Pathophysiology of the Pancreas Flashcards
Physiologic functionsof pancreas
Exocrine, Endocrine
Exocrine function of Pancreas
synthesis of enzymes for digestion, neutralizes gastric acid and chyme, secretes bicarb and water
endocrine action of pancreas
synthesisze/secrete hormones regulating glucose and lipid metabolism (insulin, glucagon)
Enzymes from pancrease
proteases, lipases, nucleases, others, amyolytic enzyme
in what form are enzymes secreted
secreted as zymogens that must be activated
2 mechanisms of preventing digestion of pancreas
- physical separation
- inactive form secreted
- trypsin inhibitor can be activated
Acute pancreatitis
acute inflammation, acute abdominal pain, elevated pancreatic enzymes in serum, self-limited (if you can alieve cause)
Chronic pancreatitis
chronic inflammation and fibrosis, ductal stones and strictures, chronic pain/malabsorption, permanent loss of pancreatic function
Acute pancreatitis mechanism
Trypsinogen and other pro-enzymes are prematurely activated within pancreas – autodigestion of gland
- leakage of enzymes around pancreas may lead to other complications
- inflammatory cascade may result in organ failure or death when severe
Causes of acute pancreatitis
most common causes = alcohol abuse or obstruction of duct from gallstone
MOST COMMON CAUSE IN 2015 of acute pancreatitis
obstruction of duct from gallstone
Acute pancreatitis from alcohol
premature activation of zymogens, increased permeability of ductules, proteinacious plugs within pancreas duct
Abrupt ductal obstruction –acute pancreatitis
- stone, trauma, etc
- bile reflux, retention of enzymes
Other etiologies of acute pancreatitis
iatrogenic, drug-induced, hypertriglyceridemia, hypercalcemia, pancreas cancer, pancreas divisum, penetrating trauma, other (1%–mumps, coccsackie virus)
Presenting features of acute pancreatitis
abdominal pain, nausea, vomiting, tachycardia, low grade fever, abdominal guarding, loss of bowel sounds, jaundice (if severe enough or large stone lodged)
Diagnosis of acute pancreatitis
blood test– amylase, lipase
- when >3x normal = acute pancreatitis
ultrasound as diagnostic tool
not that helpful for diagnosis – looks for causes (can see gallstones)
complications of acute pancreatitis
ileus (paralysis of gut), intra-abdom hemorrhage, pseudocyst formation
severe disease – pancreatic necrosis, bowel or BD obstruction, shock, respiratory or renal failure, death
Clues to diagnosis for gallstone pancreatitis (biliary)
risk factors for gallstones, gallstones seen on imaging elevated liver chemistries, dilated bile duct, absence of other risk factors (alcohol)
risk factors from gallstones
American Indian, Mexican-American, female, >60, pregnant, overweight, high fat diet, high cholesterol diet, fam hx
Pancreatic pseudocyst
walled off collection of fluid, debris surrounded by wall of granulation tissue
- not true cyst – no epithelium
- can be inside pancreas if digested pancreas tissue or outside if fat
why is pseudocyst not cyst
no epithelium
prognosis with necrosis
increased risk of infection and mortality
Adult respiratory distress syndrome
response to severe pancreatitis
- delayed onset, associated with hyperlipidemia
- Ddx = hypoxemia, normal wedge pressure
- potentially reversible
management of acute pancreatitis
- hospital admit
- NPO then slow advancement on diet
- IV narcotics for pain
- surgery consultation if gallstones
- consider ERCP for bile duct stone removal
- Severe disease– feeding tube, IV nutrition, panc debridement, pseudocyst drainage, etc
ARDS
Adult respiratory distress syndrome
- delayed onset
- associated with pancreatic necrosis
- commonly leads to respiratory failure
- fully reversible
- treatmetn = support
association of pancreatic fibrosis
more episodes of acute pancreatitis over time shows increased pancreatic fibrosis
Chronic pancreatitis
permanent destruction of pancreatic parenchyma with replacement by fibrosis (scar tissue)
What can result from chronic pancreatitis
- may lead to ductal strictures, ductal or parenchymal calcifications (stones), or pseudocyts
- may be associated with prior episodes of acute pancreatitis
Chronic panc pathophys/features
?
Chronic pancreatitis cuases
ALCOHOL, Idiopathic, Other (cystic fibrosis, hereditary pancreatitis, hyperlipidemia)
association of fat in stool with pancreatic viability/lipase output
more fat in stool with decreased lipase output (pancreatic viability)
Chromic pancreatitis clinical spectrum
?
Pancreatic insufficiency symptoms
weight loss, steatorrhea, bleeding problems, anemia, weakness, edema, watery diarrhea
Mechanisms of steatorrhea
- decreased lipase and colipase in duodenum
- decreased duodenal pH (inactivation of pancreas enzymes, bile acid precipitation)
Macrocytic anemia part of chronic pancreatitis spectrum
Macrocytic anemia part of chronic pancreatitis spectrum
Chronic pancreatitis diagnosis
Hx, PE,
- plain x-ray – calcifications in pancreas
- CT–> dilated duct, atrophy, calcifications, pseudocysts
- Secretin test, ERCP, or endoscopic ultrasound –> more accurate but invasive
Secretin test
Don’t really do anymore
- evaluates pancreatic function
- put tube in duodenum and another in stomach–>secretin given IV –> bicarb increase of
Treatment for 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)
most common pancreatic cancer
adenocarcinoma
- # new diagnosis ~ # deaths
- late diagnosis and dismal survival
- only 20% taken to OR cured
- Median survival 18 months
- 5 year survival = 5%
Pancreatic cancer is the __ leading cause of cancer death in US
4th
Pancreatic cancer presentation
jaundice, dark urine, pruritus (bile duct obstruction)
- abdominal/back pain –> late
- weight loss
- nausea/vomiting (late)
- Hormonal excess (neuroendocrine– insulin, glucagon, gastrin, VIP)
most common location/presentation of adenocarcinoma
HEAD OF PANCREAS! present with jaundice
Diagnosis of pancreatic CA
CT or MRI of abdomen
Pancreatic cancer Treatment
- surgical resection (select few that are diagnosed early)
- ERCP with stent for palliation of choestasis
- celiac nerve block for pain
Use of endoscopic ultrasound for pancreatic cancer
biopsy/pre-op/definitiive staging to see if surgical resection a possibility
Pancreatic neuroendocrine tumor
- slow-growing, prognosis favorable
- islet cell origin
- can present with symptoms of hormone excess (insulin, glucagon, somatostatin, gastrin, VIP)
- diagnosis/treatment same as pancreatic cancer?
Autoimmune pancreatitis (AIP)
- diffuse or focal enlargement of pancreatic parenchyma
- infiltration by IgG-4+ plasma cells and lymphocytes
what can AIP mascquerade as
pancreatic cancer
present with similar symptoms (chronic abdominal pain, jaundice, weight loss, (rarely) pancreatitis
typical population for AIP
males, typically ages 40-70
what else is AIP associated with
other autoimmune diseases – RA, Sjogren’s, IBD, SLE
AIP symptoms
ab pain, jaundice, weight loss, pancreatitis (rarely)
AIP on imaging
diffuse or focal enlargement of pancreas with narrowing of CPD +/- PD
Diagnosis of AIP
CT/MRI, serum IgG-4, EUS, ERCP, occasionally FNA/biopsy
Treatment of AIP
- PO corticosteroids x 6 weeks
- biliary stenting for symptom relief
