IAMSE Genetics and Biochemistry Symposium July 21, 2003

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IAMSE Genetics and Biochemistry SymposiumJuly
21, 2003

• Teaching Medicine Through a Genetic Lens

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HypertensionPathophysiology Smith and Their,
1985
2003 Endothelium ANP Endothelin Angiotensin Na/K
ATPase IlGF-1 gt14 genes
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A Case

• A 24 year old woman is admitted with 2 days of
  fever, left flank pain, dysuria, and anorexia.
• Blood pressure 100/70, HR 105, T 390C. She is
  alert and in mild distress.
• Blood and urine cultures grow E. coli at 12 hours
  after admission.

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12 Hours Later

• Despite fluids and antibiotics her BP falls
  requiring vasopressors
• Renal, Hepatic, Respiratory, Hematologic Failure
• Comatose, Gangrene, Mechanical Ventilation

• After fluids and antibiotics her BP and HR are
  normal.
• Fever, flank pain and dysuria improve over 3 days
  with oral antibiotics which she takes for 14 days

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Bad Cytokines
Good Cytokines
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Why the Difference?

• Association of TNF2, a TNF-alpha promoter
  polymorphism, with septic shock susceptibility
  and mortality a multicenter study.
• Comparison of two polymorphisms of the
  interleukin-1 gene family Interleukin-1 receptor
  antagonist polymorphism contributes to
  susceptibility to severe sepsis
• Association between a genomic polymorphism within
  the CD14 locus and septic shock susceptibility
  and mortality rate.
• Effect of the interleukin-6 promoter polymorphism
  (-174 G/C) on the incidence and outcome of
  sepsis.
• The G--gtA single nucleotide polymorphism at the
  -308 position in the tumor necrosis factor-alpha
  promoter increases the risk for severe sepsis
  after trauma.

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Utilizing Genetics to Look More Closely at the
Patient

• Disease as an inevitable consequence of evolution
  and natural selection
• Why do we have disease at all?
• How do we define it?
• Where does normal end and abnormal begin?

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Two Views of Patients and Disease

• Why does this person have this disease?
• Why now?
• How can we restore steady state?
• How can we utilize the individuality of the
  patient to prevent disease and maintain health?

• What disease does this patient have?
• How do I treat it?
• How do I prevent it?

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Health and Disease are aConstant Dynamic

• External
• Microorganisms
• Nutrition
• Culture
• Education
• Economics
• Climate
• Crowding
• Environment

• Internal
• Genes mono, poly
• Biochemical Pathways
• Proteins
• Epigenetics
• Organ systems

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Treatment and Prevention

• Genes
• Drugs
• Environment
• Risk Assessment

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Teaching Medicine Through a Genetic Lens

• Teachers must
• Integrate thinking from organs to base pairs
• Realize individual patient becomes more important
  as we understand more about physiology and
  pathophysiology
• Encourage students to ask why do patients not
  get disease?
• Recognize unanswered questions and poorly
  explained explanations

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Teaching Medicine Through a Genetic Lens

• Student must be able to answer
• Why this patient?
• Why now?

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Thanks to Dr. Barton Childs