Pancreatitis

Question 1

Describe pathology of acinus

Answer 1

Ductules lined by ductule cells that secrete bicarbonate

Blue staining nuclei at basal level with pink staining areas signifying zymogen granules in apical area

Question 2

What do zymogen granules contain?

Answer 2

Proteases (95%), lipase, amylase

Question 3

Describe the feedback regulation of pancreatic secretion:

Answer 3

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

Question 4

What is main cause of acute pancreatitis?

Answer 4

Autodigestion

Question 5

What is histology of moderate/mild acute pancreatitis? (3)

What is histology of severe pancreatic? (3)

Answer 5

Mild: inflammation, acinar cell vacuolization, preservation of architecture

Severe: Inflammatory infiltrate, Hemorrhage/necrosis, Loss of pancreatic architecture (acini)

Question 6

What are some of acinar cell responses in acute pancreatitis?

Answer 6

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

Question 7

What are examples of secretagogue hyperstimulation model? (3)

Answer 7

Cholinergic stimluation
High concentration of CCK
Caerulein

Occurs as a result of scorpion sting

Question 8

Describe duct obstruction and bile acid cause of acute pancreatitis: what is human equivalent?

Answer 8

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

Question 9

What are two mechanisms of gallstone pancreatitis?

Answer 9

Common channel mode: redirect bile acid up pancreatic duct=>probably wrong

Obstruction of pancreatic outflow or both ducts==>this is probably more correct

Question 10

Diet induced pancreatitis:

Answer 10

Choline deficiency

CDE (choline deficient diet with ethionines)=>more severe pancreatitis due to disruption of stimulus-secretion coupling

Question 11

Characteristics of autoimmune pancreatitis:
Main symptom
Histology
Treatment

Answer 11

Obstructive jaundice
Lymphoplasmacytic infiltrate and fibrosis
Steroid responsive

Question 12

Imaging: autoimmune pancreatitis

Answer 12

Enlargement of pancreas

Question 13

What are lab values in autoimmune pancreatitis: genetics (HLA), autoantibodies, Ig

Answer 13

Predisposition: HLA DRB1 and DQB1
Autoantibodies: ANA, PSTI, lactoferrin
IgG4 elavation

Question 14

Describe the histological findings in autoimmune pancreatitis

Answer 14

Fibrosis
Inflammatory infiltrate in duct cells
Stain positive for IgG plasma cells

Question 15

Describe the difference between classic AIP and IDCP

Answer 15

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

Question 16

Describe chronic pancreatitis pathogenesis: (2)

Answer 16

Multiple episodes of subclinical pancreatitis

Single injury that persists

Question 17

Describe animal models of chronic pancreatitis (5)

Answer 17

Partial/complete duct obstruction
Repeated injection of cerulean
Chronic EtOH feeding +LPS injection
IV injection of dibutyltin dichloride
CDE diet: chronic/intermittent feeding

Question 18

What is a common mutation in chronic pancreatitis?

Answer 18

KRAS– 30% of chronic pancreatitis and 90% pancreatic adenocarcinoma

Question 19

What is hereditary pancreatitis?

Describe the epidemiology: age of onset, how many people get chronic pancreatitis and pancreatic cancer respectively

Answer 19

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

Question 20

What is CF?

Answer 20

Autosomal recessive mutation in CFTR gene often diagnosed within 1st year of life

Question 21

What is SPINK mutations?

Answer 21

A mutation that predisposes to early development of pancreatitis

Question 22

What are environmental risks for pancreatitis?

Answer 22

EtOH
Smoking
EtOH and smoking are synergistic

Question 23

How is acute pancreatitis defined?

Answer 23

2 of 3:
Abdominal pain
Amylase or lipase >3x upper limit of normal
Abdominal imaging that confirms pancreatitis (calcifications)

Question 24

What are main causes of acute pancreatitis

Answer 24

Alcohol, biliary, idiopathic, autoimmune, drug-induced, IBD, infectious, inherited

Question 25

What are common causes of drug-induced pancreatitis? (6)

Answer 25

Aspariginase
Azathioprine
6MP
DDI
Pentamidine
Valproate

Question 26

What are manifestations of pancreatic insufficiency? (4)

Answer 26

Carb/protein/fat malabsorption
Malnutrition
Bone disease
Systemic disease

Question 27

What are categories of symptoms of exocrine pancreatic insufficiency? (3)

Answer 27

Steatorrhea
Fat-soluble vitamin (A,D,E,K) deficiency: metabolic bone disease, easy bruising/bleeding
Abdominal symptoms: diarrhea, bloating, pain, flatulence