Organ function testing Flashcards
State some uses of biochemical tests
- Diagnosis.
- Management.
Progression of disease.
Response to treatment.
Recurrence of disease. - Screening – detection in asymptomatic individuals.
Population - newborn screening.
Selected group - obese patients for type II diabetes mellitus.
Individual - familial hypercholesterolaemia.
Biochemical tests use biomarkers.
What are biomarkers?
How are they measured?
- Biomarkers can be enzymes, metabolites, or hormones.
- Usually measured in blood but can be in urine, faeces or CSF.
- Ions or gases are often also measured in Clinical Biochemistry.
Describe serum proteins/enzymes as biomarkers
- In normal tissue the cell membrane is intact and enzyme escapes due to normal cell turnover.
- When the membrane is damaged high levels of enzyme are released.
Increased cell number increases serum enzyme activity.
What does the induction of enzyme within a tissue do?
Induction of enzyme within a tissue increases release.
Increased serum enzyme activity does not always mean cell damage.
What could it be?
- May be hyper-proliferation.
- May be induction (synthesis of more enzyme).
- Some instances of induction can be diagnostically useful.
- Same argument applies to non-enzyme proteins in the serum e.g. albumin.
- Many of these are normally secreted.
What makes an ideal biomarker?
- Tissue specific (i.e. only present within one tissue).
- Rapid release in response to damage.
- Very low in serum of normal individuals.
- Easily measured with clear universal reference values.
- If these criteria are difficult to achieve use a battery of tests to make a profile.
Describe metabolites as biomarkers
- Useful to assess the function of the organ that produces them.
- However many metabolites are not “organ specific”.
- The concentration in serum may depend on uptake by other tissues and/or excretion by the kidney.
How are biomarkers measured?
- Spectrophotometric methods measure the activity of a serum diagnostic enzyme e.g. IU/l.
- Immunoassay will measure the amount of enzyme or other protein e.g. mg/l
- Metabolites are expressed as concentrations and are usually measured by spectrophotometric methods e.g. mmol/l.
- If you quote reference ranges make sure you get the units right.
How are abnormal results identified?
Using reference ranges
What is a population-based reference range?
- Most common means of establishing a reference range.
- Uses “local” population.
- Eliminates some social, genetic and environmental variables.
- Age§Gender§Race§Diet§Genetics
population-based reference range: As well as defining established variables exclusions should be made
- Risk Factors: e.g. obesity, hypertension.
- Drugs: e.g. alcohol, oral contraceptives.
- Physiology: e.g. pregnancy, stress, excessive exercise.
What is a reference range production?
Gather values:
- Patient’s consent.
- Sample collection.
- Specimen storage and analysis.
- Partition if necessary.
Inspect and apply data;
- Easiest if data are normally distributed.
True or False:
A result greater than 1.96 S.D. above the mean is considered “abnormal”.
True
What are the advantages of reference ranges?
Simple›Is the value within or outside the range?
Easily sourced ›Websites, textbooks, report forms.
Beware of variations!
Easily utilised ›But sometimes without due thought!
Give some common biochemistry reference ranges
What are some disadvantages of reference ranges?
- Statistical values may not reflect clinical significance.
- May be derived from inappropriate population or analyser.
- Biological variability.
Assuming we have a gold standard that always gives the correct results, a particular test can give which possible test results:
- True positive (TP) – positive test and subject has disease.
- False positive (FP) – positive test and subject does not have disease.
- True negative (TN) – negative test and subject does not have disease.
- False negative (FN) – negative test and subject has disease.
What is analytical sensitivity?
- Proportion of patients who have the disease who give a positive test.
- How good the test is at correctly identifying people with the disease.
What is analytical specificity?
- Proportion of patients without disease that give a negative test.
- How good is the test at identifying patients without disease.
Sensitivity and specificity:
Ideally each would be:
100%.
Almost impossible.Aim for >90%.
What can you do to increase the specificity?
Raising the “cut off” will increase the specificity as false positives will reduce but there may be many false negatives and the sensitivity will fall.
What is newborn screening?
- Population screen must be highly sensitive.
- Detect all disease.
- Outcome is always further investigation.
- Can tolerate false positives.
- However, these may case distress.
Heel prick blood spot sample after 1 week.
Testing for cystic fibrosis
- In babies with CF mucus can block the ducts from the pancreas to the small intestine.
- Immunoreactive trypsin (IRT) levels increase.
- Increased IRT in blood can be detected after 1-2 weeks with heel-prick test.
- Not all babies with IRT will have CF.
- Further investigation by sweat testing or genetic analysis.
