THE STORY OF ACUTE THE STORY OF ACUTE PANCREATITIS – GOD’S PANCREATITIS – GOD’S

INVISIBLE HAND IN PLACEINVISIBLE HAND IN PLACE

Yoshinobu Namihira, M.D. FACG Yoshinobu Namihira, M.D. FACG 3000 halls ferry road 3000 halls ferry road

Vicksburg MS 39180 Ph 601 638 9800, Vicksburg MS 39180 Ph 601 638 9800, fax 601 638 9808 ;e mai namihira@vicksburg.comfax 601 638 9808 ;e mai namihira@vicksburg.com

What Is Acute Pancreatitis What Is Acute Pancreatitis

•Auto-digestion of your own pancreas

phathophysiologyphathophysiology

• Pancreatic enzyme secretion

• The vagus effects gastrointestinal responses during the cephalic phase.

• Gastric distention results in changes in the function of the pancreas

• CCK release from CCK cell.

The vagus effects gastrointestinal The vagus effects gastrointestinal responses responses

• The stimulus present during cephalic phase of the meal initiates changes in the function for the entire proximal gastrointestinal tract included among these are:

• 1. Stimulus for pancreatic secretion of the digestive enzymes at about 50% of maximal

• secretory rates. In addition, this stimulus produces relaxation of the gastric and sphincter of Oddi smooth muscle as well as stimulating gallbladder contraction and gastric secretion of the acid and pepsinogen.

Gastric distentionGastric distention

• Gastric distention results in changes in the function of the pancreas, gallbladder and sphincter of Oddi. This effect is mediated through a vago-vagal reflex with processing of the signal from vagal afferents in the dorsal vagal complex and subsequent changes in parasympathetic outflow in vagal efferents. This continues the stimulus for secretion of digestive enzymes from the pancreas.

Several factors may evoke Several factors may evoke CCK CCK releaserelease from from CCK cellCCK cell. .

• It is well established that the presence of certain nutrients in the duodenum (free fatty acids [FFA] and amino acids [AA]) release CCK from CCK entero-endocrine cells. CCK releasing peptide (CCKRP), also released from cells present in the duodenum, can stimulate the release of CCK. Monitor peptide (MP) present in pancreatic secretions is also able to stimulant the release or CCK. Both MP and CCKRP can be destroyed by serine proteases secreted by the pancreas. In the absence of protein in the duodenal lumen competing for serine proteases, both MP and CCKRP are destroyed by proteases and are not available to stimulate CCK release. This appears to be an important controlling mechanism for pancreatic secretion – important.

Positive, negative, feedbackPositive, negative, feedback

AA Serine protease

FFA MP destruction

MP CCKRP destruction

CCKRP

CCK release enhanced CCK release down

Stimulation Inhibition (+) (-)

Pancreatic enzyme secretionPancreatic enzyme secretion

• Pancreatic enzyme secretion is maximally stimulated by a combination of both CCK (Cholecystokinin) and Secretin. This striking enhancement is termed “potentiation

Extreme importance of :Extreme importance of :

1. Time.

• 2. Place – Digestion of food in the duodenum – Good

• Digestion of food in the pancreas – Not good news (bad news). Extremely bad news leading to Acute pancreatitis and even death!

Five Protective Mechanisms Five Protective Mechanisms

1. Zymogen granules

2. Inactive forms

3. Enterokinase in duodenum

4. Trypsin inhibitors

5. Pressure gradient

1 Zymogen Granules 1 Zymogen Granules

• The enzymes sequestered within the acinar cell in membrane bound particles (zymogen granules) – wall of separation, sheet of protection and layer of protection.

2 Inactive forms2 Inactive forms

• The enzymes as secreted in inactive forms. These is extremely good news.

• If the enzymes are secreted in active form, autodigestion of the pancreas occurs leading to acute pancreatitis and eventual death – bad news.

3 Enterokinase in duodenum3 Enterokinase in duodenum

• The enzymes that produces activation is physically separated from the pancreas. Enterokinase in the duodenum – good news.

• Activation of the pancreatic enzymes and then digestion does not begin or occur until it reaches the duodenum (food). Extremely good news.

Digestion of the pancreas Digestion of the pancreas (autodigestion) leading to acute (autodigestion) leading to acute

pancreatitis pancreatitis • – extremely bad news.

• Physical separation – critical and

important. Enterokinase not in the pancreas but in duodenum away from the pancreas ! – Extremely good news

prevention of acute pancreatitis prevention of acute pancreatitis • n order to prevent premature activation of the

pancreatic enzyme in the pancreas. Therefore, prevention of acute pancreatitis

within the pancreas. Enterokinase is physically separated from the pancreas and present in the duodenum – important. There is a time and place for every event!

4 Trypsin inhibitors4 Trypsin inhibitors

•Trypsin inhibitors

inactivate trypsin which may be present in the pancreas– Thereby preventing pancreatitis

• In God’s wisdom, trypsin inhibitors are already put in place for protection of pancreas in case of any potential mistakes or errors

5 Pressure gradient 5 Pressure gradient

• There is a pressure gradient, which favors flow of pancreatic juice from pancreas into the duodenum

• If pressure gradient were not present, autodigestion of the pancreas would take place.

In ClosingIn Closing

• Unspeakable thankfulness for God’s protective five mechanisms in place for our own survival, our own benefit and our own good health.

•“Fearfully and wonderfully made” Psalm 139:14