Hemodynamics, Epidemiology of Cancer Flashcards
Be able to determine the Cause of Death” for a patient given a clinical scenario (e.g. anatomic findings such as myocardial infarct
intracranial hemorrhage bronchopneumonia).Distinguish between Immediate cause of death and Underlying cause of death” Ok.Immediate Cause of Death: the disease, injury, or complication – resulting from an underlying cause of death – that directly caused death- Underlying Cause of Death: the disease or injury that initiated the chain of events that lead directly to deathAvoid using mechanisms of death” (e.g. physiologic processes such as arrhythmia cardiac arrest which are the result of an anatomic abnormality) which do not belong on a death certificate”
Determine the Manner of Death” (natural
accidental suicide homicide undetermined) for a patient based on a clinical scenario” Was it a natural cause? Were they murdered? You got it.
List clinical and pathologic features for a patient who dies in the context of a pulmonary embolus. a. State possible sources for the pulmonary embolus
Clinical features: sudden deathYou would find a clot in the pulmonary arteryUsually the clots form in the deep veins of the legs (thighs and inguinal regions)
List clinical features of congestive heart failure with respect to: a. Lungs b. Liver c. Spleen
Heart failure cells (macrophages filled with hemosiderin) could be found in any of these placesNutmeg liverHepatosplenomegalyCongestion
List adverse effects of hypertension on the following organ systems: a. Brain c. Kidneys
Could have a brain hemorrhage (intraparenchymal), specifically in the basal ganglia or intraventricular spaces that start as Charot Bouchard aneurisms, as well as glomerlulosclerosis leading to infarcts and fibrosis in the kidney
List organ systems which might experience an adverse outcome if atherosclerotic plaque and thrombus from the aorta is dislodged.
CardiovascularCNSAnywhere else it could get lodged?
State adverse outcomes on the kidney glomerulus resulting from poorly controlled, chronic diabetes mellitus.
Glomerulonephritis
Understand how epidemiology implicates environmental factors causing most cases of cancer.
Studies on the epidemiology of cancer suggest that about 80% of all malignant neoplasms are caused by environmental factors.This conclusion is largely based on the variations in incidence of specific types of cancer seen among different regions of a given country and among different countries around the world, and from the different rates of specific types of cancer between immigrants and the population of the country that the immigrants left.Many types of cancer therefore might be preventable if the significant risk and anti-risk factors in the environment could be identified.
Know the three most common types of cancer (other than skin cancer) among men and women (incidence), and the three leading types responsible for cancer mortality for men and women (mortality) in the United States.
Male incidence: Prostate, lung, colon/rectumIn the U.S., the cancer death rate for males is highest for lung cancer (accounting for 34% of cancer deaths), followed by prostate (12% of deaths) and colon/rectum (11%).Female incidence: breast, lung, colon/rectumFor females, the cancer death rate is now highest for lung (21% of cancer deaths), followed by breast (18%) and colon/rectum (13%).
Explain how environmental chemicals cause cancer and the importance of “activation” by microsomal enzymes.
Four groups of compounds have received a great deal of attention:1) the polycyclic aromatic hydrocarbons (made by burning fossil fuels)2) the aromatic amines (aniline dyes)3) the nitrosamines (processed meat) and4) the aflatoxins (mold)have been identified as important environmental carcinogens and studied extensively. Although these groups of chemicals differ structurally from one another, they share a common requirement. Each must be activated” to a carcinogenic form by microsomal enzymes (cytochrome P450).Chemical carcinogens are usually metabolized by microsomal enzymes into chemically active forms.The active metabolite is a strong electrophile.These electrophilic species can chemically modify protein RNA and DNA
Understand the Ames test.
Ames test: an elegant test which measures the ability of a given chemical to mutagenize” a set of specific strains of the bacterium Salmonella typhimurium. These tester strains are His- (they require histidine for growth because one of the genes for the biosynthesis of histidine is mutated).In the test a suspected mutagen is applied to a central disc on the bacterial agar.Plate which already contains: 1)media lacking histidine; 2) approximately 108 His- bacteria; and 3) a crude fraction of liver microsomal enzymes.If a chemical is mutagenic then large numbers of His+ revertants arise around the central disc.”
Understand the “principles of carcinogenesis” learned from animal testing of carcinogens.
About 90% of the carcinogens tested (chemicals previously shown to be carcinogenic in animals) are mutagens in the Ames test.Potency of mutagens parallels their carcinogenicity.Carcinogenesis requires time, several years can elapse following exposure to the carcinogen before cancer emerges.Carcinogenesis requires cell proliferation.Cellular changes that trigger carcinogenesis are stably transmitted to daughter cells. Cancer cells resemble each other more than the tissue from which they arose.The cell at risk for becoming malignant is the stem cell; a fully differentiated cell can never become malignant.A malignant cell is a stem cell that fails to differentiate normally; differentiation is aberrant and incomplete.
Understand the two-step model of carcinogenesis, and the difference between carcinogen and tumor promoter.
Stage 1: Initiation - (This step is a direct effect of the carcinogen, an irreversible effect).Stage 2: Promotion - (This stage is an effect of a noncarcinogen; reversible and requires repeated application following initiation”).Carcinogens are mutagens that cause cancer.Promoters are not mutagens or carcinogens (the list of known promoters include: phorbol esters bile saccharin phenobarbital butylated hydroxytoluene. phenols).Promoters are often irritants but not all irritants are promoters (ex. acetic acid is not a tumor promoter). Promoters often cause inflammation. Inflammation often promotes cancer by creating O2 radicals”
Be able to propose an explanation of why cancer is much more common in the elderly compared young adults.
More exposure to carcinogens over time.
Understand the difference between somatic and germline mutations that cause cancer, and so- called “epigenetic” factors that cause cancer.
Somatic: mutations in oncogenes and tumor suppressor genes cause neoplasmsGermline: patients with inherited defects in DNA repair are prone to develop cancer (xeraderma pigmentosum, ataxia telangiectasia, fanconi’s anemia, hereditary nonpolyposis coli)Epigenetic effects”: This theory proposes that chemicals cause perturbations in cell-cell interactions and communications and selected cell death that plays some key role in neoplasia.”
