roles of pancreas (as exocrine + endocrine gland):
- The pancreas acts as an exocrine
gland by producing pancreatic
juice which empties into the small
intestine via ducts. - The pancreas also acts as an
endocrine gland to produce
insulin. - Plays an important role:
o in digestion of lipids proteins
and carbohydrates
o in metabolism (produces
insulin)
o in neutralizing the pH to
become suitable for the action
of pancreatic digestive
enzymes.
endocrine vs exocrine glands in what they do + acinar cells vs ductular cells:
- Endocrine pancreas (endocrine cells in islets of Langerhans; hormone synthesis. eg. insulin)
- Exocrine pancreas (series of blind ended ducts terminating in acini; enzyme synthesis) secretes ~1 L/day into duodenum
o Fluid consists of HCO3- and enzymes - HCO3- neutralizes H+ delivered to
duodenum from stomach - Enzymatic portion digests
carbohydrates, proteins, and lipids into
absorbable molecules - Pancreatic Exocrine Glands
o Comprises ~90% of pancreas
Rest of pancreatic tissue is endocrine
pancreas and blood vessels
o Acinar Cells
Specialized secretory cells (secr. mainly
proteins) Contain zymogen granules and secrete enzymatic protein portion of the juice via exocytosis
o Ductular Cells
Line the intercalated ducts
Secrete aqueous HCO3- component
Modifies composition of juice (dilutes it
and makes it alkaline)
Pancreatic Enzymes Secretion (diff pancreatic enzymes + where zymogens take place + what the enzymes are activated by + what causes pancreatitis:
Enzymes for digesting carbohydrate,
protein, fat (and nucleic acids).
Proteases (80% of proteins;
trypsinogen the most important
(40%), amylolytic enzymes, lipases,
nucleases, colipases, trypsin
inhibitors, monitor peptide
Most proteases are packed and
stored as inactive precursors along
with trypsin inhibitor.
Activation of zymogens takes place
in the lumen of the duodenum.
Pancreatic Enzyme Secretion
Secretion activated by Ach and CCK (induced by fatty acids,
amino acids, and peptides)
Consequences of untimely enzyme activation (e.g. due to
mutation or trauma): pancreatitis
Pancreatic Acinar Cell Secretory Products:
Composition: bicarbonate, Na+, K+ and water emitted by the
epithelial cells lining the pancreatic ducts. This neutralizes stomach
acid so that digestive enzymes can work more effectively
(slide 7!!!!) (les trucs dans le tableau = secretions)
proteolytic VS lipolytic VS glycolytic enzymes:
- proteolytic: Trypsin, chymotrypsin and carboxypeptidase digest
proteins
– Enterokinase from the duodenal mucosa
and attached to the brush border activates
trypsinogen to trypsin.
– Trypsin activates chymotrypsinogen to chymotrypsin
– Trypsin activates procarboxypeptidase
to carboxypeptidase. - glycolytic: * secreted as active enzymes
- pancreatic α-amylase
- cleaves starch and glycogen into di- and trisaccharides
- lipolytic: * secreted as active enzymes
- pancreatic lipase
- glycerol + fatty acids
Pancreatic secretion:
- Complete digestion of food
requires action of both
pancreatic and brush border
enzymes.
o Most pancreatic enzymes
are produced as zymogens.
o Trypsin (when activated by
enterokinase) triggers
activation of other
pancreatic enzymes. - Pancreatic trypsin inhibitor
attaches to trypsin.
o Inhibits its activity in the
pancreas.
functions of pancreas fluid secretion + CFTR + inducers (of CFTR):
- functions: o Neutralizes acid
o Optimizes digestion - CFTR: *The CFTR chloride channel plays a crucial role in
secretion (allows outflows of Cl- ions, in exchange for HCO3-; moves HCO3- into duct lumen) - *CFTR activity is required for fluid secretion
o CF patients: fluid shortage→ maldigestion (ducts unable to secrete HCO3 and H2O, enzyme cannot flush out - *Inducers:
o Major: secretin (activating PKA that in turn activates CFTR)
CFTR meaning?
CFTR stands for Cystic Fibrosis Transmembrane Conductance Regulator. It is a protein that functions as a chloride ion channel and is critical for regulating salt and water movement across cell membranes, particularly in the lungs, pancreas, intestines, sweat glands, and other organs.
Bicarbonate Ion Production in Pancreas:
1-CO2 diffuses to the interior of the ductule cells from
blood and combines with H2O by carbonic anhydrase
to form H2CO3 which will dissociate into HCO3- and
H+ . The HCO3- is actively transported into the lumen.
2- The H+ formed from the dissociated H2CO3 is
exchanged for Na+ ions by active transport through
blood, which will diffuse or actively be transported to
the lumen to neutralize the –charges of HCO3- .
3- The movement of HCO3- and Na+ ions to the
lumen causes an osmotic gradient that causes water to
move from blood to ductule cells of the pancreas and
eventually producing the HCO3- solution.
variation of CL- and HCO3 with high flow rate VS low flow rate:
- Low flow rate (long contact time): no secretin stimulation; more time for absorption of HCO3- and exchange for Cl-. Therefore, the concentration of HCO3 will be low and the concentration of Cl will be high in pancreatic juice.
- High flow rate (short contact time). Stimulated by secretin; less time for absorption of HCO3 and exchange for Cl-. Therefore, the concentration of HCO3- will be high and the concentration of Cl- will be low in the pancreatic juice
pancreatic secretion (secretin and CCK from vagal nerve to duodenum to pancreas) step by step:
slide 14!!!!
Secretion of Pancreatic Juice (hormonal control) ( by CCK and secretin):
- Secretion of pancreatic juice and bile is stimulated by:
- Secretin:
- Occurs in response to duodenal pH < 4.5.
- Stimulates production of HC03- by pancreas.
- Stimulates the liver to secrete HC03- into the bile.
- CCK:
- Occurs in response to fat and protein content of
chyme in duodenum. - Stimulates the production of pancreatic enzymes.
- Enhances secretin secretion.
- Stimulates contraction of gall bladder and relaxation of the sphincter of Oddi
regulation of pancreatic secretion: (acinar and ductal cells):
- Acinar cells (responsible for enzymatic secretion)
o Have receptors for CCK and muscarinic receptors for ACh
o CCK is most important stimulant - I cells secrete CCK in presence of amino acids and fatty acids in intestinal lumen
o ACh also stimulates enzyme secretion - Ductal cells (responsible for aqueous secretion of HCO3-)
o Have receptors for CCK, ACh, and secretin
o Secretin (from S cells of duodenum) is major stimulant - Secreted in response to H+ in intestine
o Effects of secretin are potentiated by both CCK and ACh
(slide 17!!!)
control of pancreatic secretion by CCK and secretin: (schémas de stomach et secretin lalal et CCK role aux organes de GI tract)
slide 18!!!! + 19!!!!! + 20!!!!
- stomach gives acid puis (chyme) = into duodenum puis secretin = into pancreas = hco3 = inhibits acid en retour
- CCK = contraction of gallbladder, relaxation of sphincter of oddi, reduced emptying of stomach, acinar secretion of pancreas
- I cells secrete CCK = go into bloodstream, (quand y a aa’s et fatty acids, (aa’s viennent de proteins et inhibit trypsin (elle vient de pancreas quand y a AcH qui s’attache à muscarinic receptors et la stimule)
Cellular Basis of Pancreatic Secretion (acinar cells and ductular ion):
Acinar cells secrete their
products via a process of
granule exocytosis.
o Calcium-dependent
signaling pathways play the
most prominent role in
enzyme secretion.
* The membrane transport
events underlie ductular ion
secretion.
o Prominently driven by
cAMP, with calcium playing
the subsidiary role.
are there CCKb receptors in pancreatic acinar cells?
Yes, there are CCK-B receptors (cholecystokinin type B receptors) present on pancreatic acinar cells. Here’s a breakdown of their role and function:
Cholecystokinin (CCK): CCK is a hormone released by the small intestine in response to the presence of fats and proteins in the food. It plays a vital role in digestion, stimulating the gallbladder to release bile and the pancreas to secrete digestive enzymes.
CCK-B Receptors: CCK has two main types of receptors: CCK-A and CCK-B. The CCK-B receptors are primarily located in the pancreas and the central nervous system. In the pancreas, they are found on the acinar cells, which are responsible for producing and secreting digestive enzymes such as amylase, lipase, and proteases.
Function in Pancreatic Secretion: When CCK binds to the CCK-B receptors on pancreatic acinar cells, it stimulates the secretion of digestive enzymes. This process is crucial for effective digestion and nutrient absorption in the small intestine.
cephalic VS gastric phases and the neural mechanisms involved in stimulation of digestion:
Cephalic: vagal cholinergic
Gastric: vago-vagal reflex
cephalic gastric phases and intestinal phase:
slides 23 + 24 + 25 !!!!!
Pancreatic duct cells secretion of ions and water – neutralize and hydrate the protein material coming from the stomach !!!!
Changes in diet =
Changes in enzyme secretion
Cystic fibrosis:
- Therefore genetic disorder of cystic fibrosis, where mutations
leads to abnormal function of the CFTR chloride channel. - Pancreatic enzyme synthesis and secretion may be normal but
the relative inability of the ducts to secrete bicarbonate
and water means that the enzymes can not be flushed
properly from the organ and limited quantities reach
the intestinal lumen. The enzymes that do reach are
inactive. - Due to the action of retained
proteolytic enzymes that become
inappropriately activated and
damage the tissue, patients with
severe CFTR mutations are known
to have pancreatic insufficiency
Pancreatitis
- Patient who experiences retention of pancreatic enzymes within the organs may experience the painful consequences of auto-digestion of the pancreatic tissue.
o Retained pancreatic secretion due to obstruction (e.g.
gallstone or a malignancy)
o Inflammation in alcoholics.
Roles of liver:
First site of processing nutrient-derived byproducts
Secretes bile acids and cholesterol
Synthesizes 80% plasma proteins
Metabolism CHO, fats, AA
Stores CHO as glycogen
Maintains adequate glucose
Metabolizes FA to ketone bodies
Scavenges cholesterol from plasma
Intercepts absorbed nutrients
Inactivates toxin and drugs
Digestion and absorption of nutrients
Secretes hormones
Detoxifies blood substances
functions of liver (ammonia conversion, glucose and protein metabolism):
- Glucose metabolism: glucose is converted to glycogen, stored in hepatocytes, & released to maintain normal blood glucose.
- Ammonia conversion: ammonia (a potential toxin) is a byproduct of glucogenesis and is converted to urea (in liver) which can be excreted in the urine. Ammonia produced by
intestinal bacteria is also removed from portal blood for urea synthesis/excretion - Protein metabolism: including almost all plasma proteins:
*Blood clotting factors are synthesized in the liver. (Vitamin K is required by the liver for synthesis of clotting
factors).
*Albumin, alpha & beta globulins
*Transport proteins - Fat metabolism: fatty acids can be broken down for
production of energy and ketones. Also produces
cholesterol and other complex lipids. - Vitamin & iron storage: A, B, D, B-complex, iron & copper are stored in large amounts.
- Drug and toxin metabolism: alcohol, barbiturates, opioids, sedative agents, anesthetics,etc.
- Bile formation: stored in gallbladder and emptied into intestine as needed
- Bilirubin excretion: bilirubin is derived from the breakdown of hemoglobin, removed from the liver, modified to make it more water soluble, and then excreted in the bile.
anatomical features (other organs than liver and their functions):
*Hepatocytes: Metabolic processing, synthesis of plasma proteins,
nutrient storage, activation of vitamin D
*Kupffer cells: the resident macrophages
*Hepatic portal circulation: venous and arterial liver blood supply
*Lobules: functional units of the liver
*Gall bladder: Stores and concentrates bile
*Sphincter of Oddi: regulates hepatic and pancreatic secretion into
duodenum
