Pancreas+Small bowel Flashcards
What are the dimensions of the entire small bowel and its 3 component parts?
Approx. 6m long & 3.5cm in diameter.
Duodenum: 25 cm
Jejunum: 2.5 m
Ileum: 3.75 m
-All are continuous
What are the 2 major functions of the mesentery
Suspends small & large bowel from posterior abdominal wall
anchoring them in place
whilst still allowing some movement
Provides a conduit for blood vessels, nerves & lymphatic vessels
What are the portions of the small intestine in order?
Duodenum
Jejunum
Ileum
Where do villi occur?
Small intestine ONLY
What is the epithelial structure on villi and what is the dominant cell type
Simple-1 cell thick
Dominated by enterocytes
What kind of cells do crypts of Lieberkühn contain?
Paneth cells
Stem cells
What primary 3 cell types are contained within the villi(mucosal layer)
Primarily enterocytes (absorptive cells)
scattered goblet cells
enteroendocrine cells
What is the lifespan of an enterocyte?
1-6 days
By how much do folds, villi and microvilli increase the surface area of the small intestine?
About 500x
What is mucous?
Large glycoprotein that facilitates passage of material through bowel.
How does the number of goblet cells vary along the GI tract?
↑ abundance of goblet cells along entire length of bowel
↓ in duodenum
↑ in colon
What are enteroendocrine cells?
Columnar epithelial cells
Scattered among enterocytes
Most often found in lower part of crypts.
Hormone secreting
e.g. to influence gut motility
-Also called chromaffin cells
Secretions inlclude:
CCK, GLP-1, GIP, peptide YY, somatostatin, ghrelin, and serotonin
Where are paneth cells found and what is their purpose?
Found only in the bases of crypts
Contain large, acidophilic granules
Granules contain:
antibacterial enzyme lysozyme (protects stem cells)
Glycoproteins & zinc (essential trace metal for a no. of enzymes)
Also engulf some bacteria & protozoa
What is the function of GI stem cells?
To migrate upwards out of the crypts to the villi to replace damaged cells
Why are GI enterocytes subject to a much shorter lifespan compared to other epithelial cells in other organs?
Enterocytes are first line of defense against GI pathogens & may be directly affected by toxic substances in diet.
Effects of agents which interfere with cell function, metabolic rate etc 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
How do you differentiate the jejunum and ileum?
Jejunum:
Thick wall
Plicae circulares
Ileum:
Thin wall
Has peyers’ patches
How is the duodenum distinguished and what is the purpose of this difference?
Distinguished by presence of Brunner’s glands
Alkaline secretions of Brunner’s glands
Neutralizes acidic chyme from stomach, protecting proximal small bowel
Help optimise pH for action of pancreatic digestive enzymes.
What is segmentational motility?
Mixes contents of lumen
Occurs by stationary contraction of circular muscles at intervals.
More frequent contractions in duodenum cf. ileum
allow pancreatic enzymes & bile to mix with chyme
Although chyme moves in both directions, net effect is movement → colon
What is peristaltic motility?
Involves sequential contraction of adjacent rings of smooth muscle
Propels chyme towards colon
Most waves of peristalsis only travel about 10cm
Segmentation & peristalsis result in chyme being segmented, mixed & propelled → colon
What kind of conditions does small bowel digestion occur in and how do pancreatic enzymes/bile enter the GI tract?
Alkaline environment
Pancreatic digestive enzymes & bile enter duodenum from MPD & CBD through the sphincter of oddi
What are simple and complex carbohydrates?
Where does most carbohydrate digestion take place and what enzyme in the saliva starts this process?
Small intestine
Salivary a-amylase
Approx numbers of carbohydrate substrate hydrolysed by each BB enzyme
Under what conditions does pancreatic a-amylase works optimally?
Needs Cl- for optimum activity & neutral/slightly alkaline pH
How is trypsin activated and what is its purpose?
Activated by enterokinase
-Trypsin → activates other proteases→hydrolyse proteins → single amino acids (AA) & oligopeptides (AA)n
How do enterocytes absorb some small amino acids?
Enterocytes directly absorb some of small (AA)n via action of H+/oligopeptide co-transporter PepT1
How are lipids digested in the small bowel?
-Are poorly soluble in water
1) Secretion of bile and pancreatic lipases
2) Emulsification by bile(Increased SA)
3) Enzymatic hydrolysis of ester linkages
4) Solubilisation of lipolytic products in bile salt micelles
What enzyme begins the digestion of proteins in the stomach?
Pepsin
How do we stop bile salts from displacing lipases in a fat droplet?
Formation of colipase complexes with lipase
How are lipids absorbed in the small bowel and what are the 2 major pathways(FFAs+MGs into TGs)?
1) FAs and MGs leave micelles and enter enterocytes
2) FAs & MGs resynthesized into tri-glycerides (TGS) by
2x pathways:
-Monoglyceride acylation (major)
-Phosphatidic acid pathway (minor)
3) Chylomicrons are formed in the golgi apparatus
4) Chylomicrons are exocytosed into lacteals(lymph capillaries)
How is the ileum separated from the colon and what are its functions?
Ileocaecal valve
-Controls material travel into colon
-Prevents bacteria/waste backflow
Outline the process of pancreatic embryological development
1) Abdominal accessory organs arise as outgrowths from the foregut
2) Proximal duodenum rotates clockwise, creating the dorsal pancreatic bud+duct
3) Ventral and dorsal pancreatic buds+ducts fuse
-Bile and pancreatic ducts join together to drain at the major papilla
General pancreatic anatomy
General pancreatic anatomy(- the panky)
What are the 3 methods you can scan the pancreas?
CT
MRCP
Angiography
Difference between exocrine and endocrine
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
What are the main hormones secreted by the pancreas and what are their functions?
Insulin: anabolic hormone
promotes glucose transport into cells & storage as glycogen
↓ blood glucose
promotes protein synthesis & lipogenesis
Glucagon: ↑s gluconeogenesis & glycogenolysis (↑s blood glucose)
Somatostatin: “Endocrine cyanide”
Is the pancreas an exocrine or endocrine gland?
Both
2% is endo
-IOL
-Insulin, glucagon, somatosatin and PP
98% is exo
-Secretes pancreatic juice into duodenum via MPD/sphincter of Oddi/ampulla
How do we differentiate the cells in the pancreas?
Acini-
Acinar cells secrete pro-enzymes into ducts
Islets-
More in tail than head
Lose contact with ducts-becoming islets
Pancreatic microanatomy
What are the cells found in pancreatic islets, what percentage of cells do they make up and what do they secrete?
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
What are the types of cells in acini and what do they look like?
Secretory acinar cells
-Large with apical secretion granules
Duct cells
-Small & pale
What are the components of pancreatic juice and where are they produced?
↓ vol, viscous, enzyme-rich - Acinar cells
↑ vol, watery, HCO3- rich - Duct & Centroacinar cells
What is the function of bicarbonate secretion in 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
How does duodenal pH influence HCO3- secretion rate?
Increases with HCO3- then levels off at 3pH
Why does pancreatic HCO3- secretion stop even at acidic pHs?
Bile also contains HCO3-, so bile is the main pH alkalinity regulator for pH>5
Describe the 1st step of HCO3- release into the pancreatic duct lumen
Catalysed by carbonic anhydrase
Separation of H+ & HCO3-
Na+ moves down gradient via paracellular (“tight”) junctions
H2O follows
Describe the 2nd step of HCO3- release into the pancreatic duct lumen
Cl-/HCO3- exchange at lumen (anion exchanger [AE])
Na+/H+ exchange at basolateral membrane into bloodstream (sodium-hydrogen exchanger (antiporter) type 1 [NHE-1])
Driven by EC gradients
(High blood Na+)
(High lumen Cl-)
Describe the 3rd step of HCO3- release into the pancreatic duct lumen
Na+ gradient into cell from blood maintained by Na+/K+ exchange pump
Uses ATP - Primary active transport
Describe the 4th step of HCO3- release into the pancreatic duct lumen
K+ returns to blood via K+-channel
Cl- returns to lumen via Cl-channel (cystic fibrosis transmembrane conductance regulator [CFTR])
How is acinar enzyme/bicarb secretion controlled?
Acinar cells:
Vagus nerve and Cholecystokinin (CCK) (Ca2+/PLC)
Cholinergic
Vagal stimulation of enzyme secretin (& communicates information from gut to brain)
Duct+centroacinar cells:
Pancreatic juice bicarbonate secretion controlled in duct & centroacinar cells by:
Secretin (cAMP)
Is gastric venous blood acidic or alkaline?
H+ → gastric juice
HCO3- → blood
Gastric venous blood is alkaline
Is pancreatic venous blood acidic or alkaline?
HCO3- secreted → juice
H+ → blood
Pancreatic venous blood is acidic
What are pancreatic proteases released as and where are pancreatic enzymes activated?
Released as inactive pro-enzymes
Activated only in the duodenum
How does the pancreas inhibit trypsin activation?
It contains a trypsin inhibitor
What does pancreatic lipase require for it to be effective?
Colipase
Bile salts
What change in pancreatic enzyme production would you see if someones’ diet increased protein content and decreased carb content?
Increased protease proportion
Decreased amylase proportion
What is the function of orlistat and what side effects may it produce?
Inhibits pancreatic lipases
-Steatorrhea
How does pancreatic secretions vary between the cephalic, gastric and intestinal phases of digestion?
Cephalic-Low volume(Mobilises enzymes)
Gastric-Stimulation of pancreatic secretion comes from food arriving in stomach
Intestinal-(70-80% of secretion)
Hormonally mediated when gastric chyme enters duodenum.
BOTH components of pancreatic juice stimulated
enzymes & HCO3- juice flows into duodenum
How+where is pancreatic juice enzyme secretion controlled?
Acinar cells:
Vagus nerve and Cholecystokinin (CCK) (Ca2+/PLC)
Cholinergic
Vagal stimulation of enzyme secretin (& communicates information from gut to brain)
How+where is pancreatic juice bicarbonate secretion controlled?
Duct+centroacinar cells:
Pancreatic juice bicarbonate secretion controlled in duct & centroacinar cells by:
Secretin (cAMP)
What factors inhibit/stimulate the release of CCK from duodenal-I cells?
Stimulatory:
Amino acids
Fatty acids
CCK-releasing peptide (CCK-RP)
Gastrin-releasing peptide (GRP)
Inhibitory:
Trypsin
What is the tonicity of acinar fluid?
Acinar fluid is isotonic
resembles plasma in its concs of Na+, K+, Cl− & HCO3−
Secretion of acinar fluid & proteins it contains is stimulated primarily by CCK
What molecule stimulates secretion of H2O & HCO3- from cells lining extralobular ducts
Secretin
Why is secretin secretion from duct+centroacinar cells more rich with HCO3-?
Secretin stimulates secretion of H2O & HCO3- from cells lining extralobular ducts.
Secretin-stimulated secretion is richer in HCO3−compared with acinar secretion because of Cl−/HCO3−exchange(CFTR)
What are the effects on HCO3- secretion of CCK and secretin alone and combined?
CCK alone-Nothing
Secretin-Small increase
CCK+Secretin-large increase
What nerve has a similar effect to CCK?
Vagus nerve
What effect does secretin have on enzyme secretion?
NO EFFECT
What would occur next if pH 2 chyme has just entered the duodenum?
H+ ions in duodenum → ↑secretin → ↑pancreatic juice
+ bile & Brunner’s gland secretions
↑s pH to neutral/alkaline.
Peptides & fat in duodenum cause sharp ↑ in CCK & vagal nerve stimulation
→ stimulates pancreatic enzyme release
CCK potentiates effects of secretin on aqueous component
Necessary as most of duodenum not at ↓pH
Where is CCK and secretin released from?
CCK-I cells
Secretin-S cells
Where is pancreatic enzyme secretion controlled?
The acini
Where is pancreatic bicarbonate secretion controlled?
The duct cells and centroacinar cells
What is the vagus nerves’ effect on secretin?
It stimulates secretin release
