Integrating Basic Science and Clinical Concepts through PBL

1. Integrating Basic Science and Clinical Concepts through PBL Sally Krasne, PhD Department of Physiology David Geffen School of Medicine

2. Block 1: Foundations of Medicine • Week 1: Genetics; Molecular Diagnostic Techniques • Week 2: Embryology; Signal Transduction • Week 3: Surface Anatomy; Membrane and Epithelial Transport; Pharmacodynamics • Week 4: Cell Injury and Adaptation; Drug Metabolism and Pharmacokinetics • Week 5: Neoplasia • Week 6: Blood, Inflammation and Innate Immunity • Week 7: Adaptive Immunity • Week 8: Electrophysiology; Animal Models, Gene Therapy, Stem Cells, & Ethics

3. Goals for the Week Be able to • Discuss the mechanisms of cell and tissue injury, and the range of responses that injury may induce, physiologically and morphologically. • Describe how cells produce energy, and use it to maintain the intracellular fluid environment. • Explain how drugs target and interact with receptors and cell membranes, are taken up by cells, and distribute within the body. • Measure blood pressure accurately. • Determine the best sources to access initially when researching a medical or basic science question and be able to get to the resources efficiently.

4. Phlebotomy Lab (Skin Biopsy) (2 hr) or Histopathology Lab – Cell Injury (2 1/2 hr) or Doctoring (2 hr) Weekly Organization (Block 1 Week 4) Formative Assessment (Friday PM to Monday AM)

5. How can this information be “stabilized” in a clinically useable way? • Information is best retained when the recipient is “emotionally aroused”. • Information needs to be applied to a problem of interest and of relevance • Students are interested in clinical medicine, and this is the field for which they are being trained. •  PBL

6. What? • Problem-based learning is learning that results from the process of working toward the understanding or resolution of a problem. The problem is encountered first in the learning process. Barrow and Tamblyn, 1980

7. HOW?

8. Characteristics of PBL • Learners struggles with real problems • The teacher is coach. • Students work together. • Students direct their own learning. • Time is protected for study • Problems are multidisciplinary.

9. The Adolescent Who Could Not Swallow Pharyngeal anatomy Membranous structures & epithelial barriers A 16 year-old girl, Marjorie Meadows, is brought to the ER by her mother after 4 days of increasing weakness, fever, and difficulty swallowing. On initial examination, you find a tightly-adherent membrane covering the pharyngeal region and pale skin covered with ecchymoses. Tissue from the inferior border of the mandible to the clavicle is markedly edematous. Diagnosis Head & neck anatomy Skin histopathology

10. Questions to Consider • What is going on here? (Facts) • What are the essential facts of the case? (Facts) • Have I had or heard about experiences like this before? (Hypotheses) • What are possible explanations? (Hypotheses) • What additional data do I need to test these explanations? (Action Plan) • How does the data support or rule out each possible explanation? (Hypotheses) • What do I need to learn to understand and/or act on this problem? (Learning Issues)

11. Data Hypotheses Action Plans Learning Issues Case Analysis Sheet

12. Essential Tutor Skills • Balancing student discussion • Keeping discussion focussed • Using one’s expertise and experience with case to help students set priorities • Probing and stimulating critical evaluation of ideas. • Creating a pleasant group environment • Providing individual and group feedback

13. Why? • Activates prior knowledge • Prompts elaboration • Organizes learning around meaningful contexts • Builds deep understanding • Develops life-long learning skills • Makes learning fun

14. Bottom Line: What We Know About Outcomes • Students enjoy learning • Students indicate an effort to learn for deeper understanding • Students seek out and employ more resources in learning • Knowledge gained is retained longer

15. The Case of Mr. Malchov • Case Goals: • Integrate principles and mechanisms of cell injury and death with a clinical case and causative agent. • Apply principles of pharmacokinetics • Always emphasize appropriate use of resources. • For tutors: Audi J, Belson M, Patel M, Schier J, Osterloh J. Ricin poisoning: a comprehensive review. JAMA 294 (18): 2342-2351, 2005.

16. The Case

17. Learning issue examples for Malchov case: • 1) What causes a fever? Why did Mr. Malchov develop a high fever (i.e. describe the pathway that led to a fever in this case)? • 2) What is induration and what caused it in this case? Why were the lymph nodes of Mr. Markov’s groin swollen? What causes lymph nodes to swell? • 3) What is a “normal” range for a white cell count? How does a white cell count of 10,600/cu mm compare with this range? Of 33,200/cu mm? How do toxins such as ricin cause an increase in WBC’s? • 4) How do ricin and similar agents get across epithelia and cell boundaries and into a cell? Where does ricin go once inside the cell? • 5) What pathways (e.g. signal transduction) are activated and/or inactivated as a result of ricin entering the cell? What are the consequences to the cell of these actions (e.g. activation and/or inhibition of protein synthesis, necrosis, apoptosis). Include the affected pathways and actions from the point of ricin’s encountering a cell until it is either destroyed or exocytosed. (Diagrammatically.) • 6) How did the ricin that was lodged in the skin of Mr. Malchov’s thigh get to the different organs it affected? How would its distribution and effects be expected to differ if it were inhaled? If it were injested?

18. . . . more learning issues • 7) How much ricin is required to kill a person, and how is it metabolized/eliminated? Compare different routes of administration. What is the half-life of ricin in the blood? Calculate the volume of ricin in the pellet that was lodged in Mr. Malchov’s thigh. • 8) Is there an antidote to ricin exposure? What therapies, if any, exist to prevent death from ricin, both before and after administration, and how do they work? • 9) What are “vascular collapse” and “shock”? What caused these to occur in Mr. Markov’s case? • 10) How are agents of bioterrorism classified? Is there a common international system of classification? Ricin is considered a Category B Select agent: What is a “select agent”? What is “Category B”? • 11) How did the ricin that was injected into Mr. Malchov lead to such extensive areas of necrosis in a variety of organs? • 12) How would you manage a patient who had inhaled ricin? Who had injested ricin? Who had been injected with ricin? • 13) If you suspect that a patient is suffering from ricin (or similar) poisoning, how could you test for this? How would such a test work?

19. Journal Club Paper Minireview Ribosome inactivating proteins and apoptosis Sriram Narayanan, Kalpana Surendranath, Namrata Bora, Avadhesha Surolia, Anjali A. Karande FEBS Letters 579 (2005) 1324–1331

20. Return Session • Students take role of “experts” in the fields of their learning issues • Students should be familiar with all learning issues • Students apply learning issue research (and other sources of learning during week) to case during case review • Reinforces and integrates learning within an interesting a “appropriate” context.

21. Problem-based Learning: Some differences • Write up Learning Issues: 500 – 700 words of text (about 1 – 1 ½ pages) exclusive of figures and tables. • Learning Issue summaries are posted to discussion boards (AND to TurnItIn). • Journal Club: All students read one article each week; one student leads a discussion of article each time.

22. Best of all . . . . . . both tutors and students love the experience! I hope you’ll give it a try!