Exocrine Pancreatic Secretions Flashcards
What does pancreatic juice consist of?
Pancreatic juice consists consists of hydrolases as well as sodium bicarbonate
What is hydrolase
Hydrolase is a pancreatic digestive enzyme which is secreted from the exocrine acini
Where is the aqueous alkaline solution secreted from
It is secreted from the epithelial cells lining the small ductules and larger ducts which lead from the acini
When is pancreatic juice juice secreted?
Pancreatic juice is secreted most abundantly in response to the presence of chyme in the upper portions of the small intestine.
What are the aqueous components of the pancreatic juice
It can be divided into acinar cell secretion as well as ductule cell secretion/output.
Discuss acinar cell secretion
80% of pancreas comprise of acinar cells which secrete small volume of isotonic fluid containing pancreatic digestive enzymes
The acinar fluid resembles plasma in its conc. of soduim,chloride, bicarbonate and potassium
It constitutes the basal exocrine secretion, but is equal to only about 2% of the maximal secretory rate of pancreatic juice
Discuss the ductule cell secretion/output
Comprise about 4% of the pancreas.
Large volumes of water and Sodium-Bicarbonate to neutralize the acidic chyme is emptied into the stomach into the duodenum is primarily secreted by the ductule cells
Discuss what happens at various rates of secretion
At all rates of secretion, pancreatic juice is essentially isotonic with plasma.
At low rates of secretion, the ionic composition remains to be a solution of Na+ and Cl-
As the rate of secretion increases in response to stimulation, Na+ and HCO3- predominate.
The ductule cells, including the centroacinar cells, and even some of the epithelial cells lining the intralobular ducts, are responsible for the high bicarbonate content.
Secretion of Bicarbonate
The ductule cells possess of a
mechanism to secrete HCO3 - against both its chemical and electrical gradient into the ductule lumen
- Stimulated ductule cells activates aCl-/HCO3-antiporter in the apical membrane.
This exchange process is based on a mechanism
known as secondary active
countertransport. (Why?)
Secretion of HCO3- depends on high
luminal Cl-, which is possible when
the Cl channels (2)are activated by cAMP in response to stimulation by secretin.
The secretin-stimulated secretion can have a HCO3-concentration as high as 145 mmol/L in the ductule lumen.
This provides a large quantity of alkali in the pancreatic juice.
The increased cAMP also let H+-pumps (3) move to fuse with the basolateral membrane. These Na+/H+ antiporters represents a secondary active transport mechanism.
The role of Na+,K+-ATPase on the basolateral membrane is that of primary active transport (4), creating an electrochemical gradient for Na+ to move into the cell on the H+ -pump (3), in exchange for H+,which leaves the cell.
CO2 now diffuses readily into the cell (5), combining with OH- of water to form HCO3-.
The formation of HCO3-is catalysed by carbonic anhydrase (CA). The continued movement of H+
across the basolateral membrane drives this reaction and leads to a build-up of HCO3-, resulting
in the movement of HCO3-across the apical membrane in exchange for Cl-
(1).
Much of the luminal Na+ diffuses through paracellular space (6).
Most of the Na+and HCO3-in pancreatic juice is derived from plasma.
The movement of these ions into the duct lumen also creates an osmotic gradient that causes osmosis of water
What is the role of bicarbonate in the pancreatic juice
It flows through the duct system,esp the larger intralobular ducts and even extralobular ducts, the HCO3 - moves down its concentration gradient, leaving the ducts in exchange for Cl-
This Cl-, HCO3 - exchange mechanism is not effective when the secretory rate begins to increase, and pancreatic juice will contain primarily HCO3-at concentrations of 115 up to 145 mmol/L.
But at low secretory rates, there is enough time for the
exchange to occur and Cl- becomes the predominant anion
How does the secretion of pancreatic digestive enzymes occur
They are secreted by acini though the stimulation of Cholecystokinin(Duodenal hormone) and Acetylcholine(Parasympathetic neurotransmitter)
They contain proteolytic enzymes.
Name the proteolytic Enzymes
Trypsin
Chymotrypsin
Carboxypolipeptidase
Pancreatic alpha-amylase
Pancreatic lipase
Cholesterol esterase
Phospholipase
Trypsin .
is an endopeptidase, splitting peptide bonds on
the C-terminal side of Lys and Arg
Chymotrypsin
An Endopeptidase, hydrolyses the peptide bond on C-terminal side of aromatic amino acids (Phe, Tyr, and Trp).
These two enzymes thus split whole
and partially digested proteins into peptides of various sizes but do not cause release of individual amino acids.
Pancreatic alpha-amylase
Hydrolyses polysaccharides such as starches and glycogen to form
disaccharides and a few trisaccharides.
The main enzymes for fat digestion:
Pancreatic Lipase
Cholesterol Esterase
Phospholipase
Pancreatic lipase
Which is capable of hydrolysing
triacylglycerols into free fatty acids and 2-monoacylglycerols.
Cholesterol esterase
Hydrolyses cholesterol esters
Phospholipase
Splits fatty acids from phospholipids
Prevention of autodigestion of the pancreatic tissue
Proteolytic enzymes are released into the pancreatic ducts in their inactive forms
trypsinogen, chymotrypsinogen, and procarboxypolypeptidase.
They only become activated when entering the duodenal and jejunal lumen.
The reason is the localisation of the enzyme called enterokinase (enteropeptidase), which is expressed on the surface of enterocytes of the upper intestinal mucosa under influence of CCK stimulation.
Enterokinase hydrolyses trypsinogen present in chyme into trypsin plus a short peptide. Active trypsin can then also convert other trypsinogen molecules, as well as chymotrypsinogen and procarboxypolypeptidase into their active peptides.
Thus, once a small amount of trypsin is
formed, a catalytic chain reaction of activating all protease precursors within the lumen of the
duodenum and jejunum occurs.
Pancreatic acini secrete a peptide called trypsin inhibitor (or Kazal inhibitor) that
complexes with any small amount of trypsin which may find its way into the pancreatic
ductal system.
Therefore, any activation of the proteolytic enzymes while they are still
in the pancreatic ducts is inhibited, preventing digestion of the pancreas itself. With
inflammation or severe injury of the pancreas or when a duct becomes blocked, large
quantities of pancreatic juice may accumulate in the damaged area and the effect of
trypsin inhibitor overwhelmed, in which case activated trypsin can initiate autoproteolysis of the entire pancreas within a few hours.
The condition is called acute
pancreatitis. In 5% of cases the condition is extremely serious and even lethal because
of accompanying circulatory shock when the enzymes leak into the abdominal cavity,
resulting in the digestion of blood vessels, formation of a haematoma, and generalised
peritonitis.
Acute pancreatitis in any case leads to a lifetime of pancreatic insufficiency.
The presence of high concentrations of alpha-amylase in the blood can confirm the diagnosis
of acute pancreatitis.
Prevention of autodigestion of the pancreatic tissue
Proteolytic enzymes are released into the pancreatic ducts in their inactive forms
trypsinogen, chymotrypsinogen, and procarboxypolypeptidase.
They only become activated when entering the duodenal and jejunal lumen.
The reason is the localisation of the enzyme called enterokinase (enteropeptidase), which is expressed on the surface of enterocytes of the upper intestinal mucosa under influence of CCK stimulation.
Enterokinase hydrolyses trypsinogen present in chyme into trypsin plus a short peptide. Active trypsin can then also convert other trypsinogen molecules, as well as chymotrypsinogen and procarboxypolypeptidase into their active peptides.
Thus, once a small amount of trypsin is
formed, a catalytic chain reaction of activating all protease precursors within the lumen of the
duodenum and jejunum occurs.
Pancreatic acini secrete a peptide called trypsin inhibitor (or Kazal inhibitor) that
complexes with any small amount of trypsin which may find its way into the pancreatic
ductal system.
Therefore, any activation of the proteolytic enzymes while they are still
in the pancreatic ducts is inhibited, preventing digestion of the pancreas itself. With
inflammation or severe injury of the pancreas or when a duct becomes blocked, large
quantities of pancreatic juice may accumulate in the damaged area and the effect of
trypsin inhibitor overwhelmed, in which case activated trypsin can initiate autoproteolysis of the entire pancreas within a few hours.
The condition is called acute
pancreatitis. In 5% of cases the condition is extremely serious and even lethal because
of accompanying circulatory shock when the enzymes leak into the abdominal cavity,
resulting in the digestion of blood vessels, formation of a haematoma, and generalised
peritonitis.
Acute pancreatitis in any case leads to a lifetime of pancreatic insufficiency.
The presence of high concentrations of alpha-amylase in the blood can confirm the diagnosis
of acute pancreatitis.
Regulation of the pancreatic secretion-Acetylcholine
Released when parasympathetic vagus nerve fibres carry impulses to the pancreas which binds to the muscarinic receptors on the basolateral surface of acinar cells.
Intracellular Ca2+ levels rise intiating phosphorylation of structural and regulatory protiens
Acetylcholine
Released when parasympathetic vagus nerve fibres carry impulses to the pancreas which binds to the muscarinic receptors on the basolateral surface of acinar cells.
Intracellular Ca2+ levels rise, initiating
phosphorylation of structural and regulatory proteins involved in the fusion
of secretory granules with the apical membrane and subsequent discharge of
the enzymes.
Although activation of gastro-pancreatic vagovagal reflexes has been described as a mechanism responsible for cholinergic impulses,
most acetylcholine is released as part of the cephalic phase of pancreatic
control.
Cholecystokinin (CCK)
a polypeptide containing 33 amino acids, is secreted by the I-cells of the
duodenal and upper jejunal mucosa when chyme enters the small intestine.
The I-cells release CCK into the interstitial space in response to smaller peptides and amino acids (products of partial protein digestion) present in the intestinal lumen, and also by the presence of long-chain fatty acids (products of partial fat digestion).
Circulating CCK has a half-life of 5 minutes. Its main functions are:
Increased pancreatic acinar fluid rich in enzymes when CCK binds to CCK-A receptors on
acinar cells, increasing the intracellular Ca2+ levels.
Rhythmical contractions of the wall of the gallbladder (with simultaneous relaxation of the
sphincter of Oddi).
Competitive inhibition of gastrin’s effect on gastric emptying and secretion.
Stimulating the expression of enterokinase on the brush border of small intestinal enterocytes
