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Laboratory tests are ordered by the clinician for one of four reasons:. Screening: - used in the general population – - to find silent disease Case finding : - to find disease in specific clinical populations at risk
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Laboratory tests are ordered by the clinician for one of four reasons: • Screening: - used in the general population – - to find silent disease • Case finding: - to find disease in specific clinical populations at risk • Diagnostic testing: - as rule-in / rule-out tool to : - convince patients of their benign condition, - - to justify the clinicians procedere, - - for medico-legal safeguarding • Monitoring: used to: - monitor the progress of disease, - “ response to therapy, - “ concentration of medication.
Sample Collecting: body substances: blood, urine, faeces, sweat etc. collected in: URINE/STOOL/BLOOD - CONTAINERS Phlebotomist’s Equipment : • VACUTAINER TUBES - o EDTA (Lavender) o SST (Gold/ Serum) o SST (Speckled/Serum) o Citrate/Clotting (Lt Blue) o Fluoride Oxalate/Glucose (Grey) o Lithium Heparin (Green) o No Additive (Red) o Sod. Heparin (Dark Blue) VACUTAINER NEEDLES o 21 Gauge (Green) o 21 Butterfly (Green) o 22 Gauge (Black) o 23 Gauge Butterfly (Blue) o VACUTAINER BARREL
How can one define a ‘Healthy Population’ ? • Health or Disease diagnosis ~ relies on findings of : true-negatives or true-positives ~ hampered by false-negatives or false positives • Is it possible to find a truly ‘normal individual’ ? – or a healthy population whose physiology is truly perfect ? • Without an ‘ideal population’ – any stated reference range will be falsly broad –( the 95% water-shed); • Optimal metabolic ranges may be quite narrow for many biochemical parameters
Laboratory / Path-Lab. Tests • Special Health Servicetests: • Cytology • Microscopy • Aspirated Material : • - Exsudates • - Transudates • Routine Health Service tests : • Blood Chemistry • Blood Film Examination • Urine-analysis • Microbiology
Blood Chemistry • Electrolytes • Lipid-Profile • Diabetes Check, RBS, GTT, HBA1c • Renal Profile • Hormone Assays Progesteron Estradiol, Testosterone, DHEA, ACTH, Catecholamines • Serum Protein Electrophoresis • Inflammation Markers ESR, CRP • Tumor Markers PSA, AFP, CEA, β-HCG CA153. CA27-29, CA19-9, CA 125, HER-2-neu, • Miscellanious LDH, AP
Serum Sodium (Na+)- major extra-cellular cation • regulates blood and volume by its osmotic activity in the plasma (Osmolality) and in the lymphatic tissues • excreted by the kidneys, sweating • increased: Cushing’s Syndrome, drug-effects • decreased: Addison’s Disease, renal failure, metabolic acidosis, malignancies, drugs
Serum Potassium (K+)- major intra-cellular cation - distal tubular secretion dependent on: mineralcorticoids, • acid-base balance drugs • major influence on muscle activity • if unbalanced : • diagnosis whether Hypo- or Hyper-kalaemia required • diagnosis whether Hypo- or Hyper-Adrenalism present • risk of metabolic / respiratory alkalosis or acidosis present
Plasma Creatinineby-product from Creatine-metabolism • – single most useful measurement of renal function • normally varies little throughout the day • best monitoring tool for : renal secretory function glomerular filtration rate GFR
UreaNH2CONH2 • - produced by protein consumption and the formation of ammonia • – raised levels (Uraemia/ Azotaemia) - sign of chronic renal failure, - can have pre-renal, renal and post-renal cause - can lead to Uraemic Syndrome, nausea, confusion . .
Uric Acid • - end product of purine metabolism • ~ ↑ (Hper-uricemia) - predictive of gout , • ~ ↑ poly-cystic kidney disease, anemias • ~ ↑ hypothyroidism • ~ ↑ diuretics, salicylate
Calcium (Ca2+) • defines clinical diagnosis whether Hypo- or Hyper-calcaemia • clinically linked with 1-ary Hyper-Parathyroidism, • “ “ effects of drugs, radiation, malignancy, • clinically linked with Hypo-Parathyroidism : associated with : other endocrine disorders, - symptomatically : cramps, spasms, tetany. nail + skin disorders
Diabetic Monitoring • Normal Serum Glucose Concentration 75mg-110mg/dl 4.2 - 6.4 (mmol/l in SI – units • Glucose Tolerance Test (GTT) < 7.8 (8.9 mmol/l ) (2 hr post-glucose loading analysis) • Glycosylated Hemoglobin ( HbA1c) n.r. ( 3.8 – 6.4) dependent on circulating erythrocyte (120 days) • Further Glycaemic Testing becomes indicated after symptom development: - excessive thirst, glycosuria, skin irritation (if Random BS > 11 mmol/l Diabetes ) - fasting glucose > 7 mmol/l - plasma glucose 2 hrs after GTT-loading > 11.1 - HBA!c, plasma-lipid profile, . . .
Serum-Lipids • Cholesterol – insoluble in water – carrier proteins : ‘Lipoproteins’ desirable borderline high . Total Cholesterol < 200 200 – 240 > 240 [mg/dl ] 5.2 6.1 [ S.I.] Triglycerides < 150 150 – 200 > 200 1.7 2.25 LDL- Cholesterol < 130 130 – 160 > 160 2.6 4.1 LDL- Cholesterol > 60 if less than 39 1.5 1.
Liver Function Tests • Serum Transaminases • Serum Aspartate Transaminase (AST or SGOT) • Serum Alamine Aminotransferase (ALT or SGPT) • Serum Alkaline Phosphatase (AP) • Serum Gamma Glutamyl Transpeptidase (GGT) • Serum Bilirubin • Serum Albumin
Bilirubin~ waste-product of the erythrocyte degradation cycle → Serum ( free or un-conjugated B. - as ‘bilirubin-albumin complex’ ) ( conjugated in liver - as ‘bilirubin glucoronide’ ) • ↑ conjugated - hepatobiliary disease - obstructive post-hepatic jaundice • ↑ un-conjugated - Gilbert’s Syndrome, neonatal jaundice - haemolysis, pre-hepatic jaundice → Urine (uro-bilinogen) hemolytic anemia, toxic hepatitis, mononucleosis
Clinical Hematology examines ( sample bottle EDTA) • BLOOD CELL DEVELOPMENT of : Red Blood Cells (RBCs, Erythrocytes) White Blood Cells (WCs, Leukocytes) • BLOOD CELL COUNTS Units Reported By Automated Counting: (RBCs), (WC), Platelets Complete blood count CBC : HEMOGLOBIN - Variants HEMATOCRIT (PACKED CELL VOLUME) REDCELL- Count - with morphology - MCV, MCH, MCHC, PLATELETS WHITE-CELL- Count with morphology WHITE-CELL- Count with DIFFERENTIAL Count Neutrophils Eosinophils Basophils onocytes Lymphocytes EXAMINATION OF THE PERIPHERAL BLOOD FILM • Microscopic Examination of the Blood Film Normal Leukocyte Morphology • Blood Cell Alterations • ADDITIONAL HEMATOLOGY PROCEDURES • Reticulocyte Counts • Erythrocyte Sedimentation Rate (ESR) • Blood-Coagulation
Red-Cell (Erythrocyte) –PopulationPERIPHERAL BLOOD FILM : differentiation by Color, Shape: -normochromic - hypochromic - hyperchromic Macro-cytosis → Megaloblastic Anemia Micro-cytosis → Iron-deficincy-An. Aniso-cytosis Poikolo-cytosis Presence of : Sickle-cells Target-cells Helmet-cells Spherocytes Hemoglobin Variants S, C, D, E Hemoglobin-Derivatives → Microcirculation (Met-, Oxy-, Carboxy-, Cyanomet- H. )
Smallest integral life forms observed under ‘Darkfield Microscopy’ seen as "tiny white dots" so calledProtits; they change according Pleomorphism or the Cyclogenia of Microbes first into: viral forms which can change into bacterial forms followed by spores and fungi.
White-Cell (Leukocyte) -Population PERIPHERAL BLOOD FILM : if increased: Myeloid Series (⅔)→ (leucocytosis) Neutrophils → (neutrophilia ) Eosinophils → (eosinophilia ) Basophils Monocytes • Lymphocytes (⅓) – small, large, reactive → (lymphocytosis) DEFICIENCIES: Leukopenia, Neutropenia, Lymphocytopenia etc …
Fatigue Signs I Symptoms I Findings • Ongoing fatigue - reduced daily activity - very limited exercise tolerance • Muscle pain - worse after exercise • Migrating polyarthralgia • Recurrent headaches • Depression • Cognitive disturbances • Low blood pressure / Postural hypotension
Commonly reported Symptoms & Findingsfrom a large number of ‘dys-functional individuals’ : • Fatigued – easily out of puff • Muscle weakness, muscle pain, - worse after exercise • Migrating polyarthralgia, joints ache, - feel stiff • Sleep disturbance -Insomnia - Hypersomnia • Low grade feverishness, sweating disorder, • Chronic sore throat, - swollen lymph nodes • Recurrent headaches, unexplained depression • Cognitive disturbances, - snowflakes, buzzing noises, - crawling sensation, brain fag • Low morning blood pressure, - postural hypotension • Reduced daily activity, - very limited exercise tolerance
Traditional Lab-testing What ? identify single cause Separation of Symptoms quantifies Pathology Functional Lab-Assessment Why? Complex InterRelationships Connectedness of Symptoms quantifies Function Disease Labeling or Health Monitoring ?
. . is there a shift in the spectrum of diseases that we see and experience ? . . need for new biochemical ( or other ! ) markers ? : - not only to diagnose disease - sensitive to monitor metabolism more dynamically - treatment progress “ “ • T1 – T2 responses • Neurotransmitters, Cytokines, Trace-elements • Antioxidfant-Activity, DNA-adducts • Endocrine Disruptors , Free • pleo-morphic shift of pathogens, life-blood-analysis • Apoptosis
Microbial Pathogens • VIRUSES -100 nanometers, multiply through host DNA • BACTERIA - at least 10 times larger than viruses, 1 mcmr (1 millionth of a meter) - reproduce independently SINGLE-CELL - at least 100 times larger, 0.1 millimeter long PARASITES • MULTI CELLULAR - can be seen with the naked eye PARASITES ======================================================= Pleomorphism = theory of dynamic changes and transmutations between pathogens