopancreatic sphincter/sphincter of Oddi opens).

Describe the route of bile from the liver to the gall bladder and from the gall bladder to the duodeum...

1) Excessive water and bile salt reabsorption 2) Excessive cholesterol in the diet 3) Inflammation of the epithelium (ie. low grade chronic infection)

Gall bladder disease can occur in several forms including gallstones (asymptomatic cholelithiasis) to biliary colic (blockage of the cystic duct). What are the commonest causes of gallstones?

Small intetsinal brush border enterokinase cleaves hexapeptide to form active trypsin from trypsinogen. Trypsin then cleaves other precursors producing active proteolytic enzymes.

How are proteolytic enzyme precursors activated?

There is a rapid turnover rate of secretory and epithelial cells (3-5 days). Stem cells are found in the base of intestinal crypts they differentiate to become goblet cells, enteroendocrine cells, absorptive cells or Paneth cells. As they get closer to the surface of the epithelium they mature except Paneth cells which mature downwards.

How are the epithelial cells of the intestinal glands produced?

Secretin, cholecystokinin, glucose dependant insulinotropic peptide (also known as gastric inhibitory peptide or GIP). Main role = regulate bile and pancreatic secretions

Name the 3 main hormones that relate to the small intestine... What is their main role?

1) Amylase = hydrolyses starch, glycogen and other carbohydrates to form di/trisaccharides 2) Lipases = hydrolyses fat into fatty acids and monoglycerides 3) Nucleases = digest RNA and DNA into nuclei acids 4) Proteolytic enzymes = Trypsinogen, chymotrypsinogen etc. -- secreted in their inactive form and responsible for the conversion of proteins to peptides

Name the enzymes produced by the pancreas and their functions...

An increase in the presence of chyme containing fat or protein products which causes ACh to be released via the vagus nerve and or CCK release. Both of these scenarios cause the pancreatic juice to be of lower volume but higher enzyme content.

Pancreatic acinar enzyme production can be upregulated by?

94%

Roughly what percentage of bile salts return to the liver via the portal vein to drive bile synthesis?

SECRETIONS OF THE SMALL INTESTINE: Intestinal juice contains electrolytes, water, lysozymes, mucous and alkaline mucous and fluid. Hormones: Cholecystokinin is secreted by I cells and stimulates pancreatic and gall bladder secretion. Secretin is secreted by S cells and stimulates pancreatic and biliary bicarbonate secretion. Gastric Inhibitory Polypeptide is secreted by K cells and inhibits acid secretion and stimulate insulin release. Bile is required for lipid emulsification to mix substances that would not usually mix. Exocrine pancreatic juice contains bicarbonate and digestive enzymes.

SECRETIONS OF THE SMALL INTESTINE: _____ _____ contains electrolytes, water, lysozymes, mucous and alkaline mucous and fluid. Hormones: _____ is secreted by I cells and stimulates _____ and _____ _____ secretion. _____ is secreted by S cells and stimulates _____ and _____ _____ secretion. Gastric Inhibitory Polypeptide is secreted by _____ cells and inhibits acid secretion and stimulate insulin release. Bile is required for _____ _____ to mix substances that would not usually mix. Exocrine pancreatic juice contains _____ and _____ _____.

HCO3- is secreted out of the cell into the lumen via a Cl-/HCO3- exchanger on the apical membrane. Cl- is them moved back out of the cell by the cystic fibrosis transmembrane conductance regulator (CFTR channel). Na+ then moves transcellularly (through the cell) down an electrochemical gradient bringing water with it.

Secretin stimulates high volume HCO3- rich pancreatic juice by acting upon ductal cells, what happens in the cell to produce the alkaline solution?

99% of the pancreas is made up of exocrine acinar clusters and 1% is islets of Langerhans.

The pancreas consists of exocrine acinar clusters and endocrine pancreatic islets. Roughly what percentage of the organ is acinar clusters and what percentage is islets?

Exocrine (bicarbonate and digestive enzyme rich pancreatic juice) and endocrine (insulin and glucagon).

The pancreas has two overall functions, what are they?

Acinar cells secrete high concentrations of sodium and chloride ions but low levels of bicarbonate ions. Ductal cells secrete high concentrations of bicarbonate and sodium but low concentrations of chloride ions.

The pancreatic acinar clusters have two main parts: the acinar cells and the ductal cells. They both secrete slightly different substances - explain the differences...

Chemical digestion and absorption of nutrients, electrolytes and water.

The small intestine is responsible for the majority of...

Intestinal juice (mucous and HCO3-) to neutralise chyme (primarily the duodenum). Pancreatic juice (digestive enzymes). Bile (bile salts) - synthesised in the liver, stored in the gall bladder

What are the primary secretions of the small intestine?

Bilirubin (from haem in red blood cell degredation) Cholesterol Drugs

What are the three main waste products from bile salt emulsification?

Alpha cells = glucagon Beta cells = insulin Delta cells = somatostatin F cells (or PP cells) = pancreatic polypeptide

What cells are found in the pancreatic islets and what do they secrete?

Enterocytes (housed by the villi) that produce isotonic fluid and have an absorptive role. Mucous secreting goblet cells (housed by the villi) produce mucous to neutralise chyme. Enteroendocrine cells produce hormones. Paneth cells produce lysozymes (a protective mechanism). DUODENUM ONLY Brunner's glands secrete mucous and HCO3- to neutralise chyme coming from the stomach.

What glands are there in the small intestine and what are their roles?

It prevents the activation of trypsin to prevent autodigestion and an inflammatory response.

What is Trypsin inhibitor and why is it needed?

They are vulnerable to chemotherapy and radiotherapy treatments as these rely on targeting cells like cancer cells, that regenerate quickly.

What is one clinical problem associated with the rapid regeneration rate of intestinal epithelial cells?

Pancreatitis is an inflammatory condition in which pancreatic enzymes are activated within the pancreas and surrounding tissues causing autodigestion of the tissues. The most common causes of pancreatitis are: Gall stones Alcohol abuse/dependence (in both obstruction of the pancreatic duct occurs).

What is pancreatitis? What are the most common causes?

The active reabsorption of bile salts in the ileum of the small intestine via the portal vein to the liver.

What is the Enterohepatic Circulation of bile salts?

GI tract reflex circuit where incoming and outgoing fibres of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain.

What is the Vasovagal reflex?

A number of drugs are secreted by the liver into bile and are therefore capable of undergoing enterohepatic recycling. These include antibiotics, NSAIDS, hormones, opioids, digoxin, and warfarin. If this type of circulation is changed, then excretion/ clearance of the drug is affected and bioavailability will be affected (excretion is affected so levels of the drug in the blood will be different than expected but how they are different depends on the drug involved).

What is the affect of Enterohepatic circulation of bile salts on drug bioavailability?

Zymogens

What is the name given to the proteolytic enzyme precursors?

Bile salts emulsify fats for digestion by pancreatic lipase. Once lipase has digested the fats bile salts can solubilise the digestion products into micelles allowing for absorption across the mucosal membrane.

What is the role of bile?

Stem cells are found at the bottom of crypts and differentiate to form other cells - these cells then move up towards the surface maturing as they go but Paneth cells move downwards as they mature insteasd.

What makes Paneth cells different with regards to stem cell regeneration?

Heoatopancreatic sphincter.

What part of the pancreas controls the amount of secretions?

1) CCK 2) Secretin 3) Vagal stimulation (less so than the other two but causes bile flow and gall bladder contraction)

What three things control bile secretion?

in the duodenum

Where are Brunner's glands found?

The intestinal phase - it controls 70% of the total activity of the pancreas.

Which of the three phases is the main regulatory phase?

To prevent autodigestion.

Why are pancreatic proteolytic enzymes secreted in an inactive form?

CCK is stimulated by an increase in protein and fat in the duodenum and an increase in enzyme-rich juice will help break these down.

Why does CCK cause an increase in enzyme-rich pancreatic juice?

Secretin stimulates HCO3- production by the ductal cells which causes the pancreatic juice to be more alkaline to neutralise the acidic chyme.

Why does low pH in the duodenum cause a release of Secretin by S cells?

It is the main factor causing alkaline secretions in the small intestine and provides a higher pH so that enzymes can work optimally. It also acts to neutralise the chyme coming from the stomach.

Why is HCO3- important in digestion?

It ensures that the volume of pancreatic juice matches that of the chyme in the duodenum.

Why is the regulation of the volume of pancreatic juice important?