L5*-Secretions of the Pancreas-Ibruhim Flashcards
(20 cards)
Give an intro to the pancreas.
-Pancreas is an elongated gland located behind the stomach.
-Has both 1.endocrine and 2.exocrine functions.
1. releases hormones to regulate the blood sugar levels.
2. directly involved in GI functions - secretes digestive enzymes and fluids rich in HCO3- ions - HCO3- ions in the pancreatic fluid help to neutralise the acidity of the chyme coming from the stomach. it prepares the chyme for entry into the s.i.
Describe the exocrine pancreas structure
Pancreas is divided into lobules, which drain into ductular network(intralobular duct,
interlobular ducts and then into a main duct) that connects the entire gland to the lumen of the GIT.
* The major pancreatic duct merges with the common bile duct to form a swelling in the duodenal wall called the ampulla of Vater. The muscular wall is thickened, forming the sphincter of Oddi.
- Function of Oddi- regulate and prevent reflux
What is a pancreatic acinus and what do pancreatic acinar cells secrete and what do they do ?
- Within the lobules reside the functional
secretory units of the gland - definition - Each secretory unit is composed of an
acinus (latin for grape/berry) and a
small intercalated duct. - Pancreatic acinar cells secrete a
plethora of zymogens (inactive enzyme
precursors), digestive enzymes and an
isotonic, plasma-like fluid that
accompanies the secretory proteins.
Name the functions of the 4 pancreatic cell types.
- Acinar cells - specialised/polarised for the production and export of large quantities of protein as predicted by cellular architecture (RER, secretory granules, exocytosis at apical pole).
- Duct cells - show a level of morphological heterogeneity along the ductal tree. These are
predominantly specialized for the transport of electrolytes. - Centroacinar cells - the very first cells of the intercalated duct and thus are located at the junction of the pancreatic acinar cells and duct cells > secreting HCO3-rich fluid, regulating enzymatic flow, supporting pancreatic regeneration.
- Goblet cells - produce mucus important for lubrication, hydration, protection and immunological role.
How is pancreatic juice found? What is it inside of ?
-Pancreatic juice which is protein-rich embedded within an alkaline fluid.
Define Fed vs Fasted state.
-The rate of pancreatic secretion is dependent on whether you are fed or fasted.
-Fasted state/Post absorptive state- low level release of pancreatic enzymes.
-Fed state/Absorptive state- Pancreatic secretion👆ses to levels that are 5-to 20-fold over basal levels.
The stimulation from the pancreas is affected by one thing. What is it?
The ‘composition of the pancreatic fluid’ will also alter with stimulation.
Role of acinar cells in the pancreas
- Acinar cells secrete digestive proteins.
- In an unstimulated state acinar cells secrete low levels of digestive proteins via a constitutive secretory pathway.
- Stimulation of acinar cells in the pancreas is predominantly mediated through CCK receptors and the muscarinic acetylcholine (ACh) receptors located on the basolateral cell membrane.
- These receptors signal through a common pathway- the phospholipase C (PLC/PKC)/Ca2+ signal-transduction pathway, leading to increased enzyme secretion from the acinar cell.
Write more about CCK.
- CCK from duodenal I cells stimulates pancreatic acinar cells to increase protein
secretion. - In response to a fatty meal, plasma CCK levels increase 5- to 10-fold within minutes. Likely to be both 1. direct through a CCKA receptor or 2. indirectly through the parasympathetic nervous system.
- CCK secretion is also stimulated by CCK-releasing factors e.g., LCRF (Luminal CCK
Releasing Factor), which are endogenously produced proteins secreted into the gut
lumen, and which stimulate CCK. - In the fasting state, LCRFs are degraded by digestive enzymes so no CCK
stimulation. However, during a meal, the digestive enzymes act on the chyme and
LCRFs stimulate I –cells to release CCK and pancreatic secretion.
Write more about secretion of the duct cell
-Function of the pancreatic duct cell > to secrete an HCO3–rich fluid that alkalinises and hydrates the protein-rich primary secretions of the acinar cell.
* This fluid is also important for enzymatic optimal pH, micelle formation and neutralising acid.
* Cl- HCO3 exchanger; Carbonic anhydrase generated.
* Ach activation also impacts on HCO3 secretion
What is secretin a stimulus for?
Secretin is the most powerful stimulus for HCO3. This induces/leads to the activation of CFTR and Na-HCO3.
Write more about secretin.
-Secretin from S cells in the small bowel mucosa stimulates HCO3- and Fluid
Secretion by the Ducts, predominantly in response to duodenal acidification. Thus,
levels increase in the fed state.
- Secretin is the most important humoral regulator of ductal secretion. Activation of
the secretin receptor on the duct cell stimulates adenylyl cyclase, which raises
[cAMP]i and triggers PKA. - Ultimately stimulating the apical CFTR Cl- channel and the basolateral Na/HCO3-
cotransporter. - HCO3- secretion is also regulated by acetylcholine and the muscarinic receptors on
the duct cell causes increased [Ca2+]i and activation of Ca2+ -dependent protein
kinases (i.e PKC) in pancreatic duct cells.
Write more about Cystic fibrosis(CF)
-From the mutations in the CF gene that alter the function of its product CFTR
-mutant CFTR is prematurely degraded. Subsequent loss of CFTR expression at the plasma membrane disrupts the apical transport processes of the duct cell and results in 👇sed secretion of HCO3 and water by the ducts.
-Results in a protein-rich primary secretion which thickens within the duct lumen and lead to ductal obstruction and eventual pancreatic tissue destruction.
-The subsequent deficiency of pancreatic enzymes that occurs leads to the maldigestion of nutrients.ie:- steatorrhea and diabetes
What are 3 phases of pancreatic secretion ?
1.Cephalic phase - Stimulated by smell, taste, chewing and swallowing. Mediated by ACh through vagus nerve(acinar cells). 25% of pancreatic enzymes.
- Gastric phase - stimulated by proteins, gastric distention, gastrin ➡ CCK receptors on acinar cells. Mediated by vago - vagal reflex.10-20% of pancreatic enzymes
- Intestinal phase - Stimulated by acid in chyme and fatty acids. Mediated by secretin, CCK and vago-vagal reflex. 70-75% of pancreatic enzymes and fluid
Name a inhibitor of pancreatic secretions.
-Somatostatin (present in various places) including D-cells in the islets of Langherhans of the pancreas.
- Pancreatic somatostatin is in S-14 form (has 14 amino acids). It inhibits the release of CCK and Secretin.
- Analogues of somatostatin (octreotide-longer half life) used clinically to inhibit pancreatic secretions.
How to prevent autodigestion of the pancreas ?
- Autodigestion is prevented by storing proteases in precursor form and synthesizing protease inhibitors.
- Enzyme inhibitors such as pancreatic trypsin inhibitor SPINK1 (serine protease inhibitor Kazal type 1) are co-packaged in the secretory granule.
- Zymogens become activated only after coming into contact with the small bowel brush border enzyme enterokinase.
- This converts trypsinogen to trypsin which in turn initiates the conversion of all other zymogens to their active forms.
Effect of a autodigestion is Acute Pancreatitis. Explain this more.
- Loss of protective mechanisms in the pancreas leads to acute pancreatitis.
- The diagnosis of acute pancreatitis requires two of the following three
features:
1) characteristic abdominal pain (located generally in the epigastrium and
radiates to the back). The pain is often associated with nausea and vomiting.
2) serum amylase and/or lipase ≥3 times the upper limit of normal, and
3) characteristic findings of acute pancreatitis on CT scan.
Treatments for Acute pancreatitis
-resting the pancreas(IV fluids to combat dehydration)
-urinary catheter due to severe hypovolemia
-pain relief 😌
-results from a therapeutic ERCP
Give more details about chronic pancreatitis
-Chronic pancreatitis is inflammation of the pancreas that does not heal or improve—it gets worse over time and leads to permanent damage.
- Most common cause of chronic pancreatitis is chronic alcohol abuse.
- Other causes of chronic pancreatitis are hereditary disorders of the pancreas, Cystic fibrosis—the most common inherited disorder
leading to chronic pancreatitis, hypercalcemia, hyperlipidemia.
Treatment for chronic pancreatitis.
- May require hospitalization for pain management, IV hydration, and nutritional support.
- When a normal diet is resumed, this may be supplemented with synthetic pancreatic enzymes if the
pancreas does not secrete enough of its own. - Plan a nutritious diet that is low in fat and includes small, frequent meals.
- As with acute pancreatitis, ERCP is used to identify and treat complications associated with chronic pancreatitis.
- Chronic pancreatitis also can lead to calcification of the fibrotic pancreas, which means the pancreatic tissue hardens from deposits of insoluble calcium salts. (of use in diagnosis-imaging).
- When pancreatic tissue is destroyed in chronic pancreatitis this can lead to diabetes.
