61 - GI Pancreas Flashcards
Case study #4
Go read case study #4
How do H. pylori survive in an acidic environment?
Urease
- It is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia
- Helicobacter species are able to thrive in the very acidic mammalian stomach by producing large quantities of the enzyme urease, which locally raises the pH from about 2 to a more biocompatible range of 6 to 7
How do H. pylori contribute to ulcer formation?
- Helicobacter pylori that colonizes the antral mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. - Thus, the bacterium can cause a chronic active gastritis (type B gastritis).
- Gastrin stimulates the production of gastric acid by parietal cells.
- In H. pylori colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation.
How does bismuth treat stomach ulcers?
Bismuth (pepto bismal)
- Bismuth provides an extra coating – replacement for the mucous barrier
How do tetracycline, metronidazole, and amoxicillin treat stomach ulcers?
Antibiotics to fight the microorganism
How do H2-receptor blockers treat stomach ulcers?
H2 receptor blockers inhibit the Histamine 2 receptor (highly expressed in the stomach) to result in decreased acid production (because histamine promotes acid production)
How do proton pump inhibitors treat stomach ulcers?
PPI inhibit the proton pump – works better than H2 blockers because it’s the final common pathway (blocks all contributing pathways to acid production)
What’s the difference between H2-receptors and PPIs?
Blocking H2 means that gastrin and Ach are unaccounted for – they all lead up to the proton pump – inhibition of this step blocks them all. NSAIDS were explained above.
How is epinephrine used to treat stomach ulcers?
Epi (can use NE also) was used here as an injection to control the bleeding by inducing vasoconstriction
What are the three cell types that are important for the exocrine function of the pancreas?
1 - Acinar cells
2 - Duct cells
3 - Goblet cells
What is the function of acinar cells?
Acinar cells are arranged in an acinus – synthesizing protein, secreting digestive enzymes and fluid into the duct (where ductal cells and goblet cells reside)
What is the function of duct cells and goblet cells?
Duct cell secrete bicarb, and transport fluid and ions where goblet cells secrete mucin (which lubricates, hydrates, protects – from acid, and has antimicrobial function).
What is a prototypic pancreatic protease?
- Enzymes secreted from acinar cells of the pancreas
- Released in the inactive form
- Need some sort of modification before they become active
What are some of these enzymes that you need to know?
- Trypsinogen
- Amylase (active)
- Lipase (active)
- Colipase (active)
- Trypsin inhibitor (active)
Trypsinogen
Trypsinogen is one of the primary prototypic pancreatic proteases (measured also for diagnostic function)
Trypsin inhibitor
Trypsin inhibitor inhibits trypsin to protect against activation and subsequent autodigestion (seen in pancreatitis)
Colipase
Colipase regulates lipase
Amylase
Amylase was also seen in saliva – pancreatic amylase is the chief carbohydrate digestion enzyme.
What are the two primary stimuli for fluid and enzyme secretion by pancreatic acinar cells?
- CCK (attaches at CCK-A receptor)
- Ach (attaches at muscarinic receptor)
How are zymogens stored in the pancreas?
- Zymogens are proenzymes – they are synthesized in an inactive form.
- They’re stored in vesicles containing trypsin inhibitor (remember trypsinogen is one of the primary proteases).
- Low pH of the vesicle also prevents activation
What happens to the stored zymogens upon secretion?
- Upon secretion into the gland and duct, the inhibitor impacts the zymogen to prevent activation but pH is changing so the effect becomes less the further out you get
- Remember that ductal cells produce the bicarb that lowers the pH
What happens if these protective abilities are defective?
Autodigestion
What is the difference between pancreatic zymogens and pepsin?
- Pancreatic zymogens are activated at high pH and pepsin is activated at low pH
- Pancreatic zymogens function in the duodenum and pepsin functions in the stomach
What is the primary stimulus for the secretion of bicarb from pancreatic duct cells?
- Secretin is released from the duodenum when pH is too low, which stimulates the pancreatic duct cells to produce bicarb
What else does secretin do?
Secretin also results in…
- delayed gastric emptying
- increase in somatostatin release (from D cells)
- decreases gastrin secretion (from G cells)
- decrease in proton pump expression
Why is it beneficial that secretin has all of these functions?
- in order to have the greatest effect of neutralizing acid in the duodenum, it is best to create a stagnation of acidic contents from the stomach
- this reduces acid production from the stomach
- this means that less bicarb is required because you only have to neutralize the acid already in the duodenum and not the extra acid that would have entered the duodenum otherwise
What is pancreatitis?
Pancreatitis is pancreas inflammation
What is acute pancreatitis associated with?
- Alcoholism (because Ca++ enzymatic docking is disrupted)
- Obstruction (because it causes buildup of enzymes and therefore activation)
What causes the inflammation?
The autodigestion causes the release of inflammatory mediators, which then cause further tissue damage
What is chronic pancreatitis associated with?
Chronic pancreatitis is due to unresolved damage and alcohol abuse
What is a consequence of pancreatitis?
- Pancreatitis can lead to malabsorption syndrome because you can’t get digestive enzymes to where they need to be in the duodenum
- Continued autodigestion/subsequent healing increases the likelihood of cancer
If pancreatitis does cause cancer, what type is it usually?
Adenocarcinoma
What is the pathophysiology of this adenocarcinoma?
- Loss of function of p53 and p16 (unregulated proliferation)
- Gain of function of Ras (promotes hyperproliferation)
A bad combo :(
What are the three phases of pancreatic secretion?
- Interdigestive phase
- Cephalic phase
- Gastric phase
What is the interdigestive phase?
- Cyclical phase of pancreatic secretion occurs between 12am and 6am
What regulates the interdigestive phase?
Regulators of the cyclical pattern include:
- stimulation by parasympathetic pathways
- stimulation by CCK
- inhibition by a-adrenergic input, somatostatin and peptide YY
What do pancreatic secretions during the interdigestive phase coordinate with? What is the significance of this?
- Pancreatic secretions during the interdigestive period parallel the migrating motor complexes
- Therefore pancreatic secretions parallel motility, secretion is highest during intestinal contractility.
What is the cephalic phase?
A pre-consumption phase that is responsible for 25% of enzyme secretion from the pancreas
What is the cephalic phase stimulated and regulated by?
- Stimulated by sight, smell, taste and mastication
- Regulated by vagal pathways
What is the gastric/intestinal phase phase?
The well fed state which is responsible for 50-80% of pancreatic enzyme secretion
What is the gastric/intestinal phase stimulated and regulated by?
- Stimulated by gastric distension, gastrin and peptides
- Regulated by vagal pathways
What stimulates the pancreas to reduce enzymatic secretions after a meal and return to the interdigestive phase?
Once the contents of the intestines, reach the ileum, there is release of peptide YY and somatostatin, which decreases pancreatic activity to return to interdigestive state
Remember distention stimulates peristaltic intestinal contractility – corresponding to gastric level of pancreatic secretion
Onto case #5…
Go read case #5
What two tissues appear to be affected in this case?
Pancreas and duodenum
What is the physiological consequence of these two tissues being dysfunction?
- Degradation of tissues (duodenal ulcers?) because losing protective factors means less protection of duodenal mucosa from stomach acid
- Hyperacid secretion may also be seen because you may lose regulatory inputs that control acid production.
- Possibly malabsorption
Give an explanation for the recurrent pain every 2-3 hours
Regular pain intervals occurred because of the MMC – as it sweeps over the area – it results in the upswing in the regular sinusoidal curve of secretion. This means that more enzymes are produced –> more damage and more pain
Why is the patient prescribed a low-protein, low-fat diet?
To decrease CCK (primary stimulant) secretion – and subsequent reduction in pancreatic enzyme secretion.
Which endocrine regulators would exacerbate the pain?
- CCK is primary
- Gastrin also plays a role
(acetylcholine?)
Compare and contrast the expected findings/presentation if an obstruction was identified in the pancreatic duct or common bile duct?
- If there was a blockage in the pancreatic duct, you would have acute pancreatitis, elevated pancreatic enzymes, decreased breakdown of food… Decreased digestion in relation to the pancreas roles (lipids, proteins, carbohydrates)
- If there was a blockage in the common bile duct, you would see elevation of bilirubin (blood and urine), decreased emulsification of fat –> there is a difference between digestion and absorption
What do his lab values indicate?
- B12 is low and folic acid is high
- This tells us there’s a problem with B12 absorption
- This can happen either at the level of the stomach (if it is a production problem) or at the level of the ileum (if it is an absorption problem)
- In the absence of the lab values, you could easily assume the pancreas as being the culprit
- What other tissue besides the pancreas is dysfunctional in this case and how does this impact the lab findings?
- A decrease in vitamin B absorption caused a compensation where folic acid got kicked up
- This is done in order to keep up high rate of division in certain cells
- Folate is involved in DNA synth and B12 recycles folate so this compensation makes sense
- Also notice how hematocrit and WBC is going down. This supports the idea of anemia.
