1. Clinical Biochemistry An Introduction
Dr Steve Smith
Consultant Clinical Biochemist
UHCW

2. Clinical Biochemistry
Meaurement of substances
Measured In:
Enzymes
Metabolites
Metal ions
Drugs and metabolites
Proteins
Hormones
Vitamins
Mutations in DNA & RNA
etc
Blood,
Mainly serum but also cells
Urine
Cerebrospinal Fluid
Faeces
Kidney stones
Saliva
etc
Mainly quantitative but also qualitative
Measure around 200 substances in house with al least another 200 possible by sending samples to other hospitals. For example due to the relatively low number of paediatric samples we receive many of the complex metabolic tests we send to the Birmingham Children’s Hospital who are funded to provide a specialist paediatric service.

3. How do we do it?
96% work is fully automated

4. Reasons for requesting a Biochemistry test
Diagnosis (confirmation or rejection of clinical diagnosis)
Glucose, TSH
Monitoring (Progression or response to treatment)
TSH, HbA1C, Lithium, Tacrolimus, PSA
Prognosis (Information about the likely outcome)
Cholesterol, Lactate Dehydrogenase (teratoma)
Screening (detection of subclinical disease)
Phenylketonuria, FOBT, Cholesterol

5. Specimen Collection Obtaining the correct specimen is crucial
Blood Samples:
Venous or arterial
Specimen bottle
Transport
Time of day
Avoid damage to sample

6. Questions which may be asked on receipt of Laboratory Results
‘If the result is not what I expected can I explain the discrepancy?’
‘Does it differ significantly from previous results and will change my diagnosis or the way I treat the patient?’
‘Is it consistent with clinical findings?’
‘what do I do next?’

7. How do we identify abnormal biochemistry?
'The Normal Range’
Defines the values of a biochemical test found in healthy subjects against which patient values can be compared.
Artificial concept - no clear boundaries exist.
Preferred term is 'Reference Interval'

8. Defining the Reference Interval
‘Normal’ Subjects
Test Value
-2.5%
+2.5%

9. Some factors which affect reference ranges
Age
Gender
Diet
Pregnancy
Time of month
Time of day
Time of year
Weight
Stimulus
Method
These need to be borne in mind when interpreting results

10. Hormone changes during the menstrual cycle

11. Some factors which affect reference ranges
Age
Gender
Diet
Pregnancy
Time of month
Time of day
Time of year
Weight
Stimulus
Method
These need to be borne in mind when interpreting results

12. Diurnal Rhythm of Cortisol

13. Some factors which affect reference ranges
Age
Gender
Diet
Pregnancy
Time of month
Time of day
Time of year
Weight
Stimulus
Method
These need to be borne in mind when interpreting results

14. Monthly variation in 25-hydroxy Vitamin D levels in UK men and women

15. Some factors which affect reference ranges
Age
Gender
Diet
Pregnancy
Time of month
Time of day
Time of year
Weight
Stimulus
Method
These need to be borne in mind when interpreting results

16. Alkaline Phosphatase Reference Intervals
30 – 120 IU/L
80 – 280 IU/L

17. Ideal Diagnostic Test Concn. ‘Normal’ Diseased Frequency
No false positives or negatives

18. Comparisons with Disease Groups
‘Normal’
Diseased
Test Value
+2.5%
False Negatives
False Positives

19. Comparisons with Disease Groups
‘Normal’
Diseased
Test Value
False Negatives
False Positives

20. Different Ranges Reference Interval (Range) Therapeutic Range
Urea
Therapeutic Range
Phenytoin
Clinical Cut Off
Cholesterol, B-Type natriuretic peptide

21. Comparisons with Disease Groups
‘Normal’
Diseased
Test Value
+2.5%
False Negatives
False Positives

22. Is the change significant?

23. Is the change significant?
A GP measured the serum creatinine of a 41-year-old man newly diagnosed as having diabetes and hypertension. The result was 105 mol/L. Six months later, both conditions were well controlled and the test repeated.

24. Is the change significant?
Investigation
Serum creatinine = 118 mol/L (105 mol/L previous)
Patient was alarmed at the increase and the GP uncertain whether the change was significant.

25. Is the change significant?
Analytical Variation
Biological Variation
Extrinsic
Time, posture, stress.
Intrinsic

26. Is the change significant?
Analyte
Level
Change required
Sodium
140 mmol/L 6
Potassium
4.2 mmol/L
0.6
Urea
5.0 mmol/L
2.1
Creatinine
60 mol/L 18
Calcium
2.40 mmol/L
0.19
Albumin
40 g/L 5

27. A 4 year old boy was seen in the paediatric out-patients’ department because of hepatomegaly, metabolic acidosis, and growth retardation. Some of his abnormal blood test results are:
Glucose 2.0 mmol/L (3.0 – 5.6 )
Uric Acid 610 μmol/L (200 – 430 )
Lactic Acid 3.7 mmol/L (0.5 – 1.5 )
Cholesterol 5.4 mmol/L (<5.0 )
Triglycerides 6.7 mmol/L (0.5 – 1.5)

28. Finding a low glucose is common in paediatrics and it triggers a whole raft of tests.
Hypoglycaemia is a feature of many inborn errors of metabolism

29. Von Gierke’s Disease This case Glucose-6 phosphatase deficiency
Hepatomegaly due to excess glycogen stores
Raised urate due to raised lactate
Abnormal lipids due to lack of glucose
Lactate raised because G6P taken down a pathway to lactate not glucose.

30. Demonstrates the knock on effects from what a first might appear common; low glucose.