Secretion II

Question 1

roles of pancreas (as exocrine + endocrine gland):

Answer 1

• 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.

Question 2

endocrine vs exocrine glands in what they do + acinar cells vs ductular cells:

Answer 2

• 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)

Question 3

Pancreatic Enzymes Secretion (diff pancreatic enzymes + where zymogens take place + what the enzymes are activated by + what causes pancreatitis:

Answer 3

 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

Question 4

Pancreatic Acinar Cell Secretory Products:

Answer 4

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)

Question 5

proteolytic VS lipolytic VS glycolytic enzymes:

Answer 5

• 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

Question 6

Pancreatic secretion:

Answer 6

• 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.

Question 7

functions of pancreas fluid secretion + CFTR + inducers (of CFTR):

Answer 7

• 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)

Question 8

CFTR meaning?

Answer 8

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.

Question 9

Bicarbonate Ion Production in Pancreas:

Answer 9

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.

Question 10

variation of CL- and HCO3 with high flow rate VS low flow rate:

Answer 10

• 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

Question 11

pancreatic secretion (secretin and CCK from vagal nerve to duodenum to pancreas) step by step:

Answer 11

slide 14!!!!

Question 12

Secretion of Pancreatic Juice (hormonal control) ( by CCK and secretin):

Answer 12

• 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

Question 13

regulation of pancreatic secretion: (acinar and ductal cells):

Answer 13

• 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!!!)

Question 14

control of pancreatic secretion by CCK and secretin: (schémas de stomach et secretin lalal et CCK role aux organes de GI tract)

Answer 14

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)

Question 15

Cellular Basis of Pancreatic Secretion (acinar cells and ductular ion):

Answer 15

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.

Question 16

are there CCKb receptors in pancreatic acinar cells?

Answer 16

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.

Question 17

cephalic VS gastric phases and the neural mechanisms involved in stimulation of digestion:

Answer 17

Cephalic: vagal cholinergic
Gastric: vago-vagal reflex

Question 18

cephalic gastric phases and intestinal phase:

Answer 18

slides 23 + 24 + 25 !!!!!
Pancreatic duct cells secretion of ions and water – neutralize and hydrate the protein material coming from the stomach !!!!

Question 19

Changes in diet =

Answer 19

Changes in enzyme secretion

Question 20

Cystic fibrosis:

Answer 20

• 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

Question 21

Pancreatitis

Answer 21

• 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.

Question 22

Roles of liver:

Answer 22

 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

Question 23

functions of liver (ammonia conversion, glucose and protein metabolism):

Answer 23

• 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.

Question 24

anatomical features (other organs than liver and their functions):

Answer 24

*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

Question 25

Enterohepatic circulation:

Answer 25

 Receives most venous blood
after a meal via portal vein.
 Some substances circulate
continuously between the
liver and intestine.
 A passage of solutes through
three different
environments:
◦ The portal vein and the
sinusoids into which it
empties
◦ The biliary system
◦ The intestinal lumen

Question 26

bile acids and salts pathway (liver to SI):

Answer 26

= synthesised in liver, stored in gallbladder, released into small intestine
- slide 42 !!!!!

Question 27

blood and bile flow in opposite directions:

Answer 27

slide 43!!!!
blood = de SI à VC et bile = de hepatocytes à SI

Question 28

hepatic secretion:

Answer 28

 Bile: (0.25 to 1 L)daily
 Components of bile: bile salts (conjugates of bile acids), bile pigments (e.g. bilirubin), cholesterol, phospholipids (lecithins), proteins, electrolytes (similar to plasma, isotonic with plasma)

Question 29

Bile secretion:

Answer 29

= watery mixture of phospholatidyl-choline, bile acid, bile salts, bilirubin and cholesterol

Question 30

Functions of bile:

Answer 30

 Digestion and absorption of fats
 Endogenous synthesis of bile salts
 Absorption of fat soluble vitamins
 Cholerectic and cholagogue action
 Laxative (cleansing action)
 Bacteriostatic action (IgA)
 Cholesterol excretion
 Excretion of bilirubin (product of hemoglobin degradation).
 Lubrication due to mucus
 Alkaline helps in neutralizing acid chyme
 Bile acids are actively absorbed and recirculated through enterohepatic circulation.

Question 31

bile salt dependant and bile salt independant: (the 2 processes in bile acid secretion):

Answer 31

*Bile salt dependent
*Uptake of bile acids (and other organic/inorganic ions) across
the basolateral (sinusoidal) by transport proteins – driven by
Na-K-ATPase in basolateral membrane
*Sodium and water follow passage of bile acids
*Bile salt independent
*Water flow is due to other osmotically active solutes e.g.
glutathione, bicarbonate

Question 32

bile acid metabolism:

Answer 32

*Bile acids are synthesised in hepatocytes from cholesterol
*Excreted into the bile and pass into duodenum
*Primary bile acids
*Cholic acid and chenodeoxycholic acid are conjugated with glycine or taurine which increases their solubility
*Secondary bile acids
*Primary bile acids converted by intestinal bacteria into
deoxycholic and lithocholic acid
*Bile acids act as detergents – main function lipid solubilisation
*Have both hydrophobic and hydrophilic end and in aq
solution aggregate forming micelles

Question 33

why should a gallbladder exist?

Answer 33

• BILE ACIDS ARE:
  *Dangerous amphipaths toxic to enterocytes
  *Subject to loss with rapid intestinal transit
  *Subject to modification by intestinal bacteria
• SOLUTION:
• BAG THEM (hence the gallbladder)
• To keep the bag small: develop mechanisms for concentration of bile
• To protect the bag: secrete mucin
• To empty detergents when needed (during a meal): develop Neurohumoral control

Question 34

Gallbladder functions:

Answer 34

slide 51 !!!!

Question 35

Regulation of bile acids:

Answer 35

• Cholerectics: substances that increase secretion of bile.
• Bile salts: stored in the gall bladder, and are secreted during meal into duodenum.
• Reabsorption from the ileum via the
  enterohepatic circulation carries them back to liver.
• Regulation by cholesterol (loss: secreted into the bile or conversion to bile acids)
• Increase bile synthesis by interrupting
  enterohepatic circulation, thus decrease cholesterol

Question 36

Bile Acid/Salt Enterohepatic Circulation

Answer 36

• 250-1500 ml of bile enter the
  duodenum daily
• Bile salts may be deconjugated by bacteria in the GI tract, resulting in bile
  acids
• The majority of the bile
  acids/salts are reabsorbed and
  returned to the liver (<10% is
  excreted)
• Returned bile acids/salts are
  actively taken up by hepatocytes
• In the hepatocytes, bile salts
  are directly secreted; bile acids are (re-) conjugated and secreted.

Question 37

ABSORPTION OF BILE ACIDS IN THE ILEUM:

Answer 37

slide 54!!!
- Absorption of conjugated bile acids is an active process, while absorption of deconjugated bile acids is passive

Question 38

bile acids = efficiently recycled (enterohepatic circulation part2):

Answer 38

(que they return to liver via portal vein et some = in feces)
slide 55 !!!!

Question 39

Disorders of the enterohepatic circulation:

Answer 39

slide 56 !!!

Question 40

neural and hormonal bile regulation:

Answer 40

• Neural: vagal stimulation
  mediates increase in bile
  production and secretion prior
  to consumption of a meal.
• Hormonal: fat and protein in
  the duodenum cause release of
  CCK, which increases bile
  secretion by contraction of the
  gallbladder and concomitant
  relaxation of the sphincter of
  Oddi.
  (les trucs que tu sais déjà de secretin et tt)
• Secretin is stimulated in
  response to acidity in
  the duodenal chyme.
• This hormone
  stimulates the pancreas
  to release bicarbonate
  and neutralize the acid.
• CCK stimulates the gall
  bladder to release bile
  and pancreas to release
  pancreatic juices.

Question 41

CONTROL OF PANCREATIC ENZYME SECRETION & GALLBLADDER EMPTYING BY HORMONAL CHOLECYSTOKININ (CCK)

Answer 41

slide 59!!!!

Question 42

Digestive Period:

Answer 42

◦ Delivered into duodenum due to
CCK which contracts gallbladder
and relaxes the Sphincter of Oddi.
◦ After emulsification of lipids and
absorption, most bile salts are
reabsorbed from the terminal ileum
to the portal vein and sent back to
liver.
◦ Small portion of bile salts are
deconjugated to yield bile acids,
which can be reabsorbed by passive
diffusion. Lower than 10% daily bile
acids are eliminated into feces.
◦ During the digestive period, bile acid
biosynthesis is inhibited.
(slide 60)

Question 43

Inter-digestive Period:

Answer 43

o Bile acids are synthesized, conjugated and secreted.
o Bile is delivered to and stored in gallbladder, until CCK signals secretion.
(slide 61)

Question 44

Cholestasis:

Answer 44

 Cholestasis: production of bile is impaired or bile flow is obstructed.
◦ Primary biliary cirrhosis (PBC) and
primary sclerosing cholangitis (PSC): PBC is an autoimmune slowly progressive,
inflammatory destruction of cholanogiocytes lining small to medium-sized intralobular bile ductules. PSC is characterized by inflammation and fibrosis of both the intra and extrahepatic bile ducts.
◦ Congenital biliary atresia: pediatric condition
in which the intrahepatic bile ducts do not form properly.
◦ Obstructive jaundice: is blockage of one of the extrahepatic bile ducts with gallstone.
◦ Cholesterol gallstones: increase in
cholesterol to point of insolubility in bile.

Question 45

Acute liver failure:

Answer 45

 Acute Liver failure: A sudden and significant loss in metabolic capacity of the liver for detoxification and bile secretion.
(Initially present with Jaundice).
◦ Hepatitis, Fibrosis, and Cirrhosis: Inflammation and reversible and irreversible deposition of excess collagen in the liver, respectively.
◦ Alcoholic Cirrhosis: Malfunction as fibrotic hardening of the liver alters several aspects of structure and function.
◦ Viral Hepatitis: Hepatitis B, C and D viruses causing chronic
hepatitis, and hepatitis A and E viruses causing acute viral hepatitis.
◦ Portal Hypertension: increase in resistance to blood flow across
the liver. Impairment of liver function and destruction of hepatocyte and replacement with fibrous tissue.