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Clinical Biochemistry An Introduction

Clinical Biochemistry An Introduction. Dr Steve Smith Consultant Clinical Biochemist UHCW. Clinical Biochemistry. Meaurement of substances. Measured In:. Blood, Mainly serum but also cells Urine Cerebrospinal Fluid Faeces Kidney stones Saliva etc. Enzymes Metabolites Metal ions

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Clinical Biochemistry An Introduction

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  1. Clinical BiochemistryAn Introduction Dr Steve Smith Consultant Clinical Biochemist UHCW

  2. Clinical Biochemistry Meaurement of substances Measured In: Blood, Mainly serum but also cells Urine Cerebrospinal Fluid Faeces Kidney stones Saliva etc • Enzymes • Metabolites • Metal ions • Drugs and metabolites • Proteins • Hormones • Vitamins • Mutations in DNA & RNA • etc

  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 TestValue -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 mindwhen 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 mindwhen 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 mindwhen 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 mindwhen interpreting results

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

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

  18. Comparisons with Disease Groups ‘Normal’ Diseased TestValue +2.5% FalseNegatives FalsePositives

  19. Comparisons with Disease Groups ‘Normal’ Diseased TestValue FalseNegatives FalsePositives

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

  21. Comparisons with Disease Groups ‘Normal’ Diseased TestValue +2.5% FalseNegatives FalsePositives

  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?

  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.

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