Reference ranges

Question 1

What are the 4 main divisions of pathology and what do they do?

Answer 1

Histology and Cytology

Tissue diagnosis – malignancy, infection, auto-immune

Bacteriology and Virology

Causes of infection – culture, antigen and antibody testing and increasingly PCR

Antibiotic use, public health, environmental testing

Haematology

Diseases of the blood

Transfusion

Coagulation

Biochemistry and Immunology

Measurement of analytes in blood, urine, CSF etc

Question 2

What type of samples are analysed in clinical biochemistry?

Answer 2

Serum

Whole blood

Urine

Faeces

Sweat

Cerebrospinal fluid

Renal stones

Post-mortem samples

Miscellaneous fluids

Question 3

What are the 5 groups of tests?

Answer 3

1. Renal function sodium, potassium, urea, creatinine
2. Liver function total protein, albumin, bilirubin, alkaline phosphatase, alanine transaminase
3. Bone profile total protein, albumin, calcium, phosphate, alkaline phosphatase
4. Thyroid function TSH (free T4, free T3)
5. Lipid profile total cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides

Question 4

How are reference ranges generated?

Answer 4

take a large number of (healthy) individuals

measure the substance of interest

calculate the mean and standard deviation of the results

the reference range is

mean - 2sd to mean + 2sd

Question 5

What is the reference range for this graph?

Answer 5

mean = 50

sd = 10

reference range = 30 - 70

Question 6

What percentage of the populatation is within the reference range?

Answer 6

95% of results (for the population) are within the reference range

2. 5% of results (for the population) are lower than the reference range
3. 5% of results (for the population) are higher than the reference range

Question 7

Why are reference ranges not 100% accurate?

Answer 7

Results outside the reference range

do not necessarily imply disease – they may be a chance finding in a healthy individual.

the more extreme the value the more likely that an abnormality / disease is present

Results inside the reference range

do not necessarily exclude disease

Question 8

Name a hormone that men and women have different reference ranges for?

Answer 8

Testosterone

Question 9

What are the 5 sources in the body of alkaline phosphatase?

Answer 9

• Liver (usually with a raised GGT)
• Bone (usually normal GGT)
• Intestine
• Kidney

Placenta

Question 10

Which enzyme varies depending on bone growth?

Answer 10

Bone alkaline phosphatase

Question 11

Which molecule varies during pregnancy?

Answer 11

Serum thyroid hormone

Question 12

Complete the table

Answer 12

Question 13

Complete the table

Answer 13

Question 14

What happens to TSH and free T4 in hypothyroidism?

Answer 14

TSH - increase

Free T4 - decrease

Question 15

What happens to TSH and free T4 in hyperthyroidism?

Answer 15

TSH - decrease

Free T4 - increase

Question 16

What do these thyroid results show?

Answer 16

The TSH is in the reference range, but it is inappropriately low.

The TSH should be very much higher

The pattern of results points to a pituitary failure.

Question 17

Interpret these results with the following clinical information -

1. clinical information = “9 am cortisol”
2. clinical information = “overnight dexamethasone test”

Answer 17

1. interpretation – this is a low result and may indicate Addison disease (adrenal failure)
2. interpretation – this is a normal result. The drug dexamethasone is given with the intention of suppressing cortisol

Question 18

How can you tell whether a raised ALP is due to liver disease or bone disease?

Answer 18

The problem is that alkaline phosphatase can be elevated in both liver disease and also bone disease

so we could now measure gGT (gamma glutamyl transferase)

an elevated result – liver dysfunction likely

a “normal” result – liver dysfunction unlikely, ALP more likely to be related to bone disease

Question 19

Interpret these creatinine results

Answer 19

Both creatinine results are within the reference range

The difference between them is 32 umol/L and this is significant

A change in creatinine of more than 26 umol/L indicates that acute kidney injury (AKI) may be a possibility.

Question 20

How are NSTEMI’s ruled in or out?

Answer 20

If initial blood test shows a troponin <5 ng/L then MI ruled out

If initial blood test shows a troponin >52 ng/L then MI ruled in

A further test can be done one hour later:

IF this result shows a change o f <3 ng/L then MI rule out

IF this result shows a change of ≥ 5ng/L then MI ruled in

Other result – grey area – observe

Question 21

Why are small changes in results not necessarily important?

Answer 21

Depends on Biological variation but also laboratory precision