Disorders of the Exocrine Pancreas Flashcards
- The pancreas extends from the “C” loop of the duodenum to the hilum of the spleen. In adults, the pancreas is approximately 20 cm in length and weighs 85 (females) to 90 (males) gm.
- It can be separated into the head, neck, body, and tail regions.
- The pancreatic duct system is highly variable.
- The main pancreatic duct is also known as the duct of Wirsung. The duct of Wirsung joins the common bile duct to form the ampulla of Vater; drainage is via the papillae of Vater.
- The accessory pancreatic duct is also known as the duct of Santorini and drains through a separate minor papillae approximately 2 cm proximal to the papilla of Vater.
Pancreas
- While the pancreas gets its name from the Greek pancreas, [meaning, “all flesh”], it is a complex lobulated organ composed of both endocrine and exocrine components.
- The exocrine pancreas comprises approximately 80-85% of the pancreas.
- The exocrine pancreas is composed of acinar cells, which produce the enzymes necessary for digestion, and ductular epithelial cells, which produce bicarbonate.
Proenzymes Secreted by the Acinar Cells
- trypsinogen
- chymotrypsinogen
- procarboxypeptidase
- proelastase
- kallikreinogen
- phospholipase A and B
- also secretes amylase and lipase
Agenesis of the Pancreas
- congenital
- Agenesis of the pancreas is a rare condition of complete absence of the pancreas.
- Pancreatic agenesis is usually associated with other malformations that are usually incompatible with life.
- PDX1 (pancreatic and duodenal homeobox-1 gene) encodes a transcription factor crucial for pancreatic development.
Pancreas Divisum
- congenital
- Pancreas divisum is the most common congenital anomaly of the pancreas, with an incidence of 3-10%.
- It is caused by a failure of fusion of the fetal duct system of the dorsal and ventral pancreatic primordial. The result is that the bulk of the pancreas drains through the dorsal pancreatic duct and the small caliber minor papilla.
- The duct of Wirsung is shorter and drains a portion of the pancreatic head through the larger caliber papilla of Vater.
- Individuals with this anomaly may be predisposed to chronic pancreatitis.
Annular Pancreas
- congenital
- Annular pancreas is a band-like ring of normal pancreatic tissue that encircles the second portion of the duodenum.
- Abnormalities in migration of the ventral bud
- Annular pancreas is often associated with other anomalies.
- Annular pancreas may present in childhood or adulthood as duodenal obstruction.
-infancy or more commonly 4th or 5th decade of life
- frequently asymptomatic
- in adults there may be
- upper abdominal clicky pain
- postprandial fullnes
- vomiting
- higher incidence of pancreatitis
- peptic ulcers may develop
Ectopic Pancreas
- Ectopic pancreas occurs when normal pancreatic tissue is aberrantly situated.
- The most common sites of ectopic pancreas are the stomach and duodenum followed by the jejunum, Meckel diverticulum, and ileum.
- These are embryologic rests that are situated within the submucosa.
- Ectopic pancreatic is composed of normal appearing acinar cells and occasionally islets of Langerhans. These are usually incidental findings.
- present in approximately 2% of autopsies
Acute Pancreatitis
- reversible pancreatic parenchymal injury associated with inflammation
- the exocrine tissue can return to normal function if the underlying cause of pancreatitis is removed
- Common – annual incidence of 10-20 cases/100,000 in Western countries
- Biliary tract disease and alcohol account for 80% of cases
- Male : female
- Biliary tract disease (gallstones): 1:3
- Alcohol: 6:1
Acute Pancreatitis Causes
- Causes can be due to duct obstruction, direct acinar injury or defective intracellular transport which all lead to acinar cell injury!
- gallstones
- alcohol
- medication (azothiaprine)
- infection (mumps)
- metabolic disorders (excessive alcohol intake, hyperlipoproteinemia, hypercalcemia)
- ischemic injury (shock, vasculitis, atheroembolism)
- iatrogenic (operative injury, procedures with dye injection)
- genetic mutations (PRSS1 and SPINK1)
Less common causes of pancreatitis include:
- obstruction of the pancreatic ductal system secondary to periampullary neoplasia
- pancreas divisum
- choledochoceles (congenital cystic dilatation of the common bile duct)
- biliary sludge
- parasites (especially Ascaris and Clonorchis)
Role of Alcohol
•Alcohol consumption may cause pancreatitis through all of these mechanisms.
– Increases contraction of the sphincter of Oddi .
– Direct toxic effect on acinar cells.
– Oxidative stress promote fusion of lysosome and zymogen granules.
Hereditary Pancreatitis
- 10-20% of patients with pancreatitis have no known underlying etiology. Patients may have recurrent attacks of severe pancreatitis, beginning in childhood.
- Although the current term “idiopathic” is used, there is increased evidence that there is an underlying genetic basis, at least in some of cases.
-Most of these cases are secondary to germline mutations in the cationic trypsinogen gene (PRSS1). This mutation prevents the cleavage of trypsin, allowing activation of other proenzymes and ultimately resulting in pancreatitis.
•This mutation is inherited in an autosomal dominant fashion.
Three Mechanisms of Pancreatic Injury
1) Duct obstruction with resultant increased retrograde intraductal pressure and leakage of pancreatic enzymes into the pancreatic interstitial tissue, causing injury. The injured tissues then release proinflammatory cytokines including IL-1β, IL-6, tumor necrosis factor, platelet-activating factor and substance P. When leaked into the interstitium, lipase causes fat necrosis. Local inflammation and interstitial edema result in further compromise of local blood flow with ischemic injury to acinar cells.
2) Primary acinar cell injury is involved in acute pancreatitis secondary to excessive alcohol use, certain viruses (mumps), drugs, pancreatic trauma, and shock with ischemia.
3) Defective intracellular transport of proenzymes within acinar cells with inappropriate delivery of pancreatic proenzymes delivery to the intracellular compartment containing lysosomal hydrolases. This results in the activation of the pancreatic proenzymes and disruption of the lysozomes with acinar injury.
Gross Findings of Acute Necrotizing Pancreatitis
•Gross findings include hemorrhage, pancreatic tissue and fat necrosis and scattered areas of calcification, which appear white and chalky.
Histology of Acute Pancreatitis
- Microscopic findings include acute inflammation with injury and necrosis of the pancreatic parenchyma and fat and hemorrhage.
- Microvascular leakage causing edem
- Fat necrosis caused by lipolytic enzymes
- Acute inflammation (neutrophils)
- Proteolytic destruction of the pancreatic parenchyma
- Destruction of blood vessels with interstitial hemorrhage
Histology of Acute Pancreatitis
Histology of Acute Pancreatitis
Acute Pancreatitis - Clinical Presentation
- abdominal pain 95-100%
- epigastric tenderness 95-100%
- nausea and vomiting 70-90%
- low grade fever 70-85%
- hypotension 20-40%
- subcutaneous fat necrosis <1%
Acute Pancreatitis - Lab Results
- elevated serum/urine amylase (during the first 24 hours)
- elevated lipase (after 72-96 hours)
- hypocalcemia
Acute Pancreatitis - Radiographic Studies
Chronic Pancreatitis - Gross Pathology
•Grossly, the pancreas appears scarred and may show hemorrhage. Patchy chalky calcifications are usually seen.
Chronic Pancreatitis - Histology
- Histologic features include:
- parenchymal fibrosis
- a reduced number and size of acini with relative sparing of the islets of Langerhans
- variable dilatation of the pancreatic ducts
- intraductal protein plugs or concretions
- ductal epithelial atrophy or hyperplasia
- ductal squamous metaplasia
- chronic inflammation
Histology of Chronic Pancreatitis
Histology of Chronic Pancreatitis
Lymphoplasmacytic Sclerosing Pancreatitis
- Autoimmune pancreatitis
- Duct-centric mixed inflammatory cell infiltrate, venulitis and increased numbers of IgG4-producing plasma cells
- Responds to steroid
Pancreatic Pseudocyst
- non neoplastic
- Localized collections of necrotic-hemorrhagic material rich in pancreatic enzymes
- Lack an epithelial lining (“pseudo”)
- Very large, up to 30 cm in diameter
- Common, approximately 75% of pancreatic cysts
- Alcohol, trauma
- Solitary, may be within the pancreatic parenchyma
Serous Cystadenoma
- neoplastic
- Benign cystic neoplasm
- Glycogen-rich cuboidal cells lining small (1-3 mm) cysts containing clear (serous) fluid
- Represent 25% of all cystic neoplasms of the pancreas
- Occur 2X more often in women
- 7 th decade of life
- Present as abdominal pain or masses
- Surgical resection is curative
Mucinous Cystic Lesions
- neoplastic
- 95% in women
- Can be associated with invasive carcinoma
- Usually arise in the body or tail
- Present as painless, slow-growing masses
- Cysts are large, filled with thick mucin
- Do not connect with pancreatic ductal system
- Cysts are lined by columnar mucinous epithelium overlying an ovarian type stroma
- Pathologic evaluation for invasive malignancy after complete removal (distal pancreatectomy)
Intraductal Papillary Mucinous Neoplasm (IPMN)
- neoplastic
- Mucin-producing intraductal neoplasm
- Occur more often in men
- Occur in the pancreatic head
- 10-20% are multifocal
- Involve a larger pancreatic duct
- Evaluate for invasive malignancy after surgical resection
Solid Pseudopapillary Neoplasm
- neoplastic
- Young women
- Large, well-circumscribed with solid and cystic components
- Cystic areas filled with hemorrhagic debris
- Neoplastic cells in sheets or in papillary projections
- Present with abdominal discomfort
- Activating mutation of β-catenin
- Surgical resection is curative
Pancreatic Intraepithelial Neoplasia (PanIN)
- Precursor lesion
- Progression of normal to low-grade PanIN to high-grade PanIn to invasive carcinoma
PanIN -Gross Findings
Pancreatic Cancer - Histology
- Same histology regardless of arising in the head, body or tail of pancreas
- Highly invasive
- Intense fibroblastic response (“desmoplastic response”)
- Often grow along nerves
- Can invade lymphovascular spaces and metastasize
- Can directly invade adjacent organs or metastasize
Whipple Procedure
