1. Al-Qassim University Faculty of Medicine Phase II – Year III GIT Block (CMD332) EXOCRINE PANCREASE Lecture Dr. Gamal Hamra Wednesday 01/12/1430 (18/11/2009)

2. Describe etio-pathogenesis and morphology of: Acute and chronic pancreatitis Carcinomas of the exocrine pancreas

4. Acute Pancreatitis Etiologic Factors Metabolic Alcoholism Drugs (e.g., thiazide diuretics) Mechanical Trauma Gallstones Iatrogenic injury ( Perioperative injury, Endoscopic procedures with dye injection) Vascular Shock Atheroembolism Infectious Mumps Coxsackievirus

5. Acute Pancreatitis Activation of pancreatic enzymes → autodigestion of the gland. Abdominal pain + raised levels of pancreatic enzymes (amylase and lipase) Mild (acute interstitial pancreatitis), edema & inflamation Severe ( acute hemorrhagic pancreatitis), extensive hemorrhage 80% associated with cholelithiasis & alcoholism.

6. Pathogenesis of acute pancreatitis

7. Morphology of Acute Pancreatitis –Leakage of the vasculature to cause edema –Necrosis of regional fat by lipolytic enzymes –Acute inflammatory reaction –Proteolytic destruction of the pancreatic substance –Destruction of the blood vessels with subsequent interstitial hemorrhage

8. Acute pancreatitis : hemorrhage & fat necrosis

9. Acute pancreatitis : fat necrosis, adipose tissue & hemorrhage

10. Chronic Pancreatitis Etiologic Factors Long-term alcohol abuse Long-standing pancreatic duct obstruction (pseudocysts, calculi, neoplasms) Tropical pancreatitis (malnutrition) Hereditary pancreatitis (gene mutation)

11. Chronic Pancreatitis Repeated bouts of mild to moderate pancreatic inflammation → loss of pancreatic parenchyma & replacement by fibrous tissue. → loss of pancreatic function CT scan ( pancreas hard with foci of calcifications) Fibrosis  number & size of acini Sparing of the islets of Langerhans Obstruction of pancreatic ducts

12. Chronic pancreatitis : pancreas (P) atrophic and replaced by rubbery, fibrous tissue, dilated ducts (D), duodenum (A)

13. Chronic pancreatitis : fibrous tissue, dilated ducts & residual acinar tissue

14. Clinical features Chronic pancreatitis Silent or recurrent attacks of pain Precipitated by alcohol abuse, overeating & drugs Mild  serum amylase and lipase, Late complications include: –Diarrhea (malabsorbtion) –Steatorrhea –Diabetes –Pseudocyst

15. Carcinoma of the Pancreas Arising from ductal epithelial cells (adenocarcinoma). Common cause of death in the US Poor prognosis Alcohol consumption increased risk 65 - 80 Y More in men and blacks

16. Development of pancreatic cancer : 1- K-RAS oncogene mutations (early stages) 2- p16 tumor suppressor gene inactivation (intermediate stages) 3- p53& BRCA2 tumor suppressor genes inactivation ( late stages) ( Multiple mutations is more important )

17. Morphology of pancreatic cancer Distribution is as follows: –Head 60% –Body 15% –Tail 5% –Diffuse or widely spread 20% Tumors may be small and ill defined or large (8-10 cm), with extensive local invasion and regional metastases. Microscopically, more or less differentiated glandular patterns (adenocarcinoma) arise from ductal epithelium, mucous or non-mucous secreting.

18. Carcinoma of the head of the pancreas T umours appear as gritty, grey, hard nodules (T), irregularly invading the adjacent gland and local structures

19. Carcinoma of the pancreas. Poorly formed glands in densely fibrotic stroma, inflammatory cells

20. Diagnosis of Carcinoma of pancreas Tumor markers : CEA, CA 19-9 & CA 125 CT, MRI, US & ERCP Cytologic and histologic specimen