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Lecture 2

Pathology 3240A - Lecture 2 Notes.docx

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Pathology 3240A
Aaron Haig

9/11/2013 5:32:00 AM Lecture 2 Today we are classifying CAUSES of diseases Classifying is not very black and white because of our understanding of disease They often change classifications Classifying Causes of Disease - Genetics versus environment - Idiopathic meaning you don’t really know what it is - Jim Fix in the 70s wrote books on running long distance - He died at 53 of a heart attack on a run - What was it about him that causes him to have heart disease at a young age - Environment or genetics? - He was overweight and smoked for 20 years before he took up this lifestyle - So all these years of abuse caught up to him - But also his father had a lot of these disorders so there may have been a genetic aspect involved - There are many grey areas - Most diseases have both environmental and genetic causes Differentiating Causes  Sickle cell anemia is only genetic  Traumatic head injury is only environment  Cancer is a big overlap disease  Different kinds of cancer however and some have a purely genetic or environmental cause  Type 2 diabetes is increasing in numbers causing mortality and morbidity  Peoples environment is changing  People are becoming more obese but they also have the predisposition due to their genetics Genetics  Wide range o Single mutation in a DNA base pair o Gain/loss of whole chromosome  Genetic abnormalities, more common to get a sporadic mutation over time, acquired throughout life  Can be inherited  A lot of cancers happen later in life because your cells have had a chance to accumulate these mutations leading to a cancerous growth  Intestinal epithelial cells is always rubbing and need to be replaced constantly  This sets them up for high mutation  Knocking out tumour suppressor genes  Causes it to keep growing and growing creating a pollup which is not malignant  Its dysplastic because it has the potential to become metastic  If you don’t catch it here, it undergoes more mutations and the cells totally lose control and they learn how to invade into other areas and you get a carcinoma Sickle cell anemia  Pathogenesis well known  Mutation in a single base pair of B-globin gene of HbA molecule  Packed full of hemoglobin molecules, essential for oxygen diffusal  They have an affinity and grab on to oxygen  If you didn’t have these cells it would take too long for O2 to diffuse  You have 2 alpha chains and 2 beta chains  When you look at the DNA you have a GCG changing to GTC (Glutamic acid to valine)  Loses affinity  When is doesn’t have the affinity the cell kind of breaks apart into a sickle shape  A portion of cells, the more they get deoxygenated  Cells when going through the capillaries you want them as close to cell wall as possible  So the capillaries are smaller than RBC  They can bend and contort through giving a lot of surface area  But the sickle cells are not designed to squeeze through properly and can cause a blockage  Complications: o Splenic infarction (blockage) o Avascular necrosis o Cutaneous ulcers o Renal insufficiency o Chronic pain o Pulmonary hypertension (heart has to pump harder to get blood through)  But this can give a little protection against malaria  If it invades a sickle cell it just dies Trisomy 21  Image of chromosomes  We have an extra chromsomes of 21 o Congenital heart affects o Simian crease on hand o Mental delay o Umblical hernia (bowel protruding) o Prediposition to leukemia o Intestinal stenosis (has a narrowing on the intenstine)  Leads to a lot of disease downstream Misconceptions  If I get a disease later in life it must not be inherited? o No, e.g. huntingtons disease does not present until adulthood  If born with a disease (ie congenital), is it always genetic? o No e.g. defects secondary to intrauterine infection Environmental Causes for Disease Physical Agents  Mechanical (falling off building)  Temperature (cells meant to work at certain temperature, outside this range they have trouble) o Frost bite ad hypothermia  Electrical (getting shocked)  Radiation (getting x rays, or the sun, radiation therapy can cause immidiate or long term consequences)  Pressure (When you are diving and scuba diving you have to change the way you breathe because its not normal for your body) Chemical Agents  Environmental or industrial exposure (bad working
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