11.2 - Pancreas and Small Bowel

Question 1

Describe the embryological development of the pancreas.

Answer 1

1. abdominal accessory organs arise as foregut outgrowths
2. proximal duodenum rotates clockwise
3. ventral and dorsal pancreatic buds and ducts fuse - the ducts form the major papilla, and the uncinate process is what used to be the ventral bud

• bile and pancreatic ducts join to drain together at the major papilla
• minor papilla - degraded away in many adults
• pancreatic duct at major papilla joins with distal common bile duct to form the ampulla

Question 2

What is the anatomy of the pancreas?

Answer 2

• retroperitoneal organ - is not actually in the abdomen, it is behind the posterior peritoneum of the abdomen
• in front of it is the transverse colon and stomach
• head of pancreas fits into head of duodenum, which is split into D1, 2, 3, 4 for orientation
• superior mesenteric artery (comes behind neck of pancreas) and vein
• coeliac axis
• splenic artery goes into, out, then in pancreas
• label diagrams to revise

Question 3

How can the pancreas be imaged?

Answer 3

• CT scan
• MRCP - magnetic resonance cholangiopancreatography
• angiography - important for treating bleeds

Question 4

What is pancreas divisum?

Answer 4

• ventral duct comes around but does not fuse with dorsal duct
• all pancreatic juice comes through minor ampulla not major = smaller = does not work as well
• causes recurrent episodes of pancreatitis since ventral duct is large enough in calibre to handle flow of pancreatic juice but divisum = large flow has to go through minor duct causing pancreatitis

Question 5

Define endocrine vs exocrine secretion.

Answer 5

• endocrine - secretion into bloodstream to have effect on distant target organ (ductless glands)
• exocrine - secretion into a duct to have a direct local effect

Question 6

What are the main endocrine secretions of the pancreas and their actions?

Answer 6

• 2% of gland secretions are endocrine secretions through islets of Langerhans
• insulin - anabolic hormone that promotes glucose transport into cells and storage as glycogen, decreases blood glucose, promotes protein synthesis and lipogenesis
• glucagon - increases gluconeogenesis and glycogenolysis (increases BGC)
• somatostatin - inhibits everything - endocrine cyanide
• pancreatic polypeptide

Question 7

What are the main exocrine secretions of the pancreas and their actions?

Answer 7

• 98% of gland
• secretes pancreatic juice into duodenum via main pancreatic duct/sphincter of Oddi/ampulla
• digestive function

Question 8

What are acini?

Answer 8

• grape-like clusters of secretory units attached to ducts
• acinar cells secrete pro-enzymes into ducts

Question 9

What are islets?

Answer 9

• derived from the branching duct system
• lose contact with ducts - become islets
• differentiate into alpha and beta cells secreting into blood
• number of islets in tail of pancreas is more than in head

Question 10

What is the composition of the islets?

Answer 10

• alpha cells form 15-20% of islet tissue and secrete glucagon
• beta cells form 60-70% of islet tissue and secrete insulin
• delta cells form 5-10% of islet tissue and secrete somatostatin
• islets are highly vascular so all endocrine cells have close access to site for secretion

Question 11

What is the composition of acini?

Answer 11

• secretory acinar cells - large with apical secretion granules
• duct cells - small and pale
• acini secrete their enzymes into duct

Question 12

What do centroacinar cells do?

Answer 12

Connect acinar cells to duct cells

Question 13

What are the two components of pancreatic juice?

Answer 13

1. acinar cell makes low volume, viscous, enzyme-rich part of juice
2. duct and centroacinar cells make high volume, watery, HCO3- rich part of juice

Question 14

What is the role of bicarbonate in pancreatic juice?

Answer 14

• produced by duct and centroacinar cells
• increases pH of juice to 7.5-8
• neutralises acid chyme from stomach - prevents damage to duodenal mucosa and raises pH to optimum range for pancreatic enzymes to work
• washes low volume enzyme secretion out of pancreas into duodenum

Question 15

What is the effect of duodenal pH on HCO3- secretion rate?

Answer 15

• duodenal pH < 5 - linear increase in pancreatic HCO3- secretion
• duodenal pH < 3 - plateaus, not much more increase in HCO3- secretion because:
• bile also contains HCO3- and helps neutralise acid chyme
• Brunner’s glands secrete alkaline fluid

Question 16

Describe the mechanism of bicarbonate release and action by the pancreas.

Answer 16

1. CO2 moves into pancreatic duct cell from blood and reacts with H2O to form H+ and HCO3- (catalysed by carbonic anhydrase) which are separated
2. Na+ moves down gradient from blood –> lumen via paracellular ‘tight’ junctions, H2O follows
3. Cl- and HCO3- are exchanged at lumen through anion exchanger (AE) - HCO3- from duct cell –> lumen, Cl- lumen –> duct cell (driven by electrochemical gradient)
4. Na+/H+ exchange at basolateral membrane into bloodstream occurs through sodium-hydrogen exchanger (antiporter) type 1 (NHE-1) - H+ out into blood, Na+ into duct cell (Na+ movement driven by electrochemical gradient)
5. Na+ gradient into cell from blood maintained by Na+/K+ exchange pump - uses ATP (primary active transport)
6. K+ returns to blood via K+ channel, and Cl- returns to lumen via Cl- channel (cystic fibrosis transmembrane conductance regulator - CFTR)

Question 17

How is the bicarbonate reaction used differently in stomach and pancreas?

Answer 17

• H2O + CO2 <–> H2CO3 <–> H+ + HCO3-
• stomach: H+ formed is secreted into gastric juice and HCO3- is secreted into blood = gastric venous blood is alkaline
• pancreas: H+ formed is secreted into blood and HCO3- is secreted into pancreatic juice = pancreatic venous blood is acidic

Question 18

What acinar cell enzymes are made and in what form initially?

Answer 18

• lipases (fat), proteases (protein), amylase (carbohydrate)
• synthesised and stored in zymogen (pro-enzyme) granules

Question 19

How are organs protected from these enzymes?

Answer 19

• proteases are released as inactive proenzymes which protects acini and ducts from auto-digestion
• pancreas contains a trypsin inhibitor to prevent trypsin activation
• enzymes are only activated in the duodenum
• blockage of main pancreatic duct may overload protection leading to auto-digestion and acute pancreatitis

Question 20

How are these acinar enzymes activated?

Answer 20

• duodenal mucosa secretes enterokinase (enteropeptidase) which converts trypsinogen to trypsin
• trypsin converts all other proteolytic and some lipolytic enzymes
• lipase is secreted in active form but requires colipase (i.e. secreted as precursor)
• lipases require presence of bile salts for effective action

Question 21

How do pancreatic secretions adapt with diet?

Answer 21

e.g. more protein and less carbs in diet lead to higher proportion of proteases and less of amylases

Question 22

What can a lack of pancreatic enzymes/bile cause?

Answer 22

• essential for normal digestion of a meal
• leads to malnutrition even if dietary input is okay
• unlike salivary and gastric enzymes

Question 23

What does Orlistat do?

Answer 23

• anti-obesity drug
• inhibits pancreatic lipases
• increases faecal fat (steatorrhea) - so does CF, chronic pancreatitis

Question 24

How is pancreatic juice secretion controlled in cephalic phase?

Answer 24

• reflex response to sight/smell/taste of food
• enzyme-rich component of the juice only made
• low volume - mobilises enzymes

Question 25

How is pancreatic juice secretion controlled in gastric phase?

Answer 25

• stimulation of pancreatic secretion originating from food arriving in stomach
• same mechanisms as cephalic phase

Question 26

How is pancreatic juice secretion controlled in intestinal phase?

Answer 26

• where 70-80% of pancreatic secretion happens
• hormonally mediated when gastric chyme enters duodenum
• both components of pancreatic juice stimulated - enzymes and HCO3- juice flows into duodenum

Question 27

How is pancreatic juice enzyme secretion controlled in acini?

Answer 27

1. vagus nerve - cholinergic and via vagal stimulation of enzyme secretion (and communicates information from gut to brain)
2. cholecystokinin (CCK) (Ca2+/PLC) made from duodenal I cells - stimulated by amino and fatty acids in duodenum and inhibited by trypsin

Question 28

How is pancreatic juice bicarbonate secretion controlled in duct and centroacinar cells?

Answer 28

• secretin (cAMP)
• acinar fluid is isotonic and resembles plasma in its concentrations of Na+, K+, Cl- and HCO3-
• secretion of acinar fluid and proteins in it is stimulated by CCK
• secretin released from S cells in jejunum + duodenum stimulates secretion of H2O and HCO3- from cells lining extralobular ducts into fluid, in response to Cl- absorption out of fluid
• secretin-stimulated secretion is richer in HCO3- than acinar secretion due to Cl-/HCO3- exchange

Question 29

How is HCO3- and secretin secretion controlled?

Answer 29

• classic negative feedback loop
• responds to decrease in luminal pH in duodenum
• decrease in luminal pH stimulates S cells to release secretin, which stimulates pancreatic ductal HCO3- secretion, which increases pH

Question 30

How do CCK and secretin work together?

Answer 30

• CCK alone has no effect on HCO3- secretion
• CCK can markedly increased HCO3- secretion that has been stimulated by secretin
• vagus nerve has similar effects to CCK
• secretin has no effect on enzyme secretion

Question 31

Describe the summary of a meal in terms of secretions.

Answer 31

1. food mixed, digested in stomach at pH 2
2. chyme squirted into duodenum
3. H+ ions in duodenum increase secretin secretion which increases pancreatic juice secretion - this along with bile and Brunner’s gland secretions increase pH to neutral/alkaline
4. peptides and fat in duodenum cause sharp increase in CCK and vagal nerve stimulation which stimulates pancreatic enzyme release
5. peaks by 30 minutes and continues until stomach is empty
6. CCK potentiates effects of secretin on aqueous components - this is necessary as most of duodenum is not at low pH

Question 32

What is the function of the small bowel?

Answer 32

To absorb nutrients, salt and water

Question 33

Describe the main parts of the small bowel and their length.

Answer 33

• approximately 6m long and 3.5cm in diameter
• stomach –> duodenum (D1,2,3) –> jejunum –> ileum
• duodenum - 25cm
• jejunum - 2.5m
• ileum - 3.75m
• no sudden transition between them
• all have the same basic histological organisation

Question 34

What are the functions of the mesentery?

Answer 34

• it is a membrane fold that suspends small and large bowel from posterior abdominal wall, anchoring them in place while still allowing for some movement
• provides a conduit for blood vessels, nerves and lymphatic vessels

Question 35

Which parts of the bowels do the specific blood vessels supply?

Answer 35

• jejunal and ileal arteries supply all of the ileum and come from superior mesenteric artery which comes from inferior border of pancreas
• the ileocolic artery supplies terminal ileum, caecum and ascending colon
• right colic artery supplies ascending colon
• middle colic artery supplies hepatic flexure, transverse colon and splenic flexure

Question 36

What are the layers of the small bowel?

Answer 36

• serosa - protective connective tissue
• muscles - longitudinal and circular - for motility and mixing
• submucosa
• mucosa (lining inside) - has plicae circulares (valves of Kerckring) to increase surface area, villi protrude from plicae circulares

Question 37

Describe villi.

Answer 37

• only occur in small intestine
• are motile
• have rich blood supply and lymph drainage for absorption of digested nutrients
• have good innervation from the submucosal plexus
• have simple one cell thick epithelium, dominated by enterocytes (columnar absorptive cells)

Question 38

What cell types are villi (mucosa) lined with?

Answer 38

• simple columnar epithelium consisting of:
• primarily enterocytes (absorptive cells)
• scattered goblet cells
• enteroendocrine cells

Question 39

What cell types are in the crypts of Lieberkuhn?

Answer 39

• Paneth cells
• stem cells

Question 40

What are primary enterocytes?

Answer 40

• most abundant cells in small bowel
• tall columnar cells with microvilli and a basal nucleus
• specialised for absorption, transport and digestion of substances
• short lifespan of 1-6 days
• cylindrical internal surface area of small bowel is 0.4m2
• folds, villi and microvilli increase surface area to 200m2 (500 fold increase)

Question 41

Describe microvilli.

Answer 41

• make up the ‘brush border’
• several thousand microvilli per cell
• surface of microvilli covered with glycocalyx

Question 42

What is glycocalyx?

Answer 42

• rich carbohydrate layer on apical membrane
• serves as protection from digestional lumen yet allows for absorption
• traps a layer of water and mucous called ‘unstirred layer’
• regulates rate of absorption from intestinal lumen

Question 43

What are scattered goblet cells?

Answer 43

• 2nd most abundant epithelial cell type
• mucous containing granules accumulate at apical end of cell, causing ‘goblet’ shape
• mucous - large glycoprotein that facilitates passage of material through bowel, lubricant of bowel
• there is increasing abundance of goblet cells along length of bowel - not many in duodenum but lots in colon because you have solid faeces which need lubricating

Question 44

What are enteroendocrine (chromaffin) cells?

Answer 44

• columnar epithelial cells
• scattered among enterocytes
• most found in lower part of crypts
• secrete hormones e.g. to influence gut motility

Question 45

What are Paneth cells?

Answer 45

• found only in bases of crypts
• contain large, acidophilic granules containing antibacterial enzyme lysozyme (protects stem cells) and glycoproteins & zinc (essential metal for many enzymes)
• also engulf some bacteria and protozoa
• may have a role in regulating intestinal flora

Question 46

What are stem cells? (in small bowel)

Answer 46

• undifferentiated cells which remain capable of cell division to replace cells which die
• epithelial stem cells are essential in the GI tract to continually replenish the surface epithelium
• continually divide by mitosis and migrate to the tip of villus, replacing older cells that die of apoptosis and are digested and reabsorbed
• differentiate into various cell types - pluripotent

Question 47

Why do enterocytes and goblet cells have such short life spans (36 hours)?

Answer 47

• enterocytes are first line of defence against GI pathogens and may be directly affected by toxic substances in diet
• effects of agents which interfere with cell function will be diminished
• any lesions will be short-lived
• if escalator-like transit of enterocytes is interrupted through impaired production of new cells e.g. radiation, severe intestinal dysfunction will occur

Question 48

What gland distinguishes the duodenum from the jejunum and what does it do?

Answer 48

• Brunner’s glands - submucosal coiled tubular mucous glands secreting alkaline fluid
• opens into base of the crypts
• the alkaline secretions neutralises acidic chyme from stomach, protecting proximal small bowel while optimising pH for action of pancreatic enzymes

Question 49

Describe the differences between the jejunum and ileum.

Answer 49

• jejunum is wider, thicker-walled and redder than ileum since its’ plicae circulares muscles are larger, more numerous and more closely set
• jejunal mesentery is above and left of aorta whereas ileal mesentery is below and right of aorta
• jejunal mesenteric vessels form 1/2 arcades with long infrequent arterial vessels to vessel wall whereas ileum has 3/4 arcades with short arterial walls
• lower ileum has Peyer’s patches on antimesenteric border - aggregations of lymphoid tissue involved with gut immunity

Question 50

What are the functions of small bowel motility?

Answer 50

• to mix ingested food with digestive secretion and enzymes
• facilitate contact between contents of intestine and intestinal mucosa
• propel intestinal contents along alimentary tract

Question 51

What are the three types of motility in small bowel?

Answer 51

• segmentation (mixing)
• peristalsis (propelling)
• migrating motor complex

Question 52

What is segmentation (mixing)?

Answer 52

• mixes contents of lumen
• occurs by stationary contraction of circular muscles at intervals - more frequent in duodenum than ileum
• allow pancreatic enzymes and bile to mix with chyme
• although chyme moves in both directions, net effect is movement –> colon

Question 53

What is peristalsis (propelling)?

Answer 53

• involves sequential contraction of adjacent rings of smooth muscle
• propels chyme towards colon
• most waves of peristalsis only travel 10cm
• segmentation and peristalsis result in chyme being segmented, mixed and propelled –> colon

Question 54

What is migrating motor complex?

Answer 54

• cycles of smooth muscle contractions sweeping through the gut
• begin in stomach –> small intestine –> colon –> next wave starts in duodenum
• prevents migration of colonic bacteria into ileum

Question 55

Describe the overall digestion in duodenum.

Answer 55

• occurs in alkaline environment
• pancreatic digestive enzymes and bile enter duodenum from main pancreatic duct and common bile duct
• duodenal epithelium also produces its own digestive enzymes
• digestion occurs in lumen and in contact with the membrane

Question 56

What types and structures of carbohydrate are in our diet?

Answer 56

• carbs contain 50% of ingested calories in western diet
• simple carbohydrates - monosaccharides (glucose and fructose) and disaccharides (sucrose and maltose)
• complex carbohydrates - starch, cellulose, pectins - sugars bonded together to form a chain

Question 57

Describe carbohydrate digestion.

Answer 57

• begins in mouth by salivary alpha-amylase which is later destroyed in stomach due to acid
• most of digestion occurs in small intestine
• pancreatic alpha-amylase secreted in duodenum and continues digestion of starch and glycogen in small bowel lumen (some also adsorbs to brush border)
• needs Cl- for optimum activity and neutral/slightly alkaline pH
• digestion of amylase products and simple carbohydrates occurs at the brush border

Question 58

Describe carbohydrate absorption.

Answer 58

• absorption of glucose and galactose is by secondary active transport by SGLT-1 carrier protein on apical membrane
• absorption of fructose is by facilitated diffusion by GLUT-5 carrier protein on apical membrane
• GLUT-2 facilitates exit at basolateral membrane
• human small bowel can absorb 10kg of simple sugars/day

Question 59

Describe the digestion of proteins.

Answer 59

• protein digestion begins in lumen of stomach by pepsin which is then inactivated in alkaline duodenum
• 5 pancreatic proteases secreted as precursors –> lumen of small bowel e.g. trypsinogen
• trypsin activated by enterokinase which is an enzyme located on duodenal brush border
• trypsin activates other proteases which hydrolyse proteins –> single AAs and oligopeptides

Question 60

Describe what happens at brush border (proteins).

Answer 60

• variety of peptidases at brush border of enterocytes progressively hydrolyse multi-AAs to mono-AAs
• enterocytes directly absorb some of small oligopeptides via action of H+/oligopeptide cotransporter PepT1
• these small peptides are digested to AAs by peptidases in cytoplasm of enterocytes

Question 61

Describe the 4 stages of lipid digestion.

Answer 61

• lipids are poorly soluble in water = more complicated

1. secretion of bile salts and pancreatic lipase
2. emulsification which increases SA for digestion
3. enzymatic hydrolysis of ester linkages - colipase complexes with lipase to prevent bile salts displacing lipase from fat droplet
4. solubilisation of lipolytic products in bile salt micelles

Question 62

Describe the absorption of lipids.

Answer 62

• lipids are transformed as absorbed via enterocytes
• FAs and monoglycerides (MG) leave micelles and enter enterocytes
• FAs and MG resynthesised into triglycerides (TGs) by the monoglyceride acylation pathway (major) and phosphatidic acid pathway (minor)
• chylomicrons are made in Golgi apparatus as an emulsion - 80-90% TGs, 8-9% phospholipids, 2% cholesterol, 2% protein, trace carbohydrate
• chylomicrons secreted across basement membrane by exocytosis
• they enter a lacteal (lymph capillary) and lymph transports them away from the bowel

Question 63

What does the ileocaecal valve do?

Answer 63

• ileum is separated from the colon by the ileocaecal valve
• relaxation and contraction controls passage of material into colon
• also prevents backflow of bacteria into ileum