(1)
Office of Research and Development, United States Environmental Protection Agency, Washington DC, USA
Abstract
The three diagnosis chapters—Hematology, Clinical Chemistry, and Urinalysis—are intended to be the most informative and most used parts of this handbook. There is a lot of useful information packed into these chapters. Once animal clinical pathology data have been evaluated and anomalous values for several parameters have been identified, these chapters can help one ascertain what these anomalies signify. Next to the name of each parameter are its common abbreviations. For each parameter, there are listings for organs that may be affected, specimen handling information, and supportive tests that may be used to confirm a diagnosis. These are followed by a brief description of the parameter including its strengths and weaknesses and other need-to-know information. Next to up and down arrows are potential diagnoses for when a parameter’s value is increased or decreased. When there is a name for an increase or decrease (e.g., hyperglycemia or hypoglycemia), that is also provided. The Clinical Chemistry Diagnosis chapter contains information for 35 parameters.
Activated Partial Thromboplastin Time
See Hematology Diagnosis
6.1 Alanine Aminotransferase [ALT, ALAT, SGPT, GPT, PGPT]
Affected Organs: Liver (hepatocellular), cardiac muscle, skeletal muscle.
Specimen Handling: Serum may be stored 24 h at room temperature or 7 days at 4 °C. Interferences: Hemolysis, freezing
Supportive Tests: ALP, ALP isoenzyme study, AST, SDH (large animals), GGT, LDH, 5′-NT, bile acids, urobilinogen, bilirubin, albumin, total globulins, CBC, erythrocyte morphology, clotting factors, prothrombin time.
Alanine aminotransferase (ALT), also known as serum glutamic pyruvic transaminase (SGPT), is present in small amounts in muscle, pancreas, spleen, lung, and erythrocytes, but in large quantities in the liver of small animals. ALT and AST are usually measured together but ALT is superior to AST for assessing hepatocyte damage. Serum levels of ALT and AST are normally low, but leaky cell membranes release these enzymes into the blood when there is cell injury or death.
Little or no increase in ALT may be seen in severe hepatobiliary disease because so little ALT remains to enter the bloodstream. In myocardial infarction, AST is markedly increased while ALT increases only slightly. Sorbitol dehydrogenase (SDH) is used to assess liver damage in large animals such as pigs, sheep, cattle, and horses because their hepatocytes have negligible amounts of ALT,
↑ | Hepatocyte leakage and necrosis, cirrhosis, cholestatic and obstructive jaundice, fatty degeneration of liver, infectious hepatitis, viral hepatitis, leptospirosis, hepatic hemangioma, liver tumors |
Myocardial infarction, myocarditis | |
Skeletal muscle trauma (extensive), myositis, myopathies, dystrophies | |
Prolonged fasting, infections, heat stroke, malaria, pancreatitis | |
Carbon tetrachloride, chloroform, arsenic, phosphorus compounds, hepatotoxic drugs, drugs that cause cholestasis, morphine, heparin, diphenylhydantoin | |
↓ | Not clinically significant |
Fasting |
6.2 Albumin [Alb]
Affected Organs: Liver, skin, G.I., kidneys, pancreas, thyroid.
Specimen Handling: Serum. Interferences: Hemoglobin, bilirubin, lipemia. Decreased in supine position, and increased in upright position.
Supportive Tests: Globulin, total protein, fibrinogen, complete blood count (CBC).
Albumin (69,000 g/mol) is produced in the liver, and constitutes 35–50 % of the serum protein in animals and 60–70 % in humans. It accounts for 75 % of plasma oncotic (colloid osmotic) pressure. Albumin attracts interstitial water into the blood vessels; so as absolute albumin increases, so too does plasma volume. Decreases in serum albumin due to hepatocellular insult, severe hemorrhage, severe burns, or protein loss through the kidneys, skin, or G.I. tract cause water to move into interstitial spaces, resulting in edema. Serum albumin slowly decreases (~3 %/day) during hepatocellular damage. Albumin replacement is slower in large animals. Albumin levels decrease with age. Because albumin binds with many substances, it serves as a carrier for cations, calcium, fatty acids, bilirubin, and drugs. This binding slows excretion from the body and allows time for detoxification.
↑ | [Hyperalbuminemia] |
Dehydration (confirm with HCT and HGB), prolonged tourniquet use, shock | |
↓ | [Hypoalbuminemia] |
Acute blood loss | |
Decreased synthesis in the liver, increased catabolism, severe diffuse liver disease, subacute hepatitis, hepatocellular damage, ascites, cirrhosis, chronic alcoholism | |
Starvation, protein malnutrition, severe malabsorption, nontropical sprue, intestinal obstruction, cachexia, peptic ulcer, ulcerative colitis, Crohn’s disease, granulomatous enteritis, acute G.I. infections | |
Chronic glomerulonephritis with protein loss, nephrotic syndromes | |
Pancreatitis, diabetes mellitus | |
Intestinal lymphangiectasia, Type II ostertagiasis (cattle), Johne’s disease (cattle), neoplasia, lymphomas, carcinomatosis, severe infections, thyrotoxicosis (Grave’s disease), heart failure, collagen diseases | |
Pregnancy, egg laying, aging, surgery, prolonged immobility, overhydration, IV fluid therapy, skin trauma and burns (protein loss), parasitism | |
Estrogen |
6.3 Albumin: Globulin Ratio [A:G, A/G]
The Albumin: Globulin Ratio is a calculated value:
↑ | Not clinically significant |
↓ | Same as for decreased albumin |
6.4 Alkaline Phosphatase, Serum [ALP, AP, SAP, ALKP, Alk Phos]
Affected Organs: Liver (hepatobiliary), bone, thyroid, lung, adrenals, intestines, kidneys, and placenta; also sepsis and pregnancy.
Specimen Handling: Fasted animal. Serum must be refrigerated immediately, and should be analyzed the same day. ALP increases with storage at 4 °C, but is stable for 20 months at −20 °C. Interferences: Hemolysis, fluoride, citrate, oxalate, EDTA, nonfasted specimen.
Supportive Tests: ALP isoenzyme study, ALT, AST, SDH (large animals), GGT, LDH, 5′-NT, bile acids, urobilinogen, bilirubin, albumin, total globulins, CBC, erythrocyte morphology, clotting factors, prothrombin time.
Distinct alkaline phosphatase isoenzymes are found in liver (especially the biliary tree), bile, bone, renal tubules, intestinal mucosa, lung, placenta, and leukocytes. The isoenzymes can be separated by electrophoresis to determine the source of increased ALP. Serum ALP, as reported in toxicology studies, is a mixture of all isoenzymes but mostly those from liver, bone, and intestines. Elevated ALP is primarily an indicator of cholestasis, liver disease, and osteoclast activity. The liver isoenzyme predominates in most species except during rapid bone growth (bone isoenzyme) and pregnancy (placental isoenzyme). Serum levels decrease after puberty. In rats, the intestinal and bone isoenzymes are the dominant isoenzymes.
Increases in serum ALP due to the bone isoenzyme are usually 2–3 fold, but increases due to the liver isoenzyme can be much greater. Marked increases in serum ALP can result from endogenous and exogenous corticosteroid induction in the liver (except in cats), and this effect can persist for weeks. In birds, most ALP consists of the intestinal isoenzyme. ALP increases due to liver disease in carnivorous birds but not in herbivorous birds. ALP is a poor indicator of cholestasis in cats. GGT is a more reliable indicator of cholestasis in large animals than ALP. The serum half-life of ALP ranges from 6 h in cats to 72 h in dogs. ALP has replaced BSP as an indicator of liver disease.
↑ | Liver disease, hepatitis, cholestasis, extrahepatic biliary obstruction, hepatocellular jaundice, portal cirrhosis, liver abscess, and nodules, liver tumors |
Increased bone metabolism (healing fractures and hyperparathyroidism), bone disease, bone tumors, rickets, osteomalacia, Paget’s disease | |
Hyperthyroidism, acromegaly, chronic illness, chronic stress, increased endogenous corticosteroid production (hyperadrenocorticoidism), pregnancy (third trimester—placental isoenzyme), peptic ulcer, congestive heart failure, diabetes mellitus, pulmonary infarction, Fanconi syndrome, hepatic lipidosis in cats | |
Hepatotoxic drugs, carbon tetrachloride, phenobarbital, estrogens, methyltestosterone, corticosteroids, anticonvulsants, drugs that cause cholestasis, erythromycin, chronic alcoholism | |
↓ | Anorexia, food avoidance, fasting, malnutrition, hypophosphatemia, hypophosphatasia |
Hypothyroidism, dwarfism, pernicious anemia (vitamin B12 deficiency) | |
Hypervitaminosis D |
6.5 Aspartate Aminotransferase [AST, ASAT, SGOT, GOT, PGOT]
Affected Organs: Liver (hepatocellular), cardiac muscle, skeletal muscle, kidney, pancreas, lung, spleen, erythrocytes.
Specimen Handling: Serum may be stored 24 h at room temperature, 24 h at 4 °C, 1 month at −20 °C. Interferences: Hemolysis, freezing
Supportive Tests: ALT, ALP, ALP isoenzyme study, SDH (large animals), GGT, LDH, 5′-NT, urobilinogen, creatine kinase, bile acids, bilirubin, albumin, total globulins, CBC, erythrocyte morphology, clotting factors, prothrombin time.
Aspartate aminotransferase (AST) is also known as serum glutamate oxalacetate transaminase (SGOT). AST is equipresent in liver and cardiac muscle, and minimally present in skeletal muscle, kidney, pancreas, lung, spleen, and erythrocytes. ALT and AST are usually measured together. AST is not as liver-specific as ALT. Serum levels of ALT and AST are normally low, but leaky cell membranes release these enzymes into the blood when there is cell injury or death.
In liver injury, ALT and AST are both increased with peak AST levels at 24–36 h. In myocardial infarction, AST is increased while ALT increases only slightly. AST is used to diagnose liver damage in large animals relative to creatine kinase (CK), an indicator of muscle damage.
↑ | Hepatocyte necrosis, cholestatic and obstructive jaundice, chronic hepatitis, viral hepatitis, alcoholic hepatitis, cirrhosis, hepatic tumors, hemochromatosis, liver flukes |
Myocardial infarction, cardiac muscle trauma or necrosis, muscular dystrophy, myoglobinuria, white muscle disease, polymyositis, skeletal muscle trauma or necrosis, trichinosis | |
Surgery, I.M. injections, infections, shock, septicemia, gangrene, intestinal complications, pancreatitis, hemolytic anemias | |
Halothane, chloroform, carbon tetrachloride, copper, phosphorus compounds, opiates, salicylates, erythromycin, phenothiazines, progesterone, androgens, methyldopa, acetaminophen, hepatotoxic drugs, drugs that cause cholestasis | |
↓ | Not clinically significant |
Vitamin B6 deficiency, uremia |
6.6 Bicarbonate [Bicarb, HCO3 −]
Affected Organs: Blood, lungs, kidneys, CNS.
Specimen Handling: Arterial blood is drawn into a heparinized syringe anaerobically, chilled on ice, and analyzed expeditiously (i.e. <20 min).
Supportive Tests: pO2, pCO2, pH.
The body’s acid-base balance is primarily regulated by the bicarbonate anion (HCO3 −). Bicarbonate is produced endogenously. Bicarbonate levels are regulated by the lungs and kidneys. It can be lost in the urine and gastrointestinal secretions. Bicarbonate can be measured, or it can be calculated using the Henderson-Hasselbalch equation (pK is 6.1 for the bicarbonate buffer system, HCO3 − is a salt, and pCO2 is an acid):
↑ | [Metabolic alkalosis or compensated respiratory acidosis]—see pH |
↓ | [Metabolic acidosis or compensated respiratory alkalosis]—see pH |
Prolonged exposure of a blood sample to air |
6.7 Bile Acids, Total [TBA]
Affected Organs: Liver (hepatobiliary, hepatocellular), kidney.
Specimen Handling: Fasting serum is stable for 6 months at 4 °C.
Supportive Tests: ALP, ALT, AST, SDH (large animals), GGT, 5′-NT, urobilinogen, bilirubin, CBC, erythrocyte morphology.
The total bile acids test is a sensitive indicator of hepatobiliary function. The liver forms bile acids from cholesterol. Bile acids are stored and concentrated in the gall bladder and then secreted into the intestine to emulsify dietary fats. Approximately 90 % of the bile acids are reabsorbed from the ileum into portal circulation and then removed by the liver. Fasting serum levels of bile acids are low in animals with normal enterohepatic recirculation, but elevated when disease interferes with enterohepatic circulation or the hepatobiliary system.
↑ | Cholestasis, cholestasis of pregnancy, acute hepatitis, viral hepatitis, chronic hepatitis, liver sclerosis, extrahepatic biliary obstruction, cholangiohepatitis, biliary cirrhosis, portal vein thrombosis, cholangitis, hemochromatosis, hepatic lipidosis, copper hepatopathy, portosystemic shunt, hepatic microvascular dysplasia, liver cancer, chronic kidney failure |
Methotrexate, cyclosporine, rifampin, isoniazid | |
↓ | Not clinically significant |
Intestinal malabsorption | |
Cholestyramine |
6.8 Bilirubin, Conjugated (Direct) [C-Bili, CB, D-Bili]
Affected Organs: Liver (hepatobiliary).
Specimen Handling: Serum should be protected from light.
Supportive Tests: Total bilirubin, unconjugated bilirubin, ALT, ALP, AST, bile acids, GGT, 5′-NT, urobilinogen, CBC, erythrocyte morphology.
Conjugated (direct) bilirubin is water-soluble, and is eliminated in bile and through the kidneys. Bilirubin measurements in dogs lack sensitivity.
↑ | [Conjugated Hyperbilirubinemia] |
Intrahepatic or extrahepatic biliary tree obstruction (cholestasis), hepatocellular damage (progressed) | |
Blood transfusions | |
↓ | Not clinically significant |
6.9 Bilirubin, Total [T-Bili, Bili]
Affected Organs: Liver (hepatobiliary).
Specimen Handling: Serum should be protected from light. Interferences: light, lipemia, turbidity.
Supportive Tests: Conjugated bilirubin, unconjugated bilirubin, ALP, bile acids, CBC, erythrocyte morphology.
Bilirubin is the breakdown product of hemoglobin. Macrophages release unconjugated, insoluble (indirect) bilirubin when they phagocytize senescent erythrocytes. Most bilirubin is bound to albumin for transport to the liver. This allows for iron to be recycled for more efficient erythropoiesis. The liver converts unconjugated bilirubin into bilirubin glucuronide that passes through the biliary system into the small intestines as conjugated bilirubin (direct), which is both water soluble and not bound to protein. Bacteria in the intestines break down unconjugated bilirubin into stercobilinogen that gives feces their characteristic brown color.
Total bilirubin is a measurement of both conjugated and nonconjugated bilirubin in the serum. Bilirubin measurements in dogs lack sensitivity. Serum bilirubin rarely increases in cattle except in cases of bile duct obstruction with decreased renal function and prolonged bile duct obstruction. Hyperbilirubinemia typically precedes bilirubinuria in most species but not in dogs.
↑ | [Hyperbilirubinemia] |
Hepatocellular damage (inflammatory, toxic, or neoplastic), cirrhosis, excessive hemolysis, disseminated intravascular coagulation, septicemia, shock | |
Intrahepatic and extrahepatic biliary tree obstruction due to parasites, calculi, or tumor, hemolytic diseases, fructose intolerance | |
Prolonged fasting, blood transfusions | |
↓ | [Hypobilirubinemia] |
Not clinically significant | |
Prolonged exposure of blood samples to light | |
Ethoxazine, phenazopyridine |
6.10 Bilirubin, Unconjugated (Indirect) [U-Bili, UB, UCB, I-Bili]
Affected Organs: Liver (hepatocellular).
Specimen Handling: Serum should be protected from light.
Supportive Tests: Total bilirubin, conjugated bilirubin, ALP, ALT, AST, GGT, SDH (large animals), LDH, CBC, erythrocyte morphology.
Unconjugated (indirect) bilirubin binds to albumin for transport to the liver. It cannot pass through the kidneys into urine. Unconjugated hyperbilirubinemia occurs when the liver is unable to process the amount of unconjugated bilirubin provided to it, such as when there is excessive erythrocyte hemolysis. Unconjugated bilirubin is an indicator of very late liver damage. In the horse, most bilirubin is unconjugated.
↑ | [Unconjugated Hyperbilirubinemia] |
Acute hepatitis, hepatocellular damage (progressed); excessive hemolysis, blood transfusion, impaired erythropoiesis due to vitamin B12 and folate deficiencies sepsis | |
↓ | Not clinically significant |
Bleeding Time
See Hematology Diagnosis
6.11 Blood Urea Nitrogen [BUN, UN]
Affected Organs: Kidneys, heart, liver.
Specimen Handling: Serum or plasma may be stored for several hours at room temperature, or for longer periods at 4 °C. Avoid high sodium fluoride concentrations. Interferences: Citrate, EDTA, oxalate, fluoride, lithium heparin, ammonia, heavy metals.
Supportive Tests: Creatinine, bicarbonate, Ca, Cl, inorganic P, K, Na, blood pH, cholesterol, serum proteins, renal clearance tests, dye excretion tests, serum amylase, urine specific gravity.
Blood urea nitrogen is produced in the liver from ammonia, then eliminated in the kidneys by glomerular filtration. BUN levels increase and decrease with food intake and dietary protein. BUN is not a sensitive test of kidney damage since more than 75 % of the nephrons must be damaged for BUN values to increase significantly. Ideally, a series of BUN measurements should be taken since a single value can be misleading. Animals should be fasted prior to testing. BUN values increase with age. Creatinine is a more specific test than BUN for kidney damage caused by disease or toxicity, but BUN is useful for assessing reversibility of damage.
↑ | [Azotemia, Hyperuremia, Uremia] |
Impaired kidney function due to chemically induced nephrotoxicity | |
High protein diet, decreased body water (vomiting, diarrhea, starvation, vigorous exercise, sweating, hemorrhage, infection, burns) | |
Shock, rcenal disease, postrenal obstruction, acute myocardial infarct, G.I. hemorrhage, infection, fever, toxemia, hypoadrenocorticism | |
Corticosteroids, tetracycline | |
↓ | [Hypouremia] |
Low protein and high carbohydrate diet, fasting | |
Severe liver damage, hepatitis, hepatic insufficiency | |
Drug poisoning, anabolic steroids |
6.12 Calcium [Ca, Ca++, Ca2+, Calc]
Affected Organs: Parathyroids, kidneys, pituitary, pancreas, liver, G.I., bone.
Specimen Handling: Plasma or whole blood may be used. Blood should be drawn anaerobically using heparin as an anticoagulant. Samples should be placed on ice, and analyzed promptly. For measurements of total calcium, serum must come from a fasted nonexercised animal. Interferences: EDTA, citrate, oxalates, fluoride, calcium salt of heparin, BSP dye, cork stoppers, precipitate.
Supportive Tests: Mg, Inorganic P, total protein, albumin, pH, BUN, creatinine.
Calcium exists as a cation (Ca2+) in body fluids. Half of plasma calcium is metabolically active (ionized) and the other half is bound to albumin. Tetany can result from a decrease in ionized calcium. When there is an increase in total proteins in plasma (hyperproteinemia), more calcium is bound to protein and the calcium level increases. The opposite occurs during hypoproteinemia. Calcium is not excreted by the kidney except in horses.
↑ | [Hypercalcemia] |
Primary hyperparathyroidism, pseudohyperparathyroidism (dogs), malignant diseases that involve bone (resorption) or marrow, acute osteoporosis, sarcoidosis, immobilization, renal failure (especially in horses), tuberculosis, hyperproteinemia | |
Alkaline antacids, calcium salts, diethylstilbestrol (DES; in case of breast cancer), mercurials, thiazides, estrogens, oral contraceptives, progesterone, hypervitaminosis A and D | |
Dehydration, prolonged use of a tourniquet | |
Cork-stoppered test tubes | |
↓ | [Hypocalcemia] |
Hypoparathyroidism, vitamin D deficiency, tetany, malabsorption of Ca, P, and vitamin D, late pregnancy, eclampsia, chronic renal disease with uremia and phosphate retention, Mg deficiency, acute pancreatitis with extensive fat necrosis, anterior pituitary hypofunction, proximal and distal renal tubular disease, alcoholism, hepatic cirrhosis, hypoproteinemia, hypoalbuminemia, hyperadrenocorticism, parturient paresis (milk fever) in dogs, sheep, cows, and horses, G.I. tract blockage in ruminants | |
Anticonvulsants, calcitonin, corticosteroids, diuretics, mercurials, fluorides, glucagon, glucose, insulin, laxatives, Mg salts, phosphates, oxalate, sulfates, EDTA |
Calculated Globulin
See Globulin
6.13 Carbon Dioxide, Partial Pressure [pCO2, p(a)CO2]
Affected Organs: Blood, lungs, kidneys, CNS.
Specimen Handling: Arterial or free-flowing capillary blood is anaerobically drawn into a heparinized syringe, chilled on ice, and analyzed expeditiously (i.e. <20 min).
Supportive Tests: pO2, pH, bicarbonate.
This parameter measures carbon dioxide dissolved in plasma (i.e., not in hemoglobin). See pH.
↑ | [Hypercapnia] |
Respiratory acidosis, metabolic alkalosis with compensatory hypoventilation, obstructed airways, increased atmospheric pCO2, pulmonary diseases as during rebreathing, asthmatic shock, chronic bronchitis, pulmonary tuberculosis, polio, emphysema, severe electrolyte disturbance, respiratory center depression, reflex bradypnea, hypothermia | |
Exposure of drawn blood to air | |
Opiates, barbiturates, diazepam, curare, succinyl choline | |
↓ | [Hypocapnia] |
Respiratory alkalosis, hyperventilation due to mechanical ventilation, hypoxia, pulmonary emboli, anxiety, hyperthermia, respiratory center disturbance from head trauma | |
Salicylates, trimethomine |
6.14 Chloride [Cl, Cl−]
Affected Organs: Kidneys, parathyroids, adrenals.
Specimen Handling: The tubes used to obtain serum or plasma must be free of contaminants. The serum should be rapidly separated, and hemolysis must be avoided.
Supportive Tests: Na, K, Ca, inorganic P, Mg, BUN, creatinine, urine specific gravity.
Chlorine exists as chloride (Cl−) in body fluids and is the predominant anion electrolyte in extracellular fluid (ECF). Very little chloride is found in intracellular fluid (ICF). Chloride and sodium are essential in regulating the osmolality and acid-base balance of ECF. Sodium and chloride levels tend to rise and fall together. Chloride readily passes through the kidney’s renal glomeruli and is then passively reabsorbed in the proximal convoluted tubules and actively reabsorbed in the loop of Henle. Because a slight increase is normal after eating, blood should be drawn from fasted animals.
↑ | [Hyperchloremia, Hyperchloridemia]
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