1. LABORATORY TESTING OVERVIEW & SEROUS FLUID ANALYSIS Daniel Albertson, PhD Sept 2011

2. TO PLACE LAB TESTING IN PERSPECTIVE  CONSIDER THE METHODS and REASONS FOR GATHERING MEDICAL DATA: METHODS  Hx, PE, et cetera REASONS  screening, diagnosis, prognosis, surveillance, choose/monitor Tx What are the cetera methods?

3. REASONS FOR ORDERING LAB TESTS SCREENING- to find silent disease in asymptomatic patients (subjects) with no specific risk factors SURVEILLANCE- monitor individuals within a specific population at risk DIAGNOSIS- R/I or R/O specific tentative hypotheses to reach final conclusion PROGNOSIS- predict future state of being PREDICT / MONITOR therapy-

4. USUAL STEPS INVOLVED IN THE DIAGNOSTIC PATIENT ENCOUNTER 1. HISTORY TAKING & PHYSICAL EXAMINATION  to gather subjective (what you are told) and objective (what you detect) “DATA”. Note: “DATA” are raw facts. They exist w/o meaning or interpretation. They are the elements obtained in the absence of medical testing. 2. ASSESSMENT  the cognitive move to analyze and interpret the data which leads to INFORMATION. 3. HYPOTHESIS GENERATION  selection & clustering of information pieces to arrive at proposed explanation(s). 4.PROCEDURES and TESTS SELECTION  R/I & R/O to arrive a unique hypothesis.

5. THE CETERA: LABORATORY TESTS & MEDICAL PROCEDURES these are MAJOR sources of obtaining medical data

6. WHAT’S THE DISTINCTION BETWEEN A MEDICAL TEST & A PROCEDURE? A MEDICAL TEST  performed on a biosample (blood, urine, etc) obtained from a subject sometimes with a little preparation(diet, position, etc); usually an in vitro analysis or observation. PROCEDURES  more extensive processes requiring subject participation (X-rays, MRI, CT, biopsy,….)

7. THE PATIENTS PERSPECTIVE OF TESTS & PROCEDURES INVASIVE –Procedures requiring skin puncture (e.g. blood draws, tissue biopsies, etc) –IV administration of contrast agents, drugs, radiopharmaceuticals, etc –Biopsy NON-INVASIVE: Hx, x-rays, ultrasound, urine, etc OBTAINED IN SHORT TIME (e.g. blood draw, urinalysis) OVER LONG INTERVALS or CONTINUOUS MONITORING (function tests: e.g.glucose tolerance (pancreas), DST (for adrenal), ECG (cardiac), EEG (brain),etc…..

8. WHAT DOES MEDICAL TESTING & PROCEDURES YIELD? ****DATA**** What is DATA?  “a number produced as a consequence of a measurement or count or a categorical observation or verbal description obtained on a subject under precisely controlled conditions.”

9. TYPES OF DATA CATEGORICAL: –Qualitative (nominal)- unrelated categories (eg: sex, handedness, race, etc.) –Semi-quantitative (ordinal, graded, ranked)- (eg:cool, warm, hot /+,++,+++ /Apgar scores /Ca staging /etc.) NOTE: sometimes grading is done with numerals. However the digits DO NOT represent numbers! Judgement is involved! METRIC: –Discrete- counts (whole numbers) –Interval- continuous scale IMAGES: radiographs, MRI, ultrasonographs, histological images w or w/o special stains, etc. GRAPHS: ECG, EEG, myleograms, etc.

10. WHAT IS REQUIRED TO MAKE MEDICAL DATA USEFUL? PLACING IT IN CONTEXT!! –WHAT DOES THIS MEAN???

11. DATA IN CONTEXT GIVEN A LAB RESULT (i.e. DATA)THAT IS A RESULT OF OBSERVATION OR MEASUREMENT  –Placing it in context via –ANALYSIS OR INTERPRETATION in order to –PROVIDE INFORMATION

12. Information Interpretation or Analysis Data (Hard/Soft)

13. THE PROCESS The INTERPRETATION of laboratory data (hard and soft) involves discerning the SIGNIFICANCE of a test result in a medical context thereby yielding INFORMATION on which to base a management decision.

14. DATA vs INFORMATION A 64 y/o woman comes to the office complaining of fatigue, frequent urination, and thirstiness. –A random blood sample is obtained and a serum glucose is ordered. –The result returned from the lab is 8.0 –What is this number?? What is needed to put it in medical context?

15. GLUCOSE 8.0 IN CONTEXT UNITS ARE IMPORTANT IN REPORTING RESULTS OF QUANTITATIVE ANALYSIS!! –Be especially cautious of serum Ca results: mEq vs mg.

16. WHAT IS NEEDED TO PLACE DATA IN CONTEXT? FOR METRIC OR SEMIQUANTITATIVE DATA: Determine if analyte measured or observed is present in non-diseased condition? If NOT  What is the sensitivity of measurement system being used? (i.e. lowest detectable amount.) If SO  What interval is available for comparison? Intra-individual? Inter- individual? Reference Population?

17. FIRST STEP IN LAB TEST INTERPRETATION COMPARISON –Of test result form a particular individual to set of results obtained on asymptomatic people Classically termed “normal range” Statistically determined to include 95% of people Thus 5% considered abnormal (falsely) –Current terminology: REFERENCE RANGE Accounts for more specific comparative groups

18. FACTORS AFFECTING INDIVIDUAL TEST RESULTS Time sample taken Gender Age Genetics Posture Diet Exercise Drugs

19. WHAT IS REQUIRED TO INTERPRET LAB DATA? Know type of data and what is required to turn data into information Understand principles of biological variation both within & between patients Appreciate analytical variation & its role in medical decision making Understand reference ranges and how they are determined Know how to evaluate the clinical performance of tests

20. PHASES OF LABORATORY INVESTIGATION OF PATIENTS PRE-ANALYTIC –Patient preparation, sample type, sampling technique, transport, preservation, etc ANALYTIC –Measurement method affects type of result POST-ANALYTIC –Medical usefulness

21. WHAT IS A TEST PANEL? DEFINITION: –“a collection of different tests related to a specific organ or disease” –Ordered as a group E.G.: Kidney panel: BUN, creatinine, uric acid, Na, K, Cl, Bicarb, Phosphate Liver Panel: Bili(T&D), LDH, SGOT, SGPT, ALB Bone Panel: Ca, Phos, Alk Phos Cardiac Risk Panel: Gluose, chol(HDL & LDL), TG

22. SENSITIVITY and SECIFICITY vs PREDICTIVE VALUE SENSITIVITY = T(+) given the DISEASE POSITIVE PREDICTIVE VALUE = D(+) given T(+) SPECIFICITY = T(-) in absence of DISEASE NEGATIVE PREDICTIVE VALUE = D(-) given T(-) NOTE difference in what is “in hand” (i.e. given)

23. PREDICTIVE VALUE FOR A POSITIVE TEST: the percentage of positive results that are actually (true) positives. PPV = TP/(TP+FP) FOR A NEGATIVE TEST: the percentage of negative results that are actually (true) negatives. NPV = TN/(TN+FN)

24. Predictive Value of a Positive Test: The Effect of Prevalence and Accuracy Predictive value of a positive test (%) Prevalence (%) Sensitivity 90% Specificity 90% Sensitivity 99% Specificity 99% 0.010.090.9 0.10.99 532.183.9 5090.099

25. USUAL CLINICAL SPECIMENS EXAMINED OR TESTED BLOOD (SERUM, PLASMA) URINE (RANDOM, OVERNIGHT, 24 Hr) SPINAL FLUID

26. OTHER FLUIDS ASSESSED SEROUS (“serum-like”) FLUIDS –Pericardial –Peritoneal –Pleural SWEAT SALIVA SYNOVIAL FLUID SEMINAL FLUID AMNIOTIC FLUID VAGINAL SECRETIONS