Pathophysiology of Pacreas Flashcards
exocrine pancreas
Synthesis of enzymes needed for digestion of fats, proteins, and carbohydrates
Neutralizes gastric acid and chyme
80% of pancreatic cells are epithelial in origin and comprise acinar glands (form exocrine component)
endocrine pancreas
Synthesizes and secretes hormones (insulin, glucagon) that regulate glucose and lipid metabolism
pancreatic islet cells
Main proteases
trypsinogen
chymotrypsinogen
carboxypeptisases A/B
(most enz of panc are secreted in zymogen form, require activation in duodenum)
acinar cells secrete many diff proteins (proteases, lipases (sec in active form), amylase (sec in active form), nucleases, trypsin inhibitors (deactivates prematurely active typsin), etc)
What forms the bulk of pancreas juice volume?
bicarb and water secreted by acinar/ductal epi cells (keep zymogens inactive w/ high pH, also neutralize gastric acid in duod)
increased secretin
increased CCK
secretin: leads to panc bicarb secretion
CCK: gallbladder emptying, panc enzyme secretion
Enzyme activation
in duodenal lumen:
enterokinase converts trypsinogen into trypsin. Trypsin cleaves/activates other zymogens into active form
Acute pancreatitis
Acute inflammation
Acute abdominal pain
Elevated pancreatic enzymes in serum
Self-limited
Trypsinogen and other pro-enzymes are prematurely activated within the pancreas
Auto-digestion of gland
Leakage of enzymes around pancreas may lead to other complications
Inflammatory cascade may result in organ failure or death when severe and systemic
chronic pancreatitis
Chronic inflammation
Ductal obstruction
Chronic pain or malabsorption
Permanent loss of pancreatic function
Most common causes of acute pancreatitis
alcohol abuse
duct obstruction from gallstone (#1 in US)
How does alcohol cause acute pancreatitis
premature release and activation of zymogens
proteinacious plugs within pancreas duct
-direct toxic effect on panc acinar cells and ductal epithelium, causing premature release and activation of trypsinogen and stagnant flow of pancreas juice
How does ductal obstruction lead to acute pancreatitis?
Abrupt ductal obstruction (stone, trauma, etc)
bile reflux or retention of enzymes
stone lodges in distal common bile duct +/- ampulla, resulting in obstruction of ventral duct and or bile reflux into panc, reinforcing zymogen activation
stagnation of pancreas enzymes within the duct lumen and activation of the enzyme activation cascade
Other causes of acute pancreatitis
- tumors blocking duct
- procedures (ERCP)
- congenital ductal abnorm (panc divisum, annular panc)
- Sphincter of Oddi dysfunc types 2 or
- severe hyperlipidemia
- penetrating trauma
- drugs
- hypercalcemia
- Mumps, Coxsackievirus
- CF
- idiopathic
Clues to dx Gallstone pancreatitis
Risk factors for gallstones Gallstones seen on imaging (in gallbladder or bile duct) Elevated liver chemistries Dilated bile duct Absence of other risk factors
Presenting features of acute pancreatitis
abdominal pain n/v tachycardia low grade fever abdominal guarding loss of bowel sounds jaundice
Dx tests for acute pancreatitis
serum enzymes (enz elevated greater than 3x upper normal): amylase (rises and falls over 24-48 hours, less specific), *lipase (rises in 1-2 hrs, falls over a week)
U/S (best for stones)
CT (edema, calcifications, fluid collections)
CT w/ contrast: detects necrosis
Complications of acute pancreatitis
Ileus (paralysis of gut)
intra-abdominal hemorrhage
pseudocyst formation
Severe: pancreatitic necrosis bowel or bile duct obstruction shock resp or renal failure Death
Pancreatic pseudocyst
Collection of pancreatic fluid, debris surrounded by wall of granulation tissue - lacks epithelial lining
Results from ductal disruption, necrosis, or both
Develop in 10-30% of cases of acute pancreatitis
Majority (60-70%) will resolve with time, others may persist or lead to chronic pain, infection, or obstruction of viscera
May need cyst gastrostomy and stent placed leading to stomach
AP or CP
Pancreatic necrosis
presence of one or more diffuse or focal areas
of nonviable pancreatic parenchyma
If necrotizing, infection and mortality are much higher rates than in interstitial acute panc
ARDS
Adult resp distress syndrome
complication of acute panc
- in severe pancreatitis
- delayed onset
- assoc w/ panc necrosis
- assoc w/ hyperlipidemia
- commonly leads to respiratory failure
- Dx: hypoxemia, normal wedge pressure
- potentially reversible
Management of acute pancreatitis
Admit to hospital (usually)
NPO, then slow advancement in diet
IV narcotics for pain
Surgery consult if gallstones present
Consider ERCP for bile duct stone removal
Severe disease → feeding tube, IV nutrition, pancreatic debridement, pseudocyst drainage, etc..
How does chronic pancreatitis develop?
- develops after repeated bouts of acute pancreatitis
- most commonly as a result of chronic alcohol abuse
- panc tissue replaced by hard fibrous tissue; atrophy of gland
- calcifications may develop in duct
- Micro: scar tissue replaces lost lobular tissue, poss lymphocytes/plasma cells (sparing of islet cells)
Permanent destruction of pancreatic parenchyma with replacement by fibrosis (scar tissue)
May lead to ductal strictures, ductal or parenchymal calcifications (stones), or pseudocysts
May be associated with prior episodes of acute pancreatitis
Most common cause of CP in western countries?
chronic alcohol abuse
- smoking contributes to fibrosis
- familial causes (CFTR gene mutations and/or cystic fibrosis; hypertriglyceridemia; tropical pancreatitis– idopathic variant)
- hereditary pancreatitis
ductal strictures/stones
pain, exocrine failure
CP
panc pseudocysts
pain, n/v
CP
