Laboratory tests are ordered by the clinician for one of four reasons: Screening: - used in the general population – - to find silent disease Case finding:

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

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

Phlebotomist’s Equipment :• VACUTAINER TUBES -

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

• Routine Health Service tests :

• Blood Chemistry

• Blood Film Examination

• Urine-analysis

• Microbiology

Special Health Service

tests:

• Cytology

• Microscopy

• Aspirated Material : - Exsudates - Transudates

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

Urea NH2CONH2

• - 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

• ↑ conjugated - hepatobiliary disease - obstructive post-hepatic

jaundice

• ↑ un-conjugated - Gilbert’s Syndrome, neonatal jaundice - haemolysis, pre-hepatic jaundice

→ Serum ( free or un-conjugated B. - as ‘bilirubin-albumin complex’ )

( conjugated in liver - as ‘bilirubin glucoronide’ )

→ 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), PlateletsComplete 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

NeutrophilsEosinophilsBasophilsonocytesLymphocytes

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) –Population PERIPHERAL 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 called Protits; 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

Disease Labeling or Health Monitoring ?

Traditional Lab-testing

What ?

identify single cause

Separation of Symptoms

quantifies Pathology

Functional Lab-Assessment

Why?

Complex InterRelationships

Connectedness of Symptoms

quantifies Function

. . 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