Pancreatitis Flashcards
Describe pathology of acinus
Ductules lined by ductule cells that secrete bicarbonate
Blue staining nuclei at basal level with pink staining areas signifying zymogen granules in apical area
What do zymogen granules contain?
Proteases (95%), lipase, amylase
Describe the feedback regulation of pancreatic secretion:
Gastric acid==>secretin==>Bicarbonate secretion, which inhibits gastric acid secretion
Digestive enzymes normally inhibit CCK stimulation. Protein in meal inhibits digestive enzymes allowing increased CCK which in turn promotes vagus nerve stimulation and release of digestive enzymes, turning off CCK secretion
What is main cause of acute pancreatitis?
Autodigestion
What is histology of moderate/mild acute pancreatitis? (3)
What is histology of severe pancreatic? (3)
Mild: inflammation, acinar cell vacuolization, preservation of architecture
Severe: Inflammatory infiltrate, Hemorrhage/necrosis, Loss of pancreatic architecture (acini)
What are some of acinar cell responses in acute pancreatitis?
Inhibited apical secretion with increased basolateral vesicle release, activation of digestive enzymes within cytoplasmic vesicles, misdirected endocytic processes, disordered autophagy and lysosomal degradation, mitochondrial dysfunction, paracellular leak, ROS generation, cytokine release
What are examples of secretagogue hyperstimulation model? (3)
Cholinergic stimluation
High concentration of CCK
Caerulein
Occurs as a result of scorpion sting
Describe duct obstruction and bile acid cause of acute pancreatitis: what is human equivalent?
Obstruction of pancreatic duct==>Release of Ca from intracellular stores==>transactivation of lysosomal cathepsins/zymogens
How? Taurolithocolic acid results in pH dysregulation
Equivalent: gallstone pancreatitis
What are two mechanisms of gallstone pancreatitis?
Common channel mode: redirect bile acid up pancreatic duct=>probably wrong
Obstruction of pancreatic outflow or both ducts==>this is probably more correct
Diet induced pancreatitis:
Choline deficiency
CDE (choline deficient diet with ethionines)=>more severe pancreatitis due to disruption of stimulus-secretion coupling
Characteristics of autoimmune pancreatitis:
Main symptom
Histology
Treatment
Obstructive jaundice
Lymphoplasmacytic infiltrate and fibrosis
Steroid responsive
Imaging: autoimmune pancreatitis
Enlargement of pancreas
What are lab values in autoimmune pancreatitis: genetics (HLA), autoantibodies, Ig
Predisposition: HLA DRB1 and DQB1
Autoantibodies: ANA, PSTI, lactoferrin
IgG4 elavation
Describe the histological findings in autoimmune pancreatitis
Fibrosis
Inflammatory infiltrate in duct cells
Stain positive for IgG plasma cells
Describe the difference between classic AIP and IDCP
Classic AIP: 7th decade, 75% male, higher IgG, risk for relapse, no GEL
IDCP: 5th decade, 50% male, 25% IgG, granulocytic epithelial lesion (GEL) with neutrophils
Describe chronic pancreatitis pathogenesis: (2)
Multiple episodes of subclinical pancreatitis
Single injury that persists
Describe animal models of chronic pancreatitis (5)
Partial/complete duct obstruction Repeated injection of cerulean Chronic EtOH feeding +LPS injection IV injection of dibutyltin dichloride CDE diet: chronic/intermittent feeding
What is a common mutation in chronic pancreatitis?
KRAS– 30% of chronic pancreatitis and 90% pancreatic adenocarcinoma
What is hereditary pancreatitis?
Describe the epidemiology: age of onset, how many people get chronic pancreatitis and pancreatic cancer respectively
Autosomal dominant disorder with mutation in PRSS1 on chr7 which leads to recurrent acute pancreatitis, chronic pancreatitis, pancreatic cancer
Onset: 0-40yrs; 40% develop chronic and 40% of chronic develop pancreatic cancer by age 70
What is CF?
Autosomal recessive mutation in CFTR gene often diagnosed within 1st year of life
What is SPINK mutations?
A mutation that predisposes to early development of pancreatitis
What are environmental risks for pancreatitis?
EtOH
Smoking
EtOH and smoking are synergistic
How is acute pancreatitis defined?
2 of 3:
Abdominal pain
Amylase or lipase >3x upper limit of normal
Abdominal imaging that confirms pancreatitis (calcifications)
What are main causes of acute pancreatitis
Alcohol, biliary, idiopathic, autoimmune, drug-induced, IBD, infectious, inherited
What are common causes of drug-induced pancreatitis? (6)
Aspariginase Azathioprine 6MP DDI Pentamidine Valproate
What are manifestations of pancreatic insufficiency? (4)
Carb/protein/fat malabsorption
Malnutrition
Bone disease
Systemic disease
What are categories of symptoms of exocrine pancreatic insufficiency? (3)
Steatorrhea
Fat-soluble vitamin (A,D,E,K) deficiency: metabolic bone disease, easy bruising/bleeding
Abdominal symptoms: diarrhea, bloating, pain, flatulence
