Transcript General Principles of Laboratory Medicine

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.
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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.