GI accessory organs

Question 1

1. List the three key cell types that are important to the exocrine function of the pancreas and their secretions.

Answer 1

• Acinar cells: secretion of pancreatic digestive enzymes.
  o Function: protein synthesis.
• Duct cells: HCO3- secretion and fluid secretion.
  o Function: ion transport/fluid transport.
• Goblet cells: mucin synthesis and secretion.
  o Function: lubrication, hydration, protection, and immune function.

Question 2

2. Identify the two primary stimuli for fluid and enzyme secretion by pancreatic acinar cells.

Answer 2

• Two primary stimuli: CCK & Ach.
• Both act by increasing intracellular calcium.
• Fluid: increased activity of Cl- channel on the luminal cell membrane  secretion of Cl-  Na+ and water follow.
• Enzyme: docking and exocytosis of vesicles containing proenzymes into lumen.

Question 3

3. Describe how zymogens are stored in the pancreas and activated in the duodenum.

Answer 3

• Zymogens are stored in vesicles in acinar cells; maintained in inactive form to protect pancreatic cells from injury.
• Once secreted, zymogens pass through pancreatic duct and common bile duct and are released into duodenum.
• Duodenal cells secrete enterokinase/enteropeptidase that converts trypsinogen  trypsin.
• Trypsin then converts the other zymogens (chymotrypsinogen  chymotrypsin, proelastase  elastase, procarboxypeptidase  carboxypeptidase).

Question 4

4. Identify the primary stimulus for the secretion of bicarbonate from pancreatic duct cells

Answer 4

• Primary stimulus: secretin.

- Secretin released by duodenal cells  acts on duct cells in response to low pH  secretion of HCo3-.

Question 5

5. Describe the three phases of pancreatic secretion and how each phases is regulated.

Answer 5

• 3 phases: cephalic, gastric, intestinal (note, these phases are preceded and followed by the interdigestive period).
• Cephalic:
  o Stimulant: sight, smell, taste, and mastication.
  o Regulation pathway: vagal pathway.
  o % of max enzyme secretion: 25%.
• Gastric:
  o Stimulation: distension, gastrin, peptides/peptones
  o Regulation pathway: vagal, gastrin
  o % of max enzyme secretion: 10 – 20%.
• Intestinal:
  o Stimulation: amino acids, fatty acids, H+
  o Regulation pathway: CCK, secretin, entero-pancreatic reflexes
  o % of max enzyme secretion: 50 – 80%.
• Note: phases of secretion between stomach and pancreas are same; the difference is when the max amount of enzyme secretion occurs (gastric: during gastric phase, pancreatic: during intestinal phase).

Question 6

6. Identify the stimulus for returning the levels of pancreatic secretion from the fed state to the interdigestive state.

Answer 6

• Contents of intestine (mainly fat) reach ileum  release of peptide YY and somatostatin  decrease pancreatic secretions  return to interdigestive state.

Question 7

7. Describe the directional flow of blood and bile through the liver.

Answer 7

• Blood flows from the portal vein and hepatic artery (at the periphery of the lobule) to the hepatic vein (at the center of the lobule).
• Bile flows from the center of the lobule to the bile duct (at the periphery of the lobule).

Question 8

8. Describe how hepatocytes “handle” or process chemical and compounds (uptake of chemicals, ions, and salts from the blood; the transport of these components through the cell to the site of biotransformation; biotransformation; and the transport of substances back into the blood for excretion by the kidneys or into the bile for fecal elimination).

Answer 8

• Four steps: uptake, transport, biotransformation, and secretion (into blood or bile).
• Uptake:
  o Import of compound across basolateral membrane.
  o Utilizes various transport proteins, or free diffusion.
• Transport:
  o Intracellular transport, directed by binding proteins.
• Biotransformation:
  o Process of making molecule more water-soluble through chemical modification or degradation.
   Two phases: phase I and phase II.
• Secretion:
  o Products of biotransformation transported into blood or bile.
  o Via transporters on apical or basolateral membranes.

Question 9

9. Compare and contrast Phase I and II biotransformation and describe the chemical result of these two processes.

Answer 9

• Phase I:
  o Goal: expose functional group on molecule.
  o Example reactions: oxidation, reduction, hydrolysis.
• Phase II:
  o Goal: conjugate molecule with larger molecule and make it water-soluble.
  o Example reactions: glucuronidation, sulfation, acetylation.

Question 10

10. Describe the bile salt biosynthetic pathway.

Answer 10

• Precursor: cholesterol
• Cholesterol is converted to bile acid by hepatocytes through Phase I and Phase II biotransformation.
• Bile acid is then converted to bile salt within the hepatocyte (primary bile acid), or secreted into the duodenum where it is converted to bile salt via the normal microbiota (secondary bile acid).
• Bile acids + salts secreted into duodenum via bile.

Question 11

11. Identify the storage site for bile and the key stimuli to promote and inhibit the secretion of bile into the duodenum.

Answer 11

• Storage site for bile: gallbladder.
• Key stimuli:
  o Cholecystokinin (CCK): stimulate contraction of gallbladder and relaxation of Sphincter of Oddi (sphincter regulation pancreatic and bile secretion into the duodenum.
  o Acetylcholine (Ach): also stimulate gallbladder to contract and Sphincter of Oddi to relax.
  o Somatostatin: inhibits gallbladder contraction and relaxation of Sphincter of Oddi.

Question 12

12. Describe enterohepatic circulation and the tissues important for the process.

Answer 12

• Enterohepatic circulation: the recycling of bile salt/acids secreted into duodenum. ~95% of secreted bile acids must be recycled.
• Tissue important for enterohepatic circulation: ileum (utilizes passive and active transport to recycle bile acids).

Question 13

13. Know and understand the following pathophysiological conditions and symptoms: pancreatitis, portal hypertension, jaundice, cirrhosis, cholestasis, cholelithiasis, and cholecystitis.

Answer 13

• Pancreatitis:
  o What it is: inflammation of pancreas.
  o Causes: mis-regulated cellular calcium (?), obstruction of common biliary or pancreatic ducts, alcoholism, and release of enzymes that digest the pancreas (autodigestion).
  o Disease process: decreased secretion of digestive enzymes  malabsorption of dietary nutrients. Recruitment of inflammatory cells  damage to sites distal to pancreas.
• Portal hypertension:
  o What it is: high blood pressure in portal venous system.
  o Causes: disorders that impede blood flow through liver or vena cava.
  o Disease process: leads to: varices (distension of collateral veins in the esophagus, rectum, and stomach), splenomegaly (enlarged spleen), ascites (accumulation of fluid in the peritoneal cavity), and hepatic encephalopathy (accumulation of toxins  cell death in CNS).
• Jaundice:
  o What it is: yellowing of skin due to elevated blood levels of bilirubin.
  o Causes: impaired hepatic excretion due to: extrahepatic obstruction (ex: bile duct) or intrahepatic obstruction (ex: impaired hepatocyte function or blocked bile caniculi).
  o Disease process: impairment of bile excretion from liver  bilirubin shunted into bloodstream instead.
• Cirrhosis:
  o What it is: fibrosis (scarring)of hepatic tissue resulting in altered hepatic blood flow and function.
  o Causes: inflammatory process (hepatitis), alcoholism, biliary obstructions, and autoimmune conditions.
  o Disease process: can cause portal hypertension, jaundice. Specifically with alcoholic cirrhosis: accumulation of ethanol and acetaldehyde (ethanol metabolite)  disruption of hepatocyte function  cell death. Biliary cirrhosis: autoimmune responses, gallstones, tumors, strictures, pancreatitis, or cystic fibrosis  impediment of bile flow out of liver.
• Cholestasis:
  o What it is: impaired bile flow.
  o Causes: include cholelithiasis and cholecystitis.
• Cholelithiasis:
  o What it is: cholesterol gallstones formation in gallbladder.
  o Causes: over-production of cholesterol or impaired production of bile salts.
• Cholecystitis:
  o What it is: inflammation of gallbladder.
  o Causes: stones become lodged in cystic duct.