Chapter 19- Pancreas Flashcards by Michael Dennis

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 well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the most common congenital abnormality of the pancreas

Pancreas divisium

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the clinical consequences as a result of pancreas divisum

Increased susceptibility to acute pancreatitis and subsequent chronic pancreatitis

How well did you know this?

Not at all

Perfectly

What is annular pancreas

Band like ring of normal pancreatic tissue that completely surrounds the second part of the duodenum

How well did you know this?

Not at all

Perfectly

What is the clinical consequence of annular pancreas

Produces duodenal obstruction

How well did you know this?

Not at all

Perfectly

What is the gene commonly seen when there is pancreatic agenesis

PDX1

How well did you know this?

Not at all

Perfectly

What is the state of reversibility of acute pancreatitis

Reversible

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the gender ratio of biliary tract disease causing acute pancreatitis

3:1 females

How well did you know this?

Not at all

Perfectly

What is the gender ration of alcoholism causing acute pancreatitis

6:1 male

How well did you know this?

Not at all

Perfectly

What is the pathogenesis that is causing acute pancreatitis

Inappropriate release and activation of pancreatic enzymes which causes an inflammatory reaction

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

How does acute pancreatitis lead to clotting and complement system involvement

Trypsin activates prelalikrein, which activates:

Coagulation factor 7
Complement fixation

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are pancreatic duct obstructions during acute pancreatitis commonly caused by

Gallstones and biliary sludge

How well did you know this?

Not at all

Perfectly

Which two organisms can readily cause pancreatic duct obstruction

Ascaris lumbricoides

- Clonorchis sinensis

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the result of primary acinar cell injury during acute pancreatitis

Release of digestive enzymes, oinflammation and autodigestion of pancreatic tissue

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What is the effect of alcohol on the pancreas

Contraction of the sphincter of Oddi
deposition of protein plugs
Toxic to acinar cells

How well did you know this?

Not at all

Perfectly

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

Chapter 19- Pancreas Flashcards

(109 cards)