Pathophysiology of Exocrine Pancreas Flashcards
Normal fxn of pancreas
- Exocrine component
- epithelial cells ==> form acinar glands
- acinar cells produce digestive pro-enzymes
- ative amylase and lipase
- proteases: trypsinogen, chymotrypsinogen, carboxypeptidase A & B
- activated @ duodenum
- also produce bicarbonate and water
- maintain flow & inactive state of zymogens
- neutralizes stomach acid @ duodenum
- endocrine component
- islet cells
Causes of acute pancreatitis
- pancreatic enzymes are innapropriately/prematurely activated ==> autolysis of the gland
- commonly occurs w/obstruction of pancreatic duct ==> stagnation of pancreas enzymes & activation
- e.g. gallstone lodges @ distal common bile duct and/or ampulla
- ethanol ==>
- direct toxic effect on pancreatic acinar cells & ductal epithelium
Presentation of acute pancreatitis
- severe upper abdominal pain
- sometimes radiating to back
- naseau/vomiting
- low-grade fevers
- elevated serum amylase & lipase
- risk factors:
- female
- gallstone risk factors
- US: shows gallstones
- CT: shows inflammatory changes @ pancreas
Complications of acute pancreatitis
- necrosis
- pseudocyst
- hemorrhage
Causes of chronic pancreatitis
- develops after repeated bouts of acute pancreatitis
- common cause: chronic alcohol abuse
- other causes/contributions:
- smoking
- familial/inherited causes
- cystic fivrosis
- mutations: trypsinogen (PRSS) or trypsin inhibitor (SPINK) genes
- familial hypertriglyceridemia
Presentation of chronic pancreatitis
- malabsorption
- steatorrhea (fecal fat excretion) occurs after 90% gland destruction
- @ 95% destruction: decreased protein/carb absorption
- ==> flatulence, weight loss, or anemia
- pain
- abdominal: epigastric w/radiation to back
- intermittent
- malnutrition
Proposed mechanisms of chronic pancreatitis development
- alcohol abuse
- changes in pH or protein secretion ==> intraductal plugs
- oxidative + non-oxidative metabolites of alcohol ==> injury
- cigarette smoking ==> promotion of fibrosis
- episodes of necrosis ==> fibrosis
- pancreatic stellate cells ==> role in fibrosis
Diagnosis of chronic pancreatitis
- clinic sx
- steatorrhea
- rapid fat stool stain
- 72hr stool collection
- weight loss, anemia
- pain
- steatorrhea
- abdominal x-ray:
- calcifications over epigastrium
- secretin stimulation test (not currently used)
- CT → dilated duct, atrophy, calcifications, pseudocysts
- ERCP (endoscopic retrograde cholangiopancreatography)
- endoscopic ultrasound → more accurate, but invasive
Tx of chronic pancreatitis
•ETOH avoidance!
•Pancreas enzyme replacement (pills) for steatorrhea
•Treatment of duct obstruction - dilation, stent placement, or stone removal
•Celiac nerve block for pain
•Surgical resection if refractory and severe
•Pancreatectomy with islet cell transplant
–Young patients, refractory disease
Clinical presentationof Pancreatic Cancer
•Jaundice, dark urine, pruritus
–Bile duct obstruction (tumors in head)
•Abdominal or back pain - late
–Capsular distension or nerve invasion
•Weight loss
•Nausea/vomiting (late) –
–Duodenal or gastric obstruction
•Hormonal excess (neuroendocrine)
–insulin, glucagon, gastrin, VIP
Dx/Tx of Pancreatic cancer
•Diagnosis and initial staging
–CT or MRI of abdomen
•Biopsy and pre-op/definitive staging
–Endoscopic ultrasound (EUS)
•Treatment
–Surgical resection - select few that are diagnosed early
–ERCP with stent for palliation of cholestasis
–Celiac nerve block for pain
General characteristics of pancreatic cancer
- 4th leading cause of cancer death in US
- main types
- adenocarcinoma = most common
- pancreatic endocrine tumors
- poor prognosis
Characteristics of pancreatic neuroendocrine tumors
•Slow-growing, prognosis favorable
•Islet cell origin
•May present with symptoms of hormone excess
–Insulin, glucagon, somatostatin, gastrin, VIP
•Diagnosis, treatment same
•Octreotide scan may be used to detect small NETs not seen on CT or EUS
Characteristics of autoimmune pancreatitis (AIP)
- Diffuse or focal enlargement of pancreatic parenchyma
- Infiltration by IgG-4 + plasma cells and lymphocytes
- Males, typically ages 40-70
- Association with other autoimmune diseases – RA, Sjogren’s, IBD, SLE
- May masquerade as pancreatic cancer!
Sx of AIP
- abdominal pain
- jaundice
- weight loss
- (rarely) other sx of acute pancreatitis
