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« on: August 09, 2017, 08:45:47 AM »

The Biochemistry Profile[/b]
The levels of a variety of enzymes, electrolytes and other substances are measured in the blood serum.  Serum is the clear (hopefully) fluid left after the blood cells have been allowed to clot.  Together with urinalysis it provides an overview of the health and function of many of the body organs.  The tests included in the profile can vary.  Idexx, the laboratory I use, offers a wellness check of 11 substances, but also offers tests or 21, 25 and 27 substances as well as a multitude of add-on tests.  Common tests are presented here.

Albumin is a small protein produced by the liver. Albumin helps to hold water in the blood vessels; if albumin levels drop, fluid leaks out of the blood as it is pumped through the body and accumulates in body cavities (e.g. ascites) or in tissues as edema. Albumin is decreased due to intestinal malabsorption or malnutrition; exocrine pancreatic insufficiency (EPI) which results in fewer enzymes to digest protein; or chronic liver disease.  Reduced levels also occur if protein is lost through kidney disease or hemorrhage.  Burns and certain other skin diseases can cause loss of protein through the skin. Increased albumin is the spurious result of dehydration.

Total protein includes albumin, fibrinogen and globulins. Fibrinogen is involved in the formation of blood clots and levels increase in inflammation or neoplastic disease.  It may also be increased mildly if the animal is dehydrated.  It can be, but is not normally, measured separately as part of the profile.  Globulins are larger proteins commonly referred to as antibodies.  Often globulin is listed as total protein minus albumin, more accurate assays separate not only albumin from globulin but alpha, beta and gamma globulins from each other.  Alpha globulins are acute reacting antibodies responding to tissue injury and inflammation, beta globulins are associated with acute liver disease, and gamma globulins are associated with chronic inflammatory diseases, immune mediated diseases and some lymph based cancers.  Some reports will include the ratio of albumin to globulin. 

Alkaline phosphatase (ALP) is a group of enzymes that originates from every tissue in the body.  High activities occur in liver, bone, intestine, kidney, placenta and white blood cells.  Although not normally done, the enzymes from the various organs can be isolated and measured.  In healthy animals most ALP is of liver origin.  Increased ALP can indicate liver disease (due to interruption of bile flow), bone disease (osteosarcoma, bone healing or hyperparathyroidism) or increased blood cortisol either because corticosteroids have been given or due to Cushing's disease (hyperadrenocorticism).  Other drugs especially phenobarbital can also increase ALP.  In acute liver disease, ALP may remain normal while other liver enzymes rise, but ALP levels may continue to rise during recovery.  In geriatric dogs certain malignant cancers (mammary, squamous cell carcinoma and hemangiosarcoma) may produce a very high ALP.

Alanine aminotransferase (ALT) {aka as glutamic pyruvic transaminase (SGPT)} is an enzyme considered liver specific in the dog. Liver damage – sublethal damage or necrosis - causes ALT to increase in the bloodstream. The level of increase reflects the number of cells that have been damaged.  In acute disease a reduction in ALT is favorable, but in chronic cases may just reflect that most of the liver is already compromised.  Elevation in ALT does not provide information as to whether the liver disease is reversible or not.

Aspartate aminotransferase (AST) {aka glutamic oxaloacetic transaminase (SGOT)} occurs in most cells but is considered diagnostic of liver and muscle disease. It is less specific and less sensitive to liver damage than ALT. 

Other enzymes used to detect liver injury include gamma glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH).

Bilirubin is produced by the liver, spleen and bone marrow as they recycle old red blood cells.  Most bilirubin is conjugated in the plasma with proteins although some will be free.  In the case of hemolytic anemia or internal hemorrhage most of the increase will be free bilirubin.  Blockage of bile flow – either in the liver of gallbladder leads to an increase in conjugated bilirubin.   Acute and chronic liver disease usually produces a combined response with increases in both types.  Large amounts of bilirubin in the bloodstream will give a yellow color to the mucus membranes, inside the ears and eye whites.  This is called icterus or jaundice. Bilirubin is further broken down and eliminated in both the urine and stool.  In dogs increases in bilirubin in urine precedes that in the serum.

Bile acids Cholic acid and chenodeoxycholic acid are produced by the liver, combined with amino acids glycine and taurine and secreted into the bile to assist in fat digestion and absorption as well as absorption of the fat soluble vitamins.  They are stored in the gall bladder.  A bile acid test is used to evaluate the function of the liver and its blood flow to the liver, and to diagnose dogs with portosystemic, shunt, where blood from the intestines by-passes the liver and goes straight to the general circulation. The bile acid test measures a fasting blood sample and a blood sample two hours after eating.  In normal dogs, bile acids released to digest a meal are recovered into the portal blood and returned to the liver.  If the dog has a portosystemic shunt the bile acids enter the general circulation and will be dramatically elevated.

Blood Urea Nitrogen (BUN) Only small amounts of urea are ingested, most is made from ammonia – either from the break down of protein or absorbed from the large intestine – in the liver.  Urea is excreted by the kidneys.  Increased protein breakdown due to increased protein in the diet, hemorrhage, necrosis, starvation, prolonged exercise, infection, fever or corticosteroids causes a mild increase in BUN.  Decreased perfusion of the kidneys caused by dehydration, shock or cardiovascular disease can also increase BUN.  In dogs with kidney disease approximately 75% of the kidneys are nonfunctional before BUN will increase. BUN doubles approximately each time the remaining number of nephrons is halved. 

Creatinine A small amount of creatinine may be ingested from diets rich in muscle meats.  Most, however, comes from the conversion of energy stores of phosphocreatine in the muscles to creatinine - a waste product that is eliminated from the body by the kidneys.  The creatinine pool is influenced by muscle mass, which in turn can be affected by muscle disease, wasting and training.  Unlike BUN, creatinine is less influenced by diet or urine flow, and elevation of creatinine is the result of kidney disease or dehydration.
Amylase is an enzyme produced by the pancreas, small intestine and liver. Amylase helps the body break down sugars. In healthy animals serum amylase is non-pancreatic in origin.  In pancreatitis (inflammation of the pancreas) or pancreatic cancer amylase can leak into the lymph system and from there to the blood.  The higher the level (3 to 4 times normal) the more likely the source is the pancreas.  Kidney disease and intestinal obstruction can also increase amylase; corticosteroids can increase it or decrease it.  Occasionally, animals with pancreatitis can have normal serum levels of amylase.   Because pancreatic disease isn’t the only cause of increased amylase, levels are assessed in conjunction with those of lipase.

Lipase is another pancreatic enzyme which is responsible for the breakdown of fats.  It takes longer to get a lipase measurement than that of amylase.  A two-fold or greater increase in lipase indicates acute pancreatic disease, and it is almost never normal if the dog has pancreatitis.   However, increase can occur in kidney or liver disease or with corticosteroids.

Creatine phosphokinase (CK, CPK) CK is an enzyme that helps store and release energy from muscle.  In healthy dogs levels vary considerably with age, at one day old puppies have 5 times the activity of adults.  Adult levels are reached at 7 months of age.  Old dogs may have lower levels.  Levels may be artificially increased by hemolysis, excess bilirubin or muscle derived from difficult or repeated venipuncture.  Elevation may indicate infection; myositis; trauma; degenerative, metabolic, ischemic or nutritional myopathy and involve heart muscle as well as skeletal muscle.  The increase does not correlate to the extent of the damage. Even minor insignificant damage can cause elevation in CK.  Two other enzymes -lactate dehydrogenase (LDH) and aspartate amintransferase (AST, GOT) - may also be measured to determine muscle function.  Results tend to mirror CK, but they are less sensitive.

Glucose is blood sugar. Its level is regulated by the pancreatic hormones insulin and glucagon.  Insulin increases the uptake of glucose by liver, skeletal muscle and fat primarily, as well as uptake of some other simple sugars, amino acids, fatty acids, potassium and magnesium.  Glucagon is released in response to low blood sugar and causes the liver to convert stored glycogen into glucose.  Corticosteroids antagonize insulin’s effects.  Glucose is increased in dogs and cats with diabetes mellitus – lack of insulin. It may be mildly increased in dogs with Cushing's disease. (Glucose can temporarily increase in the blood if the dog is stressed by having blood drawn or the general examination.  If glucose is also elevated in the urine, the blood glucose elevation is not transient.)  Low blood sugar occurs less commonly and can be indicative of pancreatic cancer or overwhelming infection (sepsis) or administration of excessive insulin.  It may also indicate improper handling of the sample.  An animal with low blood sugar will be depressed, seizuring or even in a coma.   

Cholesterol There are four major fats in plasma; the two most often measured are cholesterol and triglycerides.  They travel bound to peptides in complexes called lipoproteins.  Cholesterol levels are usually inversely related to thyroid hormone activity, and it is one of the best indicators of thyroid disease. Liver disease, acute pancreatitis, diabetes mellitus, and kidney disease (nephritic syndrome) and corticosteroid drugs, but not Cushing’s disease, can also elevate cholesterol.  High cholesterol does not predispose dogs to cardiovascular disease.

The Electrolytes usually measured include sodium (Na+), potassium (K+), chloride (Cl-) and TCO2 - which is primarily a measure of bicarbonate HCO3-).  The sum of positive ions minus the sum of negatively charged ions is called the anion gap, and is used to determine acid base abnormalities.  It increases in such diseases as lactic acidosis, diabetes mellitus, ketosis, renal insufficiency and some toxicities like ethylene glycol (antifreeze) poisoning.  A decrease is rare.

Sodium is essential for proper kidney function and water retention.  The correct balance between sodium and potassium ions inside and outside nerve and muscle cells is essential for their proper function.  Low blood sodium is most commonly seen with Addison's disease (hypoadrenocorticism), but can also be seen in diabetes mellitus or an animal that has been vomiting.

Potassium is increased in the dogs with Addison’s disease, as well as with acute kidney failure, and in animals with a ruptured or obstructed bladder.  Low potassium is associated with anorexia, vomiting, diarrhea, diabetes or the use of diuretics.  Many profiles calculate sodium potassium ratios.  If this number is less than 27 it indicates Addison’s disease. 

Chloride changes tend to parallel those of sodium, but loss of stomach hydrochloric acid can result in low chloride and normal sodium. 

TCO2 Loss of bicarbonate can occur through diarrhea.  Loss can also be relative to a build up of lactic acid, ketones, or uremic acids in kidney failure.  Some organic poisons may also lower blood acidity.  In cases of loss of stomach acid, the kidneys may excrete more bicarbonate to compensate.   

Calcium The levels of calcium potassium and magnesium are regulated by parathyroid hormone, calcitonin from the thyroid and Vitamin D.  Serum calcium is a reflection of relative bone formation and resorption.  It is rarely affected by dietary intake.  High blood calcium is most commonly associated with cancer. Less common causes of elevated calcium are chronic kidney failure, primary hyperparathyroidism, poisoning with certain types of rodent bait and bone disease.  Low blood calcium may occur in bitches shortly before giving birth or during the early nursing period. This is called eclampsia.  It causes tetany, the muscles become rigid.  Hypofunction of the parathyroid will also result in low blood calcium.  Dogs poisoned with antifreeze may have very low blood calcium.

Phosphorus Levels will be higher in young animals than in adults.  Serum phosphorus is largely regulated by the kidneys, although parathyroid hormone can increase resorption.  Dietary intake can directly affect serum levels.  Phosphorus is increased in chronic kidney disease, as with BUN and creatinine, phosphorus increases in these patients when about 75 percent of both kidneys is damaged.

Blood serum as well as urine components can vary markedly throughout the day.  Taking blood from a fasted dog will minimize those variations, but fail to show nutrient sensitive diseases.  Blood glucose will be low, as will insulin, while glucagon secretion will be elevated.  In anorexic patients, or those fasted more than 24 hours, fat will start to break down excessively to provide energy and increase levels of ketones which might make the blood more acid.  In a dog that has been eating, elevated ketones would suggest it had diabetes or liver disease, however.  BUN and phosphorus decrease in anorexic patients, so that renal failure might be missed.  Fortunately creatinine levels will not be affected.  Fasting for 24 hours increases the resorption of sodium and excretion of potassium by the kidney.  More calcium, magnesium, uric acid and ammonia will also be excreted.  In general, fasting 6 to 12 hours before a blood draw is optimal.  If lipemia persists after fasting for 24 hours it indicates problems with fat metabolism.  If the purpose of the blood test is to evaluate the effect of dietary modification on a disease process, blood should be drawn 2 to 6 hours after food consumption.  If you are reevaluating the thyroid levels of a dog already receiving supplementation, blood should be drawn 4 to 6 hours after the morning pill.  At this point thyroid levels will be maximal, and should be in the upper 50% of lab normal to 150% of the upper limit. 

Linda Aronson DVM