Pancreatic exocrine secretions and its control Flashcards
Describe the structure of the pancreas and relate this to its function
- 15cm, leafy/tadpole shaped
- Tucked under liver, near gallbladder, lies posterior to body of stomach
- Pancreatic lobules composed of acini (singular = acinus). Acinic closely arranged, they’re luminal structures which drain into a complex branching ductal system.
- Pancreatic ductular system empties secretions fro ductal structure into proximal duodenum via pancreatic duct
- Secretions flow as follows:
- Acini form sacs/lobules → connect to ductal tree → enters dudodenum at the main common bile duct
- Intercalated ducts → intralobular ducts → extralobular ducts → interolubular ducts → main duct, which enters the duodenum at the common bile duct
- Islet of Langerhans found throughout pancreas, secrete:
- B-cells (65%)- Insulin
- A-cels (20%) - Glucagon
- Delta-cells (10%) - Somatostatin
What do acinar cells secrete?
Digestive enzymes
What do acini form?
Sacs/lobules → connect to ductal tree → empty into duodenum
Describe the branches of the ductal tree
- Intercalated ducts - Squamous/cuboidal epithelial cells
- Intralobular ducts - Cuboidal or low columnar epithelial cells
- Extralobular ducts - Columnar epithelial cells
- Interlobular ducts - Columnar epithelial/goblet cells
- Pancreatic duct (columnar cells), which enters the dudodenum at the common bile duct
Where are the exocrine pancretic enzymes needed for digestion produced?
- In acinar cells, where they’re stored in cytoplasmic zymogen granules
- These granules accumulate near the apex and are releaseb by exocytosis
- Acinar cells arranged in secretory acinin which drain first into intercalated ducts, then interlobular, then extralobular, then interolobular and lastly into the main pancreatic duct
- Centroacinar cells are spindle-shaped cells in the exocrine pancreas, they’re extensions of the intercalated duct cells into each pancreatic acinus. These cells are responsible for the alkalinisation of the pancreatic juice
What do the intercalated and intralobular ducts secrete large volumes of?
Na+ and HCO3- rich fluid:
- HCO3- rich secretions helps to keep secretions from zymogens inactive - maintains pH >7.5
- Secretion mainly via HCO3-/Cl- exhchanged, regulated by CFTR
- Centroacinar cells and duct cells respond to secretin and release HCO3- to buffer the acidic chyme
- The intercalated ducts take the bicarbonate to intralobular ducts which become extralobular ducts
What’s the basal lamina?
Layer of extracellular matrix secreted by epithelial cells; epithelium sits on it
Describe the morphology of the acinus duct
- Fundamental secretory unit composed of an acinus and an intercalated duct
- Intercalated ducts merge to form intralobular ducts, which merge to form interlobular ducts, then the main pancreatid duct
- Acinar cells are specialised for protein (enzyme) secretion. Large condensing vaguoles gradually reduce in size, form zymogen granules that store digestive enzymes (proteins) in apical region of acinar cell
- Duct cell is cubiodal cell with abundant mitochondria. Small microvilli project from its apical membrane
Describe the paracrine exocrine secretions, the anions and cations and their functions
- Secretes 1.5L of fluid/day (containing Na+ and HCO3- rich juice, albumin, globulin and digestive enzymes)
- Acinar cells - Secrete digestive enzymes which breakdown carbs, fats, proteins and nucleic acids
- Enzymes secreted in an inactive form (as zymogens) to prevent auto-digestion (of pancreas)
- Activation of enzymes happens in duodenum
- Anions:
- HCO3-
- Cl-
- SO4 2-
- HPO4 2-
- Cations:
- Na+
- K+
- Ca2+
- Mg2+
Describe the effects of secretin on the composition and volume of pancreatic juice
- Stimulated pancreas has HCO3- rich secretions compared to Cl-
- There’s a reciprocal change in the concentrations of Cl- and HCO3- after the infusion of secretin
- If the rate of secretion is low, most of the fluid is sereted by intralobular ducts
- If secretin stimulates increased rate of production, most of the additional fluid is produced by extralobular ducts
What are the types of enzymes secreted by the pancreas?
3 major types:
- Proteoloytic (trypsin, chymotrypsin and carboxypeptidase)
- Trypsin, secreted as trypsinogen, activated by enteropeptidase and by trypsin. Breaks down proteins and polypeptides
- Elastase is activated by trypsin, it acts on elastin
- Phsopholipase A2 is activated by trypsin, acts on phospholipids
- Carboxypeptidase A and B, activated by trypsin, breaks up proteins and polypeptides
- Amylase
- Pancreatic alpha-amylase, activated by Cl-, breaks down starch/carbs into monosaccharides, disaccharides
- Lipase
- Pancreatic lipase breakds down and emulsifies lipids. Triglycerides → FAs + glycerol
- Colipase - Activated by trypsin, acts on fat droplets
- Pancreatic insufficiency ⇒ malabsorption of fats (steatorrheoa)
Also has ribonucleus, deoxyribonuclease etc.
Describe the function of enterokinase and where it’s found
Enterokinase (enteropeptidase) - In brush border of duodenum, secreted in response to CCK:
- Converts trypsinogen to trypsin
- Trypsin → Autocatalytic chain reaction (autoactivation and activation of other proenzymes)
Inhibitors of autodigestion:
- Kazal inhibitor, enzyme Y (chymotrypsin C, caldecrin)
- Intracellular pH of zymogen granule = acidic, keeps zymogen inactive
In acute pancreatitis: Trypsin activates phospholipase A2 (PLA2) in the pancreatic duct. Lechitin is converted into isolecithin via PLA2. In acute pancreatitis there’s increased pancreatic alpha amylase present in the blood, making it a good diagnostic test
Isolecithin → disruption of pancreatic tissue, membrane damage and necrosis
How are pancreatic secretions controlled? Describe the phases of pancreatic secretion
- Neuroendocrine signals
- Vagal (parasympathetic) stimulation enhaces the rate of enzymes and aq components of pancreatic juice
- Sympathetic stmiulation inhibits secretion
- Secretin and CCK stimulate secretion of pancreatic fluid (HCO30 and enzymes)
Cephalic phase - Vagal (Ach and VIP) stimulation of gastrin releae from antrum → some enzyme-rich pancreatic juice
Gastric phase - Distension (vago-vagal reflex on fundus or antrum), amino acid and peptide (in antrum)- stimulated gastrin secretion → release of enzyme-rich pancreatic juice
Vago-vagal reflex also causes Ach release
–Vagotomy → 50%↓ in response to acidic chyme
Intestinal phase - Secretin and CCK; enteropancreatic reflexes - Acidic chyme in duodenum an djejenum induces secretion of pancreatic juice (HCO3- and enzymes). Secretin is secreted by S cells, which act on receptors on ductal cells to secrete HCO3- and fluid.
- Protein and lipid breakdown products have 2 effects:
- Stimulate I cells to release CCK, which causes acinar cells to release digestive enzymes
- Stimulate afferent pathways, initiating vagovagal reflex that primarily stimulates acinar cells through M3 cholinergic receptors
Where is secretin secreted and what does it do?
Secreted from duodenum and jejenum:
- Induces pancreatic duct cells to secrete HCO3- rich pancreatic juice but, decreases enzymes content
- Secretin also stimulates production of bile
Where is CCK secreted and what does it do?
Duodenum and jejenum in response to FAs (amino acids and peptides:
- CCK stimulates pancreatic acinar cells to synthesise and release enzyme-rich pancreatic juice; and stimulates secretion of concentrated bile which emulsifies fats, allowing pancreatic lipase to difest and absorb the fat
- CCK contract gallbladder via acting on brain, relaxes (VIP/NO) sphincter of Oddi → Release of bile and some HCO3- into duodenum
- CCK potentiates the effects of secretin, which is a weak agonist of acinar cells
How does cystic fibrosis affect the GI tract?
- Cystic fibrosis leads to the production of thick, sticky mucus
- Abnormal, thickened mucus blocks ducts in the pancreas, affecting pancreatic secretions which can in turn alter the way carbs, proteins and lipids
- Obstruction of the pancreatic duct by thick mucus contributes to GI symptoms in patients with CF, prevents release of digestive enzymes to break down food and absorb nutrients
- To digest food, patients with cystic fibrosis need to take enzyme-replacement drugs so they can breakdown and absorb the nutrients
- Consequences of this include:
- Severe malabsorption
- Steatorrheoea
- Recurrent chest infections
- Sterility in 98% of males due to congenital bilateral aplasia of the vas deferens, don’t develop properly
Define exocrine and why is the pancreas exocrine?
A gland which secretes its products through ducts opening on to an epithelium/surface rather than directly into blood
The pancreatic duct releases its exocrine secretions into the major duodenal papilla so that it can enter the duodenum
What do the pancreatic ductal cells secrete?
HCO3-
