Pancreas

Question 1

List 11 factors that can reduce the effects of supplemental pancreatic enzymes

Answer 1

Non-adherence to prescribed dosing
Expired enzymes
Inactivated enzymes due to prolonged exposure to heat
High acidic small intestinal environment
Prolonged exposure of microspheres to alkaline foods
Taking enzymes after eating
Grazing
Generic enzymes with lower potency
Chewed or crushed microspheres
Inadequate dose of enzymes reaching the small intestine
Glycine-conjugated bile acids limit micelle formation

Question 2

What type of inheritance pattern is CF

Answer 2

Autosomal Recessive

Question 3

How many class of CFTR mutations are there

Answer 3

Class I
Little or no protein synthesis b/c of premature termination signals

Class II
Defective processing or trafficking of CFTR protein
-F508 delta
-Prevents normal glycosylation -(retained in ER where it is degraded instead of being transported and inserted into the apical cellular membrane)

Class III
Proteins processed properly but lack adequate function due to impaired ATP binding and hydrolysis limits energy dependent channel from opening or “gating”

Class IV
Characterized by alterations of conductance and have reduced cAMP-regulated currents in the chloride channel

Class V mutations
Affects splicing of messenger RNA (mRNA) producing extra or skipped exons
-Affects the stability of the protein on the cell membrane

Question 4

Which classes of CF mutations are associated with more severe disease

Answer 4

Class I, II and III associated with more severe pulmonary disease and pancreatic insufficiency

Question 5

How does CFTR Function in the Pancreas

Answer 5

CFTR in the cell membrane of centroacinar and intralobular duct epithelium

• secretes fluid with high {Na bicarb]
• functions as a bicarbonate channel
• Cl-/HCO3- exchanger in pancreatic duct cells

Question 6

How does CFTR mutations affect patients in CF

Answer 6

-abnormal CFTR limits Cl/HCO3 exchange, results in more viscous Na HCO3 depleted fluid
contributes to ductal inspissation unable to carry pancreatic enzymes adequately and efficiency from the pancreas to duodenum

Question 7

What is the histologic findings of the CF pancreas

Answer 7

• focal intraluminal eosinophilic infiltration with pancreatic duct dilation
• progression of acinar atrophy
• fibrosis with ductal ectasia
• total loss of acinar tissue and ductal obliteration
• islet of langerhans are diminished but not totally destroyed