The pancreas is a gland organ. It is located in the abdomen. It is part of the digestive system and produces insulin and other important enzymes and hormones that help break down foods.
- Its name has been driven from the Greek word
“Pankreas” meaning (all flesh) • It has an endocrine and exocrine function.
- Pancreas is a transversely oriented retroperitoneal organ extending from the “C” loop of the duodenum to the hilum of the spleen.
- It is 20cm in length weighting 85 to 90gm.
- Pancreas has a body and a tail.
- The main pancreatic duct is known as the duct of wirsung.
- Which drain into the duodenum at the papilla of vater.
- Its accessory pancreatic duct is known as the duct of Santorini.
- Embryologically it arises from the fusion of dorsal and ventral outpouchings of the foregut.
- The endocrine portion is composed of about one million clusters of cells, the islets of Langerhans which secrete…
- The exocrine part is composed of acinar cells that produce enzymes for digestion.
- ▫ Amylase
- Lipase & some proenzymes (Trypsinogen, Chymotrypsinogen, Proelastase etc…)
PATHOLOGICAL LESIONS OF PANCREAS
EXCOCRINE PART OF PANCREAS
- Acute pancreatitis
- Chronic pancreatitis
- Serous cystadenoma
- Mucinous cystadenoma
- Intraductal papillary mucinous neoplasms (IPMNs)
- Serous cystadenocarcinoma
- Mucinous cystadenocarcinoma
- Infiltrating ductal adenocarcinoma
- A non-neoplastic cyst (pseudocyst)
- Congenital cyst
D)ENDOCRINE PART OF PANCREAS
Endocrine neoplasm (Tumours lesions)
- Insulinoma (hyperinsulinism)
- Gastrinoma (Zollinger Ellison syndrome)
- Other rares
- α –cell tumors (glucagonoma)
- δ –cell tumors somatostatinomas)
- An acute pancreatitis is a group of reversible lesions characterized by inflammation of the pancreas ranging in severity from edema and fat necrosis to parenchymal necrosis with severe hemorrhage.
- Drugs (e.g. thiazide diuretics)
- Iatrogenic injury
- Preoperative injury
- Endoscopic procedures with dye injection
- Polyarteritis nodosa
- Mycoplasma pneumonia
LESS COMMON CAUSES OF ACUTE PANCREATITIS
- Obstruction of the pancreatitis duct.
- Inherited alterations genes including germline mutations.
- 10% to 20% unknown (Idiopathic)
- Autodigestion of the pancreatic by inappropriate activated pancreatic enzymes leading to inflammation small vessel thrombosis resulting in activation of trypsinogen which is an important triggering event in acute pancreatitis.
- Pancreatic duct obstruction leading to leakage of lipase causing focal fat necrosis resulting in periacinar inflammatory reaction.
- Primary acinar cell injury.
- Defective intracellular transport of proenzyme.
PROPOSED PATHWAY IN PATHOGENESIS
- Microvascular leakage causing edema.
- Necrosis of fat by lipolytic enzymes.
- Acute inflammatory reaction.
- Proteolytic destruction of pancreatic parenchyma.
- Destruction of blood vessels with subsequent interstitial hemorrhage.
In severe cases…
- Acute necrotizing pancreatitis a fact acinar and ductal tissue as well as islets of Langerhans leading to…
▫ Red black hemorrhage with chalky fat necrosis found in the omentum and the mesentery resulting in
- Medical emergency presenting severe abdominal pain (Acute Abdomen)
- Systemic effects.
- Disseminated intravascular coagulation (DIC)
- Acute respiratory syndrome
- Diffuse fat necrosis
- Vascular collapse leading to shock with acute renal tubular necrosis.
- Elevation of serum amylase within 1st 24 hours.
- Increased serum lipase level within 72 hours.
- Hypocalcemia resulting from precipitation of calcium sops in fat necrosis.
- Direct visualization of the enlarged inflamed pancreas by ultrasound and CT.
ACUTE PANCREATITIS GROSS
ACUTE PANCREATITIS MICROSCOPIC
PANCREATIC PSEUDOCYST, GROSS
- Inflammation of pancreas with the destruction of exocrine parenchyma, fibrosis & destruction of endocrine parenchyma.
- Long term alcohol abuse is usually seen in middle age males.
- Less common causes
▫ Long-standing obstruction of the pancreatic duct by pseudocysts, calculi, trauma, neoplasms.
▫ Tropical pancreatitis is seen in Africa & Asia due to malnutrition.
▫ Hereditary pancreatic & idiopathic
- Ductal obstruction by concretions due to high level of protein needs to ductal which may calcify & form calculi which obstructs the pancreatic duct.
- Toxic metabolic toxins including alcohol exert a direct toxic effect on acinar cells leading to the accumulation of lipids resulting in fibrosis of acinar cells.
- Oxidative stress promotes the fusion of lysosomes & zymogen granules, acinar cell necrosis, inflammation & fibrosis.
- Necrosis-fibrosis repeated episodes of acute pancreatitis need for chronic pancreatitis.
COMPARISON OF SEQUELAE OF ACUTE AND CHRONIC PANCREATITIS
- Paranchymical fibrosis sparing islets of Langerhans.
- Dilation of pancreatic duct grossly gland is hard & some time calcified.
- Microscopically interlobular and interlobular ducts are dilated and contain protein plugs.
- Ductal epithelial may be atrophied or hyperplastic or may show squamous metaplasia.
- Moderate to severe abdominal pains.
- Back pain.
- Diabetes militias due to pancreatic insufficiency.
- Attack of jaundice.
- Vague attack of indigestion.
- Increase the level of serum amylase
- Low level of albumin.
- Increase level serum bilirubin.
SEROUS CYST ADENOMA
MUCINOUS CYST ADENOMA
(Infiltrating Ductal Adenocarcinomas)
- 4th leading cause of cancer death in the USA. • The highest mortality rate of any cancer
- 5-year survival rate is < 5%.
Precursors pancreatic cancer:-
- Progression in pancreas from non-neoplastic epithelium to histologically well-defined noninvasive lesions in small ducts and ductules to invasive carcinoma (pancreatic intraepithelial neoplasias “PanINs”)
- PanINs are found in pancreatic parenchyma adjacent to infiltrating carcinoma
- It is a genetic disease (disease of inherited & acquired mutations in cancer-associated genes)
- K-RAS gene (chromosome 12p) is the most frequently altered oncogene in pancreatic cancer
(80% to 90%)
- P16 gene (chromosome 9p) is the most frequently inactivated tumor suppressor gene
- Inactivation of P53 tumor suppressor gene (chromosome 17p) is seen in 50% – 70% of patients.
- SMAD4 is inactivated in 55% of pancreatic CA.
- Other genes.
▫ AKT2 (10% – 20%). MYB gene (6q) in 10%
▫ BRCA2, AIB1, MKK4, TGFβ-R1, TGFβ-R2.
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- The disease of elderly people usually seen between the ages of 60 to 80.
- More common in blacks as compared to white.
- Environmental influence (smoking) is believed to be double the risk of pancreatic carcinoma.
- Fat rich diet is another contributed factor.
- Chronic pancreatitis with a history of smoking and alcohol has a strong association with carcinoma.
- Minor factor includes diabetes mellitus, familial clustering & number of inherited genetic syndromes.
- 60% of cancer arises from the head of the gland.
- 15% form body & 5% form tail.
- 20% involving the entire gland.
- The majority of the pancreatic carcinoma is ductal adenocarcinoma having a feature of …
- Gland formation
- mucin secretion
- Peripancreatic tissue invasion.
- Intense non-neoplastic host reaction comprising of fibroblast, lymphocytes & extracellular matrix (desmoplastic response)
▫ Mostly there is obstruction of common bile duct leading to distention of biliary tree.
▫ Locally invade to spleen, adrenals vertebral column, transverse colon & stomach.
▫ Peripancreatic, gastric, mesenteric, omental, & porta hepatic lymph nodes are involved.
▫ Distant metastatic involve lungs & bones.
- moderately to poorly differentiated adenocarcinoma reveal.
- Abortive tubular structures
- Cell cluster and aggressive infiltrating growth
- Lymphatic invasion is also seen
- Malignant glands are atypical, irregular, small & bizarre-looking lined by anaplastic epithelial cells.
- Rare variants are…
- Acinar cell carcinoma, adenosquamous carcinoma & undifferentiated carcinoma with osteoclast-like giant cells.
- Obstructive jaundice in most of the cases.
- Weight loss, anorexia & generalized malaise
- Migratory thrombophlebitis (Trousseau sign) in 10% cases due to the elaboration of platelet aggregating factors & procoagulant form the tumor are its necrotic products.
- < 20% pancreatic cancer is resectable at the time of diagnosis.
- Endoscopic ultrasonography & CT have great importance in diagnosis & performance of percutaneous needle biopsy.
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