Control of Pancreatic & Biliary Secretions Flashcards
Where does the ampulla open into
2nd (descending) part of the duodenum
What is the duodenums roles
1) Inhibit gastric emptying for effective absorption distally ( SS, secretin CCK)
2) Inhibit Acid secretion for a - feed-back loop (Secretin, CCK)
3) Stimulate pancreatic & biliary secretions (secretin, CCK)
How does the duodenum respond??
Endocrine cells in the 2nd part of the duodenum respond to nutrients
Vagal afferents respond to luminal contents/ distention
Enteroendocrine cells are?
the main types
Specialised endocrine cells the GI tract & pancreas. (like enterocytes)
- I cells»_space; CCK
- S cells»_space; secretin
- enterochromaffin cells»_space; serotonin (not like ECL in stomach)
I cells
Apical surface sense fats/proteins»_space; CCK release from BL
1) CCK can enter bloodstream > acinar cells and stimulate AND
2) CCK can also stimulate vagal Afferents > brain > vagal Efferents > anicar pancreatic cells
S cells
Apical surface senses HCL/ low pH»_space; secretin release from BL membrane»_space; travels through BS to pancreatic acinar cells
Enterochromaffin cells
Apical surface senses food/irritant (like chemo-drugs)»_space; serotonin from BL membrane
this stimulates gut motility > diarrhoea
High blood levels»_space; activates receptors in medulla»_space; vomiting
Structural passage a secretion takes in the pancres?
acinar > intercalated ducts > intralobular ducts > interlobular ducts > main pancreatic duct > SI
Exocrine: What does the pancreas secrete and from what cells?
Acinar cells >Digestive enzymes
(for fat and protein digestion)
Ductal cells > bicarbonate
(to neutralise acidic pH)
Structure of function of the Acinar cells
Filled with secretory Zymogen granules, that contain precursor enzymes ‘zymogens’, released via pancreatic duct.
Some zymogens are activated (by proteolytic cleavage) in SI to avoid auto-degradation of pancreas. (often by trypsin)
Filled also with rER for lots of enzyme production
What can trypsin cleave?
Give examples of protease cleavage
Trypsinogen (auto-catylytic)
Chymotrypsinogen
other zymogens
trypsinogen > (enteropeptidases) > trypsin
Chymotrypsinogen > (trypsin) > chymotrypsin
What is different about amylase and lipase, why is this important
They are released in their active forms.
In pancreatitis their levels can be used to diagnose, they will have elevated serum levels, and they can also cause pancreatic damage
Release of pancreatic enzymes is controlled by? how is this done?
CCK
1) enters blood circulation to get to acinar cells > enzyme release
2) sends message via vagal afferent fibres by I cells > vagus nerve in brainstem > efferent vagal fibres send message to pancreas > enzyme release
Why is CCK, secretin and EC cells released at the BL membrane
For easy access to blood circulation they need to enter
Ductal cells release what? Why do they do this?
Bicarbonate secretion > SI
this is to neutralise the gastric acid in the duodenum, allowing for a neutral pH which is required for the optimal function of pancreatic enzymes
What happens if the intestinal pH is not maintained near neutrality?
- Mucosal damage (no protection)
- pancreatic and brush border enzymes can’t function (not @ optimal pH)
- FA and Bile less soluble for absorption
- pepsin stays active
How does the bicarbonate get in/out of the ductule cells
VIA TWO WAYS
1) - HCO3- taken up into cell via BL surface
or
- also cells forms HCO3 from water and CO2 (by carbonic anhydrase)
2) Pumped out of cell > lumen via
Cl-/HCO3 exchanger which is maintaining electroneutrality
This can happen due to
CFTR transporter located next to exchanger (pumps Cl- into lumen, creating a high concentration gradient for Cl- to move back through the exchanger)
What controls secretin release? How does it do this
Secretin. (stimulate by HCl)
Enters blood circulation > binds to receptors on ductal cells > increases cAMP levels > activates CFTR > bicarbonate release
Gastrins extra role for the pancreas
Also stimulates acinar cells to release digestive enzymes.
Release during a meal
Vagus nerve and ACh extra role for the pancreas
applies low-level stimulas»_space; bicarbonate and enzyme release
Happens during a meal
Other actions of CCK (other then d.enzyme release)
- stimulate bile production in liver
- gallbladder contraction
- sphincter of Oddi relaxation
this is to stimulate more bile > duodenum
Secretins other roles
Stimulates release of bicarbonate from bile duct
Cystic Fibrosis
- autosomal recessive (genetic condition)
- involves various mutations of CFTR gene > defective ion channels
- Cl- trapped in cell, brings Na+ and then water in
- secretions become very thick
- thick sticky mucus clogs passages
What does cystic fibrosis affect? How does this impact the pancreas?
Multiple organs lungs, pancreas, liver and intestines
Instead of a watery bicarbonate release into ducts, you gets a thick sticky mucus , that clogs passages and leads to infection
What is the CFTR transporter?
Cystic Fibrosis Transmembrane conductance Regulator
- a chloride channel that is vital to many organs/ systems
- involved in sweat, mucus and digestive fluid production
- works with/next to Cl/HCO3 exchanger for HCO3 secretion
A defective CFTR due to CF in the pancreas can lead to?
Pancreatic insufficiency (loss of exo-endo function) from bouts of inflammation. this is because…
> Cl accumulates in ductal cells
> cells become negatively charged, draw Na+ and then water from lumen in
> Pancreatic secretions become hyperviscous
> pancreatic ducts blocked, enzymes cant be released
> enzyme build-up in pancreas > inappropriate activation > leads to autodigestion, pancreatitis, fibrosis
Acute Pancreatitis
- acute inflammation
- abdominal pain
- elevated serum lipase/amylase
- self-limiting (will resolve)
Chronic Pancreatitis
- Chronic inflammation
- Chronic abdominal pain
- Progressive loss of main exocrine (and endocrine) function
Main 2 causes of pancreatitis. Other causes?
Alcohol & Gallstones (causes 80%)
also autoimmune pancreatitis, drugs, trauma, pancreas divisum, excessive triglycerides ‘hypertriglycaemia’, CF, viral infections (mumps)
What is Pancreas Divisum
Common congenital anomaly
- in embryo, pancreas starts as 2, with dorsal and ventral buds
USUALLY THESE FUSE (pancreatic duct) - in PD, there is a failure to fuse
associated with pancreatitis
Chronic Pancreatitis can lead to ‘ENDOcrine insufficiency’. What is this?
- impaired insulin production
- Diabetes
You treat as you would diabetes (insulin injection)
Chronic Pancreatitis can lead to ‘EXOcrine insufficiency’. What is this?
Need to lose >90% of exo function before symptoms show (this is done by repeated bouts of inflammation)
- impaired digestive enzyme production ( most importantly lipase)
- fat malabsorption»_space; weight loss and steatorrhea
- impaired HCO3-
This can be treated by orally taking pancreatic enzyme supplements
Steatorrhea
pale, bulky, floating stools that are “hard to flush”, have oil-droplets.
Due to fat malabsorption
How could you visually identify chronic pancreatitis in a pancreatogram?
- Dilated main duct
- irregular side branches
Done by endoscopy and then a ‘contrast’ is injected into pancreas
How could you visually identify chronic pancreatitis in a CT scan
-calcification of the pancreas (white areas)
Bile is made of? How much per day
Water, electrolytes and organic molecules (bile salts, cholesterol, bilirubin, phospholipids)
400-800mL/day
The Enterohepatic Circulation?
Main way of bile recylcing.
Much of bile (95%) is recycled in the terminal ileum. The remaining is synthesized. 5% lost in poo
bile release> SI > terminal ileum > special receptors in TI uptake > bile enters the portal circulation (venous) > back to liver via HPV
Bile Functions
1) digestion and absorption of fats and fat soluble vitamins (D, A, K, E)
2) elimination of waste (eg- bilirubin): secreted into bile > faeces
The 2 sources of bile acids are?
1) 5% newly synthesized from cholesterol in the liver.
2) 95% reabsorbed from TI
How is bile uptaken in the Terminal ileum?
Bile in TI > EH circulation > portal vein > sinusoids > hepatocyte
Uptake of bile in TI involves bile acid/Na+ transporter (Na+K+ATPase pump)
How does bile flow through the biliary tree?
Hepatocytes secrete > enters canaliculi > larger bile ducts of portal triads (bicarbonate rich watery secretion added by ductal cells) > Left and right Hepatic ducts > Common Hepatic duct > either to GB via cystic duct
or if stimulated to duodenum via common bile duct
Bile flow is driven by the following mechanisms
1) Bile flow into canaliculi (acid-dependent/acid-independent)
2) Reabsorption and secretion of water and electrolytes by ducts/ductules
(secretion occurs in response to secretin)
Bile acid-dependent pathway
Active transport of bile acids from blood into canalicculi draws water with it (osmotic effect) aiding watery free-flowing secretion
Bile acid-independent pathway
Transport of other solutes and electrolytes draws fluid with it also aiding watery free-flowing secretion (without the need for bile-acids)
How does bile get into the gall bladder? What happens to it there?
Due to sphincter of Oddi closing. Backflow into cystic duct.
GB stores and concentrates bile when not eating (unlike the released watery secretion)
high concentration»_space; gallstones
What influences bile release from gallbladder when eating?
CCK causes GB contraction and sphincter of oddi relaxation
ANS also has an influence (vagus nerve/ACh)
Cholestasis is?
Obstruction to bile flow (benign or malignant)
-increased pressure in biliary tract
-rupture of tight junctions > bile leakage
-bile contents spill back into circulation > jaundice (due to bilirubin in bile)
main type: gallstones
Gall stone types? How do they cause issues?
Main type: Cholesterol stones
Also: Pigment stones (made of bilirubin or Ca2+ salts from bile)
Most GS are asymptomatic, BUT if they fall out of the gallbladder and are too large to pass through the bile duct > biliary obstruction
-Pain (stretch, in RUQ), jaundice, liver issues result
Where can gall stones get stuck?
Cystic duct
common bile duct (jaundice and dilated bile duct results)
This can be seen with ultra sound
How are bile duct stones removed?
Fine wire basket retrieves obstructing stones and drops into SI
Biliary Stricture
Often from repeated infection, usually benign, can cause obstruction > Cholestasis and jaundice
Malignant Causes of Biliary obstruction??
1) Cancer of Bile duct (cholangiocarcinoma)
-rare
Occur in distal bile duct or hepatic bile duct > tight stricture > jaundice
Above bile ducts get very dilated
2) Pancreatic Cancer in head of pancreas > constriction of bile duct that comes in to meet the pancreatic duct
Effects of prolonged bile duct obstruction (malignancy)
- JAUNDICE (excess bilirubin in blood)
- ITCHING (bile salt accum. in skin)
- NAUSEA (bile salts?)
- MALABSORPTION of fats and fat-soluble vitamins
- Renal failure
Not much pain (unlike acute gallstones) because the development is gradual and prolonged, so there is a degree of slow adaptation and stretching
Physical signs of malignant bile obstruction
- Yellow sclera
- skin scratch marks
- bruise easily (vit K)
- palpable gall bladder (sign of malignancy as this is due to the GB trying to adapt over TIME)
- Pancreatic mass
- pale stools
- palapable lymph node in left supraclavicular fossa
Malignant bile obstruction treated by
Put a tube through stricture, opening lumen.
Lies along bile duct
Usually so late presenting they are in-operable
When are CCK and secretin stimulated?
Intestinal phase
Undigested fats and proteins»_space; CCK
HCl»_space; Secretin
Activation of inactive proenzymes/zymogens takes place in..
The duodenal lumen (brush border) via proteolytic cleavage
Lipase and Amylases role in the duodenum
Pancreatic Lipase:
Fats to TGs, MG and FFA
Pancreatic Amylase:
Starch to sugar
