Clinical Laboratory Investigation

(PP-PDP-212)
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 Clinical Laboratory Investigation
 Modern medicine is highly complex and investigations are a key part
of the diagnostic process. With major advances in technology there
are thousands of clinical and laboratory tests available.

 Clinical Biochemistry (also known as clinical chemistry or chemical

pathology) is the laboratory service absolutely essential for medical
practice or branch of laboratory medicine in which chemical and
biochemical methods are applied to the study of disease.
 Clinical Laboratory Investigation
 The results of biochemical tests may be used in:
1. Screening for disease in asymptomatic individual.
2. Diagnosis to establish or exclude disease in symptomatic patients.
3. Assist the practitioner in the management of patients.
4. In assessing the prognosis.
5. Research into the biochemical basis of disease.
6. Clinical trials of new drugs.
 Place of Clinical Biochemistry
Patient History
Imaging [X-ray, Ultrasound,
Clinical examination Computed tomography (CT),
Magnetic resonance imaging
(MRI), Mammogram] &
Diagnostic service Physiological tests (ECG, EEG),
Electro Retino Gram (ERG).

Laboratory services
Hematology,
Histopathology
& Microbiology
Clinical examination
 Place of Clinical Biochemistry
Clinical examination

Emergency Tests Core Biochemical Specialized Tests

• Urea Tests • Hormones
• Electrolytes • Na+, K+, Cl- • Drugs
• Blood gases • Urea & Creatinine • Lipids &
• Amylase • Ca & Phosphate Lipoproteins
• Glucose • Total Protein & • Special proteins
• Ca++ Albumin • Trace Elements
• Bilirubin & alkaline • Vitamins
phosphatase • DNA analysis
• ALT & AST
• Glucose
Place of Clinical Biochemistry
 Types of Laboratory Tests
• The biochemical investigations (on blood/plasma/serum)
carried out in the clinical biochemistry laboratory may be
grouped into different types.

1. Discretionary (‫ )تقديرية‬or on-off tests:

2. Biochemical profiles:

3. Dynamic function tests:

4. Screening tests:

5. Metabolic work-up tests:

 Types of Laboratory Tests
1. Discretionary (‫ )تقديرية‬or on-off tests: Most common clinical
biochemistry tests are designed to answer specific questions,
e.g., does the patient have increased blood urea or increased
blood glucose concentration? These tests are useful to support
the diagnosis.

2. Biochemical profiles: These tests give more useful information on

the patient’s disease status & can be obtained by analyzing more
constituents rather than one e.g., plasma electrolytes (Na+, K+, Cl-),
lipid profile (Cholesterol, TAG, HDL, LDL).
 Types of Laboratory Tests
3. Dynamic function tests: These tests are designed to
measure the body's response to external stimulus e.g., Oral
Glucose Tolerance Test (to assess glucose homeostasis).

4. Screening tests: These tests are commonly employed to

identify the inborn errors of metabolism, and to check the
toxicity by pesticides or heavy metals as lead & mercury.

5. Metabolic work-up tests: The programmed intensive

investigations carried out to identify the endocrinological
disorders.
 Specimen Collection
• The biological fluids employed in the clinical
biochemistry laboratory include blood, urine,
saliva, sputum, feces, cerebrospinal fluid,
peritoneal fluid, synovial fluid, pleural fluid, stones.

• Among these, blood (directly or in the form of

plasma or serum) is frequently used for the
investigations.
 Identification of Patients & Specimens
• The correct patient must be appropriately identified on the
specimen and request form, as follows:

1. Patient identification data (PID): This usually comprises name,

gender, age plus Code number.

2. Test request information: This includes relevant clinical details:

a. Any risk of infection hazard.

b. Tests to be performed.

c. Where the report is to be sent.

 Identification of Patients & Specimens
3. Collection of specimens: In the correct tube and the appropriate

preservative. Specimens for chemical analysis must be of good quality.

• Specimens collected or preserved under unsuitable conditions,

although may appear suitable for analysis, usually provide

inaccurate results, and mislead the appropriate diagnosis of the case.

4. Matching of specimens to requests: Each specimen must be easily

and unequivocally matched to the corresponding request for

investigations.
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 Quality Control
• Quality control in clinical biochemistry laboratory refers to
the reliability of investigative service. Any error in the
laboratory will jeopardize (‫ )يعرض للخطر‬the lives of patients.

• It is therefore utmost important that the laboratory errors

are identified and rectified (‫)تصحيح‬.

• Quality control comprises of four inter-related factors

namely precision, accuracy, specificity and sensitivity.
 Quality Control
1. Precision: Refers to the reproducibility of the result ( ‫نتيجة‬
‫ )قابلة للتكرار‬when the same sample is analyzed on different
occasions (replicate measurements) by the same person.

• For instance, the precision is good, if the blood glucose

level is 78, 80 and 82 mg/dl on replicates.

• Precision depends on the technique, the reagents, as well

as on the technician.
 Quality Control
2. Accuracy: Means the closeness of the estimated
result to the true value e.g., if true blood urea level
is 50 mg/dl, the laboratory reporting 47 mg/dl is
more accurate than the one reporting 40 mg/dl.
Precision & Accuracy
 Quality Control
3. Specificity: Refers to the ability of the analytical method to
specifically determine a particular parameter e.g., glucose can be
specifically estimated by enzymatic glucose oxidase method.

• Specificity: For example, in the case of glucose oxidase method,

only glucose molecules are assayed. So it is a very specific method.

• But if the reducing property of glucose is measured by (e.g., Nelson

Somogyi method), then other reducing agents in the blood will
interfere in the reaction, and hence specificity is lowered.

• Specificity is determined by the method of the analysis.

 Quality Control
4. Sensitivity: deals with the ability of a particular method to detect
small amounts of the measured constituent.

• Sensitivity: It indicates that whether the method could be utilized to

test a very dilute solution. For example:

• Biuret method is used for solutions having a few g of protein/dl.

• Spectrophotometric method is useful to detect a few mg protein/dl.

• While ELISA method is employed if the solution has only g of

protein/dl.

• Thus ELISA method is most sensitive.

LABORATORY ERRORS

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Limit of Errors Allowable in Laboratory
• In a laboratory, error may not be totally avoided; but should be kept at a
minimum. The limits are denoted by the term, Percentage Error.

• The percentage of allowable error in an assay is given by the formula:

Difference between maximum and minimum of normal range x 100

Mean of the normal range x 4

• The percentage error, therefore, will vary from test to test.

Limit of Errors Allowable in Laboratory
• In the case of blood glucose analysis, the normal range is 80
to 100 mg/dl. If these values are substituted in the formula:

(100 – 80) x 100 = 5.55%

90 x 4

• Now, in the case of blood urea (normal range of 20-40

mg/dl), the percentage error will be:

(40 – 20) x 100 = 16.67%

30 x 4
 Units of Measurements
• The results of chemical investigations are mostly numerical.
• It is very important to realize that the units of measurement
may differ between laboratories.
• It is easy to fall into the trap of focusing on numbers.
• A plasma [glucose] of “30” in a known diabetic admitted to
hospital in coma would indicate that the patient was in?
• Hyperglycemic coma? Or Hypoglycemic coma?
• Hyperglycemic coma if the units of
measurement were assumed to be expressed in
System International (SI) units, i.e., in mmol/L.
• OR the diagnosis was Hypoglycemic coma if
the result was assumed to be expressed in
‘conventional’ or mass units, e.g., mg/dl.
• Inappropriate therapy, based on incorrect
assumption about units, could easily have
rapidly fatal consequences for this patient.
 For Glucose

mmol/l mg/dl
1.7 30
4.4 80
8.3 150
14.0 250
22.2 400
30.0 540
 Units of Measurements

• A lumber CSF [total protein] of “30” would be interpreted very

differentially.
• If the measurement was assumed to be expressed in SI units,
i.e., in g/L, hence the result would be within the reference range.
• If the measurement was assumed to be expressed in
‘conventional’ or mass units, e.g., g/dl, hence the result would be
interpreted as being of pathological significance.
SI Units & Conventional Units
Plasma SI Units Conventional
constituents Units

Albumin 36 – 47 g/L 3.6 – 4.7 g/dL

Bilirubin (total) 2 – 17 mol/L 0.1 – 1.0 mg/dL

Blood Urea 2.5 – 6.6 mmol/L 7 – 18.5 mg/dL
nitrogen (BUN)
Creatinine 55 – 120 mol/L 0.6 – 1.4 mg/dL

Glucose (fasting) 3.6 – 5.8 mmol/L 65 – 105 mg/dL

Protein (total) 63 – 83 g/L 6.3 – 8.3 g/dL

Urate (males) 0.12 – 0.42 mmol/L 2.0 – 7.0 mg/dL

Urate (females) 0.12 – 0.36 mmol/L 2.0 – 6.0 mg/dL

Urea 2.5 – 6.6 mmol/L 15 – 40 mg/dL

 Conversion Factors Between
SI Units & Conventional Units
Multiplication factor
Plasma SI Units to Conventional Units
constituents Conventional to SI Units

Albumin 0.1 10

Bilirubin 0.06 17

Creatinine 0.011 88

Glucose 18 0.055

Urate 17 0.06

Urea 6 0.17