Chapter 19- Pancreas Flashcards
Which cells in the pancreas are responsible for the majority of secreted enzymes and what is the that percentage
Acinar cells account for 80-85% of exocrine (digestion) enzymes
How does the embryological origin of the pancreas lead to congenital abnormalities
- Ventral outpouch gives rise to posterior head/main pancreatic duct
- Dorsal outpouch gives rise to body, tail, superior head/accessory duct
What is the most common congenital abnormality of the pancreas
Pancreas divisium
What is occurring during the process of pancreas divisium formation
Failure of the fetal systems of the ventral and dorsal out-pouches do not fuse
What is the structural abnormality and result of pancreas divisium
Because the ducts do not form, the majority of the pancreatic secretions drains in the duodenum drains through the minor papilla and not through the duct of Wirsung like normal
What is the clinical consequences as a result of pancreas divisum
Increased susceptibility to acute pancreatitis and subsequent chronic pancreatitis
What is annular pancreas
Band like ring of normal pancreatic tissue that completely surrounds the second part of the duodenum
What is the clinical consequence of annular pancreas
Produces duodenal obstruction
What is the gene commonly seen when there is pancreatic agenesis
PDX1
What is the state of reversibility of acute pancreatitis
Reversible
What are the two major pathways of acute pancreatitis and what percentage of cases seen do they make up
80% of cases are:
- Biliary tract disease
- Alcoholism
What is the gender ratio of biliary tract disease causing acute pancreatitis
3:1 females
What is the gender ration of alcoholism causing acute pancreatitis
6:1 male
What is the pathogenesis that is causing acute pancreatitis
Inappropriate release and activation of pancreatic enzymes which causes an inflammatory reaction
What is the process/enzymes present during acute pancreatitis that are released prematurely
-Activation of trypsin causes the activation of phospholipases and proelastases, which damage the fat and vessel of the pancreas
How does acute pancreatitis lead to clotting and complement system involvement
Trypsin activates prelalikrein, which activates:
- Coagulation factor 7
- Complement fixation
What are the three main mechanisms involved during acute pancreatitis
1-Pancreatic duct obstruction
2-Primary acinar cell injury
3-Defective intracellular transport of proenzymes within acinar cells
What are pancreatic duct obstructions during acute pancreatitis commonly caused by
Gallstones and biliary sludge
Which two organisms can readily cause pancreatic duct obstruction
- Ascaris lumbricoides
- Clonorchis sinensis
Which enzyme is released in the activated form from the pancreas and what is the result
Lipase is secreted in the activated form, so has the potential to cause local fat necrosis
What is the result of primary acinar cell injury during acute pancreatitis
Release of digestive enzymes, oinflammation and autodigestion of pancreatic tissue
What is the trigger that is linked to the inappropriate activation of enzymes during acute pancreatitis
Calcium influx, which is the regulator of trypsin activation
How can damage of acinar cells with regards to intracellular transporting cause damage in acute pancreatitis
Proenzymes are delivered to the lysosomes, where they are activated by the hydrolases and released
What is the effect of alcohol on the pancreas
- Contraction of the sphincter of Oddi
- deposition of protein plugs
- Toxic to acinar cells
How can chronic alcoholism cause damage to the pancreas
-Deposition of protein plugs that result in obstruction of the pancreatic ducts
What is the mechanism that alcohol can cause direct toxicity to the pancreas
Damages the acinar cells, which causes inflammation,
Which metabolic conditions are known to cause acute pancreatitis
- Hypertriglycerides
- Hypercalcemic
- HyperPTH
Which drugs are known to cause acute pancreatitis
- Furosemide
- azathioprine
- 2,3-dideoxyinosine
- Estrogens
Which infections are known to cause acute pancreatis
Mumps (damages acinar cells)
What is the main underlying factor that is seen in Hereditary forms of acute pancreatitis
-Defect that causes the increased activation or sustained activity of trypsin
Most hereditary cases of acute pancreatitis are caused by what kind of mutations and in which gene
Gain of function in the trypsinogen gene (aka PRSS1)
What is the lifelong risk percent of hereditary pancreatitis
40%
What are iatrogenic injuries that can cause acute pancreatitis
- Operative injury
- Endoscopic procedure with dye injection
What are the vascular events that can cause acute pancreatitis
- Shock
- Atheroembolism
- Vasculitis
What is the most common cause of hereditary cases and what is the pattern of inheritance
- Gain of function mutation in PRSS1 (aka trypsin)
- Autosomal dominant
What are the histological morphologies seen in acute interstitial pancreatitis, and what is the cause
-Fat necrosis (lipase caused), which combine with calcium to form granular blue fat cells
What are the histological morphologies seen in acute necrotizing pancreatitis, and what is the cause
Substance is red-black from the hemorrhage, with white chalky fat necrosis scattered within
During acute necrotizing pancreatitis, what is a seconadary area commonly affected and morphologically what is seen there
-Peritoneal cavity contains serous, turbid, brown tinges fluid containing fat globules
What is the cardinal manifestation of acute pancreatitis
-abdominal pain
How is the pain during acute pancreatitis characterized
-constant but intense pain in the upper back, sometimes including the left shoulder
What are the diagnostic features seen for acute pancreatitis
Elevated lipase (72 to 96 hours) and amylase (first 24 hours) in the plasma
What are the systemic consequences that are possible due to acute pancreatitis
- DIC
- Acute respiratory distress
- acute renal tubular necrosis
What is the management plan taken with acute pancreatitis
Resting the pancreas but restriction of oral intake, IV fluids, and analgesia
What is a major complication secondary to acute pancreatitis and what is the percentage
40-60% develop gram negative infection of the necrotic debris
What is the state of reversibility in chronic pancreatitis
Irreversible
What is the most common cause of chronic pancreatitis
Alcohol abuse
What are the very general features seen in chronic pancreatitis
Irreversible damages of the exocrine parenchyma and fibrosis. The endocrine may be involved in late stages
Which immunological cytokines are predominately involved in chronic pancreatitis
TGF-beta
Platelet-derived growth factor
What is the immunological effect seen in chronic pancreatitis
-TGF beta and PDGF causes proliferation of pariacinar myofibroblasts that result in fibrosis and collagen Deposition
During autoimmune pancreatitis, what is commonly associated
IgG4 secreting plasma cells in the pancreas
What condition may be mimicked by autoimmune pancreatitis, and what is the way to determine
Autoimmune pancreatitis mimics pancreatic carcinoma, but will actually respond to steroid therapy
Morphologically, how is chronic pancreatitis characterized
- ductal dilation and intraluminal protein plugs and calcification
- Dilated ducts
- Acinar loss
What are some triggers of attacks for chronic pancreatitis
- Alcohol ingestion
- overeating
- Opiates/drugs (increased tone of sphincter of Oddi)
What is the long term prognosis for patients with chronic pancreatitis
Poor
What are the clinical features of chronic pancreatitis that normally lead to morbidity and mortality
- Exocrine insufficiency
- Chronic malabsorption
- diabetes mellitus
What are the general characteristics of congenital cysts
Unilocular, thin-walled cysts that develop from the anomalous development of the pancreatic ducts
Congenital cysts usually contain which kind of fluid
Clear, serous fluid
Which two conditions are commonly associated with the formation of congenital cysts
- Von Hippel-Lindau
- Polycystic kidney disease
Congenital cysts located in the kidney, liver and pancreas are commonly associated with which condition
-Autosomal dominant polycystic kidney disease
Congenital cysts located in the pancreas, liver, and pancreas, along with neoplasms in the retina, cerebellum/Brian stem are commonly associated with which condition
Von-Hippel Lindau
What are the general characteristics of pseudocysts
-Collections of necrotic and hemorrhagic material with pancreatic enzymes and lacking epithelial lining
What is the common form of cysts seen in the pancreas
Pseudocysts (75%)
When do pseduocysts commonly occur
Following bouts of acute pancreatitis
What is the complications that arise form pseudocysts
-Spontaneously resolve, but can become infected or impinge on other structures
Which percentages of pancreatic cysts are neoplastic
5-15%, most are pseudocysts
What is the common location fo serous cystic neoplasms
Tail of the pancreas
What are the serous cystic neoplasms containing
-Glycogen rich cuboidal cells, containing clear, thin, straw colored fluid
Which population is most commonly seen to contain serous cystic neoplasms
-Females between 60 and 70
What is the prognosis of patients with serous cystic neoplasms
-Almost always benign and resection is curative
Which gene is commonly seen in serous cystic neoplasm
Inactivation of VHL
What is the patient population see to contain mutinous cystic neoplasm
95% female
What is the location that contains mutinous cystic neoplasms
Tail of the pancreas
What are the physical characteristics of the mucinous cystic neoplasm
Large cystic cavities containing mucin and lined with columnar mucin producing epithelium with a thick “ovarian” stroma
What percentage of mucinous cystic neoplasm contain invasive adenocarcinoma
1/3
What is the prognosis in those patients with mucinous cystic neoplasms
Not good, as half of the 1/3 of patients with invasive adenocarcinoma from their mucinous cystic neoplasm will die
Which genes are commonly mutated in mucinous cystic neoplasm
KRAS and TP53
What is the location that intraductal papillary mucinous neoplasms (IPMNs) are commonly found
Larger ducts of the head of pancreas
Which patient population is affected by intraductal papillary mucinous neoplasms (IPMNs)
Male
What are the distinguishing features of IPMNs that allow it to be differentiated from other mucinous cysts
- Absence of “ovarian stroma”
- Involvement of the pancreatic duct
What is the prognosis of intraductal papillary mucinous neoplasms (IPMNs)
Can developing into invading adenocarcinoma
What are the genes commonly associated with IPMNs
GNAS, KRAS, TP53, SMAD4, RNF43
Which patient population is commonly infected with solid-pseudopapillary neoplasms
Young women
What are the physical characteristics of solid-pseudopapillary neoplasms
Large, well circumcribed malignant cyst with hemorrhagic contents
-Grow in solid sheets but are poorly cohesive
What are the clinal signs of a solid-pseudopapillary neoplasm
-Abdominal discomfort due to their large size
Which gene is almost always associated with the solid-pseudopapillary neoplasm
Hyper-activation of WNT signaling due to CTNNB1 (Beta-catenin)
What is the prognosis of solid pseudopapillary neoplasms
Good, as they are only locally invasive, most are cured by surgical resection
What is the prognosis in patients with infiltrating ductal adenocarcinoma
Aka pancreatic cancer
-Highest mortality of any cancer
What are invasive pancreatic cancers believed to arise from
Well defined pancreatic intraepithelial neoplasms (aka PanIN)
What is the relation of telomere length in PanIN
Dramatic shortening of the telomere length
What is the order genetic abnormalities that allow the change from PanIN to invasive carcinoma
1-Telomere shortening, KRAS activation
2-Inactivation of CDKNA2
3-Inactivation of TP53, SMAD4, BRCA2
What is the most commonly mutated oncogene in pancreatic cancer and what percent
KRAS in 90-95%
Which pathway is activated through mutations in KRAS
MAPK and PI3K/AKT
-aka growth factor pathway and tyrosine kinase
What is the most commonly inactivated tumor suppressor gene in pancreatic carcinomas and which percentage
CDKNA2/p16 in 95%
What is the result of a loss of function in p16/CDKN2A
Loss of the cell cycle regulator
What are the three tumor suppressor genes that are commonly associated with transition from PanIN to carcinoma
- CDKN2A (95%)
- SMAD4 (55%)
- TP53 (75%)
What role does SMAD4 mutation have in the transition from PanIN to carcinoma in the pancreas
TGFBeta pathway is activated
Which carcinoma is most likely if diagnosis markers comes back with mutations in SMAD4
Pancreatic carcinoma (rarely seen out of this cancer)
Activation of which genetic signaling pathway is activated in pancreatic carcinoma
Hedgehog signaling pathway
Which patient population is commonly affected by pancreatic carcinoma
60-80 year old, black or ashkenazi jew
What is the strongest environmental influence on pancreatic cancer and what is the increased risk
Smoking, and doubles the risk
What are the preexisting conditions that are risk factors for pancreatic cancer
- DM
- Acute pancreatitis
What is a first sign that may arise in a patient with pancreatic carcinoma
Diabetes mellitus in older patients
Which genetic factor seems to be involved in the development of pancreatic carcinomas, especially in Ashkenazi Jews
BRCA2
Families with increase in which cancer is commonly developing pancreatic carcinomas, and what is the reasoning
Melanomas due to CDKN2A loss of function mutations
What portion of the pancreas is the common location for the formation of cancers
Head of the pancreas
What are the two morphological distinguishing features of pancreatic adenocarcinoma
- Highly invasive
- intense host reaction with dense fibrosis (aka desmoplastic response)
What are the common morphologies seen in ductal adenocarcinomas in the head of the pancreas
-Obstruction of the biliary tree, leading to distention and development of jaundice
What is the prognosis and time of discovery of pancreatic adenocarcinomas in the tail of the pancreas
Very bad and late because there is no obstruction of the biliary tree
What are the common sites of metabolism for ductal adenocarcinomas
Liver, lungs, nerves, and blood vessels
