{"version":"1.0.0","segments":[{"startTime":0.407,"endTime":3.3,"body":"[upbeat intro music]"},{"startTime":3.3,"endTime":5.69,"body":"[Dr. Handy] Hi, welcome"},{"startTime":3.3,"endTime":5.69,"body":"to Harrison's PodClass,"},{"startTime":5.69,"endTime":8.83,"body":"where we discuss important"},{"startTime":5.69,"endTime":8.83,"body":"concepts in internal medicine."},{"startTime":8.83,"endTime":9.96,"body":"I'm Cathy Handy."},{"startTime":9.96,"endTime":11.74,"body":"[Dr. Wiener] And I'm Charlie"},{"startTime":9.96,"endTime":11.74,"body":"Wiener and we're coming to you"},{"startTime":11.74,"endTime":13.84,"body":"from the Johns Hopkins School of Medicine."},{"startTime":15.89,"endTime":17.449,"body":"Welcome to episode 91,"},{"startTime":17.449,"endTime":20.16,"body":"a 25-year-old with chronic pancreatitis."},{"startTime":20.16,"endTime":23.085,"body":"Okay, Cathy, today we're"},{"startTime":20.16,"endTime":23.085,"body":"discussing a 25-year-old woman"},{"startTime":23.085,"endTime":25.41,"body":"who's diagnosed with chronic pancreatitis."},{"startTime":25.41,"endTime":26.87,"body":"[Dr. Handy] Well, age is"},{"startTime":25.41,"endTime":26.87,"body":"going to be important here"},{"startTime":26.87,"endTime":28.48,"body":"because the differential diagnosis"},{"startTime":28.48,"endTime":31.59,"body":"for what causes chronic"},{"startTime":28.48,"endTime":31.59,"body":"pancreatitis in a young person"},{"startTime":31.59,"endTime":32.84,"body":"is going to be a little bit different"},{"startTime":32.84,"endTime":34.47,"body":"than someone who's much older."},{"startTime":34.47,"endTime":35.64,"body":"[Dr. Wiener] What do you mean by that?"},{"startTime":35.64,"endTime":37.63,"body":"[Dr. Handy] Well, I think"},{"startTime":35.64,"endTime":37.63,"body":"more of genetic abnormalities"},{"startTime":37.63,"endTime":40.12,"body":"that would've contributed when"},{"startTime":37.63,"endTime":40.12,"body":"someone of this age presents."},{"startTime":40.12,"endTime":42.12,"body":"So maybe from cystic fibrosis"},{"startTime":42.12,"endTime":44.37,"body":"or a congenital anatomic abnormality"},{"startTime":44.37,"endTime":46.29,"body":"such as pancreas divisum."},{"startTime":46.29,"endTime":47.15,"body":"[Dr. Wiener] What would"},{"startTime":46.29,"endTime":47.15,"body":"you add to the list"},{"startTime":47.15,"endTime":49.9,"body":"if she were, say, like 65 instead of 25?"},{"startTime":49.9,"endTime":51.16,"body":"[Dr. Handy] Well, in the United States,"},{"startTime":51.16,"endTime":53.04,"body":"alcoholism is the most common cause"},{"startTime":53.04,"endTime":55.32,"body":"of clinically apparent"},{"startTime":53.04,"endTime":55.32,"body":"chronic pancreatitis."},{"startTime":55.32,"endTime":58.3,"body":"Remember, chronic pancreatitis"},{"startTime":55.32,"endTime":58.3,"body":"is typically the end result"},{"startTime":58.3,"endTime":60.74,"body":"of prior episodes of acute pancreatitis"},{"startTime":60.74,"endTime":62.28,"body":"and is essentially irreversible."},{"startTime":62.28,"endTime":64.177,"body":"However, there's probably"},{"startTime":62.28,"endTime":64.177,"body":"more to the story."},{"startTime":64.177,"endTime":66.42,"body":"[Dr. Wiener] There always is."},{"startTime":66.42,"endTime":67.477,"body":"[Dr. Handy chuckles] Yeah,"},{"startTime":66.42,"endTime":67.477,"body":"because there are many"},{"startTime":67.477,"endTime":69.93,"body":"heavy drinkers that don't"},{"startTime":67.477,"endTime":69.93,"body":"develop chronic pancreatitis"},{"startTime":69.93,"endTime":72.62,"body":"and often light drinkers develop it too."},{"startTime":72.62,"endTime":74.89,"body":"Up to 25% of patients are described"},{"startTime":74.89,"endTime":77.61,"body":"as having idiopathic chronic pancreatitis."},{"startTime":77.61,"endTime":78.77,"body":"This is really stimulated"},{"startTime":78.77,"endTime":80.55,"body":"further research into the mechanisms"},{"startTime":80.55,"endTime":82.64,"body":"and some interesting genetic associations"},{"startTime":82.64,"endTime":84.57,"body":"are being discovered in that group."},{"startTime":84.57,"endTime":86.6,"body":"We already mentioned cystic fibrosis"},{"startTime":86.6,"endTime":89.2,"body":"which is caused by a defect"},{"startTime":86.6,"endTime":89.2,"body":"in the cystic fibrosis"},{"startTime":89.2,"endTime":92.16,"body":"transmembrane conductance"},{"startTime":89.2,"endTime":92.16,"body":"regulator protein system,"},{"startTime":92.16,"endTime":94.63,"body":"and some investigators"},{"startTime":92.16,"endTime":94.63,"body":"have found abnormalities"},{"startTime":94.63,"endTime":96.9,"body":"in that system independent of a diagnosis"},{"startTime":96.9,"endTime":98.91,"body":"of traditional cystic fibrosis."},{"startTime":98.91,"endTime":100.74,"body":"[Dr. Wiener] Okay, well, let's"},{"startTime":98.91,"endTime":100.74,"body":"get back to the question."},{"startTime":100.74,"endTime":101.883,"body":"This woman does, in fact,"},{"startTime":101.883,"endTime":104.73,"body":"have a long standing"},{"startTime":101.883,"endTime":104.73,"body":"diagnosis of cystic fibrosis."},{"startTime":104.73,"endTime":106.99,"body":"And the question asks, she is at risk"},{"startTime":106.99,"endTime":110.24,"body":"for all of the following"},{"startTime":106.99,"endTime":110.24,"body":"complications, except?"},{"startTime":110.24,"endTime":113.64,"body":"Option A. is vitamin B12 deficiency;"},{"startTime":113.64,"endTime":116.58,"body":"option B. is vitamin A deficiency;"},{"startTime":116.58,"endTime":119.42,"body":"option C. is pancreatic carcinoma;"},{"startTime":119.42,"endTime":122.18,"body":"option D. is niacin deficiency;"},{"startTime":122.18,"endTime":124.54,"body":"and option E. is steatorrhea."},{"startTime":124.54,"endTime":126.42,"body":"[Dr. Handy] All right, well,"},{"startTime":124.54,"endTime":126.42,"body":"this question is not specific"},{"startTime":126.42,"endTime":128.22,"body":"to patients with cystic fibrosis"},{"startTime":128.22,"endTime":131.24,"body":"and really applies to all"},{"startTime":128.22,"endTime":131.24,"body":"patients with pancreatitis."},{"startTime":131.24,"endTime":132.463,"body":"These options all relate"},{"startTime":132.463,"endTime":134.97,"body":"to the exocrine function of the pancreas."},{"startTime":134.97,"endTime":136.86,"body":"Now patients with chronic pancreatitis"},{"startTime":136.86,"endTime":138.88,"body":"typically wind up with both endocrine"},{"startTime":138.88,"endTime":140.83,"body":"and exocrine dysfunction."},{"startTime":140.83,"endTime":141.69,"body":"While not mentioned,"},{"startTime":141.69,"endTime":144.62,"body":"patients with chronic"},{"startTime":141.69,"endTime":144.62,"body":"pancreatitis can develop diabetes"},{"startTime":144.62,"endTime":146.25,"body":"due to the endocrine insufficiency"},{"startTime":146.25,"endTime":148.33,"body":"and loss of islet cell function."},{"startTime":148.33,"endTime":150.76,"body":"While these patients may"},{"startTime":148.33,"endTime":150.76,"body":"require insulin therapy,"},{"startTime":150.76,"endTime":152.76,"body":"they're not as prone to DKA"},{"startTime":152.76,"endTime":155.3,"body":"as patients with pure type I diabetes."},{"startTime":155.3,"endTime":156.767,"body":"[Dr. Wiener] Okay, so"},{"startTime":155.3,"endTime":156.767,"body":"let's talk more about"},{"startTime":156.767,"endTime":159.72,"body":"the exocrine dysfunction"},{"startTime":156.767,"endTime":159.72,"body":"or exocrine function."},{"startTime":159.72,"endTime":161.768,"body":"[Dr. Handy] Because pancreatic"},{"startTime":159.72,"endTime":161.768,"body":"enzymes are essential"},{"startTime":161.768,"endTime":163.063,"body":"for fat digestion,"},{"startTime":163.063,"endTime":167.2,"body":"their absence leads to fat"},{"startTime":163.063,"endTime":167.2,"body":"malabsorption and steatorrhea."},{"startTime":167.2,"endTime":169.01,"body":"Patients with chronic pancreatitis"},{"startTime":169.01,"endTime":171.283,"body":"often develop maldigestion,"},{"startTime":171.283,"endTime":173.38,"body":"and they can also have weight loss."},{"startTime":173.38,"endTime":176.31,"body":"Now maldigestion is manifested"},{"startTime":173.38,"endTime":176.31,"body":"as chronic diarrhea,"},{"startTime":176.31,"endTime":178.86,"body":"steatorrhea, weight loss, and fatigue."},{"startTime":178.86,"endTime":180.95,"body":"In addition, the fat-soluble vitamins,"},{"startTime":180.95,"endTime":184.79,"body":"which, remember, are"},{"startTime":180.95,"endTime":184.79,"body":"vitamins A, D, E, and K,"},{"startTime":184.79,"endTime":186.77,"body":"are not well absorbed."},{"startTime":186.77,"endTime":189.56,"body":"Vitamin A deficiency"},{"startTime":186.77,"endTime":189.56,"body":"can lead to neuropathy."},{"startTime":189.56,"endTime":192.88,"body":"Vitamin B12 or cobalamin"},{"startTime":189.56,"endTime":192.88,"body":"is often deficient."},{"startTime":192.88,"endTime":195.27,"body":"This deficiency is hypothesized to be due"},{"startTime":195.27,"endTime":197.4,"body":"to excessive binding of cobalamin"},{"startTime":197.4,"endTime":199.43,"body":"by cobalamin-binding proteins"},{"startTime":199.43,"endTime":201.68,"body":"other than intrinsic"},{"startTime":199.43,"endTime":201.68,"body":"factors that are normally"},{"startTime":201.68,"endTime":203.96,"body":"digested by pancreatic enzymes."},{"startTime":203.96,"endTime":206.91,"body":"[Dr. Wiener] Okay, so so far"},{"startTime":203.96,"endTime":206.91,"body":"you've mentioned steatorrhea,"},{"startTime":206.91,"endTime":210.78,"body":"deficiency of vitamin A and"},{"startTime":206.91,"endTime":210.78,"body":"deficiency of vitamin B12."},{"startTime":210.78,"endTime":213.871,"body":"What about the pancreatic"},{"startTime":210.78,"endTime":213.871,"body":"carcinoma or niacin deficiency?"},{"startTime":213.871,"endTime":216.48,"body":"[Dr. Handy] Well, the incidence"},{"startTime":213.871,"endTime":216.48,"body":"of pancreatic adenocarcinoma"},{"startTime":216.48,"endTime":219.07,"body":"is increased in patients"},{"startTime":216.48,"endTime":219.07,"body":"with chronic pancreatitis"},{"startTime":219.07,"endTime":222.97,"body":"with a 20-year cumulative"},{"startTime":219.07,"endTime":222.97,"body":"incidence of about 4%."},{"startTime":222.97,"endTime":224.93,"body":"[Dr. Wiener] Okay, so that leaves niacin"},{"startTime":224.93,"endTime":227.88,"body":"or vitamin B3 as the answer, correct?"},{"startTime":227.88,"endTime":228.78,"body":"[Dr. Handy] Right. That's the answer."},{"startTime":228.78,"endTime":230.59,"body":"So that's a water-soluble vitamin"},{"startTime":230.59,"endTime":233.913,"body":"and it's not affected by"},{"startTime":230.59,"endTime":233.913,"body":"pancreatic exocrine insufficiency."},{"startTime":233.913,"endTime":236.05,"body":"[Dr. Wiener] What's the approach"},{"startTime":233.913,"endTime":236.05,"body":"to therapy in these patients?"},{"startTime":236.05,"endTime":238.678,"body":"[Dr. Handy] Replacement of"},{"startTime":236.05,"endTime":238.678,"body":"pancreatic enzymes orally with"},{"startTime":238.678,"endTime":240.785,"body":"meals will correct the"},{"startTime":238.678,"endTime":240.785,"body":"vitamin deficiencies"},{"startTime":240.785,"endTime":243.835,"body":"and the steatorrhea, and"},{"startTime":240.785,"endTime":243.835,"body":"patients may also use vitamin"},{"startTime":243.835,"endTime":246.35,"body":"supplements depending"},{"startTime":243.835,"endTime":246.35,"body":"on their overall diet."},{"startTime":246.35,"endTime":248.19,"body":"[Dr. Wiener] So finally,"},{"startTime":246.35,"endTime":248.19,"body":"there's been great excitement"},{"startTime":248.19,"endTime":251.2,"body":"in the pulmonary world about"},{"startTime":248.19,"endTime":251.2,"body":"the role of CFTR modulators"},{"startTime":251.2,"endTime":253.23,"body":"in patients with cystic fibrosis."},{"startTime":253.23,"endTime":254.67,"body":"They have the potential to correct some"},{"startTime":254.67,"endTime":257.05,"body":"of the molecular defects"},{"startTime":254.67,"endTime":257.05,"body":"in cystic fibrosis"},{"startTime":257.05,"endTime":258.61,"body":"and have been shown to improve or slow"},{"startTime":258.61,"endTime":260.54,"body":"the deterioration of lung function"},{"startTime":260.54,"endTime":263.08,"body":"and decrease respiratory exacerbations."},{"startTime":263.08,"endTime":265.038,"body":"What about the pancreatic manifestations"},{"startTime":265.038,"endTime":267.43,"body":"of CF in response to these drugs?"},{"startTime":267.43,"endTime":268.82,"body":"[Dr. Handy] Well, that's"},{"startTime":267.43,"endTime":268.82,"body":"a fascinating question"},{"startTime":268.82,"endTime":270.95,"body":"and there's active research in that area."},{"startTime":270.95,"endTime":273.23,"body":"Right now, I think"},{"startTime":270.95,"endTime":273.23,"body":"patients are still taking"},{"startTime":273.23,"endTime":274.65,"body":"their pancreatic supplements,"},{"startTime":274.65,"endTime":277.58,"body":"but many have been able"},{"startTime":274.65,"endTime":277.58,"body":"to reduce the doses."},{"startTime":277.58,"endTime":279.66,"body":"Also, there are interesting"},{"startTime":277.58,"endTime":279.66,"body":"and exciting studies"},{"startTime":279.66,"endTime":281.84,"body":"coming out that describe"},{"startTime":279.66,"endTime":281.84,"body":"dramatic reductions"},{"startTime":281.84,"endTime":284.6,"body":"in the frequency of episodes"},{"startTime":281.84,"endTime":284.6,"body":"of acute pancreatitis"},{"startTime":284.6,"endTime":287.25,"body":"in patients taking CFTR modulators."},{"startTime":287.25,"endTime":288.81,"body":"That should result in fewer chronic"},{"startTime":288.81,"endTime":290.8,"body":"pancreatitis complications."},{"startTime":290.8,"endTime":293.42,"body":"[Dr. Wiener] It's an amazing"},{"startTime":290.8,"endTime":293.42,"body":"time for cystic fibrosis."},{"startTime":293.42,"endTime":295.7,"body":"So the teaching points"},{"startTime":293.42,"endTime":295.7,"body":"in this case is that"},{"startTime":295.7,"endTime":297.44,"body":"patients with chronic pancreatitis,"},{"startTime":297.44,"endTime":299.29,"body":"including those with cystic fibrosis,"},{"startTime":299.29,"endTime":301.28,"body":"are at risk of pancreatic endocrine"},{"startTime":301.28,"endTime":303.29,"body":"and exocrine dysfunction."},{"startTime":303.29,"endTime":305.01,"body":"They have problems with fat digestion"},{"startTime":305.01,"endTime":307.79,"body":"and the absorption of"},{"startTime":305.01,"endTime":307.79,"body":"fat-soluble vitamins."},{"startTime":307.79,"endTime":309.41,"body":"Finally, there are exciting developments"},{"startTime":309.41,"endTime":312.22,"body":"regarding the potential"},{"startTime":309.41,"endTime":312.22,"body":"role of CFTR modulators"},{"startTime":312.22,"endTime":316.07,"body":"to reduce pancreatic"},{"startTime":312.22,"endTime":316.07,"body":"complications in patients with CF."},{"startTime":316.07,"endTime":317.39,"body":"[Dr. Handy] And you can"},{"startTime":316.07,"endTime":317.39,"body":"read more about this"},{"startTime":317.39,"endTime":319.984,"body":"in Harrison's chapter on cystic fibrosis."},{"startTime":319.984,"endTime":324.8,"body":"[upbeat outro music]"},{"startTime":324.8,"endTime":327.66,"body":"[Mr. Shanahan] This is Jim"},{"startTime":324.8,"endTime":327.66,"body":"Shanahan, publisher at McGraw Hill."},{"startTime":327.66,"endTime":329.28,"body":"Harrison's PodClass is brought to you"},{"startTime":329.28,"endTime":331.26,"body":"by McGraw Hill's AccessMedicine,"},{"startTime":331.26,"endTime":333.36,"body":"the online medical resource that delivers"},{"startTime":333.36,"endTime":336.59,"body":"the latest trusted content from"},{"startTime":333.36,"endTime":336.59,"body":"the best minds in medicine."},{"startTime":336.59,"endTime":339.123,"body":"Go to accessmedicine.com to learn more."}]}