by Randy Kidd, DVM, PHD I have always thought it almost magical that with only a few drops of blood, I can get a fairly comprehensive picture of what is going on with a dog’s inner chemistry. Most of the dog’s organ systems can be targeted by one chemical analysis or another, and with proper interpretation of one (or a combination of) these analyses, I can, at least in part, assess the dog’s current health/disease status. From this interpretation then, we can often derive a treatment regime, whether it is based on Western or alternative medicines. Isn’t science wonderful? However, over the years I’ve learned that interpreting blood chemistry results and then deciding on a therapeutic protocol based on the interpretations is often more art form than strictly black and white science. And while it can be frustrating when we are not able to generate specific answers from the blood chemistry findings alone, I personally find it comforting that there is still some magic and mystery in this specific area of science. As a holistic vet I’ve learned that there are many other very valid methods that can be used to interpret the patient’s health/disease status – evaluating the Qi of Traditional Chinese Medicine, or employing the intake of symptoms used in homeopathy, as just two examples. I’ve found these alternative diagnostic methods, depending on the situation, to be as good as, or better than, the “scientific” blood analysis methods employed by Western practitioners. To my way of thinking, we offer our patients the best of all worlds whenever we have the ability to accurately interpret several different methods of diagnosis (see “Personal Notes About Blood Chemistries,” at end of text). Whenever we decide to use blood chemistries as an aid for diagnosis and treatment, we need to understand what the results are telling us – and what, by design, they cannot help us with. Following are some of the basics of blood chemistry analyses. Bear in mind as you read that blood chemistries are a snapshot of what is going on inside the dog. They do not provide us a story with a beginning, middle, and end, and it is often this whole story that is the most valuable for determining our treatment protocol. To really know how a disease is progressing, we will perhaps need several progressive “snapshots,” each one giving us a better insight into the whole story of the dog’s ongoing health status. Also, remember that all blood chemistry interpretations rely on the methodology of statistical analyses, one of the mainstays of the science of Western medicine. While I appreciate that decisions based on statistical concepts can usually be justified, I always need to remind myself that each and every patient is a “statistic” of one – an individual who may or may not conform to the rules the statisticians ask us to abide by (see sidebar). Finally, keep in mind that dealing with a concept that interprets “normal” as a value that falls within the parameters of what is statistically normal in a given population. This “normal” value is completely disconnected from the holistic totality of the animal patient, and individual variability often throws a monkey wrench into the whole system. Statistics are entirely blind, and it is up to the people interpreting them to actually observe the animal to see if the statistics correlate to the symptoms seen in the dog. Woven into the concept of “statistically normal” is the fact that fully 5 percent of every perfectly healthy population will lie outside the normal range. Further, when we run a blood chemistry profile on a healthy animal using the typical 20 or so separate analyses, we almost guarantee that at least one of the values will fall outside the normal range. (Statistics can be used to prove this, but I won’t burden you with the mathematics here.) Unfortunately, even though we should expect a perfectly healthy animal to have at least one value of his chemistry profile that is outside the range of normal, I find that far too few veterinarians really understand this concept, and they will often base entire treatment protocols on the one “falsely abnormal” value they have obtained from a chemistry profile. We should instead be looking for “concordant” values – two or more values that support each other in their evaluation of a particular organ system. For example, when we have several indicators of liver disease (for example: elevated alanine transferase, aspartate transferase, and alkaline phosphatase, and decreased total protein and albumin), we can be reasonably sure the liver is involved. However, if only aspartate transferase is elevated, we need to think of other possibilities – in this case the likelihood that there is muscle rather than liver damage. The key, then, is to work with values that represent concordant indications, and to scratch your head and wonder about (or ignore) the ones that are discordant with other values. Finally, when “abnormal” values don’t match up with the aggregate of all of the dog’s physical symptoms, they should be questioned. Definitive answers not likely It is actually rather rare when blood chemistries, even with the most complete profile possible, will give us a definitive answer to the question, “Specifically, what is wrong with this dog?” When we use blood chemistries to help diagnose disease, we hope: a) We’ll be able to eliminate some of the possibilities from the long list of potential causes of disease; b) We’ll come closer, often through the process of elimination, to the real cause of the disease; and c) We can pinpoint one (or more) organ system that needs therapeutic support, thus giving us some help in developing our treatment protocol. While it can be frustrating to run a blood chemistry profile on a sick animal and not come up with the precise cause of the disease, I’ve found that “healthy animal” profiles can be very useful. Using a profile, we may be able to detect a beginning trend toward a potential problem, and this gives us a chance to design a long-range, holistic protocol that will help the dog maintain optimum health. My caveat here is that we make certain we are dealing with an actual trend and not just a few select values that are really within normal range but are slightly one side or the other of the median value. All labs are not all equal Quality control, accuracy of results, turnaround time, cost, and the chemical methodology used to establish “normal” values are all factors that enter into the reliability of the results you obtain from any lab. Veterinarians often use a local human lab to save costs and time, but very few of these labs have established their own normal values using healthy animals instead of humans, and they often are able to ease their quality control measures for the animal samples they run. And, while many vets use in-house blood chemistry instruments, it is almost impossibly expensive to run adequate controls to insure quality results. Ask your veterinarian about the laboratory he or she uses. For the reasons I just outlined, I strongly recommend using only university-based or large commercial veterinary laboratories. Inaccuracies and interactions Probably more important than “lab error” as a cause of spurious or incorrect values are interactions with other substances. Many of these interactions are caused by problems within the blood itself. For example, hemolysis (breakdown) of the RBCs can result from problems during collection, and lipemia (fat in the bloodstream) can be caused by taking the sample too soon after a meal. However, a good many of the interactions are caused by a variety of drugs the animal may be taking at the time of the test. Your veterinarian should be advised about any and every drug or herb your dog is being given, and he or she will need to know how each affects the blood chemistry results. There are many other considerations that make analysis of blood chemistries a true art form. For example, you always need to think of the various ways a chemistry can be increased – such as increased production, spillage from the rupture of cells, or lack of proper clearance or excretion – and then you need to decide which of these mechanisms is occurring in this particular patient. Finally, the veterinarian also needs to consider such individual variables as the age, sex, breed, activity level, and pregnancy status of the animal, as each of these may affect normal ranges. Here is a question I frequently get from clients and veterinarians: “What other tests should I run?” The answer is simple: What will you do with the results? If a positive (or negative) result will change your treatment regime, then the test may be warranted. If you will continue on with the treatment protocol you’ve already begun, why bother with more tests and expense? You’ll likely only confuse yourself further anyway. Common blood test results The following are a few of the more commonly run blood chemistries and some of the things to watch for when reading their values. The list is not complete and is only meant to help with more routine cases; check with your vet or a veterinary specialist (clinical pathologist or internist) for further information. Alkaline phosphatase (ALP): ALP is an enzyme found in a variety of tissues; the two tissues of diagnostic importance are bone and liver. Two common causes of increased ALP are the use of glucocorticoids (any of the many cortisone-type drugs) or anticonvulsant medications (such as Phenobarbital and primidone). Bone and liver ALP have separate isoenzymes that can be identified by special analysis (electrophoresis), but with the exception of bone disease or bone growth (growing animals or during fracture repair), increased serum activity that is non-drug-induced is usually due to liver disease. Alanine transferase (ALT): Increased values are principally due to damage of liver cells from any cause. (Red blood cells and muscle cell damage may also cause small increases.) Liver disease of any type may elevate ALT values; the list of drugs that are known to damage liver cells is extensive; further, an animal may have an idiosyncratic reaction to almost any drug or nutritional supplement. Aspartate transferase (AST): AST is found in many tissues including liver, muscle, and blood cells. The most common causes of increased AST include liver disease, muscular disease (inflammation or necrosis), or hemolysis (the breakup of red blood cells). While increased AST is often associated with liver cell damage, it is not as specific for liver as is ALT. Exercise and intramuscular injection may also increase serum AST. Finally, ALT is present in the cytosol of the cell, while AST is found in the mitochondria. Because cell membranes are more easily damaged than mitochondria (allowing for leakage of the enzyme from the cytosol), it is easier to increase serum ALT than AST. Kidney tests: Complete renal exams include BUN, creatinine, and a urinalysis. BUN is a prime example of a test where interpretation can be thought-provoking. BUN can be moderately elevated by any factor that increases body protein – possible examples include: a recent canned meat meal, hemorrhage into the gastrointestinal tract, breakdown of body tissues from fever or massive tissue trauma, or drug therapy including corticosteroids or tetracyclines. If both creatinine and BUN are increased, the kidneys are affected (decreased glomerlular filtration). However, decreased glomerlular filtration may be due to prerenal causes (diminished blood supply due to dehydration or shock); postrenal causes (diminished outflow from a “plugged” urethra); or renal causes (including a variety of true renal diseases). In early prerenal conditions, the BUN may be elevated before creatinine values, due to the highly diffusible nature of BUN. Prerenal conditions will typically be associated with urine specific gravities of greater than 1.035; a persistent specific gravity of 1.010 + 2 indicates the kidneys are unable to function. It’s important to have pretreatment values since many treatments alter one or all of the BUN, creatinine, and urine specific gravity values – fluid therapy, corticosteroids, and diuretics are just a few examples. Decreased BUN may also indicate disease and may be caused by inhibiting production (e.g., liver insufficiency or dietary protein restriction) or by increasing excretion (e.g., excessive thirst and urination or late pregnancy). Pancreatic tests (amylase and lipase): These two tests should be done simultaneously to diagnose pancreatitis. Amylase levels may rise with renal disease (and other diseases are suspected, but not proven), although the elevation is usually less than two times the upper limit of normal. However, pancreatic disease, no matter the severity, does not produce a reliable increase in amylase values. Adding lipase increases the likelihood for an accurate diagnosis of pancreatic disease, but lipase values may also elevate with renal disease (and some drugs), and not all patients with pancreatic disease will have elevated lipase values. The amount of increase of either the lipase or amylase values is not necessarily proportional to the severity of the pancreatitis, and each of these two values will have very different normal ranges between labs, depending on the lab’s methods of analysis. Cholesterol: Used as a screening test for hypothyroidism, hyperadrenocorticism (“Cushings syndrome”), diabetes, kidney disease, and other rare diseases. Feeding a very high fat diet may cause minor elevations of cholesterol in the dog. Cholesterol levels may be high immediately after eating, and there are several drugs that may falsely elevate cholesterol values. When high cholesterol values are found, other tests will be needed to help determine the cause. Glucose: A general screening test that, when out of normal range, will often require follow-up tests to further narrow down the real cause of the abnormality. There are many possibilities for lowered values, including insulin therapy, being a toy breed puppy, tumors, and prolonged starvation, but probably the most common cause is that the serum was not separated from the red blood cells. (Red blood cells continue to metabolize glucose, even out of the body, and their metabolism eats up glucose.) There are also many causes of increased glucose, although a persistent value of more than 180-200 mg/dl in a non-stressed animal not receiving medication (especially glucocorticoids) is indicative of diabetes mellitus. Note that glucose is a good example of a “snapshot” blood chemistry, good for monitoring the short-term results of therapies for diabetes. However, other chemistries (fructosamine or glycosylated hemoglobin) provide a better way to see how the therapies are progressing over a few weeks or months time. Electrolytes [sodium (Na), chloride (Cl), potassium (K)]: Electrolytes are an important component of the blood serum. In addition to providing necessary minerals for many chemical reactions, electrolytes balance the “thickness” (osmolality) of the serum as well as helping to maintain a constant acid/base balance. Depletion or excess of any of the electrolytes prevents the kidney from functioning properly, makes cellular uptake of nutrients difficult, and may alter the acid/base balance enough to be life-threatening. Physical causes that may create an imbalance include vomiting, diarrhea, inadequate kidney function, and/or improper fluid intake. Again, there are many drugs that can cause imbalances. If the sodium value is less than 135 mEq/L or if the ratio of Na:K is equal to or less than 27:1, and if we can eliminate sampling errors and other artifacts, hypoadrenocorticism (Addison’s), a potentially life-threatening disease, should be suspected. Calcium and phosphorous: Two additional electrolytes with additional importance for healthy bones and proper nerve transmission. Increased levels of calcium may be caused by many factors including endocrine disease (of the parathyroid, thyroid, or adrenal gland), renal disease, infection, inactivity, dehydration, or excess intake of vitamins A or D. Calcium is also elevated with the presence of several types of tumors, whether or not they involve bone tissue. There are many reasons for low blood calcium levels – including kidney disease, endocrine imbalance, toxicity (especially to ethylene glycol found in some antifreeze products), and thyroid surgery. But, the most common cause is a low level of the blood protein, albumin – from lack of nutrition or liver disease. Animals with very low blood calcium levels may have heart arrhythmia (from lack of proper nerve transmission), or they may go into rigid spasms (eclampsia of pregnancy, is an example of this). Although there are many causes of elevated phosphorous, the most common is kidney disease, and values can be profoundly elevated with this condition. Low levels of phosphorous are commonly, but not exclusively, associated with increased calcium seen along with malignant tumors. Serum proteins (Total proteins, albumin (the most prevalent serum protein), and globulin): Serum proteins evaluation is used as a general screening test for most patients but especially for those with edema, blood clotting problems, diarrhea, weight loss, and hepatic or renal disease. This is to say that either elevated or decreased levels point the diagnostician in the direction of trying to find the reason for the abnormal value. Elevated total proteins, for example, may be caused by many factors, but the most common one is dehydration. Albumin may be low due to lack of intake (nutrition or absorption), lack of production (liver disease), or increased loss (from the gut or kidney). Increased globulins may indicate chronic infection or immunological disease. In some cases deciding which of the globulins are increased (whether it’s the alpha-, beta-, or gamma-globulins, each of which also have several separate fractions) can be beneficial for diagnosis; the various fractions can be separated via electrophoresis. Thyroid profile: Most chemistry panels nowadays include a T-4 evaluation, a basic screening test for thyroid function. However, even as a screening test, it is generally felt to be unreliable because it can over-diagnose hypothyroidism (the most common thyroid disease in dogs), under-diagnose hyperthyroidism (the most common form in cats); may fail to detect early stages of the disease; and it doesn’t identify immune-mediated forms of thyroid disease. Further, the test is influenced by other diseases that may produce spuriously low values, and many drug therapies influence results. For a more complete diagnosis several tests are available, depending on the patient’s symptoms. These include free (unbound) T-4, free and total T-3, endogenous canine thyroid stimulating hormone (TSH), canine thyroglobin autoantibodies (TgAA), and T-3 and/or T-4 autoantibodies. Summary I’ve found both blood chemistry values and alternative methods of diagnosing to be valuable aids in my overall diagnostic process. Sometimes one method gives me a better idea for diagnosis and treatment; other times another method provides much better information. Since I’ve not been able to figure out in advance when a particular method will be the one that will work for the individual patient, I’m glad I have several very different methods to work with. I often find that working with a combination of many diagnostic methods gives me and my patient the best of many worlds. -Dr. Randy Kidd received a DVM degree from Ohio State University and a Ph.D. in Pathology/Clinical Pathology from Kansas State University. He is a past president of the American Holistic Veterinary Medical Association, and author of Dr. Kidd’s Guide to Herbal Dog Care and Dr. Kidd’s Guide to Herbal Cat Care.