Acute Pancreatitis: History, Scoring System, and Treatment

Authors:
Michael Krzyzak, MD
Department of Medicine, Staten Island University Hospital, Staten Island, New York

Stephen Mulrooney, MD
Department of Gastroenterology, Staten Island University Hospital, Staten Island, New York

Citation: Krzyzak M, Mulrooney S. Acute pancreatitis: history, scoring system, and treatment [published online September 12, 2018]. Gastroenterology Consultant.

Abstract: Acute pancreatitis is a frequent occurrence in hospital practice. Presenting with epigastric pain, it is diagnosed as fulfilling 2 of 3 criteria, including laboratory, clinical, and radiologic findings. Treatment is based on aggressive intravenous hydration of lactated Ringer solution and pain management. Enteral nutrition should be started as soon as it can be tolerated. Complications from acute pancreatitis include recurrent episodes, chronic pancreatitis, and necrosis.

The word pancreas originates from ancient Greek pan- + kreas, meaning “all flesh.”¹ Herophilus of Chalcedon, noted as one of the founders of the ancient school of medicine in Alexandria, is credited as the first person to describe the pancreas, but the organ was named by Rufus of Ephesus.² The name all flesh comes from its gross description as an organ without any bone or cartilage. By the 16th century, the pancreas had been described as ductal system into which duodenal chyme ascended.³ Pancreatitis was first described in 1652 by Nicolaes Tulp, a Dutch surgeon and lecturer of anatomy, who is remembered as the subject on Rembrandt’s “The Anatomy Lesson of Dr. Nicolaes Tulp” (Figure).^4,5 Pancreatitis was further described as hemorrhagic, suppurative, and gangrenous in the 19th century. During this time, the clinical signs of epigastric pain were described as "deep-seated, dull, epigastric pain, distention, sickness, and vomiting."⁶ 

Figure. “The Anatomy Lesson of Dr. Nicolaes Tulp” (1632), by Rembrandt.⁵

A diagnosis of acute pancreatitis requires 2 of the following 3 criteria: abdominal pain, an amylase/lipase level 3 times the upper limit of normal, and findings on imaging that are suggestive of pancreatitis.⁷

The annual incidence of pancreatitis is reported to be from 13 to 45 per 100,000 US population.⁸ Inciting events for pancreatitis vary widely. In the pediatric population, trauma, abuse, viral infections, hemolytic-uremic syndrome, gallstones, Shwachman-Diamond syndrome, and cystic fibrosis are among the causes.⁴ The African American population has a 2- to 3-fold higher risk of developing acute pancreatitis than the white population, and men and women are equally affected.⁹

Initially, pancreatitis was thought to be attributable only to gallstones.¹⁰ In a prospective US study, 37.9% of pancreatitis cases were gallstone-related, 43.5% were not gallstone-related, and 18.6% were cases of recurrent acute pancreatitis.⁹ Gallstones and alcohol use are the top 2 culprits of pancreatitis.¹¹ Smoking was found to have an association, with a hazard ratio of 2.01 reported in women with more than 20 pack-years of smoking.⁹ Less than 5% of cases of acute pancreatitis are linked to medication use, and although an extensive list of medications is associated with pancreatitis, it is difficult to determine whether a drug is responsible.¹² Medications such as proton-pump inhibitors, antibacterials, azathioprine, enalapril, mesalamine, 6-mercaptopurine, and valproic acid are among the common medication-induced causes of pancreatitis.^12,13

Chiari proposed the autodigestion of pancreatic enzymes in 1896.⁴ The agitator of the proinflammatory response can be physical, chemical, or both, such as in post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Numerous inciting factors have been noted (Table).^14-17

 
The inciting event can vary but must produce pancreatic duct obstruction, which impedes exocytosis of zymogen granules from acinar cells. Zymogen granules contain digestive enzymes that begin the process of autodigestion.¹⁸ Two hypotheses, the reflux hypothesis and colocalization hypothesis, have been developed to explain the initiation of the process. The reflux hypothesis relies on bile reflux via the pancreatic duct activating trypsinogen.¹⁹ Alternatively, the colocalization theory relies on lysosomal colocalization within the acinar cells. In cellular models, cathepsin B and N-acetylglucosaminidase become redistributed during pancreatic duct obstruction. These lysosomal hydrolases localize in zymogen granules in acinar cells.²⁰

The acinar cells initiate the cascade via 1 of 4 proposed mechanisms: cathepsin B activation, disruption in calcium signaling, trypsinogen autoactivation, and inappropriate trypsinogen activation. Trypsinogen autoactivates in the acinar cells and progresses to macrophages, which also activate trypsinogen via cathepsin B. This increases the severity of the proinflammatory response. Interleukins have been well documented as part of the inflammatory cascade. Interleukin 6 (IL-6), IL-8, IL-1β, soluble IL-2 receptor (sIL-2R), and C-reactive protein (CRP) have been documented to correlate with the severity of pancreatitis.^21-23 IL-1β and sIL-2R levels have been shown to elevate at day 1 of presentation, while IL-6, IL-8, and CRP levels have been found to be elevated at day 3.²¹ This amplification initiates a systemic response. The importance of the final pathway of inciting a proinflammatory response can be seen in the development of ameliorating strategies, such as in the use of rectal indomethacin with aggressive hydration.²⁴

Authors:
Michael Krzyzak, MD
Department of Medicine, Staten Island University Hospital, Staten Island, New York

Stephen Mulrooney, MD
Department of Gastroenterology, Staten Island University Hospital, Staten Island, New York

Citation: Krzyzak M, Mulrooney S. Acute pancreatitis: history, scoring system, and treatment [published online September 12, 2018]. Gastroenterology Consultant.

Abstract: Acute pancreatitis is a frequent occurrence in hospital practice. Presenting with epigastric pain, it is diagnosed as fulfilling 2 of 3 criteria, including laboratory, clinical, and radiologic findings. Treatment is based on aggressive intravenous hydration of lactated Ringer solution and pain management. Enteral nutrition should be started as soon as it can be tolerated. Complications from acute pancreatitis include recurrent episodes, chronic pancreatitis, and necrosis.

The word pancreas originates from ancient Greek pan- + kreas, meaning “all flesh.”¹ Herophilus of Chalcedon, noted as one of the founders of the ancient school of medicine in Alexandria, is credited as the first person to describe the pancreas, but the organ was named by Rufus of Ephesus.² The name all flesh comes from its gross description as an organ without any bone or cartilage. By the 16th century, the pancreas had been described as ductal system into which duodenal chyme ascended.³ Pancreatitis was first described in 1652 by Nicolaes Tulp, a Dutch surgeon and lecturer of anatomy, who is remembered as the subject on Rembrandt’s “The Anatomy Lesson of Dr. Nicolaes Tulp” (Figure).^4,5 Pancreatitis was further described as hemorrhagic, suppurative, and gangrenous in the 19th century. During this time, the clinical signs of epigastric pain were described as "deep-seated, dull, epigastric pain, distention, sickness, and vomiting."⁶ 

Figure. “The Anatomy Lesson of Dr. Nicolaes Tulp” (1632), by Rembrandt.⁵

A diagnosis of acute pancreatitis requires 2 of the following 3 criteria: abdominal pain, an amylase/lipase level 3 times the upper limit of normal, and findings on imaging that are suggestive of pancreatitis.⁷

The annual incidence of pancreatitis is reported to be from 13 to 45 per 100,000 US population.⁸ Inciting events for pancreatitis vary widely. In the pediatric population, trauma, abuse, viral infections, hemolytic-uremic syndrome, gallstones, Shwachman-Diamond syndrome, and cystic fibrosis are among the causes.⁴ The African American population has a 2- to 3-fold higher risk of developing acute pancreatitis than the white population, and men and women are equally affected.⁹

Initially, pancreatitis was thought to be attributable only to gallstones.¹⁰ In a prospective US study, 37.9% of pancreatitis cases were gallstone-related, 43.5% were not gallstone-related, and 18.6% were cases of recurrent acute pancreatitis.⁹ Gallstones and alcohol use are the top 2 culprits of pancreatitis.¹¹ Smoking was found to have an association, with a hazard ratio of 2.01 reported in women with more than 20 pack-years of smoking.⁹ Less than 5% of cases of acute pancreatitis are linked to medication use, and although an extensive list of medications is associated with pancreatitis, it is difficult to determine whether a drug is responsible.¹² Medications such as proton-pump inhibitors, antibacterials, azathioprine, enalapril, mesalamine, 6-mercaptopurine, and valproic acid are among the common medication-induced causes of pancreatitis.^12,13

Chiari proposed the autodigestion of pancreatic enzymes in 1896.⁴ The agitator of the proinflammatory response can be physical, chemical, or both, such as in post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Numerous inciting factors have been noted (Table).^14-17

 
The inciting event can vary but must produce pancreatic duct obstruction, which impedes exocytosis of zymogen granules from acinar cells. Zymogen granules contain digestive enzymes that begin the process of autodigestion.¹⁸ Two hypotheses, the reflux hypothesis and colocalization hypothesis, have been developed to explain the initiation of the process. The reflux hypothesis relies on bile reflux via the pancreatic duct activating trypsinogen.¹⁹ Alternatively, the colocalization theory relies on lysosomal colocalization within the acinar cells. In cellular models, cathepsin B and N-acetylglucosaminidase become redistributed during pancreatic duct obstruction. These lysosomal hydrolases localize in zymogen granules in acinar cells.²⁰

The acinar cells initiate the cascade via 1 of 4 proposed mechanisms: cathepsin B activation, disruption in calcium signaling, trypsinogen autoactivation, and inappropriate trypsinogen activation. Trypsinogen autoactivates in the acinar cells and progresses to macrophages, which also activate trypsinogen via cathepsin B. This increases the severity of the proinflammatory response. Interleukins have been well documented as part of the inflammatory cascade. Interleukin 6 (IL-6), IL-8, IL-1β, soluble IL-2 receptor (sIL-2R), and C-reactive protein (CRP) have been documented to correlate with the severity of pancreatitis.^21-23 IL-1β and sIL-2R levels have been shown to elevate at day 1 of presentation, while IL-6, IL-8, and CRP levels have been found to be elevated at day 3.²¹ This amplification initiates a systemic response. The importance of the final pathway of inciting a proinflammatory response can be seen in the development of ameliorating strategies, such as in the use of rectal indomethacin with aggressive hydration.²⁴

Authors:
Michael Krzyzak, MD
Department of Medicine, Staten Island University Hospital, Staten Island, New York

Stephen Mulrooney, MD
Department of Gastroenterology, Staten Island University Hospital, Staten Island, New York

Citation: Krzyzak M, Mulrooney S. Acute pancreatitis: history, scoring system, and treatment [published online September 12, 2018]. Gastroenterology Consultant.

Abstract: Acute pancreatitis is a frequent occurrence in hospital practice. Presenting with epigastric pain, it is diagnosed as fulfilling 2 of 3 criteria, including laboratory, clinical, and radiologic findings. Treatment is based on aggressive intravenous hydration of lactated Ringer solution and pain management. Enteral nutrition should be started as soon as it can be tolerated. Complications from acute pancreatitis include recurrent episodes, chronic pancreatitis, and necrosis.

The word pancreas originates from ancient Greek pan- + kreas, meaning “all flesh.”¹ Herophilus of Chalcedon, noted as one of the founders of the ancient school of medicine in Alexandria, is credited as the first person to describe the pancreas, but the organ was named by Rufus of Ephesus.² The name all flesh comes from its gross description as an organ without any bone or cartilage. By the 16th century, the pancreas had been described as ductal system into which duodenal chyme ascended.³ Pancreatitis was first described in 1652 by Nicolaes Tulp, a Dutch surgeon and lecturer of anatomy, who is remembered as the subject on Rembrandt’s “The Anatomy Lesson of Dr. Nicolaes Tulp” (Figure).^4,5 Pancreatitis was further described as hemorrhagic, suppurative, and gangrenous in the 19th century. During this time, the clinical signs of epigastric pain were described as "deep-seated, dull, epigastric pain, distention, sickness, and vomiting."⁶ 

Figure. “The Anatomy Lesson of Dr. Nicolaes Tulp” (1632), by Rembrandt.⁵

A diagnosis of acute pancreatitis requires 2 of the following 3 criteria: abdominal pain, an amylase/lipase level 3 times the upper limit of normal, and findings on imaging that are suggestive of pancreatitis.⁷

The annual incidence of pancreatitis is reported to be from 13 to 45 per 100,000 US population.⁸ Inciting events for pancreatitis vary widely. In the pediatric population, trauma, abuse, viral infections, hemolytic-uremic syndrome, gallstones, Shwachman-Diamond syndrome, and cystic fibrosis are among the causes.⁴ The African American population has a 2- to 3-fold higher risk of developing acute pancreatitis than the white population, and men and women are equally affected.⁹

Initially, pancreatitis was thought to be attributable only to gallstones.¹⁰ In a prospective US study, 37.9% of pancreatitis cases were gallstone-related, 43.5% were not gallstone-related, and 18.6% were cases of recurrent acute pancreatitis.⁹ Gallstones and alcohol use are the top 2 culprits of pancreatitis.¹¹ Smoking was found to have an association, with a hazard ratio of 2.01 reported in women with more than 20 pack-years of smoking.⁹ Less than 5% of cases of acute pancreatitis are linked to medication use, and although an extensive list of medications is associated with pancreatitis, it is difficult to determine whether a drug is responsible.¹² Medications such as proton-pump inhibitors, antibacterials, azathioprine, enalapril, mesalamine, 6-mercaptopurine, and valproic acid are among the common medication-induced causes of pancreatitis.^12,13

Chiari proposed the autodigestion of pancreatic enzymes in 1896.⁴ The agitator of the proinflammatory response can be physical, chemical, or both, such as in post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Numerous inciting factors have been noted (Table).^14-17

 
The inciting event can vary but must produce pancreatic duct obstruction, which impedes exocytosis of zymogen granules from acinar cells. Zymogen granules contain digestive enzymes that begin the process of autodigestion.¹⁸ Two hypotheses, the reflux hypothesis and colocalization hypothesis, have been developed to explain the initiation of the process. The reflux hypothesis relies on bile reflux via the pancreatic duct activating trypsinogen.¹⁹ Alternatively, the colocalization theory relies on lysosomal colocalization within the acinar cells. In cellular models, cathepsin B and N-acetylglucosaminidase become redistributed during pancreatic duct obstruction. These lysosomal hydrolases localize in zymogen granules in acinar cells.²⁰

The acinar cells initiate the cascade via 1 of 4 proposed mechanisms: cathepsin B activation, disruption in calcium signaling, trypsinogen autoactivation, and inappropriate trypsinogen activation. Trypsinogen autoactivates in the acinar cells and progresses to macrophages, which also activate trypsinogen via cathepsin B. This increases the severity of the proinflammatory response. Interleukins have been well documented as part of the inflammatory cascade. Interleukin 6 (IL-6), IL-8, IL-1β, soluble IL-2 receptor (sIL-2R), and C-reactive protein (CRP) have been documented to correlate with the severity of pancreatitis.^21-23 IL-1β and sIL-2R levels have been shown to elevate at day 1 of presentation, while IL-6, IL-8, and CRP levels have been found to be elevated at day 3.²¹ This amplification initiates a systemic response. The importance of the final pathway of inciting a proinflammatory response can be seen in the development of ameliorating strategies, such as in the use of rectal indomethacin with aggressive hydration.²⁴