Organ function testing Flashcards

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1
Q

State some uses of biochemical tests

A
  • 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.
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2
Q

Biochemical tests use biomarkers.

What are biomarkers?

How are they measured?

A
  • 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.
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3
Q

Describe serum proteins/enzymes as biomarkers

A
  • 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.
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4
Q

Increased cell number increases serum enzyme activity.

What does the induction of enzyme within a tissue do?

A

Induction of enzyme within a tissue increases release.

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5
Q

Increased serum enzyme activity does not always mean cell damage.

What could it be?

A
  • 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.
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6
Q

What makes an ideal biomarker?

A
  • 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.
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7
Q

Describe metabolites as biomarkers

A
  • 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.
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8
Q

How are biomarkers measured?

A
  • 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.
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9
Q

How are abnormal results identified?

A

Using reference ranges

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10
Q

What is a population-based reference range?

A
  • Most common means of establishing a reference range.
  • Uses “local” population.
  • Eliminates some social, genetic and environmental variables.
  • Age§Gender§Race§Diet§Genetics
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11
Q

population-based reference range: As well as defining established variables exclusions should be made

A
  • Risk Factors: e.g. obesity, hypertension.
  • Drugs: e.g. alcohol, oral contraceptives.
  • Physiology: e.g. pregnancy, stress, excessive exercise.
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12
Q

What is a reference range production?

A

Gather values:

  • Patient’s consent.
  • Sample collection.
  • Specimen storage and analysis.
  • Partition if necessary.

Inspect and apply data;

  • Easiest if data are normally distributed.
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13
Q

True or False:

A result greater than 1.96 S.D. above the mean is considered “abnormal”.

A

True

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14
Q

What are the advantages of reference ranges?

A

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!

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15
Q

Give some common biochemistry reference ranges

A
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16
Q

What are some disadvantages of reference ranges?

A
  • Statistical values may not reflect clinical significance.
  • May be derived from inappropriate population or analyser.
  • Biological variability.
17
Q

Assuming we have a gold standard that always gives the correct results, a particular test can give which possible test results:

A
  • 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.
18
Q

What is analytical sensitivity?

A
  • Proportion of patients who have the disease who give a positive test.
  • How good the test is at correctly identifying people with the disease.
19
Q

What is analytical specificity?

A
  • Proportion of patients without disease that give a negative test.
  • How good is the test at identifying patients without disease.
20
Q

Sensitivity and specificity:

Ideally each would be:

A

100%.

Almost impossible.Aim for >90%.

21
Q

What can you do to increase the specificity?

A

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.

22
Q

What is newborn screening?

A
  • Population screen must be highly sensitive.
  • Detect all disease.
  • Outcome is always further investigation.
  • Can tolerate false positives.
  • However, these may case distress.
23
Q

Heel prick blood spot sample after 1 week.

A
24
Q

Testing for cystic fibrosis

A
  • 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.
25
Q

Therapeutic drug monitoring:

When it is necessary?

What does it assume?

A
  • Necessary when drugs have a narrow therapeutic window.
  • Assumes relationship between concentration of the drug in blood and clinical effect.
26
Q

Give some examples therapeutic drugs that are monitored?

A