Organisation of the exocrine pancreas Flashcards
Functions of the exocrine pancreas
secretes digestive enzymes, fluid, and bicarbonate in response to food ingestion - critical digestive process
How is secretion regulated?
by neural reflexes, gastrointestinal hormones and absorbed nutrients
by both stimulatory and inhibitory influences that coordinate the delivery of digestive enzymes with food emptying into the intestine to assure adequate digestion of a meal
Complications of the absence of proper pancreatic secretion
maldigestion
malabsorption
malnutrition
4 phases of pancreatic secretion
Cephalic
Gastric
Intestinal
Absorbed nutrient
How are the phases regulated?
Each phase regulated by a complex network of neural, humoral and paracrine feedback mechanisms: maintain an optimal environment for food digestion and absorption
2 components of pancreatic exocrine secretion
Aqueous
Enzymatic
Aqueous component
neutralisation of the duodenal contents.
prevents damage to duodenal mucosa by acid and pepsin
brings the pH of contents into optimal range for activity of pancreatic enzymes.
Enzymatic component
low-volume secretion containing enzymes for the digestion of all normal constituents of a meal.
Sympathetic postganglionic fibres
from the celiac and superior mesenteric plexuses and accompany arteries to the organ.
Parasympathetic preganglionic fibres
branches of the vagal nerves in the antral-duodenal region
Vagal fibres terminate at:
acini and islets
intrinsic cholinergic nerves of the pancreas
General point about nerves for pancreatic exocrine secretion
parasympathetic nerves stimulate
sympathetic nerves inhibit
Discovery of secretin
Bayliss and Starling tied off and removed nerves then added HCl and measured pancreatic secretion then removed segment and took an extract of it, then injected extract into jugular vein of anaesthetised animals; pancreatic secretion almost immediately increased -> discovered hormones and named the first hormone ‘secretion’.
Secretin
linear peptide hormone composed of 27 amino-acids
amino acid sequence of secretin similar to glucagon, vasoactive intestinal peptide (VIP) and gastric inhibitory peptide
Where is secretin synthesised?
cytoplasmic secretory granules of S-cells, found mainly in the mucosa of the duodenum
in smaller numbers in the jejunum of the small intestine
When is secretin released?
in response to acid:
low duodenal pH (2 - 4.5)
acidity is due to HCl in chyme
What does secretin stimulate?
Ductal cells in pancreas
Cholecystokinin
Synthesized in enteroendocrine I-cells in mucosal lining of small intestine
Released into the blood circulation in response to a meal:
Fatty acids and/or amino acids in chyme entering duodenum
Also modulated by:
Monitor peptide (released by pancreatic acinar cells)
CCK-releasing protein (via paracrine signalling mediated by enterocytes in the GI mucosa)
Acetylcholine (released by parasympathetic vagal nerves)
Receptors (**????)
CCK1 (or CCKa) -> pancreas, gall bladder, vagus
CCK2 (or CCKb) -> stomach, brain
Mechanisms of pancreatin secretion
cephalic phase
intestinal phase
Cephalic phase
Sensory inputs e.g. sight, smell, taste, lead to anticipation of food.
These sensations (integrated in the dorsal vagal complex in the brainstem) transmitted to the exocrine pancreas via vagus nerve
Interaction of long chain fatty acids with receptors in the oral cavity also induces the cephalic phase.
Animal studies have implicated a gustatory vago-pancreatic reflex in mediating the cephalic phase
Interaction of CCK with CCK-1 receptors (GPCRs) on acinar cells also mediates cephalic phase of enzyme secretion
~ 20-25% of the total pancreatic exocrine secretion occurs during the cephalic phase
Intestinal phase
Release of acidic chyme into duodenum initiates the intestinal phase of pancreatic secretion.
Pancreas primed by cephalic and gastric influences, which enhance blood flow and initiate exocrine secretion.
Vagovagal reflex controls contraction of the GI muscle layers in response to distension:
GI reflex circuits where vagal afferent and efferent fibres coordinate responses to gut stimuli via the dorsal vagal complex in brain
vagal afferents carry signals from stretch, osmo- and chemoreceptors
accommodation of large amounts of food in the GI tracts
~70-80% of total pancreatic secretion occurs during the intestinal phase: - regulated by hormonal and neural mechanisms.
Feedback regulation of pancreatic secretion - positive feedback
Monitor peptide (61 aa peptide) is secreted by acinar cells
directly stimulates I cells in small intestine
amplifies pancreatic secretion once initiated
Feedback regulation of pancreatic secretion - negative feedback
Trypsin-sensitive CCK releasing factors produced by intestine
stimulate CCK secretion, but are inactivated by trypsin
Trypsin inhibition is relieved when trypsin temporarily consumed by ingested protein or other trypsin “inhibitors” causing increased secretion
Control of bicarbonate secretion
Main action of secretin is to stimulate bicarbonate release from pancreatic duct cells, but it also has a direct effect on acinar cells and potentiates enzyme secretion.
2 models of variation within bicarbonate secretion due to flow rate
Two-component hypothesis
HCO3-/Cl- exchange
Two component hypothesis
Acinar cells secrete small vol fluid (Na+ & Cl− rich)
Ductal cells secrete large vol (Na+ & HCO3− rich)
At low rates Cl− in juice is high, at high rates: Cl− is low
diluted by larger vol of HCO3−
final conc approaches pure HCO3−secretion
HCO3−/ Cl- exchange:
Predominant secretion is HCO3-
moves down ducts and is exchanged for Cl−.
Low rates: near complete exchange:
conc. of each anion equal to plasma (high Cl-)
High rates: less time for exchange
juice near that of original secreted solution containing only HCO3− and Na+
Pancreatic enzymes
Trypsinogen
Chymotrypsinogen
Carboxypeptidase
Amylase
Lipase
Ribonuclease
