Liver Path 7: Pancreas Flashcards
Exocrine pancreas
constitutes 80% to 85% of the organ composed of acinar cells that secrete enzymes needed for digestion. (~1.5L of secretions)
Endocrine pancreas
is composed of about 1 million clusters of cells, the islets of Langerhans. Islet cells secrete insulin, glucagon and somatostatin and constitute only 1% to 2% of the organ.
Congenital Anomalies of Pancreas
Pancreas divisum most common anomaly (2 ducts)
Annular pancreas can be associated with duodenal obstruction (wraps around the duodenum)
Ectopic pancreas
Agenesis (very rare)
complications of head of the pancreas tumors?
cholestasis (common bile duct obstruction)
Acute Pancreatitis
Autodigestion of the pancreas by its own enzymes *(inappropriate activation of digestive proenzymes) initiated by:
- Alcohol (65% in US)
- Pancreatic duct obstruction (calculi) (20%)
- Drugs (furosemide, associated with HIV treatment)
- Vascular injury (ischemia)
- Infections (viruses including mumps)
- Hereditary factors (Hereditary pancreatitis)
- Hypercalcemia
Mortality rate averages 10%,
prognosis - acute pancreatitis
Most attacks of acute pancreatitis do not lead to complications, and most people recover uneventfully with medical care.
A small proportion of people have a more serious illness that requires intensive medical care.
A complex combination of genetic, environmental, and metabolic factors contribute to the development and recurrence of acute and chronic pancreatitis
Multiple lines of evidence indicate that premature activation of trypsin in acinar cells damages the cells causing inflammatory response recognize clinically as acute pancreatitis
Many different genetic factors affect acinar cell function, bile duct function, trypsin inactivation and intensity of a immune response in the pancreas
Acute Pancreatitis - clinical
Peak age range for initial episode is 35 to 44 yrs
Diagnosing acute pancreatitis can be difficult because the signs and symptoms of pancreatitis are similar to other medical conditions
Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. (Moderate sensitivity, high specificity)
Serum lipase rises within 4 to 8 hours of onset of acute pancreatitis (high sensitivity and specificity)
Acute Pancreatitis Histopathology
Acute interstitial pancreatitis
Interstitial edema, and focal areas of fat necrosis in peri-pancreatic fat
Acute necrotizing pancreatitis
Necrosis of acinar and ductal tissues as well as islets of Langerhans
Hemorrhagic pancreatitis
Extensive parenchymal necrosis accompanied by dramatic hemorrhage within the pancreas
Chronic Pancreatitis
Can be initiated by recurrent acute pancreatitis myofibroblast stellate cell activation
Irreversible destruction of exocrine parenchyma with fibrosis –> destruction of endocrine parenchyma –> insulin-dependent diabetes
Loss of exocrine function is clinically apparent with loss of ~85-90% of the exocrine gland
Causes of Chronic Pancreatitis
Alcohol abuse 70-80% of cases
Repeat episodes of acute pancreatitis
(10-20%)
Obstruction of the pancreatic duct by calculi or neoplasms
Metabolic
- Primary hyperparathyroidism
- Hyperlipidemia
- Renal transplantation
- Cystic fibrosis
Chronic Pancreatitis Diagnosis
Histology remains the gold standard for the diagnosis of chronic pancreatitis
Demonstrating a reduction in bicarbonate in a duodenal aspirate after secretin stimulation
Endoscopic retrograde cholangiopancreatography (ERCP) shows abnormal pancreatic ductal system
Presence of chunky intrapancreatic calcifications on plain radiographs (minority of cases)
Autoimmune Pancreatitis Variant
Unique Mass forming inflammatory form of chronic pancreatitis
Elevated IgG4
Radiographic findings Mimic pancreatic adenocarcinoma
Approximately 25% of pancreatic resections that lack evidence of malignancy may represent AIP
20% associated with other autoimmune disorders
Responds to corticosteroid therapy
Pancreatic Pseudocyst Non-neoplastic
Most common pancreatic cyst (75%)
Associated with pancreatitis, acute or chronic
Usually do not need to be treated
Can be associated with infection, bleeding or rupture
Pancreatic Cystic Neoplasms: Serous cystadenoma
Most common cystic neoplasm of pancreas
Most are benign
Average age 66 years, female to male 2:1
Lined by a single layer of flat to cuboidal cells with clear cytoplasm
Each small cyst is lined by a flattened layer of epithelium. Cytologically, the lining cells have small, uniform, hyperchromatic nuclei.
Pancreatic cystic neoplasms: Mucinous cystadenoma
Average age 50 years, >95% in females
Can be precursors to invasive carcinoma
Almost always in the tail of the pancreas
Lining epithelium consists of tall columnar cells with abundant apical mucin
Cystic spaces lined by tall columnar mucin containing cells
Intraductal Papillary Mucinous Neoplasm (IPMN)
Involve * larger ducts of pancreas usually in the head of the pancreas
- Male > Female
Benign, borderline & malignant * (Invasive carcinoma is identified in one third of cases)
Mucinous cells with various degrees of dysplasia and papillary architecture line cystically dilated ducts of these tumors
Invasive Ductal Carcinoma of Pancreas
Most common type of pancreatic neoplasm, 60% in head of pancreas
Overall 5 year survival rate is less than 5% with median survival of 9 months
Patients often present with jaundice or back pain with weight loss
Most are sporadic with approximately 10% familial
10% associated with migratory thrombophlebitis (Trousseau sign) secondary to release of platelet activating factors and procoagulant factors
Armand Trousseau 1801-1867
French internist
coined the terms aphasia
and forme fruste
Migratory thrombophlebitis
Trousseau sign led him to diagnose his own pancreatic cancer
Pathology of Ductal Adenocarcinoma of Pancreas
Invasive pancreatic cancers appear to arise from pancreatic intraepithelial neoplasia (PanIN)
Tendency to invade peri-pancreatic tissues and elicit desmoplastic tissue reaction
KRAS is the most frequently altered oncogene
Most are moderate to poorly differentiated adenocarcinoma
Primary effects of invasive ductal carcinoma of pancreas
Metastases- lung, liver, peritoneum
abdominal pain (perineural lymphatic invasion)
secondary effects of invasive ductal carcinoma of pancreas
weight loss
obstructive jaundice
courvoisier gallbladder
migratory thrombophlebitis
Acinar Cell Carcinoma of Pancreas
Uncommon accounting for less than 2% of pancreatic cancers
Most patients are adults >60 years of age
15% develop lipase hypersecretion syndrome
Metastasizes early
Poor prognosis slightly better than invasive ductal carcinoma of pancreas
Pancreatoblastoma
Uncommon, but the most frequent type of pancreatic tumor seen in early childhood
Mean patient age at diagnosis of 4 years
Epithelial tumor that exhibits acinar differentiation and often a lesser degree of neuroendocrine and ductal differentiation
In childhood, most cases that are detected before the occurrence of metastases are curable by surgery.
Pancreatic Neuroendocrine Tumor-PanNET
Approximately 5% to 8% of clinically relevant pancreatic tumors
May occur at any age but are more common in adults (mean age at diagnosis, 55 to 60 years).
Most produce some peptide hormone but most are non-functional (no symptoms)
Preferentially metastasize to regional lymph nodes and liver
