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Lecture 2

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Pathology 3240A
P Ferguson

Causes of Disease II to treat/under stand disease, we need to know what causes the disease, when ppl come with their signs, that’s the end point of cellular damage: Genetics + Environment = idiopathic (we don’t know what the cause is), but this category is getting smaller b/c we understand more now. -otherwise, we can separate b/ genetics and environment e.g. James Fix - Fit guy, but dropped dead of heart attack at age 52  ischemic heart disease which is usually associated to fat ppl, smoking, etc -what caused this? - Before he was active, he smoked, ate terribly, , fat, etc. this oculd have contributed to his history, what also happened = his dad also died of heart attack. -what caused the heart attack? Life style or genetics  probably both. If he didn’t change diet, he would have died younger…it’s hard to put in category. If he didn’t have that father, he would have lived longer, but would have lived shorter cuz of life style. Heart disease, diabetes, cancer are unknown, both gen and env -diabetes type 2, it has very clear genetic component but also very linked to env, tahts why incidence are going up now  high caloric intake, sedentary life, etc -cancer = some are very env and others are very genetics…e..g smoking causes smoking but nto everyone who smokes gets cancer, so falls in centre Sickle cell disease = genetic Traumatic head injury = environment Genetics -Wide range: single mutation in a dna base pair  Gain/loss of whole chromosome  can be inherited, but doesn’t have to be (remember this)  far more common to be a sporadic mutation acquired through life. You can have genetic abnormality just cuz ur alive b/c cells are always subjected to injury and repair and replication…cancers happen in later life b/c you had chance to mutation to develop. Consequence of living. You can acquire mutation + inherit. -Sickle Cell anemia: -within the rbc, there are protein and there are hemoglobin. Hemo is one protein (made up for 4 parts), their job = bind oxygen. Rbc filled wit hemo.  mutation in single base pair B-globin gene of HbA molecule glutamic acid to valine…one change, the molecule works but problem = when it comes completely deoxygenated. This molecule precipitate and form crystals in rbc and rbc will collapse and form sickle shape. complications: splenic infarction, avascular necrosis (joints don’t get oxygen), cutaneous ulcers, renal insufficiency, chronic pain, pulmonary hypertension (lungs are filled wit capillaries so they jam up and everything on the other side of it, pressure gets higher). Normal shape can bend and flow. so what? These rbc, when get to smallest vessel of capillary, rbc squeezes itself through. This shape allows them to do that…bends and folds…Trouble of sickle, these cells don’t do that…they jam things up. You get ischemia from this(everything past the vessel not getting oxygen it needs)…vessles…if organ has only one blood supply. Affects mostly organs that have small vessles comin in and no others so it can cause problems…protects against malaria…if heterozygote, its proteictive so in Africa, it still survives. -Trisomy 21 -karyotype: pictures of chromosome and match em -chrosmosome has three 21 chromsome -congential heart defects -Simian crease -Mental delay -umbilical hernia -Predisposition to leukemia -intestinal stenosis (intestine narrows down so this portion of the bowel has to be removed) Misconceptions: -if I get a disease later in life, it must not be inherited? - no, e..g Huntington’s Chorea does not present until adulthood -If born with a disease (i.e. congenital  this means born with sth/ not inherited), is it always genetic? - no, e.g. defects secondary to intrauterine infection Environmental -Physical agents -Chemical Agents -Drugs -Iatrogenics -allergens - etc Physical Agents: Mechanical, temperature, electrical, radiation (also used for therapeutic ie. For cancer. Although it can kill cancer cells, if you’re young, ur prone to more cancer in the future), pressure (cells desiged at certain pressure, our whole body too  deep sea divers, nitrogen dissolves in blood, if you come up too quickly, this forms bubbles in vessel and when it goes to small capillaries, it will jam vessels down the way. Chemical Agents: env or industrial exposure Drugs: Therapeutic (man
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