Week 10- Pancreas and the Small Bowel Flashcards
What vein dives behind the neck of the pancreas?
Superior mesenteric vein
What artery supplies the whole of the small bowel?
Superior mesenteric artery
Where is the pancreas found?
Right at the back of the body
What are the 2 parts of the pancreas?
The body and the tail
What is MRCP?
A method of imaging the pancreas and gallbladder
What is pancreatic divisum?
When the ventral pancreatic duct doesn’t fuse with the dorsal pancreatic duct- often causes pancreatitis
What is endocrine secretion?
Secretion into the blood stream to have an effect on a distant target organ- ductless glands
What is exocrine secretion?
Secretion into a duct to have a direct local effect
What are the main endocrine secretions?
Insulin- anabolic hormone
Glucagon
Somatostatin-endocrine cyanide
How much of total secretion from the pancreas is endocrine?
2%
How much of total secretion from the pancreas is exocrine?
98%
What are acini?
Attached to ducts, secretory units, secrete proenzymes into ducts
What are islets?
Derived from branching duct system, differentiate into alpha and beta cells and secrete into blood
Where are more islets found?
More in the tail than the head
What are the main cells in the micro-anatomy of the pancreas?
Acinar cells
Centroacinar cells
What are the different cells found in islets?
Alpha, beta, delta and acini
What is the function of alpha cells and how much do they make up of the islet?
15-20%, secrete glucagon
What cells produce bicarbonate?
Duct and centroacinar cells
How is HCO3- secreted from the pancreas?
Catalysed by carbonic anhydrase, HCO3 formed and dissociates
Na+ is moving down a gradient via water
HCO3- moves out, Cl- moves into cell
H+ moves in as Na+ moves into cell down electrochemical gradient
K+ pumped in, Na+ pumped out to maintain electrochemical gradient
K+ is actively pumped out to restore gradient
CFTR pumps out Cl- to restore gradient
Is HCO3- secretion from the pancreas an active or passive process?
Active, pumps require ATP
Is gastric venous blood acidic or alkaline?
Alkaline
Is pancreatic venous blood acidic or alkaline?
Acidic
What are zymogens?
Proenzymes
What prevents activation of tripsin?
Trypsin inhibitor
Where are enzymes activated?
Duodenum
What enzyme activate trypsinogen to trypsin?
Enterokinase (enteropeptidase)
What does trypsin do?
Converts all proteolytic and some lipolytic enzymes
What is pancreatic juice enzyme secretion controlled in acini by?
Vagus nerve- cholinergic
CCK
What is pancreatic juice bicarbonate secretion controlled in duct and centroacinar cells by?
Secretin (cAMP)
What does CCK require to have an effect on bicarbonate secretion?
Secretin- together they greatly increase bicarbonate secretion
What effect does secretin have on enzyme secretion?
NO effect
What is the function of the small bowel?
To absorb nutrients, salt and water
What are the 3 main components of the small bowel from start to end?
Duodenum, jejunum, ileum
How long is the duodenum?
25cm
How long is the jejunum?
2.5m
How long is the ileum?
3.75m
What is the function of the mesentery
Suspends the small bowel from the posterior abdominal wall, keeping it in place while allowing movement, it is also a conduit for blood vessels, nerves and lymphatic vessels
What is the difference between thrombus and embolus?
Thrombus- comes from a vein
Embolus- comes from heart, gets stuck in an artery
Where are vili found?
Only in small intestine
Where do villi get innervation from?
Submucosal plexus
What are the main cells in the villi?
Enterocytes, each one has thousands of microvilli
What cell types are fund in a villus?
Primary enterocytes
Goblet cells
Enteroendocrine cells
What cell types are fund in a crypt?
Paneth cells
Stem cells
What are the surface of microvilli covered with?
Glycocalyx
What is the function of glycocalyx?
Rich carbohydrate layer on apical membrane, protects from digestion in lumen while allowing absorption. Traps a layer of mucous and water known as the ‘unstirred layer’ and regulates rate of absorption from intestinal lumen
Describe goblet cells
2nd most abundant cell type, granules containing mucous gather at apical end
Describe the role of mucous in the intestine?
It is a large glycoprotein that facilitates the movement of food along the bowel
How does the abundance of goblet cells vary along the bowel?
Increases as you go along the bowel, lowest abundance in duodenum, highest in colon
Where is the ileum found?
Right of aorta
Where is the jejunum found?
Upper right quadrant
Where are Peyers patches found?
In the ileum
What are the 3 main functions of motility?
To mix food w digestive enzymes
To facilitate contents and mucosa having contact
To propel contents along alimentary canal
What 2 ducts in the pancreas fuse?
Dorsal and ventral
What ducts join together and drain at the major papilla?
Bile and pancreatic ducts
Describe the endocrine secretions of the pancreas and their functions
Secreted hormones into the blood (insulin, glucagon, somatostatin, pancreatic polypeptide) for regulation of blood glucose, metabolism and growth
Describe the exocrine secretions of the pancreas and their functions
Secretes pancreatic juice into the duodenum via MPD/sphincter of Oddi/ampulla, has digestive function
What is the function of beta cells and how much do they make up of the islet?
Secrete insulin, make up 60-70% of the islets
What is the function of delta cells and how much do they make up of the islet?
Secrete somatostatin and make up 5-10% of the islets
What adaptation do islets have that help with secretion?
They are highly vascular so cells have close access to sites for secretion
How are acini composed? (what 2 main components are present)
Secretory acinar cells- with apical secretion granules
Duct cells- small and pale
What 2 cells are involved with producing pancreatic juice and how do they differ?
Acinar cells- reduce volume, viscous, enzyme rich
Duct and centeroacinar cells- increase volume, watery, HCO3- rich
Where is bicarbonate formed in the pancreas?
Duct and centeroacinar cells
Describe the composition of pancreatic juice
It is rich in bicarbonate (120 mM vs 25 mM in blood)
pH 7.5-8
What is the function of pancreatic juice?
To neutralise acid chyme from stomach to protect duodenal mucosa
To increase pH to make it optimal for pancreatic enzymes
To wash out some enzyme secretions into the duodenum
Why does HCO3- secretion increase when pH is 5 and stop when pH reaches 3?
Bile also contains HCO3- and helps neutralise acid chyme, brunners glands also secrete alkaline fluid
How do the stomach and pancreas differ in HCO3- and H+ secertion?
Stomach: secretes HCO3- into blood and H+ into juice
Pancreas: secretes H+ into blood and HCO3- into juice
Why are enzymes released as inactive pro enzymes?
To prevent autodigestion
How can blockage of MPD cause acute pancreatitis?
It may overload protection and lead to auto digestion
Where is enterokinase secreted?
By duodenal mucosa
What common enzyme is released in its active form and why?
Lipase because it requires colipase (and bile) to work effectively
How do pancreatic secretions adapt to diet?
Enzyme secretion is altered eg if theres lots of protein intake, protease synthesis increases
How does orlistat work and what does it cause?
It inhibits pancreatic lipases, fat isn’t digested and excreted in poo- steatorrhea
What happens in the cephalic phase in relation to pancreatic juice?
Reflex response to sight/smell/taste of food, low vol mobilises enzymes
What happens in the gastric phase in relation to pancreatic juice?
Food arrives in the stomach and stimulates pancreatic secretion
What happens in the intestinal phase in relation to pancreatic juice and how much of total secretion occurs in this phase?
60-70% of secretion occurs here
Hormonally mediated when gastric chyme enters the duodenum, both components of juice are secreted (HCO3- and enzymes) and flow into duodenum
What stimulates the vagus nerve, causing release of trypsin?
Acetylcholine
What stimulates release of CCK from duodenal cells?
Amino acids and fatty acids (originally from protein)
What inhibits release of CCK from duodenal cells?
Trypsin
Describe the composition of acinar fluid
It is isotonic and largely resembles plasma
What is the secretion of acinar fluid stimulated by?
CCK
What stimulates secretion of H2O and HCO3- from cells lining extralobular cells?
Secretin
Out of acinar secretion and secretin stimulated secretion, what is richer in HCO3- and why?
Secretin stimulated secretion due to Cl-/HCO3- exchange
Describe how a fall in duodenum pH leads to HCO3- secretion via the negative feedback loop
pH in duodenum falls S cells are activated Secretin is secreted Pancreatic ducts release HCO3- pH rises again
Summarise what happens during a meal
Food digested in stomach, pH 2
Chyme secreted into duodenum, H+ ions present
Fall in pH stimulates increased secretin and increased pancreatic juice secretion
pH increases to neutral/ alkaline
Peptides and fat in duodenum stimulate CCK and vagus nerve stimulation
This stimulates pancreatic enzyme release
CCK potentiates action of secretin
How long after a meal is pancreatic enzyme secretion at its peak and when does it stop?
Peak after 30 mins
Stops when stomach is empty
How long is the small bowel in total and what is its diameter?
6m long, 3.5cm diameter
Describe the motility and blood supply to villi
They are motile, they have a high blood supply and lymph drainage for the absorption of digested food
What is the lifespan of an enterocyte?
1-6 days
How much do villi and microvilli increase the surface area of the small bowel by?
500 x
From 0.4 m^2 to 200m^2
How high are microvilli?
0.5-1.5 micrometers
Describe the role and structure of enteroendocrine cells. Where are they most commonly found?
Columnar epithelial cells that are hormone secreting- influence gut motility, found in lower crypt
Describe the role and structure of paneth cells. Where are they found?
Thy are found only at the base of crypts, they have acidophilic granules that contain lysozyme (antibacterial, protects stem cells) as well as glycoproteins and zinc (trace metal for enzymes), also engulf some bacteria and protozoa
Describe the role and structure of stem cells in the small bowel. Where are they found?
They are found in the crypt, they migrate upwards to replace dead cells, they are pluripotent and essential as cell turnover in the small bowel is very high
Why do enterocytes have such a short life span compared to average epithelial cells?
They are the first line defence cells against GI pathogens so often encounter toxic substances, interference with their turnover eg by radiation, causes severe intestinal dysfunction
What is the transition from duodenum to jejunum to ileum like?
No sudden transition
How is the duodenum distinguishable from the other parts of the small bowel?
Via the presence of Brunner’s glands which produce alkaline secretions to protect the proximal small bowel from stomach acid and optimise pH for pancreatic enzymes.
What are Brunner’s glands?
Submucosal coiled tubular mucous glands that secrete alkaline fluid in the duodenum
What are the 3 types of motility?
Segmentation
Peristalsis
Migrating motor complex
Describe segmentation as a method of motility in the small bowel
Stationary contraction of circular muscle at intervals, chyme moved in both directions but overall towards bowel, allows chyme to mix with bile and pancreatic enzymes
Describe peristalsis as a method of motility in the small bowel
Sequential contraction of adjacent rings of smooth muscles, propels chyme towards colon
Describe migrating motor complex as a method of motility in the small bowel
Cycles of smooth muscle contractions sweeping through the gut
How do pancreatic enzymes and bile enter the duodenum?
Via the common bile duct and main pancreatic duct
Where does digestion occur in the duodenum?
In the lumen in contact with the epithelial cells
Where are carbohydrates digested?
Mainly in small intestine, begins in mouth with salivary alpha amylase
Describe the action of pancreatic alpha amylase
Digests carbohydrates in the small intestine, need Cl- for optimum activity and neutral/slightly alkaline pH, acts mainly in lumen, but digestion of amylase products and simple carbohydrates occurs at brush border
How are glucose and galactose absorbed?
By secondary active transport via carrier protein SGLT-1 on apical membrane
How is fructose absorbed?
By facilitated diffusion via carrier protein GLUT 5 on apical membrane
How much of simple sugar can the human intestine absorb a day?
10kg
Where does protein digestion via pepsin begin and end?
Begins in the lumen of the stomach, pepsin is inactivated in the alkaline duodenum
How many enzymes are involved with the digestion of protein in the small intestine? How are they secreted/activated?
There are 5 pancreatic proteases, they are secreted as precursors in the lumen of the small intestine
Trypsin is activated by enterokinase, trypsin also activates the other proteases
Where is enterokinase found and what is its function?
Its found on the duodenal brush border and it activates trypsin
How are peptides digested at the brush border of enterocytes?
Via peptidases that carry out progressive hydrolysis
Enterocytes also directly absorb small amino acids via H+/oligopeptide cotransporter PepT1
Describe the 4 stages of lipid digestion
Secretion of bile salts and pancreatic lipases
Emulsification
Enzymatic hydrolysis of ester linkages
Solubilisation of lipolytic products in bile salt micelles
How does colipase help in lipid digestion?
Forms complexes with lipase to stop bile displacing lipase from the fat droplet
What 2 products of lipid digestion enter enterocytes
Fatty acids and monoglycerides
What are fatty acids and monoglycerides synthesised into and by what pathways?
Into triglycerides via either:
Monoglyceride acylation (major)
Phosphatidic acid pathway (minor)
What are triglycerides converted to in enterocytes before being secreted? How are they secreted and into what?
Synthesised into chylomicrons and secreted via exocytosis into lacteal ducts where lymph transport then away from the bowel
What separates the ileum from the colon? Describe its actions
Ileocaecal valve, contraction/relaxation controls what moves into the colon and prevents backflow into the ileum