Pancreas Flashcards
Describe the embryogenesis of the pancreas
A foregut derivative arising at the foregut-midgut junction
Dorsal and ventral buds
Ventral bud is part of hepatobiliary bud
Duodenum rotates to form a C shape – ventral bud swings round to lie adjacent to the dorsal bud – both buds fuse
Ventral bud duct becomes main pancreatic duct
Essentially, what type of organ is the pancreas
secretory organ (endocrine and exocrine)
Describe the anatomical regions of the pancreas
Subdivided into head, neck, body, tail and uncinate (Latin = hook-like) process
Islet tissue most abundant in tail
Head divided into head proper and uncinate process
What does each region of the pancreas have
smaller pancreatic ducts supply each region which all combine with large pancreatic duct; uncinate process also has ducts; all ducts combine with common bile duct at Ampulla of Vater which drains to duodenum
Describe the location of the pancreas
head sits in C-shaped part of duodenum and tail within hilum of the spleen; stomach is situated posteriorly to the stomach
How does pancreatic juice reach the duodenum
Pancreatic juice reaches duodenum via main (and accessory) pancreatic ducts
accessory ducts from dorsal bud
What are the posterior relations to the pancreas
Main posterior relations are IVC, abdominal aorta and left kidney
Describe the perfusion of the pancreas
Perfusion: uses branches of superior mesenteric artery and celiac trunk; drained by the hepatic portal vein (collects blood from most of GI organs to liver before entering systemic circulation)
How may a tumour show on angiography
Blushes
Tumour are more angiogenic due to angiogenesis
Compare endocrine and exocrine
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 (ducts don’t travel far)
List some hormones released by the pancreas
Insulin: anabolic hormone, promotes glucose transport into cells and storage as glycogen, reduces blood glucose, promotes protein synthesis and lipogenesis
Glucagon: Increases gluconeogenesis and glycogenolysis (increases blood glucose)
Somatostatin: “Endocrine cyanide”
Describe the endocrine function of the pancreas
Endocrine islets (of langerhans): (2% pancreas) contain alpha (20%), beta (most abundant - 70%) and delta (10%) cells, and are highly vascularised and secrete hormones to blood not ducts
Also pancreatic peptide- F cells- regulates pancreatic secretion activities
Describe the exocrine functions of the pancreas
(98% of pancreas) secrete digestive enzymes into ducts which coalesce to pancreatic ducts lined with a columnar epithelium - arranged in circles around ducts, and contain zymogen granules (usually inactive proteases - prevents tissue degradation) alongside active amylases/lipases
What may pancreatic disease involve
Pancreatic disease may involve BOTH exocrine and endocrine effects
eg cystic fibrosis or acute pancreatitis
What is the vast majority of the pancreas
Exocrine- role in digestion
Describe the formation of the islets
Lose connections to ducts and become separated- why they are called islets
Describe pancreatic exocrine cell differentiation
Exocrine:
Ducts
Acini are grape-like clusters of secretory units
Acinar cells secrete pro-enzymes into ducts
Describe pancreatic endocrine cell differentiation
Pancreatic Cells: Endocrine § Derived from the duct system. § The braches then become islets. § Differentiate into alpha, beta and delta cells. o Alpha = glucagon, [15-20%]. o Beta = insulin, [60-70%]. o Delta = somatostatin, [5-10%]. § More prevalent at the tail-end.
Describe the composition of the islets
α-cells (A) form about 15-20% of islet tissue and secrete glucagon
β-cells (B) form about 60-70% of islet tissue and secrete insulin
δ-cells (D) form about 5-10% of islet tissue and secrete somatostatin
The islets are highly vascular, ensuring that all endocrine cells have close access to a site for secretion
What is the role of the septa of the ducts
To provide structural support
What are the two components of pancreatic juice
TWO components of pancreatic juice:-
low vol, viscous,enzyme-rich Acinar cells
high vol, watery, HCO3-rich. Duct & Centroacinar cells
Describe the acinar cells
Acinar cells: many RER and apical zymogen granules (enzymes and inhibitors) - at terminal end of duct to secrete enzyme rich, viscous, low-volume fluid into terminal end of duct
Describe the centroacinar cells
have internal characteristics of both acinar and duct cells to join terminus to duct
Describe the duct cells
modify fluid, secreting watery, dilute, bicarb rich fluid to pancreatic duct to mobilise enzyme rich component of the juice and help decrease viscosity to move towards duodenum; also neutralises acid chyme for optimum enzyme pH
prevents enzymes from the acinar cells accumulating and potentially causing damage
Compare duct cells to the acinar cells
secretory acinar cells (large with apical secretion granules) and small, pale duct cells
Describe the importance of this bicarbonate solution
Duct & centroacinar cells
Juice = RICH in bicarbonate ~ 120 mM (mmol/L) - (plasma ~25 mM). pH 7.5-8.0
Neutralises acid chyme from the stomach
prevents damage to duodenal mucosa
Raises pH to optimum range for panreatic enzymes to work
Washes low volume enzyme secretion out of pancreas into duodenum
Describe the relationship between duodenal pH and bicarbonate secretion rate
Duodenal pH <3 = not much more increase in bicarbonate secretion
Duodenal pH < 5 = significant linear increase in pancreatic bicarbonate secretion
Plateaus at pH 3
But increases as the solution becomes more acidic
Why is it not that important that bicarbonate secretion from the pancreas stops at pH 3, which is still acidic
Bile also contains bicarbonate and helps neutralise the acid chyme
Brunners glands secrete alkaline fluid
Outline the mechanism of bicarbonate secretion
CO2 diffuses into cell. Carbonic anhydrase converts it into H+ (blood) and HCO3- (lumen)
§ Sodium moves down gradient via paracellular ‘tight’ junctions.
§ Water is drawn into the lumen by sodium raising lumen osmolarity.
§ Na+/H+ antiporter = secondary active transport.
o Intracellular sodium maintained by Na+/K+ ATPase.
§ Cl-/HCO3- antiporter = secondary active transport (utilises the electrochemical gradients).
§ ‘Leak channels’ exist to allow chloride and potassium ions to return back into the cell and blood respectively.
o This enables the pumping of bicarbonate to continue.
§ Chloride channel is AKA the CFTR channel.
§ This is the same reaction that occurs in parietal cells to secrete HCl into stomach acid but reversed.
Describe how bicarbonate production in the pancreas compares to gastric acid production in the stomach
Same reaction in gastric parietal cells (acid) and pancreatic duct cells (alkaline)
In stomach, H+ goes into gastric juice, HCO3- into blood. Gastric venous blood is alkaline
In pancreas, HCO3- secreted into juice and H+ into blood. Pancreatic venous blood is acidic
How are digestive enzymes released from the pancreas acinar cells
Enzymes for digestion of fat (lipases), protein (proteases) and carbohydrates (amylase) are synthesised and stored in zymogen granules
Zymogens = pro-enzymes
Why is it important that the digestive enzymes are secreted from the acinar cells in this way
Proteases are released as inactive pro-enzymes ~ protects acini and ducts from auto-digestion
Pancreas also contains a trypsin inhibitor to prevent trypsin activation
Enzymes become activated ONLY in duodenum
Blockage of pancreatic duct may overload protection and result in auto-digestion (= acute pancreatitis)
Describe the conversion of trypsinogen to trypsin
Duodenal mucosa secretes an enzyme - Enterokinase (enteropeptidase) - that converts trypsinogen to trypsin.
cleaves the trypsinogen between a valine and an isoleucine.
Describe the role of trypsin
This active form of trypsin which can activate the other proteases in the same way.
All the proteases are fairly short lived as they are digested themselves.
trypsin can then activate protease zymogens to proteases, procolipase to colipases and autocatalyses activation of trypsinogen
Trypsin then converts all the other proteolytic and some lipolytic enzymes
Describe how lipases are secreted from the pancreatic acinar cells
Lipase is released in active form but requires colipase which is secreted as a precursor in the pancreas.
o Lipases also require the presence of bile salts to function well.
Describe the importance of trypsinogen
We are now moving onto the digestion of proteins.
Protein digestion is started in the stomach by pepsin, which acts in acid conditions.
When the chyme enters the duodenum, the pepsin that is mixed into it comes as well, but is soon inactivated by the alkaline conditions.
The pancreas produces a coctail of proteases, all released as precursors.
What happens in acute pancreatitis
Too much trypsin- overcomes inhibitors- activates other proteases- massive amplification reaction- auto-digestion
Describe the role of pancreatic amylase
Pancreatic amylase: converts polysaccharides to disaccharides (and then disaccharidases convert to monosaccharides for absorption)
Describe the roles of Trypsin, chymotrypsin, carboxypeptidases
onvert long peptides to shorter chains ready for membrane dipeptidases (e.g. Dipeptidase, endopeptidase and carboxypeptidase)
Describe the plasticity of the pancreas
Pancreatic secretions adapt to diet e.g. high protein, low carbs, increases proportion of proteases, decreases proportion of amylases
Pancreatic enzymes (+ bile) are essential for normal digestion of a meal. Lack of these can lead to malnutrition even if the dietary input is OK. (unlike salivary, gastric enzymes)
What are the side effects of orlistat
Increased faecal fat – occurs when pancreatic lipase secretion significantly reduced
Eg cystic fibrosis, chronic pancreatitis, Orlistat – a weight loss agent which inhibits pancreatic lipase and hence intestinal fat absorption
Describe the role of the liver in digestion
Liver: secretes bile; bile then emulsifies fats, allowing digestion of triglycerides by lipases and colipases to fatty acids and monoglycerides
What may be the consequences of a duct obstruction
e.g. Gallstone - can stop flow of juice; accumulation of enzymes can overpower trypsin inhibitor, and allow activation without enterokinase, leading to pancreatic autodigestion (acute pancreatitis)
Describe the role of the vagus nerve
Vagus nerve –
Cholinergic
communicates information from gut to brain
and has effector functions (cephalic and gastric response)
Describe the initial cephalic phase
Reflex response to sight/smell/taste of food
Enzyme-rich component only. Low volume - “mobilises” enzymes
Describe the gastric phase
Stimulation of pancreatic secretion originating from food arriving in the stomach (stomach distension)
Same mechanisms involved as for cephalic phase
Describe the intestinal 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)
Describe how the two components of pancreatic juice are separately controlled
The two components of pancreatic juice are separately controlled
Bicarbonate secretion is controlled by release of a hormone - Secretin (cAMP)
Enzyme secretion is controlled by vagal reflex and by a hormone - Cholecystokinin (CCK) (Ca2+/PLC)
What does CCK also cause
Secretion of bile- stimulation of smooth muscle contraction
Describe secretin control of bicarbonate secretion
§ Protons bind to the secretin receptor and stimulate secretin release into the blood which acts on the pancreatic ducts to secrete more HCO3-.
§ The feedback is switched off when there is a higher pH.
Describe the control of pancreatic enzyme secretion
fats and peptides in the duodenum detected by I-cells amongst enterocytes, and these secrete cholecystokinin (CCK) to blood; travels to pancreas via liver and heart, binding to CCK1 receptors on acinar cells; triggers PLC/IP3 second messenger system to cause Ca2+ release; triggers exocytosis of granules (enzyme zymogens, enzyme inhibitors and active enzymes e.g. Amylases/lipases) - secreted to terminal ducts of pancreatic ducts, moving into duodenum (where zymogens are activated by enterokinases/trypsin; central input: Vagus X secretes ACh which bind to muscarinic receptors on acinar cells, triggering increase in cytosolic calcium
How is CCK switched off
Cephalic phase ends when meal eaten
Absorption of fats and peptides removes local luminal stimulus for CCK release from mucosa
Possibly other mechanisms
Describe stimulus interaction for bicarbonate production
CCK alone - no effect on bicarbonate secretion
CCK can markedly increase bicarbonate secretion that has been stimulated by secretin
Vagus nerve has similar effect to CCK
Secretin NO EFFECT on enzyme secretion
What happens during a meal
Food mixed, digested in stomach, pH 2
Chyme squirted into duodenum
H+ ions in duodenum stimulate release of secretin, stimulating release of pancreatic juice (plus bile and Brunner’s gland secretions) to raise pH to neutral/alkaline.
Peptides + fat in duodenum cause sharp rise in CCK, vagal nerve, stimulating pancreatic enzyme release, peaks by 30 mins, continues until stomach empty.
CCK potentiates effects of secretin on aqueous component (necessary because most of duodenum not at low pH).
Why is it important that CCK potentiates secretin
Don’t want duodenum to be acidic before bicarbonate is released- needs to be released at a higher pH
