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University of Toronto St. George
Laboratory Medicine and Pathobiology

LECTURE ONE: INTRODUCTION TO THE BIOCHEMISTRY OF HUMAN DISEASE Diagnosis usually requires objective evidence of the pathologic process. Examples are: oDemonstration of specific biochemical abnormality oVisualization of a tumor by ultrasound imaging oFinding an inflamed appendix at surgery oIsolation of a bacillus or virus oLocation of a lesion in the tissue by biopsy MEDICAL LABORATORY SERVICES: oPathology (Anatomic) includes: Histology (tissues) and cytology (cells) oHematology includes: Blood transfusion medicine and immunology oMicrobiology includes: Bacteriology, virology, parasitology, mycology oBiochemistry or clinical chemistry includes: Chemicals and chemical markers oGenetics includes: Molecular diagnostics WHY BIOCHEMICAL TESTING? o Biochemistry analyzes chemical markers found in cells and fluids (e.g. blood, serum, urine, etc.) o Relatively non-invasive and safe o Small amount sample is often enough for analysis o Many tests (assays – lab test) have been developed to a high degree of sensitivity and accuracy, as well as fast speed of analysis o 70% of the medical decisions are based on lab test and 70% of the tests are based on biochemistry o A marker is a chance or entity that gives you some kind of indication for a particular disease OBJECTIONS OF LAB MEDICINE 1. Help define as objectively as possible the health and disease 2. Help predict the course of a disease 3. Monitor the effectiveness of treatment 4. Seek for underlying causes of disease 5. To screen for unsuspected disease USE OF BIOCHEMICAL TESTING oDiagnosis: ex. How does the glucose level indicate diabetes? There is a simple measurement of blood glucose oPrognosis: ex. What is risk of having a heart attack in cardiovascular disease? Cholesterol level can be used to indicate the percentage of risk oMonitoring: ex. Has enough of medication been given? Measure the level of drugs in the spleen oEtiology: ex: What is the cause of a drug overdose? The environment, the type of drug and amount of drug taken is key oScreening: ex. Does the patient have early kidney disease? Early diagnosis helps reduce the damage and allows for early treatment MORTALITY: disease that causes death or reduces life expectancy. How many or how often does death occur due to the disease? MORBIDITY: disease that impairs the well-being of an individual. How a disease may impair the individual? LEADING CAUSES OF DEATH (ALL COUNTRIES) 1. Ischemic heart disease (2) 2. Cerebrovascular disease (strokes) (3) 3. Lower respiratory infections 4. Chronic obstructive lung disease (4) 5. Diarrheal diseases (Infectious disease) 6. HIV/AIDS (Infectious disease) 7. Tuberculosis (Infectious disease) 8. Cancer of trachea/ lung/ bronchus (1) 9. Prematurity and low birth weight 10.Diabetes mellitus (Type 2) In Canada, the main causes of death in 2009 are indicated in blue. 5. Accidents (Unintentional Injury) In Ontario, the main causes of hospitalization are: - Young people (20 -30s): childbirth and accidents - Middle aged (50 – 60s): cardiac disease and strokes - Elderly (70 – 80s): cardiac, stroke, cancer, respiratory, mental diseases The prevalence of disease is the number of cases of disease in a given population The incidence of disease can be calculated as the number of new cases/ unit of time - Endemic is when most of the population has the disease. Ex. In some African countries, one in four people have HIV - Epidemic refers to widespread occurrence in a population where it is rare. Ex. The flu DISEASE CLASSIFICATIONS - Anatomical (based on body location): e.g. cardiac disease - Physiological (describe a particular function): e.g. endocrine disease - Systemic involves many systems or the whole body: e.g. infections - Etiology by the cause of disease HEREDITARY  the genes and genetics that have been passed on the individual  Garrod (1909) introduced the concept of inborn errors of metabolism  Inheritance leads to failure of function (Mendelian inheritance)  Identified from studies of individual gene analysis to human population studies  Often early but can occur at any age  Examples: sickle cell anemia CONGENITAL  Refers to disease appearing at birth  Not always hereditary  E.g. Maternal measles, fetal alcohol syndrome INJURY  Trauma or mechanical injury can lead to necrosis (unnatural cell death) or loss of tissue  Physical Injury: leads to disease conditions caused by mechanical stress, burns, heat stroke, frost bite, electrical hazards, radiation exposure and atmospheric pressure injuries  Chemical Injury: the study of this is toxicology. Injury from drugs, toxins or other chemicals. Poisoning could be accidental, suicide, homicide or from industrial hazards INFECTIONS  Most common are bacterial or viral  Epidemiology is the observation of the occurrence of disease in populations; pioneered by the efforts to control infectious diseases INFLAMMATION oMost infections produce inflammation but not all inflammation is due to infection oSymptoms include fever, chills and leukocytosis (production of white blood cells) (you measure your white blood cells – high count of white blood cells) oControlled with drugs even if mechanism of injury or the antigenic stimulus is not known (first line of defense) oAutoimmune diseases: rejection of self-immune system causes injury to normally functional cells. Ex. Lupus VASCULAR (circulatory system) Are likely the most  Atherosclerosis: fatty degeneration of an artery  Arteriosclerosis: hardening of the artery common diseases of the Western world.  Atherosclerosis  plaque rupture + thrombosis  ischemia  tissue anoxia (lack of oxygen)  damage and cell death  May involve inherited or acquired factors ex. Increased incidence in people with hypertension, hypercholesterolemia, diabetes mellitusm obesity or who smoke NUTRITIONAL disorders are due to diet  Most common worldwide is inadequate number of calories in the diet  In the west, we have too much food but of poor quality A  B  C  D  E  F METABOLIC  Disorders result in abnormal production of enzymes, hormones or secretory products along the metabolic pathway. (either too much or too little)  Often hereditary but some may be acquired A  B  C  D  E  F TUMOURS  Diseases of abnormal growth, neoplasia (new growth); (benign – not harmful) leading to tumors  Growth occupies space and may obstruct or compress other tissues (mass effect) and so lead to disease  Some secrete hormone-like chemicals which disrupt body functions  Cancer refers to malignant neoplasms, often with the ability to spread (metastasize) IATROGENIC (man-made): disorders are caused by physicians. Ex. The over prescription of drug or miss prescribing PSYCHOLOGICAL: disorders could include depression-related changes in body chemistry IDIOPATHIC: Diseases are those with an unknown case Two groups of reasons why physicians order test: 1. For diagnosis of disease 2. For management of illness or health DIAGNOSTIC TESTING:  To screen for disease without symptoms  Screening seeks to find hidden disease in a population deemed to be healthy, to confirm a disease that there is some evidence for, to exclude a disease that is possible but not likely  Screening Examples: + Heart disease  cholesterol test for risk factors + Prostate cancer  prostate-specific antigen (PSA)  Diagnosis Examples: + Myocardial Infarction (Heart attack)  Troponin (a marker for a heart attack) + Diabetes  Glucose Level  Exclusion test examples: + Pregnancy  chorionic gonadotropin (HCG) test MANAGEMENT TESTING:  To
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