Path GI IV Pancreas (20)

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Path GI IV Pancreas (20)
2014-03-10 19:50:25
MBS Pathology
Exam 3
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  1. Pancreas
    • large, lobulated gland with exocrine & endocrine function
    • exocrine secretions are transported through ducts
    • endocrine secretions are secreted through fenestrated capillaries directly into the blood stream
  2. Acini → Ducts
    • grape-like functional units whose ~45 secretory cells synthesize pancreatic enzymes
    • each acinar cell has zymogens made in the basal RER, glycosylated & packaged in the Golgi, stored in the apical cytoplasm until hormones signal for their release via exocytosis into intralobular ducts
  3. What are a few enzymes/zymogens that originate from the pancreas acini?
    • 1. protein degrading enzymes (trypsinogen, carboxypeptidases,
    • elastase)
    • 2. carbohydrate degrading enzymes (amylase)
    • 3. nucleic acid degrading enzymes (ribonuclease, deoxyribonuclease)
    • zymogens are activated by trypsinogen, which itself is activated by enterokinase in the small intestine
  4. Islets → Capillaries
    compact clusters of epithelial cells richly vascularized w/ fenestrated capillaries (into which the cells secrete their hormones)
  5. What are the 3 main cells in a pancreas islet?
    1. beta cells: most, secrete insulin (cellular uptake of glucose from blood)

    2. alpha cells: secrete glucagon (cellular release of glucose into the blood)

    3. delta cells: produce somatostatin (modulates secretion of insulin & glucagon)

    4. Ectopic cells

    (I Bet Girls All Suck Dick; Insulin Beta cells Glucagon Alpha cells Somatostatin Delta)
  6. Pancreatitis
    • inflammatory condition due to injury to acini cells in the EXOCRINE portion of the pancreas
    • most common causes: Gallstones & Alcohol
  7. Acute Pancreatitis
    • varies from a mild, self-limited condition w/ acute inflammation & stromal edema to severe, acute hemorrhagic disorder w/ massive necrosis (may be fatal)
    • organ can return to normal if the underlying cause of inflammation is removed
  8. Causes of Pancreatitis
    • Inappropriate activation of pancreatic enzymes
    • Overwhelmed anti-activation mechanisms
    • Injury to the acinar cells
    • Secretion against obstruction
    • Gallstones (45% of patients w/ Acute have)
    • Alcohol consumption (1/3 of acute cases, 2/3 of chronic cases; causes spasm)
    • Viral infection
    • Drugs
    • Blunt Trauma
    • Cystic fibrosis
    • Hyperlipidemia
    • Hypercalcemia
    • Unknown causes (10–20%)
  9. Macroscopic Pathology of Acute Pancreatitis
    • fat necrosis
    • chalky calcium deposits
    • hemorrhage
    • in severe cases, most of the organ is destroyed & converted into a retroperitoneal hematoma
  10. Microscopic Pathology of Acute Pancreatitis
    • Edema
    • Fat necrosis
    • Saponification
    • Calcium deposits
    • Hemorrhage
    • Parenchymal destruction
    • Intense acute inflammation (Inflammatory response)
    • Fibrosis, reduction in functional parenchyma
    • Acini cell necrosis
    • Destruction of BVs w/ extravasation of blood cells
  11. Clinical Features of Acute Pancreatitis
    • severe epigastric pain, referred to the upper back
    • nausea & vomiting
    • catastrophic peripheral vascular collapse & shock
    • elevated serum amylase (first 24 hr) & lipase (within 72-96 hours)
    • may be infected with gram-negative bacteria from the gut (50% of cases)
    • 80% of cases are mild & self limiting
    • 20% the disease is severe
  12. Chronic Pancreatitis
    • can happen b/c of repeated episodes of acute pancreatitis
    • characterized by recurrent attacks of severe abdominal pain, progressive destruction of pancreatic parenchyma, dilated pancreatic ducts, chronic inflammation, progressive fibrosis, & eventually pancreatic insufficiency
    • there is irreversible destruction of parenchyma, especially the EXOCRINE portion (eventually islets are also lost)
  13. What develops in about half the patients who survive acute pancreatitis?
    • Pancreatic Pseudocyst
    • delimited by connective tissue
    • contains degraded blood, debris of necrotic pancreatic tissue, & fluid rich in pancreatic enzymes
    • does NOT have an epithelial lining
    • may become secondarily infected & form an abscess
  14. Benign Pancreatic Neoplasms
    Serous cystadenomas vs. Mucinous cystic adenomas (which can actually also be borderline malignant or malignant, not just benign)
  15. Serous Cystadenomas
    • 25% of all pancreatic cystic neoplasms
    • glycogen-rich cuboidal cells surround cysts filled w/ clear, straw-colored fluid
    • grow usually in 7th decade of life in 2 females for every 1 male
  16. Mucinous Cystic Adenomas
    • almost always occur in women
    • usually in body or tail of pancreas
    • columnar mucinous epithelium w/ dense cellular stroma surround cysts filled w/ thick, tenacious mucin
    • can be benign, borderline malignant, or malignant
  17. Cancer of the pancreas is the WHAT most common cause of cancer-related death in the US?
    • 4th most common cause of cancer-related death in the US
    • it accounts for 3% of active cases in both men & women
    • 5 year survival is about 5%
    • Ductal adenocarcinoma in 90% of all pancreatic cancers
    • Occurs later in life, greatest incidence in >60 yrs. of age
  18. Clinical features of Pancreatic cancer?
    • jaundice (seen in 50% of those with ca of the head of the pancreas)
    • early metastasis
    • presents w/ anorexia, conspicuous weight loss & a growing pain in the epigastrium, which often radiates to the back
    • Courvoisier Sign: acute, painless gallbladder dilation accompanied by jaundice as a result of common bile duct OBSTRUCTION by tumor
    • most cases have already metastasized at the time of diagnosis
    • 50% die within 6 months of diagnosis
    • 5 year survival rate is less than 5%
  19. What Paraneoplastic syndrome is associated with Pancreatic Cancer?
    • Migratory Thrombophlebitis
    • is related to hypercoagulability
    • deep venous thrombosis or Trousseau syndrome
    • develops in 10% of patients (especially those w/ body & tail ca)
  20. Islet Cell Tumors
    • endocrine tumors (PETS) account for about 10% of pancreatic neoplasms
    • most common islet cell neoplasms (75%) = Insulinomas (Beta cell tumors)
    • most of these are benign lesions in the body or the tail
    • Insulinomas cells resemble normal beta cells but form trabecular or solid patterns
    • Amyloid (secreted peptide hormone amylin) found in the stroma
    • causes severe HYPOglycemia
    • sweating, nervousness, hunger → confusion, lethargy, coma
    • high levels of insulin in the blood & tumor cells
  21. Pathogenesis of Pancreatic Cancer
    • smoking may be associated in 25% of the cases
    • diabetes mellitus patients are at increased risk; there's DM in 80% of patients w/ pancreatic cancer
    • involves the head (60%), body (10%), tail (5%), rest is diffused
    • Ca of the head may cause biliary obstruction & jaundice by compressing the ampulla of Vater & common bile duct
    • Ca of the body & tail DO NOT impinge on the biliary tract and can remain silent for some time
    • forms a FIRM, gray, poorly demarcated, multinodular mass
    • more than 75% are well-differentiated ductal adenocarcinoma that secrete mucin & are associated with collagen deposition
    • perineural infiltration can cause early & persistent pain
    • commonly metastasizes to regional lymph nodes and liver
  22. Molecular Changes in Pancreatic Cancer
    • a number of genetic alterations & a tumor progression model based on specific mutations has been proposed
    • pancreatic Intraductal neoplasia (PanINs)
    • mutational activation of K-ras (early event)
    • mutations in tumor suppressor genes (occurs later, eg. p53 etc.)
    • several familial cancer syndromes have a high risk of developing pancreatic cancer
  23. What is the most frequently altered oncogene in pancreatic cancer?
    • K-RAS gene is
    • the p16 gene is the most frequently inactivated tumor suppressor gene in PC
    • SMAD4 tumor suppressor gene is inactivated in 55% oc PC
    • inactivation of the p53 tumor suppressor gene occurs in 50–70% of PC
    • while there is a general temporal sequence of changes, the accumulation of MULTIPLE mutations is more important than their occurrence in a specific order
  24. Syndromes Associated w/ Islet Cell Tumors of the Pancreas
    • Gastrinomas, Zollinger-Ellison syndrome (G gastric cells)
    • Glucagonomas (alpha-cells)
    • Somatostatinomas ( delta-cell tumors)
  25. Gastrinomas, Zollinger-Ellison Syndrome (G cells)
    • Intractable gastric hypersecretion
    • severe peptic ulceration of the duodenum & jejunum
    • high blood gastrin levels
    • MOST gastrinomas are malignant
  26. Glucagonomas (alpha-cells)
    • associated w/ mild diabetes, necrotizing migratory, erythematous rash, anemia, venous thrombosis & severe infections
    • plasma glucagon levels can be as high as 30x above normal
    • 2/3 of these are malignant
  27. Somatostatinomas ( delta-cell tumors)
    • associated w/ a syndrome consisting of mild diabetes, gallstones, steatorrhea, & hypochlorhydria
    • most of these are malignant
  28. Vasointestinal Polypeptide-secreting Tumors (VIPomas)
    • elevated levels of vasoactive intestinal peptide
    • haracterized by explosive & profuse watery diarrhea
    • accompanied by hypokalemia (low K+) & hypochlorhydria (pancreatic cholera, aka low stomach acid)
    • most of these are malignant