Understanding the results of your pathology report

Introduction

To most people a standard pathology laboratory list of results is more akin to an Egyptian obelisk than anything actually meaningful or useful.This article provides our own plain English equivalent of the Rosetta Stone in order to translate some of the pathological hieroglyphs.

For example:

Results from the Path Lab – what do they mean?

The first column of hieroglyphs is normally the list of tests. Many of these tests have long names, especially the enzymes and so the name of the substance being tested is usually shortened to either the chemical symbol (e.g. Na for sodium), or to its initials (e.g. GGT for Gamma Glutamyl Transferase). A fuller explanation for some of these tests is given below. The second, or ‘result’ column is normally the actual concentration of the substance found in blood or urine samples. The third column gives the measurement units of the test.  The fourth column gives the reference range, which is the range of results usually found in healthy people.

Some reports also highlight results in the second column with an asterisk or other symbol if the result lies outside the laboratory reference range. It is important to note that just because a result is outside the reference range this does not mean to say that there is necessarily a problem. We are all different and a level that is ‘normal’ for one person, may not be for another. However, the reference range is very useful as a guide to those people who may need further investigations.

A standard pathology report is normally divided into four disciplines for historical reasons, depending primarily on what is being tested in the samples (chemicals, blood cells, bacteria or viruses, and thin sections of body tissue). As technology improves, modern laboratory diagnostic analysers become increasingly capable of handling samples from across the different disciplines, but doctors still find it useful to be able to classify the different tests into their areas of specialist knowledge – and so this description will stick to the conventional format. 

The four principle disciplines are as follows:

1. Chemical Pathology or Clinical Biochemistry
2. Haematology
3. Microbiology (including)
4. Histopathology and Cytology

Chemical Pathology / Clinical Biochemistry

Laboratories for this discipline may be single, or further subdivided into sections such as those with large automated analysers, Immunology (testing the immune system), Toxicology (looking for drugs) and Endocrinology (measuring hormones)

Depending on the size and additional research and teaching functions within a discipline, each one will normally be headed by either medical Chemical Pathologists and/or Clinical Scientists. The former are medical doctors who often combine their laboratory role with clinical duties such as seeing outpatients and supervising inpatients’ nutrition.

More importantly, these senior hospital staff oversee the management of the laboratory and ensure that their procedures  follow national guidelines for good laboratory practice and are examined by regular external quality inspections similar to the school OFSTED inspection This job is pivotal for good patient care in that two thirds of diagnoses in medicine depend on the quality and accuracy of test results. If a patient’s diagnosis is based on the wrong results, then no matter how excellent the other hospital staff, their work may amount to nothing and could make things worse.

Many doctors, especially junior doctors, tend to ask for as many biochemical tests as possible in order to get an indication of the health of the body’s major organs. Tests are often grouped together in profiles, indicating the health of a particular organ (such as the liver). However, this multiple testing approach, which is more prevalent in the USA,  has to be balanced against decisions on the use of resources and the time it takes to perform multiple combinations of tests - or profiles. For those tests which are highly automated, and cheaper and quicker to perform, there is more justification for performing bigger test profiles.

Below are some of the common Biochemistry profiles, requested by clinicians when investigating a patient. Each subsection below contains a brief description of the test or profile of tests, the underlying reasons why the test or profile would be requested and the resulting knowledge gained by the clinician and subsequent treatment and benefit to the patient. 

Urea & Electrolytes Test

Sodium, Potassium and Bicarbonate

These are termed the electrolytes and are essential for the normal function of our cells. Salt is made of sodium and chloride, and too much or too little sodium can disturb the body’s normal functions and in extreme cases can be fatal. The modern diet and in particular ‘processed’ food often contains high levels of salt and this is a cause for concern as people may not be aware of the amount of salt they are ingesting. A high salt diet is linked to various disease states including high blood pressure (hypertension) which can lead to strokes, heart attacks and kidney disease.

Abnormal levels of potassium can affect the nervous system and increase the chance of irregular heartbeat. Potassium is normally excreted by the kidneys and so high levels could be indicative of kidney damage, which may be the result of taking particular prescription drugs or absorbing toxic substances in our environment. Low levels of potassium can be due to excessive fluid loss such as vomiting and diarrhoea as well as eating disorders and tablets such as diuretics (water tablets).

Urea and Creatinine

Urea is a breakdown product of a normal protein diet and is excreted by the kidney. Creatinine is also derived from muscle protein but is less influenced by diet and more influenced by the sex of the patient than urea is. Hence a thorough understanding of these variations is required in order to arrive at the correct diagnosis. Raised levels of these substances usually indicate impaired kidney function. Creatinine in particular is used to measure the health of the kidneys both diagnostically and following treatment such as dialysis. As with many laboratory tests, there are national guidelines for kidney tests to assist clinicians in staging levels of kidney disease.

Clinicians commonly request U and Es or “urea and electrolytes” which is a profile containing variously a combination of these first two categories. 

Glucose

Glucose is an important carbohydrate and when combined in nature with fructose forms what we commonly call sugar. An elevated blood glucose level may indicate diabetes mellitus or “sugar diabetes”. Diabetes is acknowledged by clinicians and governments as one of the increasingly common diseases of the 21st century as a result of obesity and sedentary life styles.

Mild elevations are occasionally found in normal pregnancy or may simply relate to a recent high carbohydrate intake. Hence, a ‘fasting’ sample is required by the international guidelines for the diagnosis of diabetes. Further confirmatory testing called a “glucose tolerance test” may be required before a diagnosis of diabetes can be made, particularly in pregnancy.

Calcium and Phosphate

Calcium is involved in many of the body’s processes, including nerve conduction and the maintenance of normal action of muscle, particularly the muscle of the heart. Most of our body’s calcium and phosphate is in our bones. Dietary calcium intake, vitamin D production in the skin from sun exposure, together with normal liver and kidney function, are all required to maintain optimum utilisation of calcium and phosphate in the body. Any disease that interferes with calcium absorption in the gut can lower the level. Excessive milk drinking or the use of indigestion treatment such as antacids can also raise the blood level. It’s also important to take the blood sample correctly as calcium levels in blood samples can sometimes be artificially raised by the prolonged use of a tourniquet whilst taking the sample, thus giving a falsely high level and possibly leading to a misdiagnosis.

Bilirubin

This is a breakdown product of haemoglobin, the oxygen-carrying protein in the blood. It is removed from the body via the liver, gall bladder and bowel. Very high levels of bilirubin in the blood cause the appearance of jaundice (yellowing of the skin). A significantly increased level of bilirubin can result from obstructed outflow of bile due to gallstones, from destruction of liver cells due to hepatitis or toxins, or from certain uncommon blood disorders. It is usual also to measure other liver enzymes as part of the “liver profile” in order to differentiate these different liver disorders eg ALP and GGT (see below).  A slightly raised bilirubin is found in Gilbert’s syndrome which is a harmless condition in 5% of the normal population but sometimes leads to unnecessary investigations despite all other liver tests being normal.

The Liver Enzymes ALP, ALT, AST and GGT

Alkaline Phosphatase (ALP)

This is an enzyme produced mainly in the liver, bones and kidney. Abnormally high levels may occur in liver and bone disease and in this situation it is useful to know the results of other enzymes to distinguish bone from liver disease.  Where liver disease is present this test helps to distinguish hepatitis from bile tract obstruction due to gall stones. The patient’s age and situation need to be taken into account as higher levels occur during bone growth in childhood, after fractures and in pregnancy.

Alanine Transaminase (ALT) and Aspartate Transaminase (AST)

These enzymes are produced by the liver and other organs such as heart. Diseases that affect the liver, such as hepatitis and the excessive consumption of some tablets and alcohol, may raise them. Viral illnesses, such as the common cold and influenza, can also cause a temporary rise in these enzyme levels.

Gamma GT or GGT (Gamma Glutamyl Transferase)

This is an enzyme that is mainly found in the liver, kidneys and pancreas. Serum GGT activity has been commonly used as a marker for excessive alcohol consumption or liver disease. GGT is raised by some tablets and by prolonged excessive alcohol consumption where its level roughly correlates with alcohol intake. It can be temporarily raised during generalised viral illness and after excessive paracetamol intake, e.g. self-medication for colds and influenza. GGT measurement provides a very sensitive indicator of the presence or absence of liver disease but it is not specific and raised levels have been reported in a variety of clinical conditions including:

• kidney failure
• chronic obstructive lung disease
• diabetes
• obesity
• alcoholism
• pancreatic disease
• heart disease

Uric Acid  

This is a waste product produced after protein digestion. Levels can be raised as a result of a high protein diet and by excessive alcohol intake. A raised level is also caused by an inherited problem causing the body  too much of it. Too high a level can lead to excess uric acid being deposited as crystals in the tissues of the body. When this occurs in joints, it causes the painful condition gout. More rarely, deposits in the kidneys can cause kidney damage.

Total Proteins, Albumin and Globulin

These are measurements that can further help to assess organ function, immunity and the adequacy of dietary intake.

Lipids – Cholesterol, HDL-cholesterol, LDL-cholesterol, Cholesterol:HDL ratio and Triglycerides

These tests constitute the ‘lipid profile’.  The total cholesterol can be subdivided into the ‘good cholesterol’, HDL-cholesterol, and the ‘bad cholesterol’, LDL-cholesterol.  These two do not add up to the total cholesterol because there is another type which does not normally need to be measured.  The HDL and LDL components are very important because they are used to assess the clinical importance of a raised cholesterol level.  Some lucky people have a naturally high level of the good cholesterol, whilst others may inherit a low level which increases their risk of heart disease and strokes.  The ratio between total cholesterol and HDL-cholesterol gives a good indication of this risk and is helpful when deciding whether to offer a patient lipid lowering tablets.   Patients with a family history of early heart disease, strokes or high blood pressure are particularly vulnerable and can be successfully treated with lipid lowering tablets to reduce their risk of early death. The most commonly used lipid lowering tablets are the statins, such as simvastatin and atorvastatin.  These tablets, usually taken once a day, ensure that the body makes less cholesterol by slowing down (but not stopping) its production in the liver.  They also seem to work directly on blood vessel walls, making it less likely that the blood clots which lead to heart attacks and strokes will be formed. It is important that patients taking statins or other lipid lowering treatment have regular blood tests to check that they are taking the right amount of treatment and that there are no untoward side effects.

Occasionally a patient with an abnormal lipid profile may turn out to have diabetes or thyroid deficiency.  It is important that these disorders are treated as well, and some patients with thyroid deficiency may have normal lipids once this has been treated.  Patients with diabetes should be treated with statins if possible because they have an increased risk of heart disease and strokes no matter what their cholesterol level is.

Endocrinology: Thyroid Profile: TSH , Free T4 and Free T3

The thyroid regulates the activity of most of the major body organs, particularly the heart. Its main products, thyroxine (T4) and tri-iodothyronine (T3) are controlled by the production of thyroid stimulating hormone (TSH) from the pituitary gland located in the lower brain.  When assessing thyroid activity, the laboratory measures TSH and, when required, the small active free fractions of T4 and T3, called free T4 and free T3.

An overactive thyroid can cause heart, bone and kidney damage whilst an underactive thyroid can lead to mental deterioration and weight gain. It is particularly important to detect thyroid disease in the newborn to prevent poor mental and physical development and there are national screening programmes in place for this. Both over and underactive conditions can be successfully treated medically. 

Infertility Investigations

The laboratory measures various individual hormone tests and profiles depending on the initial suspicion of the clinician, based for example on a woman’s menstrual history. The control of fertility hormones is similar to the control of thyroid hormones in that the pituitary gland produces luteinising hormone (LH) and follicle stimulating hormone (FSH) which regulate production of oestrogen and progesterone in women and testosterone in men.  All these hormones can be measured in the laboratory to help in the investigation of infertility and related disorders in women and men. Hormone treatment is available for some of these conditions.