Explain why cystic fibrosis is associated with abnormalities in pancreatic exocrine function

[Guest guest]

Kathleen O’Connell

Fish

Henkle

Case5, Objective 6

1.Explain why cystic fibrosis is associated with abnormalities in pancreatic

exocrine function.

The absence of a functional CFTR Cl- channel in the apical membrane of

pancreatic duct epithelium limits the function of a HCO3-/Cl- exchanger to

secrete bicarbonate and sodium into the duct.The absence of NaHCO3 and water in

the duct leads to retention of the digestive enzymes of the pancreas (amylases,

nucleases, proteases, and lipases) due to thick, sticky, dehydrated secretions

obstructing the duct and necrosis of the pancreatic acinar (exocrine) tissue

because of the ductular obstruction with the thick secretions.In addition, the

duodenum is at a pH well below the optimal range for pancreatic enzymes because

no bicarbonate is present to neutralize the acidity of the chyme from the

stomach, leading to sub-threshold activity or denaturing of the pancreatic

enzymes.1,2

2.Explain the steatorrhea in these patients and the impaired absorption of fat

soluble vitamins.Explain why gastric lipase activity assumes greater importance

in fat digestion in patients with cystic fibrosis.

Pancreatic lipase is an enzyme secreted by the pancreas into the duodenum that

digests triacylglycerols into free fatty acids and 2-monoacylglycerol.These

molecules are then packaged into micelles and absorbed by the intestinal

epithelia.1In CF patients, pancreatic lipase never makes it into the duodenum

and thus lipids are never broken down.Because of this, gastic lipase, an enzyme

of the stomach, assumes a greater role in lipid digestion because it is the only

enzyme left to digest lipids.Gastric lipase emulsifies fat in the stomach prior

to digestion of pancreatic lipase.However, gastric lipase cannot compensate for

the lack of pancreatic lipase and thus steatorrhea is produced.2Steatorrhea is

defined as bulky, foul smelling, and fat droplet filled stool, and is

characteristic of most CF patients.Normally, about 5 grams of fat are excreted

in stool each day; however, CF patients excrete as much as 50 grams/day.1In

addition, a deficiency of fat soluble vitamins (A,D,E, and K) results because

not enough micelles containing these vitamins are being absorbed.4

3.Explain why some patients with cystic fibrosis may eventually develop diabetes

mellitus.

Diabetes mellitus, resulting in hyperglycemia, is caused by the increased

destruction of pancreatic tissue as CF progresses, including the endocrine cells

(Islets of Langerhans) which produce insulin and glucagon.Necrosis of the

pancreatic tissue is caused by ductular obstruction of the exocrine tissue.2

1)Rhoades and Tanner.Medical Physiology.Boston:Little, Brown, and Co.,

(1995).pp. 556, 559, 562.

2)Rudolf’s Pediatrics-20th Ed.(1996)

21.The Respiratory System- Hazinski Associate Editor

21.6Lung Diseases in Kids

21.6.5 Cystic Fibrosis

<http://www.dana.medlib.iupui.edu/tserver/statref.dll>

3)Beers M.H. and Berkow R.The Merck Manual of Diagnosis and

Therapy.17th(1999).pp. 2366-2368.

4)Stein Internal Medicine-4th Ed. (1994)

Part Two-Alimentary Tract, Liver, Biliary Tree, and Pancreas

VI.Liver, Biliary Tree, and Pancreas-Clinical syndromes and specific disease

Chapter 67.Pancreatic Diseases

<http://www.dana.medlib.iupui.edu/tserver/statref.dll>

Mark E. Armstrong

www.top5plus5.com

Oregon State Chapter Rep

Pancreatitis Association, International