{"version":"1.0.0","segments":[{"startTime":0.319,"endTime":3.3,"body":"[upbeat intro music]"},{"startTime":3.3,"endTime":5.602,"body":"[Dr. Handy] Hi, welcome"},{"startTime":3.3,"endTime":5.602,"body":"to Harrison's PodClass,"},{"startTime":5.602,"endTime":8.85,"body":"where we discuss important"},{"startTime":5.602,"endTime":8.85,"body":"concepts in internal medicine."},{"startTime":8.85,"endTime":10.0,"body":"I'm Cathy Handy."},{"startTime":10.0,"endTime":11.721,"body":"[Dr. Wiener] And I'm Charlie"},{"startTime":10.0,"endTime":11.721,"body":"Wiener, and we're coming to you"},{"startTime":11.721,"endTime":13.85,"body":"from the Johns Hopkins School of Medicine."},{"startTime":15.93,"endTime":18.45,"body":"[Dr. Handy] Welcome back,"},{"startTime":15.93,"endTime":18.45,"body":"everyone, to Harrison's PodClass."},{"startTime":18.45,"endTime":20.723,"body":"Today's episode is a 28-year-old woman"},{"startTime":20.723,"endTime":22.58,"body":"with sickle cell disease."},{"startTime":22.58,"endTime":25.243,"body":"[Dr. Wiener] So, today's"},{"startTime":22.58,"endTime":25.243,"body":"patient is a 28-year-old"},{"startTime":25.243,"endTime":26.803,"body":"who presents to you for follow-up"},{"startTime":26.803,"endTime":28.718,"body":"after she's had a recent hospitalization"},{"startTime":28.718,"endTime":30.76,"body":"for a sickle cell pain crisis."},{"startTime":30.76,"endTime":31.84,"body":"Before we get to the question,"},{"startTime":31.84,"endTime":33.39,"body":"let's start today by talking a little bit"},{"startTime":33.39,"endTime":35.963,"body":"about the pathophysiology"},{"startTime":33.39,"endTime":35.963,"body":"about sickle cell disease,"},{"startTime":35.963,"endTime":38.273,"body":"since I think that'll help"},{"startTime":35.963,"endTime":38.273,"body":"us with today's question."},{"startTime":38.273,"endTime":40.682,"body":"[Dr. Handy] Okay, the sickle"},{"startTime":38.273,"endTime":40.682,"body":"cell syndromes are caused"},{"startTime":40.682,"endTime":42.9,"body":"by a mutation in the beta-globin gene"},{"startTime":42.9,"endTime":44.845,"body":"that changes the sixth amino acid"},{"startTime":44.845,"endTime":47.2,"body":"from glutamic acid to valine."},{"startTime":47.2,"endTime":50.62,"body":"Hemoglobin S polymerizes"},{"startTime":47.2,"endTime":50.62,"body":"reversibly when deoxygenated"},{"startTime":50.62,"endTime":52.633,"body":"to form a network of fibrous polymers"},{"startTime":52.633,"endTime":54.647,"body":"that stiffen the red blood cell membrane,"},{"startTime":54.647,"endTime":57.1,"body":"increase viscosity, and cause dehydration"},{"startTime":57.1,"endTime":59.511,"body":"due to potassium leakage"},{"startTime":57.1,"endTime":59.511,"body":"and calcium influx."},{"startTime":59.511,"endTime":61.34,"body":"[Dr. Wiener] So these are"},{"startTime":59.511,"endTime":61.34,"body":"the changes that produce"},{"startTime":61.34,"endTime":63.995,"body":"the characteristic red blood"},{"startTime":61.34,"endTime":63.995,"body":"cell sickle shape, right?"},{"startTime":63.995,"endTime":66.75,"body":"[Dr. Handy] Right, and sickled"},{"startTime":63.995,"endTime":66.75,"body":"cells lose the pliability"},{"startTime":66.75,"endTime":68.85,"body":"needed to traverse small capillaries."},{"startTime":68.85,"endTime":71.603,"body":"They also possess altered"},{"startTime":68.85,"endTime":71.603,"body":"or sticky membranes"},{"startTime":71.603,"endTime":73.04,"body":"that are abnormally adherent"},{"startTime":73.04,"endTime":75.318,"body":"to the endothelium of small venules."},{"startTime":75.318,"endTime":78.083,"body":"These abnormalities provoke"},{"startTime":75.318,"endTime":78.083,"body":"unpredictable episodes"},{"startTime":78.083,"endTime":80.13,"body":"of microvascular vaso-occlusion"},{"startTime":80.13,"endTime":82.14,"body":"and premature red blood cell destruction"},{"startTime":82.14,"endTime":83.87,"body":"in the liver and the spleen."},{"startTime":83.87,"endTime":86.23,"body":"They also clog small"},{"startTime":83.87,"endTime":86.23,"body":"capillaries and venules,"},{"startTime":86.23,"endTime":88.528,"body":"causing tissue ischemia, acute pain,"},{"startTime":88.528,"endTime":90.623,"body":"and gradually end organ damage."},{"startTime":90.623,"endTime":92.37,"body":"And this veno-occlusive component"},{"startTime":92.37,"endTime":94.518,"body":"usually dominates the clinical course."},{"startTime":94.518,"endTime":96.89,"body":"[Dr. Wiener] Okay, well, let's get"},{"startTime":94.518,"endTime":96.89,"body":"back to our patient for a moment."},{"startTime":96.89,"endTime":100.56,"body":"So, her clinical course has"},{"startTime":96.89,"endTime":100.56,"body":"been characterized by having,"},{"startTime":100.56,"endTime":103.27,"body":"on average, about one"},{"startTime":100.56,"endTime":103.27,"body":"hospitalization a month"},{"startTime":103.27,"endTime":105.54,"body":"for painful crises over the past year."},{"startTime":105.54,"endTime":107.96,"body":"And she's also had at least one episode"},{"startTime":107.96,"endTime":110.58,"body":"of an acute chest syndrome"},{"startTime":107.96,"endTime":110.58,"body":"within the last year."},{"startTime":110.58,"endTime":112.89,"body":"So, tell me more about painful crises."},{"startTime":112.89,"endTime":115.12,"body":"[Dr. Handy] So, these"},{"startTime":112.89,"endTime":115.12,"body":"recurrent painful episodes"},{"startTime":115.12,"endTime":117.243,"body":"are the most common clinical manifestation"},{"startTime":117.243,"endTime":120.202,"body":"and their frequency and"},{"startTime":117.243,"endTime":120.202,"body":"severity can vary greatly."},{"startTime":120.202,"endTime":122.28,"body":"Pain can develop almost"},{"startTime":120.202,"endTime":122.28,"body":"anywhere in the body,"},{"startTime":122.28,"endTime":125.453,"body":"it may last from a few"},{"startTime":122.28,"endTime":125.453,"body":"hours to a couple of weeks."},{"startTime":125.453,"endTime":128.363,"body":"Now, repeated crises"},{"startTime":125.453,"endTime":128.363,"body":"requiring hospitalization"},{"startTime":128.363,"endTime":131.048,"body":"can correlate with reduced"},{"startTime":128.363,"endTime":131.048,"body":"survival in adult life,"},{"startTime":131.048,"endTime":133.29,"body":"suggesting that these"},{"startTime":131.048,"endTime":133.29,"body":"episodes are associated"},{"startTime":133.29,"endTime":135.94,"body":"with accumulation of"},{"startTime":133.29,"endTime":135.94,"body":"chronic end organ damage."},{"startTime":135.94,"endTime":138.837,"body":"[Dr. Wiener] So given that"},{"startTime":135.94,"endTime":138.837,"body":"this woman has had 12 episodes"},{"startTime":138.837,"endTime":139.87,"body":"in the past year,"},{"startTime":139.87,"endTime":142.95,"body":"she is in that really worrisome"},{"startTime":139.87,"endTime":142.95,"body":"prognostic category, right?"},{"startTime":142.95,"endTime":143.783,"body":"[Dr. Handy] Yeah."},{"startTime":143.783,"endTime":145.62,"body":"[Dr. Wiener] What provokes"},{"startTime":143.783,"endTime":145.62,"body":"the painful crises?"},{"startTime":145.62,"endTime":146.52,"body":"[Dr. Handy] Well, we don't always know,"},{"startTime":146.52,"endTime":150.26,"body":"but some provocative factors"},{"startTime":146.52,"endTime":150.26,"body":"include infection, fever,"},{"startTime":150.26,"endTime":154.45,"body":"excessive exercise, anxiety,"},{"startTime":150.26,"endTime":154.45,"body":"abrupt changes in temperature,"},{"startTime":154.45,"endTime":157.0,"body":"hypoxia or hypertonic dyes."},{"startTime":157.0,"endTime":159.23,"body":"[Dr. Wiener] Okay, and what"},{"startTime":157.0,"endTime":159.23,"body":"about acute chest syndrome?"},{"startTime":159.23,"endTime":161.15,"body":"[Dr. Handy] So that's a"},{"startTime":159.23,"endTime":161.15,"body":"distinctive manifestation"},{"startTime":161.15,"endTime":164.1,"body":"characterized by chest"},{"startTime":161.15,"endTime":164.1,"body":"pain, tachypnea, fever,"},{"startTime":164.1,"endTime":167.088,"body":"cough and arterial oxygen desaturation."},{"startTime":167.088,"endTime":168.93,"body":"Acute chest syndrome is thought to be"},{"startTime":168.93,"endTime":171.37,"body":"due to in-situ sickling within the lung"},{"startTime":171.37,"endTime":173.46,"body":"and/or the bone marrow microemboli,"},{"startTime":173.46,"endTime":176.89,"body":"producing pain and temporary"},{"startTime":173.46,"endTime":176.89,"body":"pulmonary dysfunction."},{"startTime":176.89,"endTime":179.162,"body":"Often, it's difficult or impossible even"},{"startTime":179.162,"endTime":181.597,"body":"to distinguish among other possibilities."},{"startTime":181.597,"endTime":183.33,"body":"Pulmonary infarction and pneumonia"},{"startTime":183.33,"endTime":186.13,"body":"are the most frequent underlying"},{"startTime":183.33,"endTime":186.13,"body":"or concomitant conditions"},{"startTime":186.13,"endTime":187.95,"body":"in patients with this syndrome."},{"startTime":187.95,"endTime":189.88,"body":"[Dr. Wiener] I could see"},{"startTime":187.95,"endTime":189.88,"body":"where that would be confusing."},{"startTime":189.88,"endTime":192.29,"body":"Okay. Let's talk about her labs."},{"startTime":192.29,"endTime":194.643,"body":"On review of her labs, you"},{"startTime":192.29,"endTime":194.643,"body":"note that she has a hemoglobin"},{"startTime":194.643,"endTime":196.828,"body":"of 9.8 g/dL,"},{"startTime":196.828,"endTime":198.882,"body":"a hematocrit of 28%,"},{"startTime":198.882,"endTime":200.39,"body":"an MCV of 88,"},{"startTime":200.39,"endTime":202.218,"body":"and an MCH of 30."},{"startTime":202.218,"endTime":203.58,"body":"Are these typical?"},{"startTime":203.58,"endTime":204.89,"body":"[Dr. Handy] Yes, so most patients"},{"startTime":204.89,"endTime":207.63,"body":"with sickling syndrome"},{"startTime":204.89,"endTime":207.63,"body":"suffer from hemolytic anemia"},{"startTime":207.63,"endTime":210.82,"body":"with hematocrits from 15% to 30%,"},{"startTime":210.82,"endTime":213.208,"body":"and significant reticulocytosis."},{"startTime":213.208,"endTime":217.37,"body":"It is a microcytic or"},{"startTime":213.208,"endTime":217.37,"body":"normocytic normochromic anemia."},{"startTime":217.37,"endTime":219.96,"body":"Anemia was once thought to"},{"startTime":217.37,"endTime":219.96,"body":"exert protective effects"},{"startTime":219.96,"endTime":223.08,"body":"against vaso-occlusion by"},{"startTime":219.96,"endTime":223.08,"body":"reducing blood viscosity."},{"startTime":223.08,"endTime":226.2,"body":"However, natural history and"},{"startTime":223.08,"endTime":226.2,"body":"drug therapy trials suggest"},{"startTime":226.2,"endTime":228.27,"body":"that actually an increase"},{"startTime":226.2,"endTime":228.27,"body":"in the hematocrit"},{"startTime":228.27,"endTime":230.76,"body":"and feedback inhibition of reticulocytosis"},{"startTime":230.76,"endTime":233.368,"body":"might be beneficial, even"},{"startTime":230.76,"endTime":233.368,"body":"if it's at the expense of"},{"startTime":233.368,"endTime":235.8,"body":"slightly increased blood viscosity."},{"startTime":235.8,"endTime":237.937,"body":"Granulocytosis is also common."},{"startTime":237.937,"endTime":239.337,"body":"[Dr. Wiener] Okay, well,"},{"startTime":237.937,"endTime":239.337,"body":"we've finally gotten to"},{"startTime":239.337,"endTime":241.137,"body":"the question, and the"},{"startTime":239.337,"endTime":241.137,"body":"question's going to ask"},{"startTime":241.137,"endTime":243.2,"body":"about her peripheral blood smear."},{"startTime":243.2,"endTime":246.732,"body":"It asks, on review of her"},{"startTime":243.2,"endTime":246.732,"body":"peripheral blood smear,"},{"startTime":246.732,"endTime":249.72,"body":"in addition to seeing"},{"startTime":246.732,"endTime":249.72,"body":"sickled red blood cells,"},{"startTime":249.72,"endTime":252.59,"body":"what other characteristic"},{"startTime":249.72,"endTime":252.59,"body":"finding would you expect to see?"},{"startTime":252.59,"endTime":256.19,"body":"And the options are, A. burr cells;"},{"startTime":256.19,"endTime":259.19,"body":"option B. is Howell-Jolly bodies;"},{"startTime":259.19,"endTime":261.93,"body":"option C. is schistocytes;"},{"startTime":261.93,"endTime":264.4,"body":"option D. is spherocytes;"},{"startTime":264.4,"endTime":267.05,"body":"and option E. is target cells."},{"startTime":267.05,"endTime":269.052,"body":"[Dr. Handy] Okay, well, the"},{"startTime":267.05,"endTime":269.052,"body":"key to answering this question"},{"startTime":269.052,"endTime":272.01,"body":"is to know that repeated"},{"startTime":269.052,"endTime":272.01,"body":"microinfarction can destroy tissues"},{"startTime":272.01,"endTime":274.61,"body":"having microvascular"},{"startTime":272.01,"endTime":274.61,"body":"beds prone to sickling."},{"startTime":274.61,"endTime":276.458,"body":"So splenic function is frequently lost"},{"startTime":276.458,"endTime":279.225,"body":"within the first 18 to 36 months of life,"},{"startTime":279.225,"endTime":281.407,"body":"and in the absence of a functional spleen,"},{"startTime":281.407,"endTime":284.127,"body":"nuclear remnants are not"},{"startTime":281.407,"endTime":284.127,"body":"culled from the red cells"},{"startTime":284.127,"endTime":287.482,"body":"and remain as small homogeneously"},{"startTime":284.127,"endTime":287.482,"body":"staining blue inclusions"},{"startTime":287.482,"endTime":290.24,"body":"on Wright's stain, called"},{"startTime":287.482,"endTime":290.24,"body":"Howell-Jolly bodies."},{"startTime":290.24,"endTime":292.16,"body":"So the answer to the question is B."},{"startTime":292.16,"endTime":294.37,"body":"you would likely see Howell-Jolly bodies."},{"startTime":294.37,"endTime":295.3,"body":"[Dr. Wiener] And importantly,"},{"startTime":295.3,"endTime":298.12,"body":"the presence of those Howell-Jolly"},{"startTime":295.3,"endTime":298.12,"body":"bodies probably tell you"},{"startTime":298.12,"endTime":300.54,"body":"that this patient is"},{"startTime":298.12,"endTime":300.54,"body":"functionally hyposplenic."},{"startTime":300.54,"endTime":302.84,"body":"[Dr. Handy] Correct, and we"},{"startTime":300.54,"endTime":302.84,"body":"have a couple other episodes"},{"startTime":302.84,"endTime":305.33,"body":"that talk about clinical"},{"startTime":302.84,"endTime":305.33,"body":"consequences of that."},{"startTime":305.33,"endTime":306.858,"body":"[Dr. Wiener] Cool, so"},{"startTime":305.33,"endTime":306.858,"body":"where do you see the other"},{"startTime":306.858,"endTime":308.92,"body":"abnormalities? Let's go"},{"startTime":306.858,"endTime":308.92,"body":"through them quickly."},{"startTime":308.92,"endTime":311.17,"body":"[Dr. Handy] Burr cells are"},{"startTime":308.92,"endTime":311.17,"body":"typically seen in uremia"},{"startTime":311.17,"endTime":313.79,"body":"and show multiple spiny projections."},{"startTime":313.79,"endTime":315.68,"body":"Schistocytes are helmet-shaped cells"},{"startTime":315.68,"endTime":318.53,"body":"that reflect microangiopathic"},{"startTime":315.68,"endTime":318.53,"body":"hemolytic anemia"},{"startTime":318.53,"endTime":321.24,"body":"or fragmentation on an"},{"startTime":318.53,"endTime":321.24,"body":"artificial heart valve,"},{"startTime":321.24,"endTime":323.74,"body":"for example, these are also commonly seen"},{"startTime":323.74,"endTime":327.623,"body":"in disseminated intravascular"},{"startTime":323.74,"endTime":327.623,"body":"coagulation, or DIC."},{"startTime":327.623,"endTime":330.24,"body":"Spherocytes are small"},{"startTime":327.623,"endTime":330.24,"body":"dense red blood cells"},{"startTime":330.24,"endTime":332.83,"body":"that lack central pallor and biconcavity,"},{"startTime":332.83,"endTime":335.93,"body":"they are typically seen in"},{"startTime":332.83,"endTime":335.93,"body":"hereditary spherocytosis,"},{"startTime":335.93,"endTime":339.64,"body":"but can also be seen in other"},{"startTime":335.93,"endTime":339.64,"body":"autoimmune hemolytic anemias."},{"startTime":339.64,"endTime":341.63,"body":"Target cells have a bull's eye appearance"},{"startTime":341.63,"endTime":344.59,"body":"and are seen in thalassemia"},{"startTime":341.63,"endTime":344.59,"body":"and in liver disease."},{"startTime":344.59,"endTime":345.79,"body":"[Dr. Wiener] Okay, great."},{"startTime":345.79,"endTime":347.22,"body":"So the teaching point in this case"},{"startTime":347.22,"endTime":349.22,"body":"is that sickle cell"},{"startTime":347.22,"endTime":349.22,"body":"disease is characterized"},{"startTime":349.22,"endTime":351.6,"body":"by recurrent veno-occlusive episodes,"},{"startTime":351.6,"endTime":353.623,"body":"which, clinically, most often manifest"},{"startTime":353.623,"endTime":355.43,"body":"in the form of painful crises,"},{"startTime":355.43,"endTime":356.92,"body":"and repeated microinfarction"},{"startTime":356.92,"endTime":359.95,"body":"can also lead to the loss"},{"startTime":356.92,"endTime":359.95,"body":"of a functional spleen."},{"startTime":359.95,"endTime":360.97,"body":"On peripheral smear,"},{"startTime":360.97,"endTime":363.37,"body":"it is common to find"},{"startTime":360.97,"endTime":363.37,"body":"sickled red blood cells"},{"startTime":363.37,"endTime":365.1,"body":"along with Howell-Jolly bodies,"},{"startTime":365.1,"endTime":368.09,"body":"which are small homogeneously"},{"startTime":365.1,"endTime":368.09,"body":"staining blue inclusions"},{"startTime":368.09,"endTime":370.95,"body":"that are the nuclear remnants of RBCs."},{"startTime":370.95,"endTime":373.137,"body":"[Dr. Handy] And you can learn"},{"startTime":370.95,"endTime":373.137,"body":"more about this in Harrison's"},{"startTime":373.137,"endTime":374.92,"body":"chapter on disorders of hemoglobin"},{"startTime":374.92,"endTime":378.349,"body":"but also in the chapter on"},{"startTime":374.92,"endTime":378.349,"body":"anemias and polycythemia."},{"startTime":378.349,"endTime":382.582,"body":"[upbeat outro music]"},{"startTime":382.582,"endTime":385.58,"body":"[Dr. Shanahan] This is Jim"},{"startTime":382.582,"endTime":385.58,"body":"Shanahan, publisher at McGraw Hill."},{"startTime":385.58,"endTime":387.22,"body":"Harrison's PodClass is brought to you"},{"startTime":387.22,"endTime":389.2,"body":"by McGraw Hill's AccessMedicine,"},{"startTime":389.2,"endTime":391.292,"body":"the online medical resource that delivers"},{"startTime":391.292,"endTime":394.425,"body":"the latest trusted content from"},{"startTime":391.292,"endTime":394.425,"body":"the best minds in medicine."},{"startTime":394.425,"endTime":397.083,"body":"Go to accessmedicine.com to learn more."}]}