The pancreas Flashcards
Pancrease - exocrine vs endocrine secretion:
How do you define endocrine vs exocrine secretion?
Endocrine: secretion into the blood stream to have effect on distant target organ
(Autocrine/paracrine) - ductless glands
Exocrine: secretion into a duct to have direct local effect
What are the main endocrine secretions of the pancreas and their actions?
Insulin: anabolic hormone
- promotes glucose transport into cells & storage as glycogen
- decreases blood glucose
- promotes protein synthesis & lipogenesis
Glucagon:
Increases gluconeogenesis & glycogenolysis (-> inc blood glucose)
Somatostatin: endocrine cyanide
Pancreas - endocrine vs exocrine secretion:
What % of glands are endocrine?
What cells are involved in endocrine secretion?
What % of glands are exocrine?
Where do they secrete pancreatic juices into? What is the function of these?
Endocrine - 2% of gland
- islets of langerhans
- secrete hormones into blood - insulin & glucagon (+ somatostatin and pancreatic polypeptide)
- regulation of blood glucose & growth effects
Exocrine - 98% of gland
- secretes pancreatic juice into duodenum via MPD/sphincter of oddi/ampulla
- digestive function
Pancreatic cell differentiation:
Describe the structure and function of the acini
Islets - what are they derived from? How do they become islets? What do they differentiate into? Which portion of the islet is greater than the head?
Acini:
Ducts
Acini are grape like clusters of secretory units
Acinar cells secrete pro enzymes into ducts
Islets:
Derived from the branching system
Islets lose contact w ducts —> become islets
Islets differentiate into alpha and beta cells, secreting into blood
Tail > head
Endocrine - composition of islets
What types of tissues are found in the islets and in what proportions? What do these tissues secrete?
How do the islets ensure that all endocrine cells have close access to a site for secretion?
- alpha cells (A) form 15-20% of islet tissue and secrete glucagon
- Beta cells (B) form 60-70% of islet tissue and secrete insulin
- delta cells (D) form 5-10% of islet tissue and secrete somatostatin
Acini (2)
Islets are highly vascular, ensuring all endocrine cells have close access to a site for secretion
Exocrine - composition of acini:
What cells make up the acini?
Exocrine pancreatic units - acini:
Secretory acinar cells - large w apical secretion granules
Duct cells - small & pale
Exocrine - pancreatic juice:
What are the two components of pancreatic juice?
Detail the effect on volume, viscosity and contents of these components
Acinar cells - decrease volume, viscous, enzyme rich
Duct & centroacinar cells - increase volume, watery, HCO3- rich
Pancreatic juice - bicarbonate secretion
What produces bicarbonate secretions?
What are the consequences of bicarbonate secretions into pancreatic juices? (pH, enzymes)
Produced by duct & centroacinar cells
Pancreatic juice = increases bicarbonate
- ~120mM (mmol/L) - (plasma ~25 mM)
- pH 7.5-8
Neutralises acid chyme from stomach:
- prevents damage to duodenal mucosa
- raises pH to optimum range for pancreatic enzymes to work
Washes low volume enzyme secretion out of pancreas into duodenum
Pancreatic juice - bicarbonate secretion:
At what duodenal pH is HCO3- secreted?
At what duodenal pH does HCO3- secretion stop? Why?
Duodenal pH <5 -> linear increases in pancreatic HCO3- secretion
Duodenal pH <3 -> not much more increases in HCO3- secretion
Why HCO3- secretion stops when pH is still acid:
- bile also contains HCO3- and helps neutralise acid chyme
- brunners glands secrete alkaline fluid
HCO3- mechanism:
What catalyses pancreatic HCO3- secretion?
Describe the movement of carbon dioxide, water and sodium
What is exchanged at the lumen?
What is exchanged at the basolateral membrane into the bloodstream?
What is exchange driven by?
Pancreatic HCO3- secretion:
- catalysed by carbonic anhydrase
- separation of H+ & HCO3-
- Na+ moves down gradient via paracellular (tight) junctions
- H2O follows
Cl-/HCO3- exchange at lumen (anion exchanger [AE])
Na+/H+ exchange at basolateral membrane into blood stream (via sodium hydrogen exchanger, antiporter type 1 [NHE-1])
Exchange driven by electrochemical gradients: High EC (blood) Na+ compared to IC (duct cell) High Cl- in lumen compared to IC (duct cell)
HCO3- mechanism:
What maintains the Na+ gradient into the pancreatic duct cell? What type of transport is this?
Na+ gradient into cell from blood maintained by Na+/K+ exchange pump
Uses ATP - primary active transport
HCO3- mechanism:
How does K+ return to the blood?
How does Cl- return to the lumen?
K+ returns to blood via K+ channel
Cl- returns to lumen via Cl- channel (cystic fibrosis transmembrane conductance regulator [CFTR])
Pancreatic juice bicarbonate secretion:
What is the reaction that occurs in gastric parietal cells (acid) and pancreatic duct cells (alkaline)
What is secreted into gastric juices at the stomach / pancreas?
H2O + CO2 —> H2CO3 —> H+ + HCO3-
gastric juices
HCO3- -> blood
Gastric venous blood is alkaline
Pancreas:
HCO3- secreted -> juice
H+ -> blood
Pancreatic venous blood is acidic
Pancreatic juice - acinar cell enzyme secretion:
What enzymes are secreted by acinar cells?
Where are digestive enzymes synthesised and stored?
What are zymogens?
Why are proteases released as inactive pro enzymes?
What does the pancreas contain to try to prevent trypsin activation?
Where are the digestive enzymes activated?
What could lead to acute pancreatitis?
Acinar cells secrete enzymes for digestion of:
Fat - lipases
Proteins - proteases
Carbohydrates - amylase
-> digestive enzymes are synthesised & stored in zymogen granules
Zymogens = pro enzymes
Proteases are released as inactive pro-enzymes -> protects acini & ducts from auto digestion
Pancreas also contains a trypsin inhibitor to prevent trypsin activation
Enzymes only activated in duodenum
Blockage of MPD may over overload protection
-> auto digestion (= acute pancreatitis)
Acinar enzyme secretion:
What enzyme does duodenal mucosa secrete and what is its function? What is the function of the end product of the reaction this enzyme catalyses?
What does lipase secretion require?
What does the action of lipases require in order to be effective?
Duodenal Mucosa secretes an enzyme - enterokinase (enteropeptidase): converts trypsinogen-> trypsin
Trypsin then converts all other proteolytic & some lipolytic enzymes
-lipase secreted in active form but requires colipase (secreted as precursor)
Lipases require the presence of bile salts for effective action
Altered pancreatic enzyme function:
What can pancreatic secretions do to adapt to diet?
What can happen if you lack pancreatic enzymes? What happens if you lack salivary/gastric enzymes?
What are the side effects of orlistat (an anti obesity drug that inhibits
pancreatic lipases)?
Pancreatic secretions adapt to diet:
Eg inc protein, decreased carbs -> increased proteases, decreased amylases
Pancreatic enzymes (+bile) essential for digestion of meal Lack of these -> malnutrition (Unlike salivary, gastric enzymes)
Side effects of olistat (anti obesity drug):
-increased faecal fat - occurs when pancreatic lipase secretion decreased
-eg cystic fibrosis, chronic pancreatitis,
Orlistat (decreases intestinal fat absorption)
Control of pancreatic juice secretion:
Describe the processes involved in each of the following phases of pancreatic juice secretion:
- Cephalic phase
- Gastric Phase
- Intestinal phase
Cephalic phase:
- reflex response to sight/smell/taste of food
- enzyme rich component only
- low volume - mobilises enzymes
Gastric phase:
- stimulation of pancreatic secretion originating from food arriving in the stomach
- same mechs as for cephalic phase
Intestinal phase (=70-80% of pancreatic secretion):
- Hormonally mediated when gastric chyme enters duodenum
- both components of pancreatic juice stimulated
- enzymes & HCO3- juice flows into duodenum
Control of secretion:
What is pancreatic juice enzyme secretion controlled by in acini?
What is pancreatic juice bicarbonate secretion controlled by in duct and centroacinar cells?
Pancreatic juice enzyme secretion controlled in acini by:
- Vagus nerve:
- cholinergic
- vagaries stimulation of enzyme secretn (communicates info from gut to brain) - Cholecystokinin (CCK) (Ca2+/PLC)
Pancreatic juice bicarbonate secretion controlled in duct and centroacinar cells by:
-Secretin (cAMP)
Control of enzyme secretion in acini:
Which nerve controls enzyme secretion in acini?
What has stimulatory effects on the release of CCK from duodenal I cells?
What has inhibitory effects on the release of CCK from duodenal I cells?
- Vagus nerve (Acetylcholine, [ACh])
- Mechanisms responsible for controlling release of CCK from duodenal I cells:
-stimulatory effects:
Amino acids
Fatty acids
- inhibitory effects:
- trypsin
CCK-releasing peptide (CCK-RP)
Gastrin releasing peptide (GRP)
Control of HCO3- secretion in Acini & Ducts:
What does it mean that acinar fluid is isotonic?
What primarily stimulates the secretion of acinar fluid?
What stimulates the secretion of H2O and HCO3- from cells lining extralobular ducts?
What is secretion stimulated by the above richer in HCO3- than acinar secretion?
Acinar fluid is isotonic:
Resembles plasma in its concs of Na+, K+, Cl- & HCO3-
Secretion of acinar fluid & its protein contents is stimulated mainly by CCK
Secretin stimulates secretion of H2O & HCO3- from cells lining extralobular ducts
Secretion stimulated secretion richer in HCO3- cf acinar secretion because of Cl-/HCO3- exchange
Control of HCO3- secretion in ducts:
What type of feedback loop is involved in the control of HCO3- secretion in ducts?
The feedback loop responds to changes in what?
- secretin & HCO3- secretion
- negative feedback loop
- responds to decrease in luminal pH in duodenum
Decrease in pH in duodenum —> stimulates S cells —> increases secretin release —> increases/stimulates pancreatic ductal HCO3- secretion —-> inhibits decrease in pH in duodenum
Stimulus interaction:
Effect of CCK alone on HCO3-?
Effect of CCK + secretin on HCO3-?
Effect of vagus nerve on HCO3-?
Effect of secretin on enzyme secretion?
CCK alone - no effect on HCO3- secretion
CCK stimulated by secretin - can significantly increase HCO3- secretion
Vagus nerve has similar effect to CCK
Secretin - no effect on enzyme secretion
Summary of a meal:
- Food mixed, digested in stomach, pH 2
- Chyme squirted into duodenum
- H+ ions in duodenum -> increase secretin -> increase pancreatic juice
- bile & brunners gland secretions
Steps 3 & 4 increase pH to neutral/alkaline
- bile & brunners gland secretions
Peptides & fat in duodenum cause sharp increase in CCK and vagal nerve stimulation
-> stimulates pancreatic enzyme release
Peaks by 30 mins, continues until stomach empty
CCK potentiates effects of secretin on aqueous component
Necessary as most of duodenum not at low pH
