1. Pathology and pathogenesis of acute and chronic pancreatitis
Dr. Mamlook Elmagraby

2. Objectives of the lecture:
Upon completion of this lecture, students should be able to: Recognize the predisposing factors of pancreatitis Understand the pathogenesis of acute and chronic pancreatitis Describe the different types of pancreatitis

3. Acute Pancreatitis

4. Acute Pancreatitis
Pancreatitis is inflammation in the pancreas associated with injury to the exocrine parenchyma Acute pancreatitis is reversible pancreatic parenchymal injury associated with inflammation The clinical manifestations range in severity from a mild to a life-threatening process Biliary tract disease and alcoholism account for approximately 80% of acute pancreatitis cases

5. Hyperlipoproteinemia Hypercalcemia Drugs (e.g., azathioprine)
METABOLIC
Alcoholism
Hyperlipoproteinemia
Hypercalcemia
Drugs (e.g., azathioprine)
GENETIC
Cationic trypsinogen (PRSS1) gene
Trypsin inhibitor (SPINK1) gene
MECHANICAL   
Gallstones
Trauma
Iatrogenic injury
VASCULAR
Shock
Atheroembolism
Vasculitis
INFECTIOUS
Mumps
Etiologic Factors in Acute Pancreatitis

7. Acute Pancreatitis Morphology The basic alterations are:
Acute inflammation
Microvascular leakage causing edema
Necrosis of fat by lipolytic enzymes
Proteolytic destruction of pancreatic parenchyma
Destruction of blood vessels and interstitial hemorrhage
The extent of these alterations depends on the duration and severity of the process

8. Acute Pancreatitis In the milder form, there are: Mild inflammation
Interstitial edema
Focal areas of fat necrosis
In the more severe form:
The acinar, ductal, the islets of Langerhans cells are necrotic
Areas of red-black hemorrhage interspersed with foci of yellow- white, chalky fat necrosis
A serous, turbid, brown-tinged fluid in the peritoneal cavity
In the most severe form (hemorrhagic pancreatitis) :
Extensive parenchymal necrosis accompanied by massive hemorrhage within the substance of the gland can occur

9. Acute pancreatitis.
The pancreas has been sectioned longitudinally to reveal dark areas of hemorrhage in the head of the pancreas and
a focal area of pale fat necrosis in the peripancreatic fat (upper left) 

10. Acute pancreatitis.
The microscopic field shows a region of fat necrosis on the right and
focal pancreatic parenchymal necrosis (center) 

11. Acute Pancreatitis Clinical Features
Abdominal pain is the cardinal manifestation of acute pancreatitis
Suspected acute pancreatitis is diagnosed by:
↑ plasma levels of amylase and lipase
The exclusion of other causes of abdominal pain
Severe acute pancreatitis is a medical emergency
Direct visualization of the enlarged inflamed pancreas by radiography is useful

12. Acute Pancreatitis
The systemic features of severe disease can be due to release of toxic enzymes, cytokines, other mediators into the circulation Explosive activation of the systemic inflammatory response → leukocytosis, hemolysis, DIC, ARDS and diffuse fat necrosis Shock with acute renal tubular necrosis may occur Most individuals with acute pancreatitis recover completely 5% with severe acute pancreatitis die from shock

13. Acute Pancreatitis Sequelae can include: a pancreatic pseudocyst
The necrotic debris becomes infected

14. Chronic Pancreatitis

15. It is as inflammation of the pancreas with:
irreversible destruction of exocrine parenchyma
Fibrosis
the destruction of endocrine parenchyma (late stages)
The cause of chronic pancreatitis include:
long-term alcohol abuse
Long-standing obstruction of the pancreatic duct
Tropical pancreatitis
Hereditary pancreatitis
CFTR gene mutations

16. Chronic Pancreatitis It is as inflammation of the pancreas with:
irreversible destruction of exocrine parenchyma
Fibrosis
the destruction of endocrine parenchyma (late stages)
The cause of chronic pancreatitis include:
long-term alcohol abuse
Long-standing obstruction of the pancreatic duct
Tropical pancreatitis
Hereditary pancreatitis
CFTR gene mutations

17. Chronic Pancreatitis Pathogenesis
The events that lead to the development of the disease include:
Ductal obstruction by concretions
Toxic effects
Oxidative stress
Several chemokines have been identified in chronic pancreatitis (IL-8, MCP, TGF-β, PDGF)
The profibrogenic chemokines tend to predominate in chronic pancreatitis

18. Comparison of the mediators in acute and chronic pancreatitis.
In acute pancreatitis acinar injury results in release of proteolytic enzymes, leading to a cascade of events including activation of the clotting cascade, acute and chronic inflammation, vascular injury, and edema.
In most patients, complete resolution of the acute injury occurs with restoration of acinar cell mass.
In chronic pancreatitis, repeated episodes of acinar cell injury lead to
the production of profibrogenic cytokines such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF),
resulting in the proliferation of myofibroblasts, the secretion of collagen, and remodeling of the extracellular matrix (ECM).
Repeated injury produces irreversible loss of acinar cell mass, fibrosis, and pancreatic insufficiency

19. Chronic Pancreatitis Morphology
Grossly, the gland is hard, sometimes with dilated ducts and visible calcified concretions
Chronic pancreatitis is characterized by:
parenchymal fibrosis
reduced number and size of acini
dilation of the pancreatic ducts which may contain protein plugs in their lumens
atrophied or hyperplastic or metaplastic ductal epithelium
a chronic inflammatory infiltrate around lobules and ducts
relative sparing of the islets of Langerhans

20. Chronic pancreatitis.
A, Extensive fibrosis and atrophy has left only residual islets (left) and ducts (right), with a sprinkling of chronic inflammatory cells and acinar tissue.
B, A higher power view demonstrating dilated ducts with inspissated eosinophilic ductal concretions in a person with alcoholic chronic pancreatitis

21. Chronic Pancreatitis Clinical Features
Chronic pancreatitis may present in many different forms:
repeated attacks of abdominal pain
persistent abdominal and back pain
pancreatic insufficiency
diabetes mellitus
The long-term outlook for individuals with chronic pancreatitis is poor

22. Chronic Pancreatitis
Patients with hereditary pancreatitis have a 40% lifetime risk of developing pancreatic cancer
Pancreatic pseudocysts develop in about 10% of patients