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Pathogenesis Review . September 17, 2012. Ashkan Afshin, MD, MPH ScD Candidate, Department of Epidemiology ScD Candidate, Department of Global Health  & Population Harvard School of Public Health Kresge Building, Room 913 677 Huntington Avenue Boston, Massachusetts 02115

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pathogenesis review

PathogenesisReview

September 17, 2012

slide2

Ashkan Afshin, MD, MPH

ScD Candidate, Department of Epidemiology

ScD Candidate, Department of Global Health & Population

Harvard School of Public Health

Kresge Building, Room 913

677 Huntington Avenue

Boston, Massachusetts 02115

Phone: (949) 235-6137

Email: aafshin@hsph.harvard.edu

review sessions
Review Sessions
  • Format:
    • Brief review of the last lecture (20 min)
    • Discussing the questions received by email (10 min)
    • Q & A (30min)
questions
Questions

Please send your questions or suggestions to:

  • Text Message:  (949) 235-6137
  • Email: aafshin@hsph.harvard.edu
factors that contribute to disease
Factors that Contribute to Disease
  • Intrinsic Factors
    • Hereditary factors (Genetic Disorders)
    • Immunologic factors (Immune Dysfunction, allergies, autoimmune diseases, immunodeficiencies)
    • Psychological factors (depression)
  • Extrinsic Factors
    • Biological factors (Bacteria, Virus, Fungi, etc.)
    • Nutritional factors (Iron deficiency Anemia)
    • Physical factors (radiation, temperature, electricity, etc. )
    • Chemical factors (dugs, carbon monoxide, acids, etc.)
mutation
Mutation
  • A mutation is an error in the genetic code, causing you to make an incorrect form of the protein
  • Genetic diseases: cystic fibrosis, sickle cell anemia.
brca genes
BRCA Genes
  • BRCA1 is expressed in the cells of breast and other tissue.
    • Helps repair damaged DNA, or destroy cells if DNA cannot be repaired.
    • If BRCA1 is damaged, damaged DNA is not repaired properly and this increases risks for cancers
  • BRCA2belongs to the tumor suppressor gene family.
    • The protein encoded by BRCA2 is involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double strand breaks.
brca genes1
BRCA Genes
  • BRCA1 and BRCA 2are associated with increased risk of breast cancer, and prostate cancer.
  • BRCA2 increases the risk of pancreatic cancer.
gene environment interactions
Gene-environment Interactions
  • Some genes promote disease, but only under certain environmental conditions.
  • Example?
thrifty gene hypothesis
Thrifty Gene Hypothesis
  • Thrifty Genes: Genes which enable individuals to efficiently collect and process food to deposit fat during periods of food abundance.
  • Thrifty Gene Hypothesis: populations whose ancestral environments were characterized by periods of feast and famine experienced positive selection for Thrifty Genes. Under modern conditions, populations with such thrifty metabolisms are expected to have high rates of diabetes and obesity. (e.g., Pima Indians)
pima indians
Pima Indians
  • Among Pima Indians living in the US
    • 75% of Adult Pima Indians are obese
    • 50% have type II diabetes
  • Among Pima Indians living a more traditional lifestyle in Mexico
    • Most are not obese
    • About 10% have diabetes
epigenetics
Epigenetics
  • Altered expression of genes based on environment during critical periods of development.
  • Can explain discrepancy between genotype and phenotype
  • Can be persist for generations
  • May also explain why adult lifestyle and genetic background alone fail to predict who is at greatest risk of heart disease and other conditions.
dna methylation one mechanism of e pigenetic change
DNA Methylation One mechanism of Epigenetic change

https://www.hgu.mrc.ac.uk/Research/Meehan/images/4.jpg

injury and toxicity
Injury and Toxicity
  • Injury can be caused by trauma or by toxic exposure
    • The significance of an injury depends on how much extra capacity an organ has leftover.
  • Safety factor:
    • How much beyond the expected maximal load a structure is designed to handle
    • Ratio of capacity to load
biological safety factors ratio of capacity to load
Biological Safety Factors(ratio of capacity to load)
  • Human Pancreas (enzyme secretion)
    • About 10
  • Human Kidney (plasma filtration)
    • About 4
  • Human Mammary Gland (milk production)
    • About 3
  • Mammalian Lungs (aerobic capacity)
    • About 1.25 - 2

From: Jared Diamond “Quantitative Evolutionary Design’ J. Physiol 2002, 542: 337-345

inflammation
Inflammation
  • Signs
    • Rubor (redness)
    • Tumor (swelling)
    • Calor (heat)
    • Dolor (pain)
  • Biologic Mechanisms
    • Increased blood flow to affected area
    • Increased capillary permeability
    • Movement of phagocytic cells into site of injury
is inflammation a good thing or a bad thing
Is inflammation a good thing or a bad thing?
  • Good:
    • Helps with defense against infection
    • Helps with tissue repair
  • Bad:
    • Causes pain
    • Can damage healthy tissue
    • Sometimes occurs inappropriately, eg: allergy, autoimmune disease
    • Chronic inflammation as been implicated in atherosclerosis, which increases risk of heart attack and stroke
necrosis vs apoptosis
Necrosis vs Apoptosis
  • Necrosis
    • Generally a pathological process
    • Promotes inflammation
    • Often leads to loss of function
  • Apoptosis
    • Often part of normal development
    • Can minimize the “biological backfire” associated with injury
    • Minimizes loss of function