Functions and Secretions of the Pancreas Flashcards
What are the overall functions of the pancreas?
- important in digestion of nutrients- fat + protein
- provides the appropriate environment for enzymatic digestion in the small bowel
- regulate fed and fasted states
What is the pancreas divided into?
lobules
What do lobules drain into?
the ductular network (intralobular, interlobular and then main duct which connects gland to GI tract lumen)
What is the ampulla of Vater?
the swelling in the duodenal wall where the major pancreatic duct merges with the common bile duct
What is the sphincter of Oddi?
an area of the ampulla of Vater where the muscular wall is thickened. Its role is to regulate and prevent reflux
What are the secretory units made up of and where are they found?
- found in lobules
- made up of acinus (cluster of acinar cells) and small intercalated disk
Role of acinus?
- synthesise and secrete proteins into the lumen of the epithelial structure
- secrete zymogens, digestive enzymes and an isotonic plasma-like fluid that accompanies secretory proteins
What is a zymogen?
an inactive enzyme precursor
What are the ducts lined with and what is their role?
- duct cells which dilute thick, protein rich secretions of acinar cells and secrete bicarbonate to neutralise acidic chyme
- specialised for transport of electrolytes.
Role of acinar cells?
-produce and export large quantities of protein (e.g digestive enzymes)
Role of goblet cells?
produce mucus for lubrication, hydration, mechanical protection of surface epithelial cells, immunologically binding to pathogens and interacting with immune competent cells (prevent pancreatic infections)
How are pancreatic acinar cells stimulated to produce digestive proteins?
- through CCK receptor and the muscarinic ACh receptors on basolateral membrane can signal two ways:
- ACh and CCK both activate PKC and release of calcium
- VIP and secretin both activate adenyl cyclase leading to production of cAMP and activation of PKA
What else do pancreatic acinar cells secrete and why?
isotonic NaCl rich fluid which hydrates the dense protein rich acinar secretion
How is NaCl secreted by the acinar cells?
- the Na-K pump creates an inward Na+ gradient across the basolateral membrane
- The Na/K/Cl transporter produces net Cl- uptake driven by Na+ gradient
- The rise in intracellular K (caused by influx) is balanced by K+ channels which provide an exit
- Intracellular accumulation of Cl- establishes the electrochemical gradient that drives Cl- secretion into the lumen though apical Cl- channels
- The movement of Cl- into the lumen males the transepithelial voltage more lumen negative driving Na+ into the lumen via the tight junctions
Why is the HCO3- rich secretion from duct cells important?
- alkalinzes and hydrates protein rich secretions of acinar cells
- maintains enzymatic optimal PH
- micelle formation
- neutralises acid
How are the duct cells stimulated to secrete bicarbonate?
acid in chyme stimulates S cells in the lumen of the small bowel. S cells make secretion and secretin stimulates the duct cells to produce bicarbonate
Whats the cystic fibrosis transmembrane conductance regulator and why is it important?
- a cAMP activated Cl- channel that is present on the apical membrane of pancreatic duct cells
- important in Cl- recycling
- when open CFTR allows Cl- to diffuse from the cytoplasm into the lumen, after which the Cl- cycles back into the cell via the Cl-HCO3 exchanger
What happens when the the secretin receptor on the duct cell is activated?
- stimulates adenylyl cyclase which increases conc of cAMP which triggers PKA
- this stimulates apical CFTR Cl- channel and the basolateral Na/HCO3- transporter
- causing HCO3- and fluid secretion
Explain why cystic fibrosis occurs
- mutation in the CF gene which alters function of CFTR
- this means bicarbonate and fluids are not being secreted whilst thick protein secretion of acinar cells still is. This can cause ductal obstructions
What can cystic fibrosis cause?
maldigestion and diabetes
What does the rate of pancreatic secretion depend on?
whether or not the person is fed or fasted
What is the role of CCK in pancreatic secretions?
stimulates acinar cells to increase protein secretion via direct pathway via CCK receptor or indirectly through the parasympathetic nervous system
What else can stimulate CCK production?
-CCK releasing factors e.g LCRF (Luminal CCK releasing factor)
Where are CCK releasing factors produced?
endogenously in proteins secreted into the gut and lumen
What inhibits pancreatic secretions and how?
- somatostatin
- inhibits release of CCK and secretin as well as insulin and glucagon
What are the phases of pancreatic secretion?
- cephalic stage (sight, smells etc) mediated by stimulation of ACh receptors on acinar cells and lesser in duct cells
- gastric phase (pancreatic secretion caused by release of hormones such as gastrin which signals through CCK receptor (weak CCK agonist) gastric distension stimulates low levels of pancreatic secretion through a vasovagal gastropancreatic reflex
- intestinal phase (largest amount of secretion) (chyme stimulates pancreatic secretion: gastric acid stimulates duodenal S cells to release secretin which stimulates duct cell release of HCO3 and fluid. Lipids stimulate duodenal I cells to release CCK which stimulates acinar cells to release digestive enzymes. Lipids also activate a vasovagal enteropancreatic reflex that stimulates acinar cells
What is auto digestion?
when pancreas enzymes destroy self tissue
How is auto digestion prevented in the pancreas?
- digestive proteins are stored in secretory granules as inactive precursors and only become activated once coming into contact with the small bowel brush border enzyme enterokinase which converts trypsinogen to trypsin which turns other zymogens into their active forms
- secretory granule is impermeable to proteins so are separated from cellular proteins
- enzyme inhibitors such as pancreatic trypsin inhibitor SPINK1 are copackaged in the secretory granule
- condensation of zymogens, low PH, ionic conditions within the secretory pathway limit enzyme activity
What are the causes of acute pancreatitis?
GET SMASHED
Gall stones
Ethanol
Trauma
Steroids Mumps Autoimmune Scorpion sting Hypercalcaemia ERCP Drugs (paracetamol, cisplatin)
2 of what 3 features are required for acute pancreatitis diagnosis?
- abdominal pain
- serum amylase and/or lipase greater than three times the upper limit of normal
- characteristic findings of disease on CT scan
What is phase 1 of AP?
premature activation of trypsin within pancreatic acinar cells this can be due to a number of reasons (e.g disruption of calcium signalling in acinar cells)
-this causes activation of other pancreatic enzymes
What is phase 2 of acute pancreatitis?
intra-pancreatic inflammation
What is phase 3 of acute pancreatitis?
extra-pancreatic inflammation including systemic sepsis and multi organ failure
How is acute pancreatitis treated?
- rest pancreas (use fluid to prevent dehydration)
- hourly fluid balance due to hypovaelamia
- pain relief
- organ support in bad cases
- ultrasound and CT sound
- ERCP (open up ducts to remove gall stones)
What is chronic pancreatitis?
inflammation of the pancreas that doesn’t heal or improve. Gets worse over time and doesn’t heal leading to permanent damage
What are the causes of chronic pancreatitis?
- alcohol (main)
- hereditary disorders
- cystic fibrosis
- hypercalcemia
- hyperlipidemia
How is chronic pancreatitis treated?
- may need hospital due to pain management, IV hydration and nutritional support
- when on normal diet may be supplemented with synthetic pancreatic enzymes
- nutritious diet that includes small frequent meals
- complications treated with ERCP
What can chronic pancreatitis lead to?
- calcification of fibrotic pancreas
- tissue damage can lead to diabetes
