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Immunology and Microbiology Unit Department Head and Staff Members Offices Emergency Room Clinical Pathology Department Orientation What we do in clinical Lab General Principles of Laboratory Medicine) Chemistry Hematology Microbiology Blood Bank Importance of proper lab tests Correct diagnosis Appropriate therapy Restoration of patient health to normal How to use laboratory tests in clinical practice? Mass screening (Diabetes Mellitus in adults and children, and Hypothyroidsm in newborn). Confirm a diagnosis (as the situation in daily medical practice e.g., Kidney disease, hepatitis). Monitor a patient’s disease status (e.g., serum glucose in a person with uncontrolled diabetes). Non-specific Complaints 1. Battery of chemistry tests 2. CBC 3. Urinalysis Laboratory Screening Criteria 1. There must be a high enough prevalence of the disease to justify the expense. 2. Significant morbidity and mortality must be associated with the disease if it is left untreated. 3. The disease must be detectable before symptoms surface in the patient. 4. An effective therapy must be available that is safe and inexpensive. 5. The test must be cost effective and easily performed in the laboratory. Sequence of Tests Depends on many factors: 1. Situation critical - test with the highest yield is done, even though there may be some risks 2. If there is time - lower yield, less risky procedure done first. Order of Testing 1. From cheap to costly 2. From less to more risky 3. And from simple to more complex Within the constraints of time, risk, and cost, try to do the test or procedure with the most efficiency as soon as possible; That is, use the procedure with the highest sensitivity, specificity, and predictive values. Order of Testing - Not always practical! One or more objectives may be sacrificed for speed, convenience, accuracy, parsimony, a waiting list for procedures, time needed to await the results, and the condition of the patient. Some times it may be best to get the costly test done first; it may solve the problem quickly and save money in the long run. Normal Range Reference values: urea - 10-20 mg/dl 200 mg/dl? 40 mg/dl? 25 mg/dl? could be a false positive? How much above normal must the test result be before an intensive chain of studies is set into motion to determine the cause of the alleged abnormality? How abnormal must a test result be before you become concerned? Common sense tells you to ignore a slightly abnormal result if the implied diagnosis is clinically highly unlikely, but to regard it seriously if the implied diagnosis is clinically likely. Perfect Test 1). Accurate 2). Precise 3). Discriminating 4). Pain free 5). Risk free 6). Inexpensive 7). Useful There is no excuse for ordering a test, and then ignoring or overlooking the result which are actions that are commonly done. Variables affecting lab tests -1. Preanalytical a. collection of sample b. age c. sex d. habits e. underlying diseases -2. Analytical-turbidity, hypoalbuminemia, mostly QC practices -3. Postanalytical a. reporting b. interpretation Normal variations in reference intervals a. Newborns b. Children c. Adult men d. Adult women e. Pregnant women f. Geriatric population Preanalytical Variables Preanalytical variables related to the collection of the sample (e.g., blood, urine) and patient factors that alter test results, such as age, sex, habits, and underlying disease 1. Compared with that of a child, the hemoglobin (Hb) and RBC count in a newborn is higher owing to the increased concentration of HbF (fetal Hb) and its effect on left-shifting the oxygen dissociation curve, which leads to tissue hypoxia and the release of Erythropoietin. 2. Compared with that of an adult alkaline phosphatase (located in osteoblasts) and serum phosphate (which drives calcium, into bone) concentrations are higher in children because of active bone growth. 3. Adult men have higher TESTOSTERONE, Hb, serum iron, and serum ferritin (the circulating fraction of iron that correlates with iron stores) levels than adult women do, since adult women lose iron during menses and pregnancy if they do not take an iron supplement. 4. Pregnant women have notable test variations. a. b. c. d. The plasma volume increases three times more than the RBC mass, so the Hb concentration is reduced (dilutional effect). The increase in plasma volume increases the glomerular filtration rate (GFR), which increases the creatinine clearance and the clearance of analytes such as creatinine, blood urea nitrogen, and uric acid, hence lowering their serum concentrations. The increase in estrogen results in an increased synthesis of binding proteins such as thyroid-binding globulin and transcortin, which in turn results in an increase in the total thyroxine and total cortisol concentration, respectively, without altering the free hormone level. There is a mild glucose intolerance, secondary to the anti-insulin effect of human placental lactogen, and a lower renal threshold for glucose, which often results in glucosuria in the presence of normal serum glucose concentration. 5. Elderly patients have significant variations in test results that may be misinterpreted as representing disease. a. They have a significant drop in the GFR, which renders them susceptible to drug toxicity if they are given drugs that are excreted by the kidneys. b. There is a reduction in the number of suppressor CD8 T cells, leading to an increased production of autoantibodies. c. An increase in adipose tissue in the elderly down-regulates the synthesis of insulin receptors thus leading to mild glucose intolerance. 6. A hemolyzed sample of blood results in a false elevation of serum lactate dehydrogenase, potassium, AST, and iron, since they are present in RBCs. 7. A fasting blood sample is necessary in order to obtain accurate serum glucose and serum triacylglycerol (TG) levels, since diet affects these two analytes. 8. Because alcohol enhances the activity of the cytochrome P-450 system in the liver, which is involved in drug metabolism, the serum concentration of a prescribed drug is likely to be lower than expected if alcohol is consumed. Analytical Variables Analytical variable refers to problems with performance of the test in the laboratory such as turbidity (due to Triglycerides) or hypoalbuminemia, which automatically lowers the total calcium concentration (40% of calcium is normally bound to albumin) Post-Analytical Variables Most of post-analytical error are due to reporting errors, so a good and fully barcoded labeling system will minimize the clerical error.