Exocrine Pancreas Pathology Flashcards by Kevin N

What do the small ductules secrete?

Bicarbonate

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What do the large ductules secrete?

Mucin

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What do the Islets of Langerhans secrete?

Insulin, glucagon, somatostatin

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What are some of the ways that the pancreas prevents autodigestion?

Inactive proenzymes are synthesized
Enzymes are in membrane bound zymogen granules
Activation of proenzymes requires activation of trypsinogen to trypsin
Resistance of acinar cells

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What is acute pancreatitis?

It is an acute inflammatory process of the pancreas that is associated with acinar cell injury. With respect to severity it can range from mild self-limited disease to a life threatening acute inflammatory process.

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What are the 2 most common causes of acute pancreatitis?

Alcohol and gallstones (biliary obstruction)

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What is the pathogenesis of acute pancreatitis?

There is inappropriate activation of trypsinogen to trypsin and a lack of prompt elimination of active trypsin inside the pancreas. Activation of digestive enzymes causes pancreatic injury and results in an inflammatory response that is out of proportion to the response of other organs with a similar insult.

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How does alcohol cause acute pancreatitis?

Alcohol may act as a toxin that directly injures acinar cells releasing activated enzymes which autodigest the pancreas.

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How do gallstones cause acute pancreatitis?

Biliary obstruction, such as by gallstones, can lead to reflux of bile into the pancreatic ducts. This increased back-pressure leads to acinar cell injury.

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What is the cause of acute pancreatitis seen most often in males? Females?

Males - alchohol

Females - gallstones

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What are some drugs that can cause acute pancreatitis?

Azathioprine and estrogens

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What is hemorrhagic pancreatitis?

This is the most severe form of acute pancreatitis – extensive parenchymal necrosis is accompanied by diffuse hemorrhage within the gland.

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What are the typical clinical manifestations of acute pancreatitis?

Sudden onset of severe abdominal pain which may radiate to the back and non-specific symptoms:

Nausea and vomiting, fever, sweating, tachypnea, and tachycardia.

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Which enzymes appear in high concentration in the blood during acute pancreatitis?

Amylase and lipase

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Why can hypocalcemia develop during acute pancreatitis?

Fat necrosis leads to local formation of calcium soaps, called suponificiation and this process consumes calcium from the blood, typically leading to hypocalcemia 2 to 4 days after the onset of acute pancreatitis.

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What is the approach to treatment of acute pancreatits?

Supportive treatment and address the underlying cause

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What is chronic pancreatitis?

A progressive fibroinlammatory process of the pancreas that results in permanent structural damage and loss of exocrine followed by endocrine function.

What is the most common cause of chronic pancreatitis?

Chronic alcohol abuse

What are the other causes of chronic pancreatitis?

Chronic biliary obstruction
Hereditary
Tropical Pancreatitis

What are the proposed pathogenetic mechanisms of chronic pancreatitis?

Hypersecretion of protein with insufficient ductal bicarbonate leading to proteinacious plug formation within ducts. This obstruct ducts and serves as a nidus for calcification and stone formation. Duct injury leads to scar formation and further obstruction.

What are the morphologic changes seen in chronic pancreatitis?

Fibrosis
Reduced number and size of acini
Obstruction and dilatation of pancreatic ducts
Pseudocyst formation

What are the clinical manifestations of chronic pancreatitis?

Persistent upper abdominal pain radiating to the back, often precipitated by alcohol
Malabsorption due to pancreatic insufficiency—steatorrhea and vitamins A, D, E, and K deficiency

What is a pancreatic pseudocyst?

A localized collection of pancreatic secretions in pancreatic interstitium as a result of damaged ducts.

Importantly – a pseudocyst LACKS a true epithelial lining.

A 42‐year old obese woman presents with a 1 day history of severe abdominal pain which radiates to her back. She has no known medical problems. She does not smoke cigarettes. She drinks one glass of wine ~twice per month. There is no history of drug abuse. She takes ranitidine as needed for heartburn. Her BP is 90/45, respirations 32/min, pulse 104/min. Physical exam shows marked epigastric tenderness to palpation. Laboratory studies reveal elevated serum amylase (850 U/L) and lipase (675 U/L) and hypocalcemia. Which of the following is most likely associated with the pathogenesis of this patient’s condition?

A. Alcohol abuse
B. Carcinoid tumor
C. Cholelithiasis
D. Hypoparathyroidism
E. Hypercholesterolemia

C. Cholelithiasis

What are causes of pancreatic pseudocyst?

Acute pancreatitis, chronic pancreatitis, trauma.

What are some risk factors for pancreatic cancer?

Smoking Long standing diabetes mellitus Chronic pancreatitis

What is the precursor lesion and associated molecular pathogenesis of pancreatic adenocarcinoma?

The precursor lesion is pancreatic intraepithelial neoplasia (PanIN). There is a stepwise progression of pancreatic intraepithelial neoplasia from low grade to high grade. These are associated with accumulating genetic alterations.

What is a common mutation seen in pancreatic adenocarcinoma?

There is a very high rate of KRAS mutations in pancreatic adenocarcinoma and a majority are ductal in origin.

What is the main location of the pancreas where adenocarcinoma arises in?

The head

What are the clinical manifestations of pancreatic cancer?

- Most cancers remain clinically silent until the tumor impinges on other structures - Pain is usually first symptom - Obstructive jaundice with tumors arising in the head of the pancreas

What is a sign with pancreatic carcinoma of the head?

Obstructive jaundice • Tumor obstructs ampullary region/common bile duct • Obstruction prevents conjugated bile from entering duodenum, bile pressure increases in the biliary tract and it enters the vascular space

What is “Trousseau’s Sign”?

Mucin is a pro-coagulation factor that is overproduced in pancreatic adenocarcinoma as some of it will leak into the blood leading to migratory thrombophlebitis of spontaneously appearing and disappearing venous thromboses.

What is a “Whipple Procedure”?

A type of surgical resection for tumors in the head and neck of the pancreas - a pancreaticoduodenectomy

What are some of the features of serous cystoadenoma?

- Benign - Cuboidal cells - Elderly females - Cysts with clear fluid

What are some of the features of mucinous cystic neoplasms?

- Can be benign or malignant - Columnar epithelium - Almost exclusively in female - Cysts with mucin

What are some of the features of intraductal papillary mucinous neoplasms?

- Can be benign or malignant - Columnar epithelium - More in men - Head of pancreas

What is pancreatic agenesis?

Absence of the pancreas; usually associated with multiple other congenital organ anomalies.

What is an Annular pancreas?

The head of the pancreas encircles the duodenum. This may narrow the duodenum and interfere with passage of food.

Where can “ectopic” pancreatic tissue be found?

Ectopic pancreatic tissue refers to displaced pancreatic tissue. Glands (ducts and acinar tissue) and Islets of Langerhans and be found in the Stomach and duodenum, jejunum, Meckel diverticulum, ileum. There are usually in the submucosa.

Describe pancreas divisum.

It is a congenital anomaly of the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts. Normally, in embryogenesis, the two ducts will fuse together to form one main pancreatic duct. In pancreas divisum the major drainage of the pancreas is done by the dorsal duct which opens up into the minor papilla.

What are the complications of pancreas divisium?

The majority of patients with pancreas divisum have no symptoms. A small subgroup of patients may develop chronic pancreatitis.

A 51‐year‐old man has a history of chronic alcohol abuse. He has had multiple bouts of epigastric abdominal pain in the past year. For the past month, he has had more frequent and worsening abdominal pain. Physical examination reveals right upper and left upper quadrant pain. An abdominal plain film radiograph reveals no free air, but there is extensive peritoneal fluid collection along with dilated loops of small bowel. An abdominal CT scan reveals a an 8 cm cystic mass in the tail of the pancreas. Which of the following is the most likely diagnosis? ``` A. Pancreatic adenocarcinoma B. Pancreatic pseudocyst C. Acute pancreatitis D. Pancreatic mucinous cystadenoma ```

B. Pancreatic pseudocyst