Slp dr rafidah

• Sphincter of Oddi


  Smooth muscle that controls the entry of pancreatic juice and bile into the small intestine
• Exocrine dysfunction of the pancreas may be due to disorders of the pancreas itself, or to blockage of the main ducts which prevents the exocrine secretions reaching the duodenum
• Duct blockage may also result in impaired bile flow from the liver and so cause jaundice
• Pancreatic juice


  • Provides most of the important digestive enzymes
  • Contains HCO3- which helps provide the appropriate pH in the intestinal lumen for the enzymes to act on their nutrient substrates
• The functional importance of the pancreas to the digestive processes can be illustrated by the problems arising in an individual suffering from chronic pancreatitis, a condition in which pancreatic tissue is destroyed
• Exocrine tissue


  • Tubuloacinar glands organised like bunches of grapes
  • Surround the islets of Langerhans (endocrine tissue)
• Endocrine tissue (islets of Langerhans)


  • Clusters of cells that secrete hormones like insulin and glucagon into the blood
• The major endocrine cell types present are α, β, δ, and PP cells which secrete glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively
• Glucagon and insulin are taken up by the local blood vessels to act systemically, while somatostatin and pancreatic polypeptide act locally in a paracrine manner
• Acinar cells


  • Nucleus at the base, cytoplasm in basal region contains rough endoplasmic reticulum and mitochondria
  • Apical region contains Golgi apparatus and zymogen granules with digestive enzymes
  • Microvilli extend from apical surface into the lumen
  • Neighbouring cells joined by tight junctions (zonulae adherens)
• Tight junctions (zonulae adherens)


  Separate the fluid in the lumen of the acinus from the fluid in the intercellular spaces, permeable to water and ions but not macromolecules like digestive enzymes
• Disruption of the tight junctions may be an aetiological factor in the development of chronic pancreatitis
• Alkaline secretion


  Secreted by the duct cells, rich in bicarbonate, helps provide the appropriate pH in the intestinal lumen for the enzymes to act
• Enzyme-rich secretion


  Secreted by the acinar cells, contains the digestive enzymes
• If the ducts are ligated near the acini, the secretion of the alkaline component is largely unaltered, but the secretion of enzymes is markedly reduced
• Pancreatic juice


  Contains Na+, K+, HCO3-, Mg2+, Ca2+, Cl- and other ions, present in concentrations similar to those of plasma. It therefore resembles an ultrafiltrate of plasma. It is alkaline by virtue of its high HCO3- content.
• Intercalated duct


  • Begins within the acinus, a unique feature of secretory glands. The duct cells within the acinus are known as centroacinar cells.
• Intercalated ducts


  • Lined by flattened squamous epithelial cells. The neighbouring duct cells are joined by tight junctions which separate the duct lumen from the intercellular spaces and function to exclude large molecules from the spaces. They also have gap junctions which permit the transmission of membrane electrical changes between the cells.
• Larger ducts


  • Contain interlobular connective tissue cells and APUD cells.
• Functions of the alkaline pancreatic secretion

  Neutralise the acid chyme arriving from the stomach, which is important for: 1) the pancreatic enzymes require a neutral or slightly alkaline pH for their activity, 2) the absorption of fat depends on the formation of micelles in the intestinal lumen, which only takes place at neutral or slightly alkaline pH, 3) it protects the intestinal mucosa from excess acid in the duodenum which can damage it and lead to ulcers.
• Cellular mechanism of HCO3- secretion

  CO2 and water react to form carbonic acid, catalysed by carbonic anhydrase II, 2) Carbonic acid dissociates to give HCO3- and H+, 3) HCO3- is secreted from the luminal membrane by Cl-/HCO3- exchange, 4) H+ is secreted into the blood.
• For every HCO3- ion secreted into the duct lumen, one H+ ion is secreted into the blood, making the blood flowing through the pancreas transiently acidic.
• In post-surgical conditions where the patient has a draining pancreatic fistula, the loss of HCO3- results in a metabolic acidosis.
• CFTR (cystic fibrosis transmembrane conductance regulator)


  A chloride conductance channel localised to the apical region of centroacinar and intralobular duct cells, which is coupled to the HCO3-/Cl- exchanger. Failure of this secretory mechanism is seen in cystic fibrosis.
• Regulation of the CFTR Cl- channel

  Via phosphorylation and dephosphorylation by protein kinase A and a phosphatase, which serves as a molecular switch involved in the gating of the channel, 2) Via activation by hydrolysis of ATP and other nucleotides.
• Variation in pancreatic juice composition with flow rate

  As flow rate increases, the HCO3- concentration increases and the Cl- concentration decreases, due to the action of ion exchange pumps. This makes the juice more alkaline at higher flow rates.
• The changes in ionic composition with flow rate are due to transport systems in the membranes of the duct cells, which modify the primary alkaline secretion as it passes down the ducts.
• Pancreatic duct cells


  At high flow rates, the juice composition resembles the primary secretion more closely than juice secreted at low flow rates
• Ion transport relationships in pancreatic duct cells


  • Proton pumps in apical tubulovesicles are translocated to basolateral surface and fuse with plasma membrane when cell is stimulated
  • H+ ions actively pumped out of cell into interstitial fluid
  • Cl- ions secreted into lumen via CFTR
  • Na+ and K+ reach pancreatic juice via paracellular route
  • Water flows down osmotic gradient either transcellularly or paracellularly
• Na+/K+-ATPase pump in lateral borders of cell transports Na+ out and maintains low intracellular and high extracellular Na+ concentration
• Na+/H+ exchange mechanism operates at basolateral pole to keep intracellular pH stable, but not activated during secretion
• Cystic fibrosis


  Autosomal recessive inherited disorder with defect in cyclic AMP-regulated chloride conductance via CFTR
• In cystic fibrosis, defect in CFTR leads to defective secretion of bicarbonate and water, causing inspissated protein plugs that obstruct pancreatic ducts
• In cystic fibrosis, reduced fluid secretion in gastrointestinal tract results in mucous plugging and intestinal obstruction (meconium ileus)
• In cystic fibrosis, mucous plugging also blocks bronchioles, leading to recurrent respiratory infections and respiratory failure
• Pancreatic enzymes


  Major enzymes involved in digestion of foodstuffs, many secreted as inactive precursors
• Mechanism of enzyme secretion in acinar cells

  1. Enzymes/precursors synthesised on rough ER, released into ER cisternae

  2. Buds containing enzymes/precursors form condensing vacuoles

  3. Vacuoles migrate to luminal membrane and fuse, releasing contents by exocytosis
• Activation of enzyme precursors

  Trypsinogen converted to trypsin by enterokinase, then trypsin activates other precursors in catalytic chain reaction
• Acute pancreatitis


  • Involves abnormal release of activated enzymes into pancreatic ducts, leading to autodigestion of tissue
  • Often associated with gallstones obstructing ampulla of Vater, allowing reflux of duodenal contents into pancreatic duct
• Diagnosis of acute pancreatitis based on high blood and urine α-amylase levels, and hypocalcaemia