Reference Ranges and What They Mean

Reference Ranges and What They Mean

The "Normal" or Reference Range

"Your test was out of the normal range," your doctor says to you, handing you a sheet of paper with a set of test results, numbers on a page. Your heart starts to race in fear that you are really sick. But what does this statement mean, "Out of the normal range"? Is it cause for concern? The brief answer is that a result out of the normal or reference range is a signal that further investigation is needed.
The term "normal range" is not used very much today because it is considered to be misleading. If a patient's results are outside the range for that test, it does not automatically mean that the result is abnormal. Therefore, today "reference range" or "reference values" are considered the more appropriate terms, for reasons explained on the next page. The term reference values is increasing in use and is often used interchangeably with reference range. For simplicity, we use the term reference range in this article.
Tests results—all medical data—can only be understood once all the pieces are together. Take one of the simplest medical indicators of all—your heart rate. You can take your resting heart rate right now by putting your fingers on your pulse and counting for a minute. Most people know that the "average" heart rate is about 70 beats per minute. How do you know what a "normal" heart rate is? We know this on the basis of taking the pulse rate of millions of people over time.
You probably also know that if you are a regular runner or are otherwise in good physical condition, your pulse rate could be considerably lower—so a pulse rate of 55 could also be "normal." Say you walk up a hill—your heart rate is now 120 beats a minute. That would be high for a resting heart rate but "normal" for the rate during this kind of activity.
Your heart rate, like any medical observation, must be considered in context. Without the proper context, any observation or test result is meaningless. To understand what is normal for you, your doctor must know what is normal for most other people of your age and what you were doing at the time—or just before—the test or observation was conducted.
The interpretation of any clinical laboratory test must consider this important concept when comparing the patient's results to the test's "reference range."
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Deciphering Your Lab Report

Deciphering Your Lab Report

If you’ve had laboratory tests performed, you may have been given a copy of the report by the laboratory or your health care provider. If not, you may wish to request one from your physician. Once you get your report, however, it may not be easy for you to read or understand, leaving you with more questions than answers. This article points out some of the different sections that may be found on a typical lab report and explains some of the information that may be found in those sections.
Different laboratories generate reports that can vary greatly in appearance and in the order and kind of information included. Here is one example of what a lab report may look like.
(Note: Pathology reports, such as for a biopsy, will look different than this representative lab report. For some examples of what a pathology report may look like, see The Doctor’s Doctor: A Typical Pathology Report or download the following PDF from the College of American Pathologists web site.)
Despite the differences in format and presentation, all laboratory reports must contain certain elements as mandated by federal legislation known as the Clinical Laboratory Improvement Amendments (CLIA). (CLIA '88 REGULATIONS, Section 493.1291; for more on regulation of laboratories, see Lab Oversight: A Building Block of Trust.) Your lab report may look very different than the sample report, but it will contain each of the elements required by CLIA. It may also contain additional items not specifically required but which the lab chooses to include to aid in the timely reporting, delivery, and interpretation of your results.
Some items included on lab reports deal with administrative or clerical information:
  • Patient name and identification number or a unique patient identifier and identification number. These are required for proper patient identification and to ensure that the test results included in the report are correctly linked to the patient on whom the tests were run.
  • Name and address of the laboratory location where the test was performed. Tests may be run in a physician office laboratory, a laboratory located in a clinic or hospital, and/or samples may be sent to a reference laboratory for analysis.
  • Date report printed. This is the date this copy of the report was printed. Often, the time that the report was printed will also be included. The date of printing may be different than the date the results were generated (see below), especially on cumulative reports. This report is an example of a cumulative report which is a report that includes results of several different tests run on different days.
  • Test report date. This is the day the results were generated and reported to the ordering physician or to the responsible person. Tests may be run on a particular patient’s samples on different dates. Since a patient may have multiple results of the same test from different days, it’s important that the report includes this information for correct interpretation of results.
  • Name of doctor or legally authorized person ordering the test(s). This information enables the lab to forward your results to the person who requested the test(s). Sometimes a report will also include the name of other doctors requesting a copy of your report. For example, a specialist may order tests and request that a copy of the results be sent to your primary physician.
Other elements found on reports deal with the specimen that was collected and with the test itself:
  • Specimen source, when appropriate. Some tests can be performed on more than one type of sample. For example, protein can be measured in blood, urine or cerebrospinal fluid, and the results from these different types of specimens can indicate very different things.
  • Date and time of specimen collection. Some test results may be affected by the day and time of sample collection. This information may help your doctor interpret the results. For example, blood levels of drugs are affected by the time a dose of the drug was last taken, so results of the test and its interpretation can be affected by when the sample was collected.
  • Laboratory accession number. Number(s) assigned to the sample(s) when it arrives at the laboratory. Some labs will have a single accession number for all your tests and other labs may have multiple accession numbers that help the lab identify the samples.
  • Name of the test performed. Test names are often abbreviated on lab reports. You may want to look for abbreviated test names in the pull down menu on the home page of this site or type the acronym into the search box to find information on specific tests.
  • Test result. Some results are written as numbers when a substance is measured in a sample as with a cholesterol level (quantitative). Other reports may simply give a positive or negative result as in pregnancy tests (qualitative). Still others may include text, such as the name of bacteria for the result of a sample taken from an infected site.
  • Abnormal test results. Lab reports will often draw attention to results that are abnormal or outside the reference range (see “Reference intervals” below) by setting them apart or highlighting them in some way. For example, “H” next to a result may mean that it is higher than the reference range. “L” may mean “low” and “WNL” usually means “within normal limits.”
  • Critical results. Those results that are dangerously abnormal must be reported immediately to the responsible person, such as the ordering physician. The laboratory will often draw attention to such results with an asterisk (*) or something similar and will usually note on the report the date and time the responsible person was notified.
  • Units of measurement (for quantitative results). The units of measurement that labs use to report your results can vary from lab to lab. It is similar to the way, for example, your doctor chooses to record your weight during an examination. He may decide to note your weight in pounds or in kilograms. In this same way, labs may choose to use different units of measurement for your test results. Regardless of the units that the lab uses, your results will be interpreted in relation to the reference ranges supplied by the laboratory.
  • Reference intervals (or reference ranges). These are the ranges in which “normal” values are expected to fall. The ranges that appear on your report are established and supplied by the laboratory that performed your test. They are made available to the doctor who requested the test(s) and to other health care providers to aid in the interpretation of the results. For more on this, see the article on Reference Ranges and What They Mean.
  • Interpretation of results. In certain circumstances, the lab may note on the report what certain test results may indicate.
  • Condition of specimen. Any pertinent information regarding the condition of specimens that do not meet the laboratory's criteria for acceptability will be noted. This type of information may include a variety of situations in which the specimen was not the best possible sample needed for testing. For example, if the specimen was not collected or stored in optimal conditions or if it was visually apparent that a blood sample was hemolyzed or lipemic, it will be noted on the report. In some cases, the condition of the specimen may preclude analysis (the test is not run and results are not generated) or may generate additional comments directing the use of caution in interpreting results.
  • Deviations from test preparation procedures. Some tests have specific procedures to follow before a sample is collected or a test is performed. If such procedures are not followed for some reason, it may be noted on the report. For example, if a patient forgets to fast before having a glucose test performed, the report may reflect this fact.
  • Medications, health supplements, etc. taken by the patient. Some tests results are affected by medications, vitamins and other health supplements, so laboratories may obtain this information from the test request form and transcribe it onto the lab report.

Raynaud's Disease

What Is Raynaud's Disease? What Causes Raynaud's Phenomenon?

Raynaud's disease, also known as Raynaud's phenomenon and sometimes simply Raynaud's, is a condition that causes some areas of the body to feel numb and cool in response to cold temperatures or emotional stress, caused by a problem with the blood supply to the skin. Raynaud's disease is a vasospastic disorder - spasms in the blood vessels lead to vasoconstriction (narrowing).

The disease mostly affects the fingers, toes, tip of the nose and the ears. The problem is in the blood vessels that supply the skin. Smaller arteries narrow and limit blood circulation to affected areas. Areas of the body subsequently become cold and very pale. Patients typically feel pins and needles, numbness, and even burning. The sensation can be unpleasant and painful.

According to Medilexicon's medical dictionary:

Raynaud's phenomenon is an idiopathic paroxysmal bilateral cyanosis of the digits due to arterial and arteriolar contraction; caused by cold or emotion.

The disease is named for Maurice Raynaud (1834 - 1881), a French physician who first described it in 1862.

The condition is either:
  • Primary Raynaud's. This is the most common form, there is no apparent cause (idiopathic). It is possible for the primary form to move to the secondary form.
  • Secondary Rayndaud's. It is associated with an underlying disease, such as rheumatoid arthritis. In extreme cases this form can progress to necrosis or gangrene of the fingertips.
Doctors may measure hand-temperature to distinguish between primary and secondary forms of the condition.

The National Health Service (NHS), UK, says that there could be as many as 10 million British people affected by Raynaud's disease. The NHS adds that a significant number of individuals never see their doctor about it because they think it is just part of their makeup, not knowing it is a disease with a name and treatment.

Raynaud's disease will usually affect people during or after middle age, although it can develop in all age groups. The majority of sufferers are women. As cold temperatures is one of the possible triggers, the condition becomes more common the further you move from the equator.

Most people have mild symptoms and do not find their daily tasks or general quality of life is affected. Even if symptoms are more severe, treatment (with medications) is usually effective.

What are the signs and symptoms of Raynaud´s disease?

A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign.
Generally, primary Reynaud's disease symptoms are mild, while the secondary form's may be more severe. In the primary form both hands are affected simultaneously, usually all fingers at the same time. In the secondary form the development and appearance of symptoms is more patchy, with perhaps a couple of fingers on one side being affected.

The affected areas will become very pale (pallor), and then take on a bluish color (cyanosis) due to hypoxia (lack of oxygen to that area). They will feel very cold and numb. If all fingers are affected, trying to rummage in your pockets for specific coins becomes much more difficult. This can sometimes be distressing.

When the episode subsides and bloodflow returns to the affected area the skin may turn red (rubor). During the recovery period there may be tingling and swelling.

Meanings in medicine:
  • Pallor - whiteness.
  • Cyanosis - a bluish color of skin (or mucous membranes) due to lack of oxygen in the blood.
  • Rubor - redness
Not all sufferers go through the three color process - pallor, cyanosis, rubor - especially those with mild symptoms.

Symptoms may not only affect the fingers, but also the toes, lips, ears and nose.

An episode may range from a few minutes to a number of hours.

Breastfeeding - Raynaud's-type symptoms may occur during breastfeeding; the nipples will turn white and become extremely painful.

What are the risk factors?

A risk factor is something which increases the likelihood of developing a condition or disease. For example, obesity significantly raises the risk of developing diabetes type 2. Therefore, obesity is a risk factor for diabetes type 2.
  • Gender. The phenomenon is more common in women than men; the Framingham Study found that 5% of men and 8% of women suffer from it.
  • Age. Although any age group can be affected, middle-aged and elderly individuals have a higher risk, compared to young people.
  • Geography. A significantly higher percentage of adults in, for example, Alaska suffer from the phenomenon compared to individuals in Florida.
  • Genes. A significant number of individuals with Raynaud's disease have a parent or sibling who also has it.
  • Underlying diseases - people with some other underlying diseases have a much higher risk of developing the phenomenon, such as people:

    • with connective tissue disorders, including scleroderma, systemic lupus erythematosus, rheumatoid arthritis, Sj√∂gren's syndrome, dermatomyositis, polymyositis, mixed connective tissue disease, cold agglutinin disease, and Ehlers-Danlos Syndrome.
    • with eating disorders, such as anorexia nervosa.
    • with obstructive disorders, such as atherosclerosis, Buerger's disease, Takayasu's arteritis, subclavian aneurysms, and thoracic outlet syndrome.
    • on certain medications, such as beta-blockers, cytotoxic drugs - particularly chemotherapeutics and most especially bleomycin, ciclosporin, ergotamine, sulfasalazine, and anthrax vaccines whose primary ingredient is the Anthrax Protective Antigen.
    • some other conditions, such as hypothyroidism, cryoglobulinemia, malignancy, reflex sympathetic dystrophy, carpal tunnel syndrome, and Magnesium Deficiency Erythromelalgia

What causes Raynaud's disease?

When the body is exposed to the cold, heat is lost through the extremities (fingers and toes) as capillaries (small blood vessels) under the skin constrict - become narrower, resulting in less blood getting to tissue in that area. For people with Raynaud's disease, the narrowing is more severe, and the consequent blood supply is much less than other people. If the blood supply is very low, that part of the body experiences an abnormal drop in temperature - hence the sensation of cold fingers.

For some people it needs to get really cold for symptoms to appear, while for others even a slight drop in temperature can trigger symptoms.

Stress, specifically emotional stress, which includes anxiety or anger can also trigger symptoms.

In secondary Raynaud's, where there is an underlying condition/disease, we know that the cause is that condition. In primary Raynaud's, nobody really knows why the blood vessels narrow so much.

Some occupations - there may be a link between repetitive movements and Raynaud's type symptoms, as may happen with a typist whose fingertips receive little blows for prolonged periods. Certain occupations may make individuals more susceptible, especially those where vibrating equipment is used, such as hammer drills, chainsaws or hedge trimmers (vibration white finger). Some people who work in the plastics industry develop Raynaud's type symptoms.

Smoking - smoking causes the blood vessels to narrow, increasing the risk of developing Raynaud's disese.

What are the complications of Raynaud´s disease?

A combination of thickening blood vessel walls and narrowing can lead to permanent reduction of blood flow to susceptible areas. If blood flow is seriously impaired there is a risk of finger or toe deformity, and even gangrene.

Some people with Raynaud's syndrome go on to develop scleroderma, where scar tissue (fibrosis) forms in the skin and sometimes other organs of the body.

How is Raynaud´s disease diagnosed?

Most doctors, after a careful examination, will be able to determine whether the patient has the primary or secondary form of Raynaud's. Possible secondary causes need to be identified or excluded. The following diagnostic tests may be ordered:
  • Digital artery pressure - the pressure of the arteries of the fingers are measured before and after they are cooled. A drop of 15mmHg or more allows for a positive diagnosis.
  • Blood test - to determine blood count (may reveal anemia or renal failure). Urea and electrolyte levels may also be tested to rule out a kidney problem (renal impairment).
  • Thyroid function test - to rule out hypothyroidism (underactive thyroid gland)
  • An auto-antibody screen - to test for rheumatoid factor, Erythrocyte sedimentation rate, or C-reactive protein. These may reveal either an inflammatory process or some illnesses.
  • Nail fold vasculature capillaroscopy - a fold of hard skin overlapping the base and sides of a finger/toe nail is examined under a microscope and the tiny blood vessels are observed. This test can help determine whether the patient has the primary or secondary form of the disease.

What is the treatment for Raynaud´s disease?

Treatment options depend on the type (secondary or primary), and the severity of symptoms. Treatment for primary Raynaud's concentrates primarily on avoiding triggers.

If symptoms are mild, most patients find that simply avoiding the triggers, such as staying warm, learning to relax (to avoid stress, anxiety and anger), and avoiding vibrating machines is all they need to do. Smokers should seriously consider giving up.

Avoiding caffeine, stimulants and substances that cause the blood vessels to constrict (vasoconstrictors) may help alleviate symptoms.

If the fingers become extremely white, run tepid to slightly warm water over them and massage them gently. If no warm water is available, place your fingers under your arms, crotch, or even in your mouth. Keep the affected digits warm until their normal color is restored.

  • Nifedipine - this medication, a dihydropyridine calcium channel blocker, rapidly lowers blood pressure and opens up the capillaries (tiny blood vessels); this helps speed up the return of proper bloodflow to affected areas. Patients should not drink grapefruit juice while on this medication.
  • Angiotensin blocking vasodilators - angiotensin is a protein that makes our blood vessels narrow (constrict) and drives up blood pressure. A vasodilator is anything which opens up (widens) blood vessels. An angiotensin blocking vasodilator is a medication that blocks angiotensin and widens the blood vessels.
  • Iloprost - if symptoms are severe and other therapies were not effective, this medication may be administered by intravenous infusion (through a drip). Iloprost widens the blood vessels, helping proper blood flow reach the affected areas.
Counseling - if the patient has the primary form of Raynaud's and emotional stress is identified as one of the triggers, counseling may help control stress, anger, frustration and anxiety. In some cases the patient may be prescribed an antidepressant.

Surgery - in extreme cases that have not responded to other therapies, some nerves in the affected area may be cut. This procedure is known as sympathectomy.


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