Physiology of exocrine secretion Flashcards
What is the pancreas?
It is a dual gland with an exocrine part for digestion and an endocrine part for the metabolic process
What is the exocrine part of the pancreas responsible for?
Digestion
What composes the endocrine part of the pancreas?
- Responsible for metabolism
- Islets of cells that are surrounded by the exocrine gland named as the islets of langerhans (with three subunits: alpha, beta and delta)
1) Alpha is responsible for 25% of the glucagon
2) Beta is responsible for 60% of the insulin
3) Delta are responsible for 10% of the somatostatin
What is the exocrine part of the pancreas composed of?
1) Acinar cells (produces digestive enzymes)
2) Ductal cells (secretes bicarbonate and transports the enzymes)
- These cells form acinus structures, which are blind-ended and lead to small ducts.
Small ducts merge into intercalated ducts, which join to form intralobular ducts, then interlobular ducts, eventually forming the main pancreatic duct (duct of Wirsung).The main pancreatic duct usually joins the common bile duct before entering the duodenum at the ampulla of Vater, regulated by the sphincter of Oddi
What is the endocrine function of the pancreas?
It secretes hormones directly into the blood to regulate metabolism
What stimulates the exocrine function of the pancreas?
- For digestion
1) The chyme in the upper part of the small intestine (main stimulus)
2) CCK (stimulates the secretion of the digestive enzymes) which has a role for the protein, carbohydrates and fats, from the acini
3) Secretin (stimulates the secretion of the aqueous component, bicarbonate ions, and water) from the epithelial cells of the duct
4) Neural control: sympathetic (inhibitory) and parasympathetic(vagus) which increases the enzymatic component of the secretions
What is the main stimulus for the exocrine function of the pancreas?
CCK
How does the exocrine function of the pancreas protects the mucosa of the S.I?
Due to the acidic pH of the stomach content, when this acid reaches to the duodenum the secretion of Secretin from the duodenal mucosa increases, which will stimulate the pancreatic duct cells to increase the secretion of NaHCO3 into the duodenal lumen, for both the protection of the mucosa and the activation of the pancreatic enzyme (like lipase)
Describe the pH sensing mechanism of the duodenum
When the pH drops to an acidic level as a result of the acidic chyme, the S-cells of the duodenum and jejunum are stimulated to release secretin which will increase the bicarbonate secretion from the pancreas
What is the cellular mechanism for the secretion of the bicarbonate?
The exocrine secretions of the pancreas are formed in two phases:
1) The acinar produces the enzymes
2) Enzymes will flow through the ducts and the ductal cells will add an aqueous bicarbonate solution into it
- Bicarbonate enters the ductal cells via
- In the ductal cells the carbon dioxide enters the cell from the blood side (basolateral side), which will then react with the water via carbonic anhydrase forming bicarbonate acid (which will accumulate inside the cell)
- Sodium bicarbonate channel which causes the entry of both the sodium and bicarbonate into the cell
- These two mechanisms will lead to the accumulation of bicarbonate inside the cell, allowing it to leave into the lumen
3) Sodium also enters the cell via the Na+ H+ exchanger found on the found on the basolateral membrane
4) From the basolateral membrane 3 sodium can also exit in exchange for 2
potassium
5) Bicarbonate exits from the luminal side into the lumen via the Cl_/HCO3 exchanger (getting the chloride into the cell)
6) Chloride ions are secreted into the lumen via the CFTR found in the luminal side
What is the mechanism of action of secretin?
It induces the secretion of the bicarbonate via the activation of the cystic fibrosis transmembrane (CFTR), increasing the outflow of Cl- into the ductal lumen, which will activate the Cl-/HCO3 exchanges increasing the secretion of bicarbonate
How is CCK regulated?
1) Fats and proteins products in the duodenum
2) Increased CCK release from the duodenal mucosa
3) CCK is then carried by the blood
4) The pancreatic acinar cells will thus increase the secretion of the pancreatic digestive enzymes into the duodenal lumen
Describe the neurohormonal control of the pancreatic secretion
Hormones:
1) Secretin is released postprandially into the circulation to stimulate the watery secretions (by increasing the bicarbonate)
2) CCK stimulates the exocrine gland of the pancreas to secrete digestive enzymes
- Neural:
3) The stimulation of the vagus nerve (ACh) results in an increase in the digestive enzymes
How are the pancreatic secretions regulated?
1) Acid from the stomach releases secretin from the wall of the duodenum
2) Fats and AA causes the release of CCK
3) Secretin and CCK are absorbed into the blood stream
4) Secretin will cause copious secretions of the pancreatic fluid and bicarbonate
5) CCK causes the secretion of enzymes
6) The vagal stimulation releases enzymes into the acini
What are the cells that releases CCK in the mucosa of the duodenum and jejunum?
I-Cells
What stimulates the secretion of CCK by the i-cells?
1) Direct stimulation of the I-cells (Which is stimulated by the presence of (proteoses, peptones and fatty acids))
2) CCK-RF (CCK-releasing factor) which is secreted by the paracrine cells within the epithelium into the lumen of the S.I
3) MP (monitor peptide), which is secreted by the pancreatic acinar cells into the pancreatic juice
How is the degradation of the indirect protein stimuli (CCK-RF & MP) are protected?
Mainly by the competition between the dietary proteins and the regulatory proteins, as all dietary proteins are being digested, the need for CCK would naturally decline, and thus the digestion of CCK-RF and MP will terminate the stimuli for CCK (FYI nothi directly inhibits the release of CCK but the digestion of the indirect signals via trypsin)
What are the pancreatic enzymes?
- They form 100 grams of the 1.5L pancreatic juice per day
- It contains multiple enzymes like:
1) Protease (for the digestion of proteins)
2) Amylase (for the digestion of carbs)
3) Lipase (for the digestion of fats)
What are the different digestive lipolytic enzymes of the pancreas?
1) Lipase
2) Prophospholipase A2
3) Carboxylesterase
What is the function of the pancreatic lipolytic enzymes?
It cleaves the ester linkages of the dietary fats
What are the proteolytic enzymes of the pancreas?
1) Trypsin
2) Chymotrypsin
3) Proelastase/elastase
4) Procarboxypeptidase A & B
What is the function of the proteolytic enzymes of the pancreas?
It converts the proenzymes to active enzymes
What are the nucleases of the pancreas?
1) DNase
2) RNAse
What is the function of the nucleases?
They cleave the phosphodiester linkages in the DNA backbone
What are the enzymes that prevents the autodigestion of the pancreas?
1) Trypsin inhibitor
2) Procolipase
What are the factors that protects the pancreas from its enzymatic secretions?
1) Releases the enzyme as inactive enzymes (only the protease)
2) It stores the enzyme in zymogen granules
3) It produces trypsin inhibitor (which prevents the premature activation of trypsin within the pancreas and protects against autodigestion)
What activates trypsinogen?
Enterokinase, which converts trypsinogen into trypsin, trypsin would then activate chymotrypsinogen and procarboxypeptidase into chymotrypsin and carboxypeptidase
How are the proteins digested?
- Mainly in the upper intestine
- In the stomach
1) Pepsin will digest 10-20% of the proteins, converting it into proteoses, peptones and few polypeptides, pepsin will become inactive in the alkaline lumen of the S.I
2) Trypsin and chymotrypsin will split the whole and partially digested proteins into peptides of various sizes
3) Carboxypolypeptidase cleaves individual amino acids from the carboxyl end of the polypeptide
How is carbohydrate digested?
1) Saliva contains amylase, which converts the starch into maltose and small polymers of glucose
2) Pancreatic juice (contains a more powerful amylase which digests all of the carbohydrates)
Describe the digestion of fats
1) Small amount of triglyceride is digested in the stomach by the lingual lipase
2) Physical break-up of fat into small sizes (emulsification) which occurs in the duodenum mainly by the bile (acid + lecithin) and in the stomach
3) Powerful pancreatic lipase splits all of the triglycerides into fatty acids and 2-monoglycerides
What are the different phases of pancreatic secretions?
1) Cephalic phase
2) Gastric phase
3) Intestinal phase
Describe the cephalic phase of pancreatic secretion
- Only vagal stimulation
The ACh from the vagal stimulation will stimulate the exocrine part of the pancreas to release 20% of its enzymes
What is secreted during the gastric phase of the pancreatic secretion?
- Mainly vagal stimulation
1) Continuation of the nervous signals to secrete pancreatic enzymes
2) 5-10% of the pancreatic enzymes are secreted
- Small amounts reaches the duodenum due to the continued lack of significant fluid secretion
What gets secreted during the intestinal phase of the pancreatic secretion?
- Hormones are the key players here
- Once the chyme leaves the stomach and enters into the S.I, their will be a significant pancreatic secretion
1) Secretin will stimulate the release of bicarbonate
2) CCK will stimulate the secretion of pancreatic digestive enzymes via the acinar cells
- This is the main phase of the three phases
