Diagnostic Tests 06.12.2011

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    Diagnostic tests

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    A diagnostic test is any kind ofmedical test

    performed to aid in the diagnosis or detection

    ofdisease

    http://en.wikipedia.org/wiki/Medical_testhttp://en.wikipedia.org/wiki/Medical_diagnosishttp://en.wikipedia.org/wiki/Diseasehttp://en.wikipedia.org/wiki/Diseasehttp://en.wikipedia.org/wiki/Medical_diagnosishttp://en.wikipedia.org/wiki/Medical_test
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    Helps to understand

    Patients health

    Physiological functioning

    Results are reported with a reference range

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    Why interpretation?

    Appropriateness of patients current drug

    therapy

    Adequacy of drug response

    Efficacy of treatment

    Serious drug toxicity

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    Medications may alter laboratory test values

    through a variety of pharmacological, physical

    or chemical mechanisms.

    Pharmacologically, a drug may cause a true

    change in the concentration of the particular

    substance being measured.

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    Chemically, a drug or its metabolite may

    interfere with the accurate determination of

    the desired constituent.

    In addition to chemical interferences by drugs,

    one should also consider the effects of

    anticoagulants and of marked changes in

    concentrations of normally occurringsubstances in body fluids which alter

    laboratory test values.

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    Chemical interferences arise primarily from

    lack of specificity of the methods used to

    measure desired constituents

    Another problem is to determine whether a

    reported drug interference was observed at

    realistic concentrations which are likely to

    occur in serum or urine during a typicaltherapeutic regimen.

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    Renal function tests

    Serum urea(3-8 mmol/L):

    Catabolism of amino acids

    Undergoes tubular reabsorption

    Vary with diet, rate of protein metabolism, liver

    production and GFR.

    Upto 10 mmol/L

    Non-renal and renal factors influence the increaseand decrease in the levels.

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    Uric acid(0.15-0.47 mmol/L):

    End product of purine metabolism

    Increased rate of formation or reduced excretion

    Gouty arthritis

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    Drugs interfering with uric acid

    measurementInterfering agent

    Ascorbic acid

    Phenacetin

    Caffeine

    ChlorineErgothioneine

    Salicylates

    Levodopa

    Methyldopa

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    Serum creatinine(55-120 mmol/L or 0.6-1.35

    mg/dL):

    Product of muscle metabolism

    Surrogate marker for GFR

    Increase: insult to the kidney

    Decrease: no pathological significance

    Estimation of GFR

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    GFR:

    Glomerular filtration rate (GFR) describes the

    flow rate of filtered fluid through the kidney

    Estimated GFR= (140-age) x weight

    Serum creatinine mmol/l x0.84

    120-150ml/min

    Helps to monitor drug action, transplant

    Poses a problem (muscle mass and consumption

    of diet)

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    Measurement of alternate agent i.e., cystatin

    C

    Equations are developed considering the

    same.

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    Drugs interfering with creatinine

    measurementInterfering agent Concentration equivalent

    Acetoacetic acid. IOO mg/dl of acetoacetic acid =3.4 mg/dl ofcreatinine.

    Acetone 500 mg/dl of acetone =1.4

    mg/dl of creatinine.

    Aminohippurate

    Ascorbic acid

    Fructose IOOOm g/d1 of glucose

    =1 mg/dl of creatinine.

    Glucose IOOOm l/d1 of glucose

    =0.2 mg/dl of creatinine.

    Methyl dopa IO mg/dl of methyldopa = 1.0 mg/dl of creatinine.

    Nitrofuran derivatives

    Phenolsulphtalein

    Pyruvate 10 mgldl of pyruvic acid = 0.3 mgidl of creatinine.

    Protein 5 g/d1 of crystalline human serum albumin =2.2 mg/dl

    of creatinine.

    Sulphbromthalein

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    Blood urea nitrogen(2.9-7.1 mmol/L or 8-20

    mmol/L):

    Alongwith serum creatinine, is very useful

    Another prognostic marker for kidney disease

    is an elevated level of protein in the urine. The

    most sensitive marker of proteinuria is

    elevated urine albumin

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    Drugs interfering with blood urea nitrogen

    measurementInterfering agent

    Citrulline

    Hydantoin

    MethylureaPhenylurea

    Sulfonylureas,

    Acetone

    Chloral hydrate

    Creatinine

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    Drugs interfering with urobilinogen

    measurement

    Interfering agent

    P-amino salicylate

    Chlorpromazine

    Bilirubin

    Sulphonamides

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    SERUM ELECTROLYTES

    1. Serum sodium(135-145 mmol/l)

    Hyponatraemia: not enough sodium (salt) in the body fluids

    Lethargy, nausea, drowsiness and confusion

    Pseudohyponatremia, clinical fluid overload, diuretic

    therapy, salt wasting nephropathy, The syndrome of

    inappropriate antidiuretic hormone hypersecretion

    (SIADH)

    Acute or chronic

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    Hypernatraemia

    Excessive loss of hypotonic fluids, severe vomitting

    /diarrhea

    Diabetes mellitus, acute renal failure, diabetes insipidus Address the underlying dehydration

    Causes CNS pathology

    Controlled by thirst reflex, ADH, renin-angiotensin-

    aldosterone system and renal tubular handling

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    2. Serum potassium(3.4-4.8 mmol/l)

    Hypokalemia

    Vomitting, diarrhea and gastric suction, drug related

    Intravenous potassium should be diluted and infused

    slowly

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    Hyperkalemia

    Serious cardiac effects

    Administration of intravenous glucose insulin,

    treatment with cation exchange resin, hemodialysis Drug related: potassium sparing diuretics, ACE

    inhibitors, AT antagonists and NSAIDs

    Present in acute renal failure

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    3. Serum calcium(2.2-2.5mmol/l or 8.8-10.2

    mg/dl)

    Ca corr (mg/dl)= {(4-albumin g/dl)x0.8 mg/gl} + Ca

    uncorr (mg/dl)

    Hypocalcemia : vit D deficiency, hypparathyroidism and

    chronic renal failure

    Hypercalcemia : overuse of Vit. D or thiazide diruetics.

    Constipation, confusion, conjunctivits, drowsiness,

    lethargy and polyuria. Most common cause is release of

    calcium from bones

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    Blood picture

    1. Hemoglobin (13.5-17.5 g/dl for men, 12-16

    g/dl for women)

    Higher in polycythemia rubra vera, patients who

    live at high altitude or those with chronic hypoxiclung disease

    Anemia :

    Types depending on MCV(80-100fl) and MCHC (33-37g/dl)

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    Microcytic anemia

    Low MCV and/or low MCHC

    Microcytic hypochromic anemia is associated with

    iron deficiency

    Normocytic anemia

    MCV and MCHC are within normal ranges

    Associated chronic infections, rheumatoid

    arthritis, hypothyroidism and malignancy, chronic

    renal failure, blood loss

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    Macrocytic anemia

    High MCV

    Liver disease, deficient dietary intake of folic acid

    or vit B12

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    2. White cell count (4.5-10.5 x 103/mcl)

    Luecopenia (neutropenia or lymphopenia)

    Elevated levels seen with infections,

    corticosteroids and lithium can also increase the

    count, eosinophilia (allergic reaction)

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    3. Platelet count(150-450 x 103/mcl)

    Surrogate marker for inflammatory reaction

    Thrombocytopenia : liver disease, infections, drug

    induced

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    Other blood tests

    Erythrocyte sedimentation rate (ESR)

    Normal volume is less than 10mm/h

    Westergren method

    High ESR indicates increased protein level

    (inflammatory condition)

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    C-reactive protein

    Secreted by liver in response to inflammation

    Haptoglobin

    Functions as an antioxidant

    Helps to monitor inflammatory conditions

    Coombs test

    Anti-human immunoglobulin antibody and

    anticomplement antibody autoimmune anemia

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    Xanthochromia

    Several hours after subarachnoid haemorrhage,

    distinguishes from traumatic lumbar puncture

    Iron, transferrin and iron binding

    Transferrin total iron binding capacity

    Ferritin measurement- decrease in iron deficiency

    Free protporhyrinincrease in iron deficiency

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    Liver function test

    Albumin Present in ECF and serum

    Important role in binding

    Concentration depends on synthesis, volume of

    distribution and rate of catabolism Synthesis- fall with increasing severity of liver disease or

    malnutrition in response to inflammatory mediators

    Volume of distribution increases, causes reduced serum albumin

    in case of cirrhosis, fluid retention states

    Increased capillary permeability results in movement of albuminfrom serum into interstitial fluid

    Other causes include catabolic states- kidney, skin, intestinal wall

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    Bilirubin

    Elevation of bilirubin above 50micromole/l reveal

    presence of jaundice.

    Elevation may be due to

    Increased production of bilirubin- haemolyis,

    ineffective erythropoesis

    Impaired transport in hepatocytes- hepatitis or drug

    induced

    Decreased excretion- drugs, cirrhosis, tumours

    Intra-hepatic obstruction- cirrhosis, tumours

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    Enzymes

    Alanine transaminase

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    Ammonia

    Indicative of impairment of urea cycle function or

    extensive hepatic damage

    Hyperammonaemia >60mmol/L Valproic acid can induce encephalopathy

    Amylase

    Rises within 24 h of pancreatitis, then declines to

    normal over 1 week

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    Cardiac markers Troponins

    Cardiac troponin I(cTn I) and Cardiac troponin

    T(cTn T)

    Creatine kinase

    Increased during shock, myocardial infarction and

    muscular dystrophies

    Drug induced

    Two protein subunits M and B

    Lactate dehydrogenase

    LD-1-LD-5, increase levels in damage to liver,

    skeletal muscle and kidneys, anemia

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    Tumor markers

    Prostate specific antigen

    Human chorionic gonadotropin

    Carcinoembyronic antigen

    Cancer antigen (CA125 and CA 19)

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    Immunoglobulins

    Detected by electrophoresis as bands in , ,

    regions

    Increased levels found in infections chronic

    liver disease, autoimmune disease

    Lymphatic leukaemia, lymphoma and multiple

    myeloma

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    Lab Test-Drug Interaction:

    Pharmacological Mechanisms

    Pharmacologically, a drug may cause a true change in

    the concentration of the particular substance being

    measured.

    Allopurinol, a xanthine oxidase inhibitor, is used toreduce plasma uric acid levels in selected patients.

    Incidental pharmacologic effects, other than those

    primarily intended, may also occur.

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    Antiovulatory drugs, used for contraceptive

    purposes, cause an increase in total serum thyroxine-

    binding globulin.

    This results in an increase in both total serumthyroxine and unsaturated thyroxine-binding

    globulin, but no significant change in unbound

    (free) thyroxine.

    Recognition of these effects is essential in the

    interpretation of thyroid function tests.

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    Drugs may also cause undesirable toxic or side

    effects, as evidenced by changes in liver or renal

    function tests.

    Thus, in some individuals, phenothiazines willproduce a picture of obstructive jaundice, with

    elevation in serum bilirubin and alkaline

    phosphatase.

    Knowledge of the pharmacologic effects of drugs

    helps to explain a number of correct but otherwise

    unexpected laboratory results.

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    Lab Test-Drug Interaction:

    Chemical Mechanisms

    Chemically, a drug or its metabolite may interfere

    with the accurate determination of the desired

    constituent.

    Methyldopa, used in the treatment of hypertension,will produce a false positive result for urinary

    catecholamines, since it reacts in the method to

    produce a green fluorescence similar to that

    produced by norepinephrine.

    This could lead to an erroneous diagnosis of

    pheochromocytoma.

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    Radiographic contrast media, containing iodinated

    organic compounds, invalidate protein-bound iodine

    determinations because of their own high iodine

    content. Other drugs can interfere by producing extraneous

    color reactions, by chelation, or by inhibition of

    enzyme activity.

    In uremia, associated high levels of creatinine and

    uric acid can result in falsely elevated values for

    glucose as measured by alkaline ferricyanide

    methods.