• We're going to predominantly be looking at reference ranges, how they are used, how they are established, how effective they are in the healthcare environment specifically organ function testing.
• The learning outcomes are, you have an appreciation for how biomedical scientists use biochemi...
Aston University, Birmingham (Aston)
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Clinical sciences
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1. Organ Function Testing
1
We're going to predominantly be looking at reference ranges, how they are used, how they
are established, how effective they are in the healthcare environment specifically organ
function testing.
The learning outcomes are, you have an appreciation for how biomedical scientists use
biochemical tests, you’ll have an understanding of how we identify abnormal results, and we
will also evaluate how good a particular test is at providing a diagnosis.
The most common and routine use of a biochemical test is to diagnose a particular condition
so diagnosis is the key so for example if you knew that there was a particular protein or an
enzyme for that matter that would appear in the blood after a specific organ was let's say
deteriorating so you've got a particular organ, it is deteriorating and it releases a protein in
the blood now if you had the technology to identify that protein you would be able to run a
test to quantify the level of that protein therefore you could correlate it to the progression
of that particular disease.
If we look at HIV for instance, the number of virus particles is a very good indication that
individual has HIV and of course once you’ve diagnosed someone the use of that
biochemical test will then do three things.
One you could monitor the progression of that particular disease so how is that patient
responding to treatment again if we stick to the example of HIV, if you know that the person
has a high viral load and you are giving them a particular drug you could then quantify that
viral load to see how it's increasing in line with treatment and that shows you the
progression of the disease, is it getting worse or is it improving and …
It gives you the response to the treatment, if you gave a drug and the viral load isn’t
reducing then you need to look at different medication.
It also highlights the reoccurrence of the disease so again if we stick with the example of HIV
once you've administered the drug and that viral load does decrease to safe levels you might
still want to take a blood sample a few months after to see whether that viral load has
increased.
Biochemical tests are predominantly used for diagnosis but also allow you to track the
progression of a disease, how a patient responds to treatment and if there are any rare
occurrences of remission.
On a larger scale you could use biochemical tests to conduct screening and detect
asymptomatic individuals so screening is the use of a biochemical test to screen otherwise
healthy individuals so if you already consider what we already know about biochemical
markers if they can be accurately used to diagnose a condition and they are specific to a
particular disease then screening programmes take advantage of this and they try to find
individuals who are at an increased risk of developing the disease or could be asymptomatic
carriers as well.
We've established what a biochemical test is but what are we looking for in these tests?
Biomarkers, a biomarker can be defined as a naturally occurring molecule, gene or a
characteristic by which a particular pathological disease can be identified.
Usually, biomarkers are found in the blood which is great because we have plenty of it and
taking a blood sample is not particularly dangerous or expensive. Ideally, we could use
samples which are naturally excreted by the body so you will find certain biomarkers in the
, 1. Organ Function Testing
sweat for instance, in the urine, in the faeces and again all of these body fluids are easy to
obtain and offer very little risk to the patient that's giving these samples.
In certain instances of course you do require more precious samples and this can be things
like retrieving a cerebral spinal fluid sample which is the fluid found in the brain and in the
spinal code and your brain kind of floats around in the CSF encapsulated within the blood
brain barrier, in normal instances you can't access that it's a very precious sample and it's
difficult to retrieve but when the medical staff are querying things like meningitis for
instance and they want to see whether there is inflammation in the cerebral spinal fluid
they'll take a sample from the from the lower region of the spine of this point, it can be
painful and those tests have to be conducted very quickly to identify a higher white blood
count which would be indicative of an inflammatory process going on.
The majority of our biomarkers will be found in the blood, which is great, things like urine
faeces, sweat but they can be in a more precious samples like the CSF.
Biomarkers come in various forms, they can be enzymes, metabolites or hormones. They
tend to be metabolites when a disease specifically alters a biological mechanism, and you
may get an increase in a by-product as a result of the disorder.
They could even be hormones and the most common example that comes to mind is type 2
diabetes which can be diagnosed with dysregulations of insulin, if you have a very low insulin
concentration you know that maybe the pancreas is not functioning properly and it could be
indicative of type one diabetes which is an autoimmune disorder where your immune
system attacks the pancreas and therefore destroys it, logically you would have less insulin
circulating in the body.
In individuals who suffer from acromegaly which is a condition where you have excess
production of growth hormone quantifying growth hormone will be a biomarker for that
particular condition.
In rare instances it can even ions or gases and these are often measured in clinical
biochemistry.
This is a background on how an enzyme, or a particular protein would function as a
biomarker.
On the diagram we have a healthy cell which is surrounded by a membrane which is
impermeable to proteins, so the enzyme is present inside the tissue, and you've got that
blood capillary line quite close to it.
But if this particular tissue was to undergo some sort of disease or pathological disorder and
that cell membrane becomes damaged that the membrane will become leaky which means
that the enzyme which was originally present inside the tissue will leak out into large
quantities and will be found in the blood and therefore can be used to identify the disease
which damaged the cell to begin with.
That's the kind of promise for a biomarker but there are problems with this approach.
There may be natural instances where you have an increase in cell proliferation and general
cell turnover so there could be a condition in the body where cells are just naturally
multiplying at a faster rate and therefore coming to the natural end of their life cycle as well,
so they are growing and dying more,
You would then have a falsely elevated level of that particular enzyme in the blood another
example can be where an external event leads to an increase in the expression or
concentration of a particular enzyme as well. E.g., as a compensatory mechanism for too
much alcohol, the liver upregulates the production of alcohol dehydrogenase so that's the
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