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Alimentary system > Pancreas > Flashcards

Pancreas Flashcards

1
Q

Describe the embryogenesis of the pancreas

A

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

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2
Q

Essentially, what type of organ is the pancreas

A

secretory organ (endocrine and exocrine)

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3
Q

Describe the anatomical regions of the pancreas

A

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

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4
Q

What does each region of the pancreas have

A

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

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5
Q

Describe the location of the pancreas

A

head sits in C-shaped part of duodenum and tail within hilum of the spleen; stomach is situated posteriorly to the stomach

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6
Q

How does pancreatic juice reach the duodenum

A

Pancreatic juice reaches duodenum via main (and accessory) pancreatic ducts
accessory ducts from dorsal bud

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7
Q

What are the posterior relations to the pancreas

A

Main posterior relations are IVC, abdominal aorta and left kidney

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8
Q

Describe the perfusion of the pancreas

A

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)

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9
Q

How may a tumour show on angiography

A

Blushes

Tumour are more angiogenic due to angiogenesis

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10
Q

Compare endocrine and exocrine

A

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)

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11
Q

List some hormones released by the pancreas

A

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”

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12
Q

Describe the endocrine function of the pancreas

A

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

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13
Q

Describe the exocrine functions of the pancreas

A

(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

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14
Q

What may pancreatic disease involve

A

Pancreatic disease may involve BOTH exocrine and endocrine effects
eg cystic fibrosis or acute pancreatitis

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15
Q

What is the vast majority of the pancreas

A

Exocrine- role in digestion

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16
Q

Describe the formation of the islets

A

Lose connections to ducts and become separated- why they are called islets

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17
Q

Describe pancreatic exocrine cell differentiation

A

Exocrine:
Ducts
Acini are grape-like clusters of secretory units
Acinar cells secrete pro-enzymes into ducts

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18
Q

Describe pancreatic endocrine cell differentiation

A 
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.
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19
Q

Describe the composition of the islets

A

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

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20
Q

What is the role of the septa of the ducts

A

To provide structural support

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21
Q

What are the two components of pancreatic juice

A

TWO components of pancreatic juice:-
low vol, viscous,enzyme-rich Acinar cells
high vol, watery, HCO3-rich. Duct & Centroacinar cells

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22
Q

Describe the acinar cells

A

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

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23
Q

Describe the centroacinar cells

A

have internal characteristics of both acinar and duct cells to join terminus to duct

24
Q

Describe the duct cells

A

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

25
Q

Compare duct cells to the acinar cells

A

secretory acinar cells (large with apical secretion granules) and small, pale duct cells

26
Q

Describe the importance of this bicarbonate solution

A

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

27
Q

Describe the relationship between duodenal pH and bicarbonate secretion rate

A

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

28
Q

Why is it not that important that bicarbonate secretion from the pancreas stops at pH 3, which is still acidic

A

Bile also contains bicarbonate and helps neutralise the acid chyme
Brunners glands secrete alkaline fluid

29
Q

Outline the mechanism of bicarbonate secretion

A

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.

30
Q

Describe how bicarbonate production in the pancreas compares to gastric acid production in the stomach

A

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

31
Q

How are digestive enzymes released from the pancreas acinar cells

A

Enzymes for digestion of fat (lipases), protein (proteases) and carbohydrates (amylase) are synthesised and stored in zymogen granules
Zymogens = pro-enzymes

32
Q

Why is it important that the digestive enzymes are secreted from the acinar cells in this way

A

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)

33
Q

Describe the conversion of trypsinogen to trypsin

A

Duodenal mucosa secretes an enzyme - Enterokinase (enteropeptidase) - that converts trypsinogen to trypsin.
cleaves the trypsinogen between a valine and an isoleucine.

34
Q

Describe the role of trypsin

A

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

35
Q

Describe how lipases are secreted from the pancreatic acinar cells

A

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.

36
Q

Describe the importance of trypsinogen

A

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.

37
Q

What happens in acute pancreatitis

A

Too much trypsin- overcomes inhibitors- activates other proteases- massive amplification reaction- auto-digestion

38
Q

Describe the role of pancreatic amylase

A

Pancreatic amylase: converts polysaccharides to disaccharides (and then disaccharidases convert to monosaccharides for absorption)

39
Q

Describe the roles of Trypsin, chymotrypsin, carboxypeptidases

A

onvert long peptides to shorter chains ready for membrane dipeptidases (e.g. Dipeptidase, endopeptidase and carboxypeptidase)

40
Q

Describe the plasticity of the pancreas

A

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)
41
Q

What are the side effects of orlistat

A

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

42
Q

Describe the role of the liver in digestion

A

Liver: secretes bile; bile then emulsifies fats, allowing digestion of triglycerides by lipases and colipases to fatty acids and monoglycerides

43
Q

What may be the consequences of a duct obstruction

A

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)

44
Q

Describe the role of the vagus nerve

A

Vagus nerve –
Cholinergic
communicates information from gut to brain
and has effector functions (cephalic and gastric response)

45
Q

Describe the initial cephalic phase

A

Reflex response to sight/smell/taste of food

Enzyme-rich component only. Low volume - “mobilises” enzymes

46
Q

Describe the gastric phase

A

Stimulation of pancreatic secretion originating from food arriving in the stomach (stomach distension)
Same mechanisms involved as for cephalic phase

47
Q

Describe the intestinal phase

A 
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)
48
Q

Describe how the two components of pancreatic juice are separately controlled

A

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)

49
Q

What does CCK also cause

A

Secretion of bile- stimulation of smooth muscle contraction

50
Q

Describe secretin control of bicarbonate secretion

A

§ 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.

51
Q

Describe the control of pancreatic enzyme secretion

A

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

52
Q

How is CCK switched off

A

Cephalic phase ends when meal eaten
Absorption of fats and peptides removes local luminal stimulus for CCK release from mucosa
Possibly other mechanisms

53
Q

Describe stimulus interaction for bicarbonate production

A

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

54
Q

What happens during a meal

A

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).

55
Q

Why is it important that CCK potentiates secretin

A

Don’t want duodenum to be acidic before bicarbonate is released- needs to be released at a higher pH

Alimentary system (15 decks)

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