8.2: The pancreas and small bowel Flashcards
Pancreatic embryology (3 steps)
1) abdominal accessory organs arise as foregut outgrowths
2) proximal duodenum rotates clockwise
3) ventral and dorsal pancreatic buds and ducts fuse. Bile and pancreatic ducts join to drain together at major papilla
What is the uncinate process of the pancreas originated from?
Ventral bud and duct
What do ventral and dorsal ducts emerge as respectively?
Ventral - main pancreatic duct at the major papilla
Dorsal - accessory pancreatic duct at major papilla
Is the accessory pancreatic duct present in all individuals?
No, In most adults it has been degenerated
What 2 ducts join at the major papilla?
Main pancreatic duct
Bile duct
What is meant by the pancreas having a retroperitoneal structure
It does not exist within the abdomen
It is behind the posterior to the peritoneum
What vein is formed by joining of the splenic vein and superior masenteric vein?
Portal vein
What two diagnostic techniques are used when looking at the pancreas
CT scan
MRCP
What is MRCP used for and how does it work?
Procedure can be used to determine wether gallstones are lodged in any ducts surrounding gallbladder
Uses MRI to visualise biliary pancreatic ducts non-invasively
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 secretion
Secretion into the blood stream to have effect on distant target organ
Define exocrine secretion
Secretion into a duct to have direct local effect
3 main endocrine secretions of pancreas
Insulin
Glucagon
Somatostatin
4 actions of insulin
Anabolic hormone
Promotes glucose transport into cells and storage as glycogen
Decreased blood glucose
Promotes protein synthesis and lipogenesis
2 actions of glucagon
Increases gluconeogenesis and glycogenolysis
Increases blood glucose
What percentage of the pancreatic secretion is endocrine and what part of the pancreas does this?
2%
Islets of Langerhans
What percentage of the pancreatic secretion is exocrine and what does this involve?
98%
Secretion of pancreatic juice into duodenum vis MDP/sphincter of Oddi/ampulla
Describe the structure of acini in the pancreas
Attached to ducts
Grape-like clusters of secretory units
What do acini secrete into ducts?
Pro-enzymes
Describe the structure of islets
Derived from branching duct system but lose contact with the ducts to become islets
Differentiate into alpha and beta cells secreting into the blood
Are there more islets in the head or tail of the pancreas?
Tail
Why are the pancreatic islets highly vasculated?
Very good blood supply
Ensures that all endocrine cells have a site for close access to a site for secretion
What proportion of pancreatic islets are composed of alpha, beta and gamma cells respectively
alpha = 15-20%
beta = 60-70%
gamma = 5-10%
Compare the structures of the secretory acinar cells and the duct cells in the acini of the pancreas
Secretory acinar cells - large with apical secretions
Duct cells - small and pale
Describe the components of pancreatic juice formed by Acinar cells
Low volume
Viscous
Enzyme - rich
Describe the other components of pancreatic juice formed by the Duct and Centroacinar cells
High volume
Watery
HCO3 - rich
What are the functions of the bicarbonate secretion in the pancreatic juice?
Neutralises acid chyme from stomach - prevents damage to duodenal mucosa, raises pH to optimum range for pancreatic enzymes to work
Washes low volume enzyme secretion out of pancreas into duodenum
Why does HCO3- secretion stop increasing when pH goes below 3?
Bile also contains HCO3 and helps neutralise acid chyme
Burners glands secrete alkaline fluid
Describe how HCO3- is produced and secreted by the pancreatic duct cells
- CO2 enters pancreatic duct cell from blood and catalysed by carbonic anhydrase it reacts with H20 to form H+ and HCO3-Na+ moves down gradient via paracellular junctions and H20 follows from the blood to the lumenAE1 transporter exchanges HCO3- from duct cell into lumen with Cl- into the duct cellNa+/H+ antiporter active on the basolateral membrane and Na+ enters the cell down gradientTo maintain Na+ concn. gradient in the cell, Na+/K+ATPase transports Na+ into blood and K+ into cellTo maintain K+ concn. gradient in cell, K+ returns to blood via K+ channelsCl- returns to lumen via Cl- channel (CFTR) to maintain concn. gradient established by AE1 transporter
What makes gastric venous blood alkaline and pancreatic venous blood acidic?
Stomach
H+ → Gastric Juice
HCO3- → blood
Pancreas
HCO3- secreted → juice
H+ → blood
Which classes of digestive enzymes are present in the Acinar cell enzyme secretion?
Lipases - fat
Proteases - protein
Amylase - carbohydrates
Why are proteases released as inactive pro-enzymes?
Protects acini and ducts from auto-digestion
What other protective mechanisms against auto-digestion of the pancreas are there?
Pancreas contains trypsin inhibitor to prevent trypsin activation
Enzymes only activated in duodenum where they have to start digesting food
What enzyme is secreted by the duodenal mucosa and what does it do?
Enterokinase (enteropeptidase)
Converts trypsinogen into trypsin
What is the function of trypsin?
Converts all other proteolytic and some lipolytic enzymes into their active form
Why is it not dangerous to secrete lipase in its active form?
Requires colipase for action and the presence of bile salts for effective action
What can a lack of pancreatic enzymes lead to?
Malnourishment
What is a side effect you might expect from anti-obesity drug Orlistat which inhibits pancreatic lipases?
Steatorrhoea
What are the 3 phases involved in the control of pancreatic juice secretion?
Cephalic phase
Gastric phase
Intestinal phase
Describe the Cephalic phase of pancreatic juice secretion
Reflex response to sight/smell/taste of food
Enzyme-rich component only
Low volume - ‘mobilises’ enzymes
Describe the gastric phase of Pancreatic juice secretion
Stimulation of pancreatic secretion originating from food arriving in the stomach
Same mechanisms involved as for cephalic phase
Describe the intestinal phase of pancreatic juice secretion.
Hormonally mediated when gastric chyme enters duodenum
Both components of pancreatic juice stimulated enzymes & HCO3- juice flows into duodenum
What 2 components is the pancreatic juice enzyme secretion controlled in the acini by?
Vagus nerve (Cholinergic,
Vagal stimulation of enzyme secretion (& communicates info from gut to brain))
Cholecystokinin (CCK) (Ca2+/PLC)
What hormone controls the pancreatic juice bicarbonate secretion in the duct and centroacinar cells?
Secretin (cAMP)
What 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
Is 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 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-
Does CCK alone have any effect on HCO3- secretion?
No
When does CCK have an effect on HCO3- secretion?
It markedly increases HCO3- secretion that has been stimulated by secretin
What effect does secretin have on enzyme secretion?
None
What effect does bile and Brunei’s gland secretions have on pH?
Increase pH
What is the general function of the small bowel?
To absorb nutrients, salt and water
How long is the small bowel ?
6m long
3.5cm in diameter
What are the functions of the mesentery?
Suspends small and large bowel from the posterior abdominal wall
Provides a conduit for blood vessels, nerves and lymphatic vessels
What are the 3 main regions of the small intestine/bowel?
Duodenum
Jejunum
Ileum
What are the 3 layers of the small intestine from superficial to deep?
Serosa, longitudinal muscle layer and circular muscle layer.
Are villi found in the large bowel?
No; only occur in the small intestine
What innervates villi?
Innervation from submucosal plexus (part of the enteric nervous system)
How thick is the epithelium of villi?
1 cell thick
(dominated by enterocytes - simple columnar absorptive cells)
What are villi (mucosa) lined with?
Simple columnar epithelium consisting of:
Primarily enterocytes
Scattered goblet cells
Enteroendocrine cells
What types of cells does the epithelium of the Crypts of Leiberkuhn include?
Paneth and stem cells
What is the most abundant type of cell in the small bowel?
Enterocytes (tall columnar cells with microvilli and a basal nucleus)
What are these cells specialised for and what are their lifespans?
Absorption and transport of substances
1-6 days (relatively short)
What is the cylindrical internal surface area of the small bowel?
0.4m^2
What increases the surface are of the small bowel and by how much?
Villi and microvilli
~500 fold ^
What structure makes up the ‘brush border’?
Microvilli - several thousand microvilli per cell
What is glycocalyx?
Rich carbohydrate layer on apical membrane of microvilli
What is the purpose of glycoalyx?
Covers surface of microvilli
Serves as protection from digestional lumen yet allows for absorption
Traps a layer of water and mucous known as ‘unstirred layer’ → regulates rate of absorption from intestinal lumen
-
What is the second most abundant epithelial cell type?
Goblet cells
What is mucous and what does it do?
Large glycoprotein that facilitates passage of material through bowel
What happens to the number of goblet cells along the entire length of bowel?
Abundance increases along entire length of bowel
Low in duodenum and high in colon
What classification of epithelial cells are enteroendocrine cells and where are they most often found?
Columnar epithelial cells
Lower parts of crypts
What is the function of enteroendocrine cells?
Hormone secretion for example to influence gut motility
What do enteroendocrine cells have a high affinity for in terms of staining?
Chromium/silver salts
Where are Paneth cells exclusively found?
Bases of crypts
What do Paneth cells contain that are important for their functions and what are some of these functions?
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
Why are epithelial stem cells essential in the GI tract?
To continually replenish the surface epithelium as cells such as enterocytes have a very short life span
They continually divide by mitosis and migrate to the top of villus, replacing older cells that die by apoptosis → digested and reabsorbed
How long is the lifespan of enterocytes and goblet cells present in the small bowel?
~36 hours (relatively short)
List reasons why enterocytes and goblet cells in the small bowel have this lifespan
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, metabolic rate will be diminished
Any lesions → short-lived
If escalator-like transit of enterocytes is interrupted through impaired production of new cells, severe intestinal dysfunction will occur
What structure distinguishes the duodenum from the jejunum and ileum?
Brunners glands
What does the brunners gland secrete and why?
Alkaline fluid to neutralise chyme from stomach, protecting proximal small bowel
And to help optimise pH for action of pancreatic digestive enzymes
Compare the walls of the jejuum and the ileum and what is the reason for this difference
Jejunum is wider and thicker walled and redder than the ileum
The plicae circulares in the jejunum are larger and more numerous and so they are more closely set
Compare the jejunal and ileal mesenteries
Jejunal mesentery forms 1-2 arterial arcades whereas ileal forms 3-4, but these 3-4 are shorter
Jejunal mesentery is above and to left of aorta whereas ileal mesentery is attached below and to the right of the aorta
Where in the small intestine are Peyer’s Patches found?
Lower part of the ileum
List the functions of small intestine motility?
Mix ingested food with digestive secretions and enzymes
Facilitate contact between contents of intestine and intestinal mucosa
Propel intestinal contents along alimentary contact
Outline the 3 steps of small bowel motility
Segmentation (mixing)
Peristalsis (propelling)
Migrating motor complex
Outline the step of segmentation
Mixes contents of lumen
Occurs due to stationary contraction of circular muscles at intervals. More frequent contraction in duodenum
Contractions allow pancreatic enzymes and bile to mix with chyme
Although chyme moves in both directions, net effect is movement into the colon
Outline the step of peristalsis
Involves sequential contraction of adjacent rings of smooth muscle
Propels chyme towards colon. Most waves of peristalsis only travel about 10cm. Segmentation and peristalsis result in chyme being segmented, mixed and propelled into the colon.
Outline the steps of migrating motor complex
Cycles of smooth muscle contractions sweeping through gut. Begin in the stomach → small intestine → colon → next wave starts in duodenum.
Prevents migration of colonic bacteria into ileum.
Describe the environment that digestion in the small bowel occurs in
Alkaline environment
How do bile and pancreatic digestive enzymes enter the duodenum
Main pancreatic duct (MPD) and common bile duct (CBD)
What does duodenal epithelium produce to aid digestion?
It’s own digestive enzymes
Where does digestion of carbohydrates begin and by what enzyme?
Mouth by salivary alpha amylase, which is destroyed in stomach by acidic pH
Where does most carbohydrate digestion occur
Small intestine
Give examples of simple and complex carbohydrates
Simple: monosaccharides such as glucose and fructose; disaccharides such as sucrose and maltose.
Complex: starch, cellulose and pectin.
What is secreted into the duodenum in response to a meal to aid digestion of carbs
Pancreatic-alpha-amylase
What conditions does pancreatic-alpha-amylase need for optimal activity
Cl- and neutral or slightly alkaline pH
Where does digestion of amylase products and simple carbs occur?
Brush border
What carrier protein is used for absorption of glucose and galactose?
SGLT-1 on apical membrane (absorption is by secondary active transport)
What carrier protein is used for absorption of fructose?
GLUT-5 on apical membrane (facilitated diffusion)
What carrier protein facilitates exit of digestion products of carbs into the intestinal space at the basolateral membrane?
GLUT-2
How much simple sugar can the human small intestine absorb daily?
10kg
Where does protein digestion begin and by what enzyme?
Lumen of stomach by pepsin (pepsin inactivated in alkaline duodenum)
List the 5 pancreatic proteases secreted as precursors into the lumen of the small bowel
Trypsinogen → Trypsin (via enterokinase)
Chymotrypsinogen → Chymotrypsin
Proelastase → Elastase
Procarboxypeptidase A - Carboxypeptidase A
Procarboxypeptidase B - Carboxypeptidase B
Where is the enzyme enterokinase located?
Duodenal brush border
What are oligopeptides?
Peptide whose molecules contain a relatively small number of amino-acid residues, but more than 2
How do enterocytes directly absorb small amino acids and transport them into the interstitial space?
- Via action of H+/oligopeptide cotransporter → PepT1 and other cotransporters, **some AAs will be absorbed into the epithelial cellsOther AAs are broken down to form smaller AAs by variety of peptidases on the brush borderThese AAs are then taken into epithelial cells by transporters and broken down by enzymes such as dipeptidases and tripeptidases so that the individual AAs can be transported into the interstitial space
Why are lipids most complicated to digest?
They are poorly soluble in water
Outline the 4 stage process of lipid digestion in the small bowel
Secretion of bile salts and pancreatic lipases
Emulsification of lipids to increase SA for digestion
Enzymatic hydrolysis of ester linkages via colipase-lipase complex
Solubilisation of lipolytic products in bile salt micelles (Holding station)
What is the purpose of colipases in lipid digestion?
Prevents bile salts from displacing lipase from fat droplet
Outline lipid absorption
Fatty acids (FAs) and monoglycerides (MGs) leave micelles and enter enterocytes.
FAs and MGs resynthesised into triglycerides (TGs) via 2 pathways:
Monoglyceride acylation (major)
Phosphatidic acid pathway (minor)
Chylomicrons synthesised and secreted across basement membrane by exocytosis
Chylomicrons enter a lacteal (lymph capillary) → lymph transports them away from bowel
What are chylomicrons synthesised by and describe their composition
Golgi apparatus
80-90% Triglycerides
2% Cholesterol
2% Protein
Small traces of carbohydrate
What separates the ileum from the colon and what is its purpose?
Ileocaecal valve
Relaxation and contraction controls passage of material into colon and it prevents backflow of bacteria into ileum
