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[Dr. Handy] Hi, welcome to Harrison's PodClass, where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener and we're coming to you from the Johns Hopkins School of Medicine. Welcome to episode 91, a 25-year-old with chronic pancreatitis. Okay, Cathy, today we're discussing a 25-year-old woman who's diagnosed with chronic pancreatitis.
[Dr. Handy] Well, age is going to be important here because the differential diagnosis for what causes chronic pancreatitis in a young person is going to be a little bit different than someone who's much older. [Dr. Wiener] What do you mean by that? [Dr. Handy] Well, I think more of genetic abnormalities that would've contributed when someone of this age presents. So maybe from cystic fibrosis or a congenital anatomic abnormality such as pancreas divisum.
[Dr. Wiener] What would you add to the list if she were, say, like 65 instead of 25? [Dr. Handy] Well, in the United States, alcoholism is the most common cause of clinically apparent chronic pancreatitis. Remember, chronic pancreatitis is typically the end result of prior episodes of acute pancreatitis and is essentially irreversible. However, there's probably more to the story. [Dr. Wiener] There always is.
[Dr. Handy chuckles] Yeah, because there are many heavy drinkers that don't develop chronic pancreatitis and often light drinkers develop it too. Up to 25% of patients are described as having idiopathic chronic pancreatitis. This is really stimulated further research into the mechanisms and some interesting genetic associations are being discovered in that group.
We already mentioned cystic fibrosis which is caused by a defect in the cystic fibrosis transmembrane conductance regulator protein system, and some investigators have found abnormalities in that system independent of a diagnosis of traditional cystic fibrosis. [Dr. Wiener] Okay, well, let's get back to the question. This woman does, in fact, have a long standing diagnosis of cystic fibrosis. And the question asks, she is at risk for all of the following complications, except?
Option A. is vitamin B12 deficiency; option B. is vitamin A deficiency; option C. is pancreatic carcinoma; option D. is niacin deficiency; and option E. is steatorrhea. [Dr. Handy] All right, well, this question is not specific to patients with cystic fibrosis and really applies to all patients with pancreatitis. These options all relate to the exocrine function of the pancreas. Now patients with chronic pancreatitis typically wind up with both endocrine and exocrine dysfunction.
While not mentioned, patients with chronic pancreatitis can develop diabetes due to the endocrine insufficiency and loss of islet cell function. While these patients may require insulin therapy, they're not as prone to DKA as patients with pure type I diabetes. [Dr. Wiener] Okay, so let's talk more about the exocrine dysfunction or exocrine function. [Dr. Handy] Because pancreatic enzymes are essential for fat digestion, their absence leads to fat malabsorption and steatorrhea.
Patients with chronic pancreatitis often develop maldigestion, and they can also have weight loss. Now maldigestion is manifested as chronic diarrhea, steatorrhea, weight loss, and fatigue. In addition, the fat-soluble vitamins, which, remember, are vitamins A, D, E, and K, are not well absorbed. Vitamin A deficiency can lead to neuropathy. Vitamin B12 or cobalamin is often deficient.
This deficiency is hypothesized to be due to excessive binding of cobalamin by cobalamin-binding proteins other than intrinsic factors that are normally digested by pancreatic enzymes. [Dr. Wiener] Okay, so so far you've mentioned steatorrhea, deficiency of vitamin A and deficiency of vitamin B12. What about the pancreatic carcinoma or niacin deficiency?
[Dr. Handy] Well, the incidence of pancreatic adenocarcinoma is increased in patients with chronic pancreatitis with a 20-year cumulative incidence of about 4%. [Dr. Wiener] Okay, so that leaves niacin or vitamin B3 as the answer, correct? [Dr. Handy] Right. That's the answer. So that's a water-soluble vitamin and it's not affected by pancreatic exocrine insufficiency. [Dr. Wiener] What's the approach to therapy in these patients?
[Dr. Handy] Replacement of pancreatic enzymes orally with meals will correct the vitamin deficiencies and the steatorrhea, and patients may also use vitamin supplements depending on their overall diet. [Dr. Wiener] So finally, there's been great excitement in the pulmonary world about the role of CFTR modulators in patients with cystic fibrosis.
They have the potential to correct some of the molecular defects in cystic fibrosis and have been shown to improve or slow the deterioration of lung function and decrease respiratory exacerbations. What about the pancreatic manifestations of CF in response to these drugs? [Dr. Handy] Well, that's a fascinating question and there's active research in that area. Right now, I think patients are still taking their pancreatic supplements, but many have been able to reduce the doses.
Also, there are interesting and exciting studies coming out that describe dramatic reductions in the frequency of episodes of acute pancreatitis in patients taking CFTR modulators. That should result in fewer chronic pancreatitis complications. [Dr. Wiener] It's an amazing time for cystic fibrosis. So the teaching points in this case is that patients with chronic pancreatitis, including those with cystic fibrosis, are at risk of pancreatic endocrine and exocrine dysfunction.
They have problems with fat digestion and the absorption of fat-soluble vitamins. Finally, there are exciting developments regarding the potential role of CFTR modulators to reduce pancreatic complications in patients with CF. [Dr. Handy] And you can read more about this in Harrison's chapter on cystic fibrosis. [upbeat outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill.
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