Term
| what is acute pancreatitis? |
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Definition
| injury to the *exocrine parenchyma*, which ranges from mild-severe. if the insulting agent is removed, the pancreas can return to normal (only for acute). |
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Term
| what characterizes the incidence of acute pancreatitis? what is often involved in its etiology? |
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Definition
| it is fairly common and associated with biliary tract disease. alcohol abuse accounts for most US cases. gallstones are often present and may or may not be involved in the etiology. obstruction of the pancreatic duct system, neoplasms, parasites and biliary sludge are other possible causes. |
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Term
| what are some medications associated with acute pancreatitis? |
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Definition
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Term
| can mumps lead to acute pancreatitis? |
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Definition
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Term
| can metabolic disorders lead to acute pancreatitis? |
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Definition
| yes, specifically hypertriglyceridemia and hyperparathyroidism |
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Term
| what kinds of trauma are associated with acute pancreatitis? |
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Definition
| blunt abdominal trauma and iatrogenic injury. also ischemic injury from shock, vascular thrombosis, embolism and vasculitis. |
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Term
| what is associated with acute pancreatitis genetically? |
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Definition
| inherited mutations in genes encoding for pancreatic enzymes/their inhibitors such as cationic trypsinogen (PRSS1) and trypsinogen inhibitor (SPINK1) genes |
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Term
| what is the pathophysiology of acute pancreatitis? |
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Definition
| autodigestion of the pancreas due to inappropriate activation of pancreatic enzymes. trypsin may activate prophospholipase and proelastase which degrade fat cells and destroy the elastic fibers of *blood vessels (risk of hemorrhage). trypsin also converts prekalikrein to its activated form, initiating the actions of the kinin system and activating factor XII (hageman factor), and thus the clotting/complement systems. *usually centers around trypsin. |
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Term
| what is hereditary pancreatitis? |
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Definition
| recurrent attacks of severe pancreatitis, often starting in childhood usually due to mutations in the cationic trypsinogen gene (PRSS1) which causes an alteration on the gene needed for inactivation of trypsin by itself. this results in trypsin being inappropriately activated, resulting in activation of digestive proenzymes. a mutation in the serine protease inhibitor gene SPINK1 which codes for a pancreatic secretory trypsin inhibitor may also be involved. |
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Term
| what characterizes pancreatitis? |
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Definition
| findings may range from mild inflammation/edema (microvascular leakage) to marked necrosis and hemorrhage due to release of lipolytic enzymes and others, leading to fat necrosis (=waxy, white material), proteolytic destruction of the pancreatic parenchyma, acute inflammation, destruction of blood vessels (= shock, death) and free fatty acids combining w/Ca++, creating insoluble salts |
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Term
| what is acute necrotizing pancreatitis? |
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Definition
| a more severe condition consisting of necrosis of the islets of langerhans/acinar/ductal tissues (*endocrine*), vascular injury with hemorrhage, and possible fat necrosis of extrahepatic fat in the omentum/mesentery/subcutaneous fat. the peritoneal cavity contains turbid, brown tinged fluid w/globules of fat. |
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Term
| what are common causes of pancreatic enzyme activation (which leads to acute pancreatitis)? |
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Definition
| pancreatic duct obstruction, primary acinar cell injury, and defective intracellular transport of proenzymes w/in acinar cells |
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Term
| what are common causes of pancreatic duct obstruction? |
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Definition
| gallstones/biliary sludge impacting in the ampulla of vater, an increase in ductal pressure causing enzyme rich fluid to accumulate in the interstitium, release of lipase (fat necrosis), injured tissues and leukocytes releasing proinflammatory cytokines causing inflammation and leaky microvasculature, and edema compressing blood vessels |
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Term
| what are common causes of primary acinar cell injury? |
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Definition
| viruses such as mumps, direct trauma to the pancreas, and ischemia/shock |
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Term
| how does defective intracellular transport of proenzymes occur in the pancreas? |
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Definition
| in acinar injury, the pancreatic proenzymes may be inappropriately delivered to the intracellular compartments containing lysosomal hydrolases, activating and releasing them |
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Term
| how can alcohol cause acute pancreatitis? |
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Definition
| chronic alcohol intake causes release of *protein rich pancreatic fluid w/deposition of protein plugs and obstruction of small pancreatic ducts. alcohol can also increase pancreatic exocrine secretion and have a direct toxic effect on acinar cells. |
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Term
| how do pts present with acute pancreatitis? |
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Definition
| abdominal pain (mild-severe) radiating to the back/L shoulder, n/v, anorexia, elevated amylase/lipase levels, and secondary hemolysis, leukocytosis, DIC, ARDS, vascular collapse, shock, and ATN |
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Term
| what are some complications of acute pancreatitis? |
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Definition
| glycosuria (problems with glucose metabolism), hypocalcemia (from precipiation of Ca++ soaps in necrotic fat), pseudocysts, and abscesses |
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Term
| what is chronic pancreatitis? |
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Definition
| inflammation of the pancreas w/*irreversible destruction of the exocrine parenchyma, fibrosis (Ca++ deposits), and late destruction of endocrine parenchyma. it is marked by irreversible impairment of pancreatic function and may be associated with repeated bouts of acute pancreatitis. the most common cause is long term alcohol abuse. |
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Term
| what are other causes of chronic pancreatitis besides alcohol abuse? |
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Definition
| long standing obstruction: trauma/stones. hereditary pancreatitis: due to germline mutations of PRSS1/SPINK1. cystic fibrosis: cystic fibrosis transmembrane conductance regulator mechanisms gene mutations which cause a *decrease in bicarb secretion by pancreatic duct cells, promoting protein plugging and chronic pancreatitis. |
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Term
| what can repeated bouts of acute pancreatitis result in? |
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Definition
| perilobular fibrosis, duct distortion, altered pancreatic secretions and eventually chronic pancreatitis |
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Term
| what characterizes the ductal destruction, toxic effects and oxidative stress seen in chronic pancreatitis? |
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Definition
| ductal destruction: an increase in protein in pancreatic fluid can plug ducts and calcify. toxic effects: alcohol and its metabolites can have a direct toxic effect on acinar cells. oxidative stress: generation of free radicals causing membrane lipid oxidation and activation of transcription factors which attract mononuclear cells. |
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Term
| how does chronic pancreatitis appear histologically? |
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Definition
| fibrotic and atrophic. ducts may be dilated as well as plugged. |
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Term
| what causes the deposition of collagen and fibrosis seen in chronic pancreatitis? |
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Definition
| chemokines, TGF-beta, PDGF which induce activation and proliferation of myofibroblasts (occurs over years) |
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Term
| what characterizes the effect of chronic pancreatitis on the pancreas? |
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Definition
| parenchymal fibrosis, reduced number of acini, *relative sparing of the islets of langerhans - which are surrounded by fibrous tissue and may fuse and *eventually disappear. there is variable dilation of the pancreatic ducts w/protein plugs and the ductal epithelium may be *atrophied or hyperplastic. chronic inflammation is seen around lobules and ducts. |
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Term
| how does a pancreas affected by chronic pancreatitis appear grossly? |
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Definition
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Term
| what is lymphoplasmacytic sclerosing pancreatitis? |
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Definition
| an autoimmune form of chronic pancreatitis w/duct centric mixed inflammatory infiltrate, venulitis, and an increased number of **plasma cells**. this can clinically mimic pancreatic CA and is treatable w/steroids. |
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Term
| what is the clinical course of chronic pancreatitis? |
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Definition
| variable, can be mild, severe or silent until DM develops. attacks may be precipitated by alcohol or overeating or the use of medications which increase the tone of the sphincter of oddi |
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Term
| how do chronic pancreatitis pts present? |
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Definition
| pts may have a fever, mild elevation of serum amylase and CT/MRI may show Ca++. |
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Term
| what is the prognosis for chronic pancreatitis? |
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Definition
| around 50% survival for 20-25 yrs |
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Term
| what are congenital cysts? |
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Definition
| these arise from anomalous development of the pancreatic ducts and are usually unilocular and thin walled (lined by a single layer of cuboidal epithelium). they vary in size and may be seen w/polycystic ovary disease and von-hippel-lindau disease. they have a thin fibrous capsule and contain serous fluid. |
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Term
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Definition
| localized, walled of areas of pancreatic hemorrhagic fat necrosis w/fibrous tissue which arise as complications of (acute) pancreatitis or trauma. these lack an epithelial lining, are usually solitary, small or large, and may develop secondary infection. the fact that they *lack a true capsule is what defines them as "pseudocysts" |
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Term
| what are the different kinds of cystic neoplasms? |
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Definition
| serous cystadenoma, mucinous, intraductal papillary mucinous (IPMNs), and solid pseudopapillary |
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Term
| what are serous cystadenomas? |
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Definition
| these are benign cysts of glandular tissue (composed of high glycogen content cells) containing clear, straw-colored fluid. serous cystadenomas are more common in women in their 60s and are almost always benign. they present as vague abdominal pain w/ or w/o palpable masses. |
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Term
| what are mucinous cystic neoplasms (adenoma)? |
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Definition
| these are larger and filled w/more turbid fluid than serous cystadenomas. most of these arise in women and *1/3 of cases are associated with invasive CA. they are lined by columnar mucin-secreting epithelium w/a dense stroma and are painless, slow-growing masses found in the body or tail. |
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Term
| what are intraductal papillary mucinous neoplasms (IPMNs)? |
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Definition
| these mucin secreting intraductal neoplasms are often found in the *head of the pancreas of *men. they can be multifocal and benign or malignant (malignant will invade tissue). IPMNs lack dense stroma and involve larger pancreatic *ducts. |
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Term
| what is a solid pseudopapillary neoplasm? |
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Definition
| these unusual, well circumscribed masses consist of solid and cystic components - the cystic portions being filled with hemorrhagic debris. they are more common in young women and tend to be large and cause abdominal pain. solid pseudopapillary neoplasms are called such b/c their neoplastic cells can grow in sheets or as papillary projections. mutations of beta-catenin are involved in activation and these can be locally aggressive, therefore sx is usually curative. |
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Term
| what is the main problem with pancreatic CA tx? |
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Definition
| there are no good screening protocols for checking on the invasive status of well defined neoplasms, or even determining if they exist |
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Term
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Definition
| pancreatic intraepithelial neoplasias: which are often found adjacent to infiltrating CA. they are seen histologically to express atypical ductal changes as well as contain the typical high n/c ratio and crowding of cells. |
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Term
| what is pancreatic CA almost always? |
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Definition
| an *infiltrating ductal adenocarcinoma* |
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Term
| what characterizes the incidence of pancreatic CA? |
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Definition
| pancreatic CA is the 4th leading cause of CA deaths in the US and has one of the highest mortality rates of any CA (5 year survival rate is <5%) |
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Term
| what is the most frequently altered genes in pancreatic CA? |
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Definition
| *K-RAS, seen in 80-90% of cases. the point mutations impair the intrinsic guanosine triphosphate activity of the K-RAS protein, causing it to *stay active, which in turn continues to activate intracellular signal transduction pathways activating transcription factors that regulate cell growth. |
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Term
| what is the role of CDKN2A(16) in pancreatic CA? |
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Definition
| this tumor suppressor gene is inactivated in *95% of pancreatic CA, where it causes the P16 protein (CDKN2A(16)) to be mutated and unable to control cell growth |
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Term
| are SMAD4 mutations related to pancreatic CA? |
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Definition
| yes, SMAD4, a tumor suppressor gene is inactivated in 55% of pancreatic CA. |
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Term
| are p53 mutations involved in pancreatic CA? |
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Definition
| yes, ~50-70% of the time this nuclear DNA-binding protein which acts as a cell-cycle checkpoint (induces apoptosis/senescence) is mutated in pancreatic CA |
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Term
| what are risk factors for pancreatic CA? |
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Definition
| pancreatic CA is more common in elderly black folks. cigarette smoking increases risk x2. a diet high in fat, alcohol abuse, DM and chronic pancreatitis are also all risk factors. |
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Term
| what characterizes pancreatic CA morphologically? |
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Definition
| most pancreatic CA arises in the head, and appears as a hard, stellate/grey-white poorly defined mass w/glands and mucin. pancreatic CA is highly invasive and elicits an intense desmoplastic reaction. |
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Term
| why do most pancreatic CA pts develop jaundice? why might this be a good thing? |
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Definition
| lesions in the head of the pancreas may obstruct the common bile duct - leading to jaundice, which can be good as it alerts the pt/dr. lesions in the body and tail may not cause jaundice and thus may remain undiagnosed for longer. |
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Term
| how do most pancreatic CAs appear upon dx? |
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Definition
| large and disseminated, often growing along the nerves (painful) and invading the retroperitoneum. |
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Term
| how does pancreatic CA appear histologically? |
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Definition
| irregular, abnormal glands w/lining cells that are large/fibroblastic (desmoplastic response around glands) |
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Term
| where does pancreatic CA often metastasize? |
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Definition
| to the liver, lungs, and bones. large vessel and lymphatic invasion is common. |
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Term
| what are the symptoms of pancreatic CA? |
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Definition
| pain (usually 1st), obstructive jaundice, wt loss, anorexia, and weakness. the *trousseau sign*: (migratory thrombophebitis due to elaborations of platelet-activating factors/procoagulants. |
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Term
| what is the course of pancreatic CA? |
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Definition
| brief and progressive. less than 20% are resectable at the time of dx. |
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Term
| what are some available pancreatic CA screening tools? |
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Definition
| CEA and CA19-9 (not that great yet) |
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Term
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Definition
| another kind of pancreatic CA w/prominent acinar cell differentitation. acinar cell CA is characterized by formation of *zymogen granules and *production of trypsin & lipase. acinar cell CA may develop the syndrome of metastatic fat necrosis from the release of lipase into circulation. |
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Term
| what is a pancreatoblastoma? |
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Definition
| a rare lesion, usually seen in children between 1-15 yrs old (blastoma = younger). pancreatoblastomas are malignant *squamous islands* mixed with acinar cells. |
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