Introduction
Algorithms - Do's and Don'ts
Ways to View Laboratory Results
Videos
What You Need
to Know About Laboratory Tests
Example - Why Order a Hemoglobin Test?
CBC Road Map
More on Hemoglobin Test - Interpretation
Further Interpretation
of the CBC
Basic Chemistry Analytes |
Introduction
This is a crash course (workshop) in the utilization of laboratory
tests and an introduction to a way of thinking about laboratory tests.
You are about to start applied discussions and lectures in which laboratory
values are discussed in relationship to various organ systems and disease
processes. You will be using these values in a controlled environment,
someone has already done the analysis and told you what lab values are
important. In the real world, you may be confronted with a patient
with vague symptoms, you develop a differential diagnosis and you select
the laboratory tests and you interpret the results and come up with
a working diagnosis and a management and monitoring plan or refer.
As you develop your professional knowledge base, you will also develop
a data base for laboratory tests and applications. There is No way that we can convey this information to you predigested and ready to
file. In order for you to truly be able to use it you will have to
see the results, gain experience and make mistakes. You already know more
than you think you do. Neither the laboratory nor the professional
exist in a vacuum. The laboratory tests are based on practical measurements
of analytes which reflect normal or pathological processes. You have
been introduced to those processes in your preparatory courses, including
Dr. Spalls "pathophysiology". |
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Algorithms - Do's and Don'ts
There are computer programs and algorithms that you can use or
memorize which guide you through the use and ordering of tests. For
many of patients you can probably use these formulas without thinking and
get to where you need to be. For the rest of the patients, it is
imperative that you know what you are doing and why, so as you build
your professional knowledge base it will be much more important for you
to know the details of these tests or become very chummy with someone who
does. My philosophy is that if you understand the concepts and as
you come across the tests you fill in the blanks, it is a whole lot easier
than memorizing lists. |
What you think you need right now is a list that goes something like
this:
- the BUN is x number
- the diseases that result in an elevated BUN of X are:
- (list of diseases) and the confirmatory tests are: (list of additional
tests for each of the diseases listed, preferably one per diagnosis).
This is exactly how you will probably think and use the tests. As
mentioned, there are several books that will help you this way. But
to intelligently use them, you should be thinking initially in terms
of processes. When you understand these, you can jump intuitively to diagnoses.
- Taking a BUN of 50, you know this is elevated because the lab says
it is (see sample lab report).
- You should also know that this is a normal byproduct of protein metabolism
in all tissues except muscle, it is made in the liver and passively filtered
through the kidneys (from your previous classes).
- Therefore you should consider processes that will result in a high BUN and they might include -
- fluid balance - decrease in water results in a relative increase (dehydration
);
- increase due to increased protein metabolism (internal bleeding, increased
dietary protein intake (Atkins diet) , or conversely carbohydrate
restricted diet); or
- decreased glomerular filtration (prerenal-shock) renal (glomerular nephritis,
renal disease).
- A low BUN may indicate
- fluid overload,
- increased plasma volume,
- increased glomerular filtration,
- decreased dietary intake of protein or
- liver failure
Yet what you will see in most of the books is BUN is a renal function test.
The values may be modified by any of the above so someone who has renal
function problems may present with BUN levels that are ambiguous, especially
if the patient is pregnant or suffering from another disease, on IV fluids,
or have concomitant liver failure. Therefore, depending on the suspected
process, you will choose additional tests, or look at them next if they
are available. The creatinine is similar to BUN in that it is a normal
by product of muscle metabolism (creatine to creatinine and formed in direct
proportion to muscle mass independently of liver or dietary). Like
BUN it is passively filtered by the glomerulus. Therefore a high
BUN coupled with a high creatinine point to glomerular dysfunction (can
be prerenal - acute higher BUN than creatinine, can be renal BUN to creatinine
increases proportional 1:20). IF the patients muscle
mass is normal - But if not, then you will need to adjust how you
look at the tests. A patient with muscular dystrophy may have a lower creatinine
even in the face of renal compromise. |
| The more intelligent way to look at laboratory tests is as parts
of algorithms. |
| What I would like to do today is introduce you to developing algorithms
on your own, but also throw you some lifelines in terms of shortcuts you
can use while you are learning the rest of the stuff. You will
have access to this presentation, a version of the M&M lab from Dr.
Spall's, and a series of discussions of individual tests. We will also
make available regular case studies as you go through your clinical medicine
class. |
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Ways to View Laboratory
Results
There are at least two different ways to look at Laboratory Results
as you start to analyze them. For ease of remembering but nothing
that has to be memorized, I divide them into horizontal and longitudinal.
In horizontal analysis, the practitioner analyzes the laboratory data in
relationship to the population from which his patient is derived and sub
populations which have the disease in question. You might want to
review the sections on:
- Normal Range
- Sensitivity
- Specificity
- Positive/Negative Predictive Value
|
| I presented these concepts in Dr. Spalls class. For those of
you who did not attend that class I will provide a link for you to get
to the exercise that explains these terms. (This is on streaming video
and for best results should be viewed on campus or a T1, cable internet
connection). Click Here for free RealPlayer download.
|
| In longitudinal analysis, the patient data are analyzed only in relationship
to that patient i.e. has there been a change in the analyte. In order
to begin this type of analysis, you might want to review the concepts of
preanalytical/analytical/and post analytical variation as well as the terms
accuracy and precision (also covered in the video). |
| The construction of algorithms (keys) will become very important to
you as you start to look at patient data. You may use pre constructed
algorithms as presented in books or you may construct your own. The
basis for algorithms is the understanding that no one individual test is
appropriate to use to diagnose any disorder or disease. A series
of tests are used. The specific order in which they are applied is
critical to the diagnosis and will vary according to the conditions which
you wish to "rule in" or "rule out". Availability, turn around time,
cost and reimbursement will affect the tests which you will use in your
algorithms and therefore, they will change from location to location. |
| For the purposes of this exercise, as you are preparing for your clinical
classes, we will assume that the test values you are given are the best
possible in terms of pre analytical and analytical error and that there
are no constraints concerning either availability or reimbursement issues.
We will address those practicalities at a later date. |
| Please discard any notion that you have that there is a test for a
condition or disease or that a single test can be used for diagnosis. Redundancy
is built into laboratory analysis. Laboratory data without intelligent
interpretation is worse than useless. I am counting on you to provide
the intelligent interpretation. In order to do that interpretation,
you have to know or be able to find rapidly certain things about the analyte.
Before you order a test, you need to know what it can and cannot tell you.
If you do not know-do not order it because you will have to deal with the
results. By the way, if you have maintained consciousness in your previous
classes, very few of the situations I am going to give as examples will
be foreign. You have the information or were at one time or another
exposed, you just need to drag it out, dust it off and use it. Going
back to the BUN analogy you should realize that you do already have much
of this knowledge. |
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What You
Need to Know About Laboratory Tests
When you order a laboratory test and it is performed on a sample from
the patient, the number you get represents the level in that patient at
the exact moment it was drawn. It is a snapshot-----no more-no less.
Unless you are doing a longitudinal analysis ( same analyte over a period
of time on the patient) you do not know whether it is rising, falling or
is the same as it has been for some time. The measurable level of
any analyte exists as a dynamic equilibrium at the moment you took the
snapshot. That is a balance between the production or acquisition
of the analyte and the destruction, passive or active removal of
the analyte. Therefore in order to intelligently interpret the analyte
you must know:
- What is it?
- How and where is it made? or
- How is it acquired?
- Is it consumed or produced as part of a natural process or only in pathological
states?
- How is it metabolized (destroyed)?
- How is it removed if not destroyed (active/passive)?
- What regulates these processes? (none, induction, feed back inhibition
etc.)
- Are there other tests that measure related analytes but differ in one or
more of these processes?
|
Let's Look at a Few Examples
The most common tests that you will be dealing with at first are probably
a CBC with or without differential, a reticulocyte count, a urinalysis,
and a chem panel (basic, metabolic or other iteration) and a Thyroid test
(T-4 or TSH). These tests account for over 80% of all laboratory
work ordered. As part of your own professional development, it would be
wise for you to disassemble these tests (each is really a battery of individual
tests) and look up the answers to the eight questions above for each one.
Lets pick some individual tests out of these panels, each of which
may have profound implications for your patient and look at them first
in terms of the eight questions and then in terms of how they might vary
in different disease states. |
Using the 8 questions listed above - Let's look at Hemoglobin
1. What is it? Hemoglobin is the normal respiratory
pigment of all vertebrates. It consists of a heme core (porphyries
and iron) and globin chains. The intact molecule is found only in red blood
cells.
2. How and where is it made? Hemoglobin is made by and
contained in red blood cells which are made in the bone marrow.
4. Is it consumed or produced as part of a natural process or only
in pathological states? It is a naturally occurring compound
which is degraded by the reticuloendothelial system after phagocytosis
of senescent or damaged red cells (120+ days is normal).
5. How is it metabolized (destroyed)? Its destruction requires
processing of the protein chains with either recycling of amino acids or
formation of urea; disassembly of the iron which is recycled via ferritin
and transferrin and solubilization of the heme ring derivative (bilirubin)
by conjugation to glucuronide in the liver and elimination from the body
through the urine and bile.
7. What regulates these processes? Regulation of
production is indirect via formation of red cells. Replacement of
red cells occurs at a steady state by mitosis and differentiation of bone
marrow stem cells, the rate normally controlled by demand for oxygen, monitored
by the kidney and actually controlled by erythropoietin. Bone marrow
production of Red Blood Cells (containing Hemoglobin) can be accelerated
ten fold in response to erythropoietin. In the absence of erythropoietin,
rbc production drops regardless of O2 tension. Replacement
of bone marrow or interference with maturation or differentiation of Red
Blood Cells indirectly affects the production of hemoglobin.
8. Are there other tests that measure related analytes but
differ in one or more of these processes? Hematocrit, RBC, MCV,
MCH, MCHC, visual inspection and reticulocyte count and bilirubin are related
tests which are used in conjunction with HGB to assess HGB functionality,
RBC production and or turnover. |
Some of the physiological mechanisms that control the hemoglobin production:
- Renal sensors that respond to oxygen concentration
- Renal cells producing erythropoietin
- Mitotic and maturational processes in bone marrow of Red Blood Cells
- Availability of raw materials
- iron - acquired from environment
- amino acids - globins production, a result of genetic expression
- porphyrin ring production, the result of a series of enzymatic changes
starting with ALA.
- Red Blood Cell life span
- Red Blood Cell loss or gain (transfusion/bleeding)
|
| Depending on the individual person and circumstances one or all of
these factors will contribute pressure on the balance. If the positive
balance the negative then a steady state will be achieved and a "normal
result" may occur in the presence of a life threatening disease or just
the opposite a steady state may be achieved outside the normal range or
a steady state may not be achieved. It is then the clinicians objective
to "correct" these forces to achieve a steady state within the physiologically
"normal range". (Fancy for make a diagnosis and suggest a management
or treatment). |
| If you were to draw Hemoglobin concentration as an old fashioned balance
or teeter totter, you can visualize those forces which are contributing
to the actual measurement. |
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| Also refer to CBC
Road Map |
More on Hemoglobin Test - Interpretation
Hemoglobin becomes one of our best estimates of the state of the
erythron (red cell mass). It is used to "rule in" or "out" anemia,
monitor malignant processes such as polycythemia or leukemia, and is used
for the screening test for blood doping in the olympics among other applications.
It is sensitive but not specific.
A low hemoglobin may indicate any of the following:
- Lower number of red cells in relation to plasma (increased plasma volume
/natural or acquired) fluid overload - anemia of pregnancy (RELATIVE)
- Bleeding (uncompensated by red blood cell production.)(REMOVAL of
red cells)
- Iron deficiency or availability (dietary, secondary to other conditions,
chronic disease, sideroblastic anemias (PRODUCTION)
- Porphyrin production (lead poisoning/hereditary porphyrurias)
- Globin chain production (thalassemias alpha and beta)
- Reduced Red Cell survival greater than bone marrow capacity to replace
(hemolytic anemias, hemoglobinopathies)
- Inadequate mitosis (toxins, bone marrow suppression or replacement, renal
failure, thyroid deficiency, chronic disease)
- Inadequate maturation (acute leukemia - erythroleukemia, B-12, Folate,
Alcohol).
A high hemoglobin may indicate
- Greater number of Red Cells in relation to plasma (dehydration ).
- Polycythemia ( reactive - due to decreased O2 tension - COPD-methemoglobinemias
or malignant polycythemia vera)
- Exogenous erythropoietin - tumor or blood doping
A hemoglobin in the normal range by itself may indicate:
- A person in which no pathological processes that can affect hemoglobin
are occurring OR:
- A compensated pathological process is occurring where production
is ramped up to meet destruction.
Hemoglobin is a good screening test, the other parts of the CBC
and a few additional tests will sort out all these possibilities. |
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Further Interpretation
of the CBC
Lets look at the other measurements related to the erythron in the CBC.
You should have access to them because it is unusual to order only a hemoglobin
(hematocrit however in a Drs. office is a common test ).
Does the RBC/HGB/HCT obey the Rule of Threes?
- If yes, then B-12, Folate,Alcohol,Thalassemias, Porphyurias, and
iron deficiencies are unlikely. (reflected also in an MCV in the
79-96 range and an MCHC around 33%.)
- If MCV low look for hemoglobin production problems (iron/lead/thalassemias).
- If high look for nuclear maturation problems (B-12/Folate/Alcohol).
Reticulocytes - Indicator of bone marrow activity
- Look for inadequate mitosis or maturation (Corrected reticulocyte
count low). May require a bone marrow evaluation.
- If reticulocyte count HIGH consider excessive in destruction or
bleeding. Look for biological destruction- if none consider bleeding. If
bilirubin high - consider excessive destruction, if low, bleeding.
If you are doing a longitudinal analysis - say the patient has been perking
along fine and there is a change in hemoglobin your "rule in/rule out"
is similar. It is not unusual for a person with thalassemias/ sickle
cell or other destructive process to function fine and maintain a dynamic
equilibrium in the normal range until an additional stress is put on the
system - other illness, pregnancy , stress or drugs.
This is an over simplified presentation but it will provide a framework
upon which you can start hanging your own algorithms.
Lets look at WBC (with its associated tests) and Platelet
Count round out the CBC. In a hemogram you will get only at total
WBC, which can be very misleading. But now we will pull in the elements
of the CBC simultaneously.
Look at examples in tabular fashion. Hemoglobin, WBC and Diff, BUN,
Glucose, Nitrite. (Link Under Construction) |
From this analysis, you can do it with each analyte in the panels I
have given you, build yourself some tables. Once you have done that,
you can use the reference books and lists such as the shortie ones we have
on the website.
Basic
Chemistry Analytes - Brief overview of common analytes |
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