Biochemical tests in clinical

medicine

Dr. Hala Kamel

MBChB, MSc, MD

Assist. prof. Biochemistry Dep.,

Faculty of Medicine

ASU & UQ

Clinical Biochemistry

History

Clinical Examination

Diagnostic services

Laboratory services

Clinical Biochemistry

Clinical Biochemistry Laboratory

Clinical biochemistry Laboratory play an

important, often unrecognised role, in disease

diagnosis and the monitoring of treatment.

•They are responsible for most laboratory testing

performed on samples sent to the diagnostic

laboratory by medical practitioners.

•Laboratory results produced by MLS‟s are used

by medical staff in the diagnosis of disorders in

approx. 70% of all patient cases.

Clinical Biochemistry

• Analysis of the chemical constituents of the blood, urine, faeces and tissues.

• Most of the laboratory testing uses sophisticated instrumentation interfaced to a laboratory information system.

• Diseases such as diabetes, renal failure, heart attack, drug analysis and hepatitis are some of the conditions investigated by clinical biochemists.

Introduction

• Clinical Biochemistry

• Dissolved elements in body fluids

• Concentration and type e.g. glucose,

electrolytes, hormones and significance of

levels and interpretation.

• Accurate and precise laboratory

measurements can aid in diagnosis and

management of disease

Uses of Biochemical tests

• 1- Diagnosis

• 2- Screening

• 3-Prognosis

• 4- Treatment

Use of Biochemical Tests

• 1-Diagnosis

• History and Physical Examination of patient --form

Differential Diagnosis i.e. Hypothesis

• Lab tests and Radiology to support or reject hypothesis.

Limitations of tests must be appreciated

• Interpretation must be carefully done in context of clinical

details

2-Screening

• Detection of sub-clinical

• Neonatal screening PKU, CHT

• Criteria for same.

• Natural history known

• Acceptable tests no false negatives, few

false positives

• Ease of treatment

• Positive outcome

Screening

• Natural history of disease

• Acceptable and reliable screening Tests,

FP issues

• Therapy available

• Prevalence

• Entire population

• or “at risk groups”

3-Prognosis

• Serial tests to identify progressive

disease creatinine in renal failure

• Tests to identify risks of disease in future

in certain groups cholesterol in “at risk

families”

• Calculation of risk depends on

epidemiological data

• Likely outcome of disease

Sampling

• Test Request

• Clinician requests that analysis be conducted.

• Requirements

• Name, DOB, Gender, Hos. No. MRN

• Ward, Address

• Requesting Clinician

• Hypothesis / Problem

• Tests sought,time of sampling,date

• Clinical details, Drugs or Therapy.

Sampling Issues.

• Patient Centred Factors

• Age

• Gender

• Posture

• Physiological State

• Pregnancy

• Exercise

• Fasting / Fed

• Time

Sampling contd.• Plasma,serum

• Bottle and preservative, anti coagulant used

• Age of sample

• Time of sampling

• Guidance from lab on sample requirements

• Correct label

• Transport

• High risk specimen.

VariationPatient Variables :

• Age, gender, fasting, time of day, exercise, posture, need to document these.

• Biological Variation

• Pre-Analytical Variation

• Sample site, type of bottle

• Transportation to lab.

• Stability of analyte age

• Analytical Variation

• Post Analytical Interpretation

Analysis

• Accuracy & Precision

• Detection limits

• Specificity& sensitivity

• quality assurance

• reference ranges

Precision and accuracy

• Precision is the reproducibility of an

analytical method.

• If there is 2 methods performed for the

same analyte repeated measurement of

the same analyte will show more closed

results to each others ( less scattering )

• Repeated measurement of an analyte will

be close to each other if precise

Precision and accuracy

• Accuracy defines how close the measured

value is to the actual value.

• Accuracy is therefore poor, as if the „sights‟ are off. so

repeated measurement of an analyte is accurate if it is

very close to actual value known before

• It is the objective in every biochemical method to

provide good precision and accuracy.

• Automation of analyses has improved precision

in most cases.

Precision and Accuracy

Diagnostic SensitivityPositive test result in presence of disease.

Diagnostic Specificity

Negative test result with no disease.

Diagnostic Sensitivity = TPTP + FN

Diagnostic Specificity = TN

FP+ TN

Analytical sensitivity and

specificity

• The analytical sensitivity of an assay is a

measure of how little of the analyte the method

can detect to improve the detection limit to help

in discrimination normal results and those with

suspected disease( Positivity in disease)

• Analytical specificity of an assay relates to how

good the assay is at discriminating between the

requested analyte and potentially interfering

substances. So it measures the negativity in

normal results

ROC CURVES A,B,C

Test Efficiency and Predictive

Values

TE = TP +TN X 100

Total No. of Tests

PV Pos = TP X 100

TP + FP

PV Neg = TN X 100

TN + FN

Features of PD pos. and PD neg.

• Prevalence of disease in population.

• Low prevalence with less than 100%

specificity high FP will result in low PV

• Screening with follow up testing should have

a high PV neg.

Likelihood Ratios

• LR pos = Sens. /1 – Spec.

• LR neg = Spec. / 1- Sens.

Reference Ranges

• Mean ± 2SD Mean

-1SD +1SD

-2SD +2SD

Healthy and Diseased Reference range

healthy

diseased

Biological Factors affecting

interpretation • Sex

• Age

• Diet

• Time of sampling

• Stress and anxiety

• Posture

• Exercise

• Medical History

• Pregnancy

• Menstrual cycle

• Drug History

Is It Different?

SD2 = SD2anal + SD2biol.

Receiving the report

• Does the results fit in with the excepted?

• If not, how to explain the discrepancy?

• How can the results change the

diagnosis?

• How to manage that patient?

• What should be done?

Interpretation

• Is Result Normal?

• Has it changed?

• Does it support the clinical hypothesis?

Does it Support the Hypothesis?• Consistent support diagnosis

• Inconsistent needs explanation

• Error in sampling, patient labelling

analysis,or reporting.

• Repeat test

• ? Diagnosis

• Statistical random event abnormal test no

disease.

• Diagnostic Utility : Sensitivity, Specificity

Errors

• Pre-analytical

• Analytical

• Post-analytical,

• Interpretation,

• Delays

• Wrong records

Biochemical tests performed outside laboratory

(Blood)

Point of care testing

Analyte Test when investing Operator

Blood Gasses

Glucose

Urea/Creatinine

Bilirubin

Salicylates /Paracetamol

Therapeutic drugs

Acid – Base status

DM

Renal disease

Neonatal Jaundice

Detection of poisoning

Compliance or toxicity

Medical or Nursing

setting

Glucose

cholesterol

Diabetic monitoring

Coronary heart disease

risk

Home or clinical

setting

Alcohol Fitness to drive/

confusion ,comaAlcohol test

Biochemical tests performed

outside laboratory (Urine)

Analyte Test when investing Operator

Ketones

Protein

Red cells/Hemoglobin

Bilirubin

Urobilinogen

PH

Diabetic ketoacidosis

Renal disease

Renal disease

Liver disease/ Jaundice

Jaundice/ Haemolysis

Renal tubular acidosis

Medical or Nursing

setting

Glucose

hCG

D.M.

Pregnancy testHome or clinical

setting

POCT: Advantages

• Faster stabilization of life-threatening crises (eg drug overdose, electrolyte disturbance)

• Immediate risk stratification (eg chest pain)

• Closer therapeutic management (eg diabetes)

• Better patient compliance with therapy (diabetes, anticoagulation, hyperlipidaemia)

• Reduce:

– repeat clinic/practice visits

– length of stay in hospital

– complications (intra- & postoperative)

– use of blood products (surgery)