Pancreas And Small Bowel Flashcards
Describe the embryological development of the pancreas
1) Abdominal accessory organs arise as foregut outgrowths
2) Proximal duodenum rotates clockwise- all organs are in their place by 11 weeks
3) Ventral and dorsal pancreatic buds and ducts fuse- the ducts form the major papilla . Bile and pancreatic ducts join to drain together at major papilla
There’s also a minor papilla which has been degraded away in many adults
Pancreatic duct at major papilla joins with distal common bile duct to form the ampulla
What 2 ducts join at the major papilla?
pancreatic duct
Bile duct
What is the uncinate process of the pancreas originated from?
Ventral bud and duct
What do the ventral and dorsal ducts emerge as respectively?
Ventral - Main pancreatic duct at the major papilla
Dorsal - Accessory pancreatic duct at the minor papilla
the accessory pancreatic duct present in everyone?
No in most adults it has been degenerated
What does the fact the the pancreas is a retroperitoneal structure mean?
does not exist within the abdomen
It is behind the posterior to the peritoneum
MRCP imaging diagram and when is it used?
Magnetic Resonance CholangioPancreatography
Procedure can be used to determine whether gallstones are lodged in any of the ducts surrounding the gallbladder
Uses magnetic resonance imaging to visualise the biliary and pancreatic ducts non-invasively
Can’t see pancreatic duct
Angiography diagrams and when is it used?
Angiography - accessing femoral artery, put needle in and thread wire via femoral artery to aorta. Then put dye into the coeliac axis
When patients are bleeding
What is pancreas divisum and why does it cause the patient to have recurrent episodes of pancreatitis?
Ventral bud and dorsal buds fail to fuse and so the ventral duct which usually has a large enough capacity to cope with the flow of the pancreatic juice can no longer do so
The large flow has to therefore go through a minor duct and so they get recurrent episodes of pancreatits
Define endocrine vs exocrine secretion
Endocrine- secretion into bloodstream to have effect on distant target organ (ductless glands)
Exocrine- secretion into a duct to have direct local effect
What are the 3 main endocrine secretions of the pancreas and their actions?
- 2% of gland secretions are endocrine 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 blood glucose)
- Somatostatin- inhibits everything- known as ‘endocrine cyanide’
What are the main exocrine secretions of the pancreas and their actions?
- Secretes pancreatic juice into duodenum via main pancreatic duct/sphincter of Oddi/ampulla
- Exocrine acinar cells
- Digestive function
- What is the composition of the islets?
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- 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
Why are Islets highly vascular
so all endocrine cells have close access to site for secretion
What is the composition of acini
- Secretory acinar cells- large with apical secretion granules
- Duct cells- small and pale
- Acini secrete their enzymes into ducts
What are the 2 components of pancreatic juice and what are they produced by?
1) Acinar cell makes low volume, viscous, enzyme-rich part of the juice
2) Duct and centroacinar cells make high volume, watery, HCO3- rich part of juice
What are the (2) functions of the bicarbonate secretion in the pancreatic juice?
Increases pH of the juice to 7.5-8
- Neutralises acid chyme from stomach, what does this do (2)Prevents damage to duodenal mucosaRaises pH to optimum range for pancreatic enzymes to work
- Washes low volume enzyme secretion out of pancreas into duodenum
What is the effect of duodenal pH on HCO3- secretion rate?
When duodenal pH < 5 → there’s linear increase in pancreatic HCO3- secretion
Why does HCO3- secretion stop increasing when duodenal pH goes below 3 (2 reasons)?
- Bile also contains HCO3- and helps neutralise acid chyme
- Brunners glands secrete alkaline fluid
Describe the mechanism of bicarbonate release and action by pancreas
1) CO2 moves into pancreatic duct cell from blood and reacts with H2O (catalysed by carbonic anhydrase) to form H+ and HCO3- which are separated
2) Na+ and H2O move down gradient via paracellular ‘tight’ junctions, into lumen
3) Cl- and HCO3- are exchanged at pancreatic lumen through anion exchanger (AE1) → Cl- movement driven by electrochem grad
4) Na+/H+ exchange at basolateral membrane into bloodstream happening through sodium-hydrogen exchanger (antiporter) type 1 (NHE-1) → Na+ enters the cell down gradient
5) Na+ gradient into cell from blood maintained by Na+/K+ exchange pump → uses ATP to transport Na+ out of cell and K+ into cell
6) K+ returns to blood via K+ channel and Cl- returns to lumen via Cl- channel (CFTR), to maintain their electrochemical gradients.
How is the bicarbonate reaction used differently in stomach and pancreas? (i.e. state the difference in venous blood of the stomach and venous blood of the pancreas, and explain why)
- In stomach, H+ formed is secreted into gastric juice and HCO3- is secreted into blood so gastric venous blood is alkaline
- In pancreas, H+ formed is secreted into blood and HCO3- is secreted into pancreatic juice so pancreatic venous blood is acidic
Which 3 classes of digestive enzymes are present in the acinar cell enzyme secretion and in what form are they initially stored as?
- Lipases, proteases and amylase
- Synthesised and stored in zymogen (pro-enzyme) granules
Why are proteases released as inactive pro-enzymes?
Protects acini and ducts from auto-digestion
- Blockage of main pancreatic duct may overload protection leading to auto-digestion and acute pancreatitis
What other protective mechanisms against auto-digestion of the pancreas are there (2)
Pancreas contains trypsin inhibitor to prevent trypsin activation
Enzymes only activated in the duodenum - where they have to start digesting food
Trypsin converts all other proteolytic and some lipotyic enzymes into active form
What enzyme is secreted by the duodenal mucosa and what does it do?
Enterokinase
Converts trypsinogen to trypsin
Why is it not dangerous to secrete lipase in its active form?
Requires colipase (i.e. secreted as precursor) for action and the presence of bile salts for effective action
What can lack of pancreatic enzymes cause?
- Malnutrition even if dietary input is OK
- This is unlike salivary and gastric enzymes
What 2 components is the pancreatic juice enzyme secretion controlled in the acini by?
1) Vagus nerve- cholinergic and via vagal stimulation of enzyme secretion & feedback from gut to brain
2) Cholecystokinin (CCK) (Ca2+/PLC) made from duodenal I cells
Which 2 compounds stimulate the release of CCK from the duodenal I cells
Amino acids and fatty acids
What effect does trypsin have on the release of CCK from duodenal I cells?
Inhibitory
- What hormone controls the pancreatic juice bicarbonate secretion in the duct and centroacinar cells?
Secretin (cAMP)
How is pancreatic juice bicarbonate secretion controlled in duct and centroacinar cells?
- Acinar fluid is isotonic and resembles plasma in its concs of Na+ Cl- K+ and HCO3-
- Secretion of acinar fluid & proteins in it is stimulated by CCK
- Secretin (cAMP) released from S cells in jejunum + duodenum stimulates secretion of H2O and HCO3- from cells lining extralobular ducts
- Secretin-stimulated secretion is richer in HCO3- than acinar secretion due to Cl-/HCO3- exchange
acinar fluid isotonic?
Yes and it resembles plasma in its concentrations of Na+, K+, Cl- and HCO3-
Why is secretin-stimulated secretion richer in HCO3- than acinar secretion?
Because of the Cl-/HCO3- exchange in the extralobular duct
As it flows down into the larger pancreatic ducts, it becomes richer in HCO3- due to there being more duct and centroacinar cells
Describe the negative feedback loop involved in the secretin release & control of HCO3- secretion in ducts?
Decrease in pH in duodenum activates S cells to release Secretin
Secretin stimulates pancreatic ductal HCO3- secretion which increases pH
Since pH is increased, the S cells cannot be stimulated to release more secretin, controlling the secretion of HCO3
When does CCK have an effect on HCO3- secretion?
It markedly increases HCO3- secretion that has already been stimulated by secretin
What effect does bile and Brunner’s gland secretions have on the pH?
Increases pH
Describe the summary of a meal in terms of things secreted
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) This peaks by 30 mins and continues until the stomach is empty
6) CCK potentiates effects of secretin on aqueous component- this is necessary as most of duodenum isn’t at a low pH
What effect does secretin have in enzyme secretion
None
What is the function of the the small bowel?
Absorbs nutrients salt and water
Describe the 3 main parts of the small bowel and their length
- Approx 6m long and 3.5cm in diameter
- Duodenum- 25cm
- Jejunum- 2.5m
- Ileum- 3.75m
- No sudden transition between them and all have same basic histological organisation
What are the functions of the mesentery (part of peritoneum)
- 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
- It provides a conduit for blood and lymphatic vessels and nerves
Which parts of the bowels do the below blood vessels supply?
- The 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
Describe villi
- Only occur in small intestine
- Are motile
- Have rich blood supply and lymph drainage for absorption of digested nutrients
- Have good innervation from submucosal plexus
- Have a simple 1 cell thick epithelium dominated by enterocytes (columnar absorptive cells)
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What 3 cells are villi mucosa lined with
Primary eneterocytes– Most abundant cell in small bowel
- Tall columnar cells with microvilli and a basal nucleus
- Specialised for absorption and transport of substances
- Short lifespan of 1-6 days
Scattered goblet cells– 2nd most abundant epithelial cell type
- Mucous containing granules accumulate at apical end of cell, causing goblet shape
Enteroendocrine cells aka chromaffin cells-secrete hormones to influence gut motility,scattered among enetrocytes and are columnar epithelial cells in lower part of crypts
Microvilli
Make up brush border
Surface covered in glycocalyx which is a rich carb layer protects from digestion Al lumen ,traps a layer of water and mucous,regulates rate of absorption
2 cell types in lieberkuhn
Paneth cells- found in bases of crypts. Contain Large, acidophilic granules containing anti-bacterial lysozyme (protects stem cells) and glycoproteins and zinc (essential trace metal for a number of enzymes)
Engulf some bacteria and protozoa
May have a role in regulating intestinal flora
Stem cells– They are essential in GI tract to continually replenish the surface epithelium
- Continually divide by mitosis and migrate up to tip of villus, replacing older cells that die of apoptosis and are digested and reabsorbed
- Differentiate into various cell types so are pluripotent
Why do enterocytes and goblet cells have such short life spans (~36 hours)?
- 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 due to quick turnover of cells
- 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 occu
What gland distinguishes the duodenum from the jejunum and what does it do?
- Brunner’s glands (present in duodenum)- submucosal coiled tubular mucous gland secreting alkaline fluid
- Open 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
Describe the differences between the jejunum and ileum (4)
- Jejunum is wider, thicker walled and redder than ileum since its plicae circulares muscles are larger, more numerous and more closely set
- Lower ileum has Peyer’s patches on antimesenteric border- aggregations of lymphoid tissue involved with gut immunity
- 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 vessels
What are the 3 types of motility in small bowel?
- Segmentation (mixing)- describe it (what does it do and how does it do it)?
- Mixes contents of lumen
- Stationary contraction of circular muscles at intervals- more frequent in duodenum than ileum
- Allow pancreatic enzymes & bile to mix with chyme
- Although chyme moves in both directions, net movement is towards colon
- Peristalsis (propelling)- describe it (what does it do and how does it do it)?
- 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 towards colon
- Migrating motor complex- describe it, and what does it prevent?
- Cycles of smooth muscle contractions sweeping through gut
- Begin in stomach → small intestine → colon → next wave starts in duodenum
- Prevents migration of colonic bacteria into ileum
Overall digestion in duodenum
Alkaline environment
Bile and pancreatic enzymes entered through main pancreatic duct and common bile duct
Carb digestion
Mouth by salivary-alpha-amylase, which is destroyed in stomach by acidic pH
- Most of digestion occurs in small bowel
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Pancreatic alpha-amylase is secreted in duodenum and continues digestion of starch and glycogen in lumen (some also adsorbs to brush border)
Enzyme needs cl- and slightly alkaline ph
Occurs at brush border
Describe carbohydrate absorption glucose, galactose & fructose
- 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
Describe protein digestion
- 5 pancreatic proteases secreted as precursors into lumen of small bowel e.g. trypsinogen
- Trypsin activated by enterokinase which is on duodenal brush border
- ## Trypsin activates other proteases which hydrolyse proteins into single amino acids and oligopeptides
- Why are lipids more complicated to digest than carbohydrates and proteins?
Lipids are poorly soluble in water
Describe the 4 stages of lipid digestion
1) Secretion of bile salts and pancreatic lipase
2) Emulsification which increases SA for digestion
3) Enzymatic hydrolysis of ester linkages- forms colipase complexes with lipase
4) Solubilisation of lipolytic products in bile salt micelles
Colipases
Prevents bile salts from displacing lipase from fat droplet
How are triglycerides resynthesised (2 pathways)?
monoglyceride acylation pathway
phosphatidic acid pathway
Describe absorption of lipids
- Lipids are transformed as absorbed via enterocytes
- Fatty acids and monoglycerides leave micelles and enter enterocytes
- These 2 are resynthesised into triglycerides by the monoglyceride acylation pathway (major) and the phosphatidic acid pathway (minor)
- Chylomicrons are made in Golgi apparatus- 80-90% triglycerides, 8-9% phospholipids, 2% cholesterol, 2% protein and trace carbs
- Chylomicrons secreted across basement membrane by exocytosis
- They enter a lacteal (lymph capillary) and lymph transports them away from bowel
What does the ileocaecal valve do and what are its 2 functions?
- separates the ileum from the colon
- Relaxation and contraction controls passage of material into colon
- Also prevents back flow of bacteria into ileum
