Human Biochemistry Volume 2 - Murray R. 1993

Appendix
Standard Clinical Laboratory Reference Values in Conventional and SI Units

Serum or plasma albumin (see "Serum or Plasma Proteins")

Serum aminotransferases (transaminases)

Normal range (varies by method): aspartate aminotransferase (AST)—6–25 IU/L at 30° C; Alanine aminotransferase (ALT)—3–26 IU/L at 30°C.

A. Precautions. Avoid hemolysis; promptly separate serum from the clot.

B. Physiological basis. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and Lactate dehydrogenase are intracellular Enzymes involved in Amino Acid and Carbohydrate METABOLISM. They are present in high concentrations in Muscle, Liver, and Brain tissue. Elevated Blood levels of these enzymes primarily indicate necrosis or damage to these Tissues.

C. Interpretation.

1. Levels are elevated in myocardial infarction (especially AST); acute infectious hepatitis (ALT is usually elevated more than AST); cirrhosis of the liver (AST is elevated more than ALT); and in primary or metastatic liver tumors. When serous cavities are involved by tumor processes, enzyme levels are elevated in the transudates. AST is also elevated in muscular dystrophy, dermatomyositis, and paroxysmal myoglobinuria.

2. Levels are decreased in pyridoxine (vitamin B₆) deficiency, often As a result of repeated hemodialysis Procedures; in renal failure; and during Pregnancy.

Blood ammonia

Normal range (Conway method): 10–110 mcg% in whole blood (SI: 6–65 mcmol/L).

A. Precautions. Do not use anticoagulants containing ammonia. Potassium oxalate, calcium disodium EDTA, and ammonia-free heparin should be used as anticoagulants. Determinations must be performed immediately after blood collection or within one hour if the sample is kept on ice.

B. Physiological basis. Ammonia enters the bloodstream from two primary sources: 1) large amounts are released in the Large Intestine from The breakdown of nitrogenous compounds by putrefactive Bacteria; 2) ammonia is released during Protein metabolism. Ammonia entering the portal Venous system or general Circulation is rapidly converted into urea in the liver. Liver failure can lead to elevated blood ammonia levels, particularly when accompanied by high protein intake or intestinal bleeding.

C. Interpretation. Blood ammonia is elevated in liver failure or when portal blood flow is shunted via a portacaval anastomosis, especially against the Background of a high-protein diet or intestinal Hemorrhage.

Serum amylase

Normal range (varies by method): 80–180 Somogyi units per 100 ml of serum (one such unit corresponds to The amount of enzyme that produces 1 mg of reducing sugar from starch at pH 7.2); 0.8–3.2 IU/L.

A. Precautions. If storage for more than 1 hour is required, blood and serum should be frozen.

B. Physiological basis. Normally, amylase (diastase) (molecular weight approx. 50,000) is present in the blood in small amounts; it is produced by the Pancreas and Salivary Glands. Inflammation of these glands or obstruction of their ducts leads to the release of large quantities of the enzyme into the blood and increased renal excretion.

C. Interpretation.

1. Levels are elevated in acute pancreatitis, pancreatic cysts, and obstruction of the pancreatic duct (by tumor, calculi, adhesions, or due to sphincter spasm following morphine administration), as well as in mumps. In addition, elevated amylase levels may occasionally result from renal failure, diabetic acidosis, or pancreatic inflammation associated with a perforated peptic ulcer. A rare cause of elevated amylase is The formation of amylase-immunoglobulin complexes (macroamylasemia) which, owing to their high molecular weight, are not filtered by the glomeruli.

2. Levels are decreased in acute and chronic hepatitis, pancreatic insufficiency, and occasionally in pregnancy toxemia.

Urine amylase

Normal range (varies by method): 40–250 Somogyi units/h.

A. Precautions. If testing is delayed for more than 1 hour after sample collection, the urine must be frozen.

B. Physiological basis (see "Serum amylase"). With adequate renal function, amylase is rapidly excreted in the urine. To determine the excretion rate, urine is collected over a 2-, 6-, or 24-hour period.

C. Interpretation. Increases in urinary amylase parallel those in the blood. However, after blood amylase levels return to normal following an attack of pancreatitis, urinary levels remain elevated for up to 7 days. Therefore, urinalysis can be useful when the patient is evaluated after an attack has subsided. Elevated serum amylase with normal or decreased urinary excretion is encountered in renal failure or macroamylasemia.

Serum or plasma bicarbonates

Normal range: 24—28 mEq/L (SI: 24—28 mmol/L).

A. Precautions. Plasma or serum must be separated from Blood Cells and stored frozen in closed tubes. B. Physiological basis. The bicarbonate buffer system is one of the most critical systems maintaining the normal pH of Body Fluids. The determination of bicarbonate and pH in arterial blood serves as a key indicator in assessing acid-base balance.

B. Interpretation.

1. Elevated levels occur in

a) metabolic alkalosis (arterial blood pH is elevated) caused by the intake of large amounts of sodium bicarbonate, persistent vomiting with the expulsion of acidic gastric contents, and potassium deficiency;

б) respiratory acidosis (arterial blood pH is decreased) due to inadequate CO₂ elimination (leading to elevated P_CO2) in pulmonary emphysema, impaired diffusion associated with alveolar membrane lesions, Heart Failure accompanied by pulmonary congestion or edema, or impaired pulmonary ventilation of any Etiology, including overdose of sedatives, narcotics, or inadequate mechanical ventilation.

2. Decreased levels occur in

a) metabolic acidosis (arterial blood pH is decreased) due to diabetic ketoacidosis, lactic acidosis, starvation, persistent diarrhea, renal failure, or salicylate intoxication;

б) respiratory alkalosis (arterial blood pH is elevated) due to hyperventilation (decreased PCO₂).

Serum bilirubin

Normal range: total 0.2—1.2 mg% (SI: 3.5—19 µmol/L). Direct (glucuronide) - 0.1 -0.4 mg%. Indirect (unconjugated) — 0.2—0.7 mg% (SI: direct up to 7 µmol/L, indirect up to 12 µmol/L).

A. Precautions. Blood should be drawn on an empty Stomach to avoid serum turbidity. To maintain stability, serum samples must be stored frozen in the dark.

Б. Physiological basis. Bilirubin is formed during the breakdown of Hemoglobin. In the liver, it binds to glucuronate and is excreted in Bile as diglucuronide. Bilirubin accumulates in plasma in liver failure, biliary obstruction, and increased hemoglobin breakdown. Changes in concentration may also be associated with defects in enzyme systems involved in bilirubin metabolism (e.g., in the absence of glucuronyltransferase).

B. Interpretation.

1. Direct and Indirect serum bilirubin are elevated in acute or chronic hepatitis, biliary obstruction (at the level of the bile ducts or the common bile duct), toxic reactions to numerous drugs, chemicals, and toxins, as well as in Dubin-Johnson and Rotor syndromes.

2. Indirect serum bilirubin is elevated in hemolytic anemias and other hemolytic reactions, as well as in the absence or deficiency of glucuronyltransferase (e.g., in Gilbert and Crigler-Najjar syndromes).

3. Direct and total bilirubin can be significantly elevated in healthy individuals after 24—48 hours of fasting (sometimes even after 12 hours) and during prolonged low-calorie diets.

Serum calcium

Normal range: total - 8.5—10.3 mg% or 4.2—5.2 mEq/L; ionized - 4.2—5.2 mg% or 2.1—2.6 mEq/L (SI: total — 2.1—2.6 mmol/L; ionized - 1.05—1.3 mmol/L).

A. Precautions. The glassware used for the assay must be free of calcium contamination that could leach into the sample. Blood collection must be performed while fasting. Serum should be rapidly separated from the clot.

Б. Physiological basis. Plasma and body fluid calcium levels are influenced by Nutrition, endocrine function, renal status, and the gastrointestinal tract. To interpret results accurately, plasma albumin concentration must also be determined, as a fraction of calcium circulates bound to plasma proteins. B. Interpretation

1. Elevated levels occur in hyperparathyroidism, ectopic parathyroid hormone-like peptide secretion by malignant tumors, hypervitaminosis D, milk-alkali syndrome, osteolytic processes such as multiple myeloma, bone metastases, Paget's Disease, Boeck's disease, immobilization, and familial hypocalciuria. Occasionally, elevated levels are observed in hyperthyroidism and during Treatment with thiazide Diuretics.

2. Decreased levels occur in hypoparathyroidism, Vitamin D deficiency (Rickets, Osteomalacia), renal failure, hypoproteinemia, malabsorption syndrome (ileitis, pancreatic insufficiency), severe pancreatitis with pancreatic necrosis, and pseudohypoparathyroidism.

Urine calcium (24-hour excretion)

Normally, urinary calcium excretion ranges from 50–150 mg per 24 h, depending on intake (SI: 1.2–3.7 mmol/24h).

A. Precautions. For three days prior to the test, the patient must abstain from milk and cheese; for quantitative determination, a three-day diet containing approximately 150 mg of calcium per day is prescribed. To accurately assess calcium excretion, urine must be collected over an exact 24-hour period.

B. Interpretation. On a "quantitative" diet, normal calcium excretion is 125 ± 50 mg (3.1 mmol/L) per 24 h. In hyperparathyroidism, calcium excretion typically exceeds 200 mg/24 h (5 mmol). Urinary excretion is almost invariably elevated whenever serum concentrations are increased.

Serum Ceruloplasmin and Copper

Normal values: ceruloplasmin — 25–43 mg% (SI: 1.7–2.9 µmol/L); copper — 100–200 mg% (SI: 16–31 µmol/L).

A. Precautions. None.

B. Physiological basis. Approximately 5% of serum copper is loosely bound to albumin, and 95% to ceruloplasmin, a blue copper-containing oxidase which is an a₂-globulin. In Wilson's disease, serum copper and ceruloplasmin levels are decreased, whereas urinary copper concentration is high.

C. Interpretation

1. Elevated levels occur in pregnancy, hyperthyroidism, infection, aplastic anemia, acute leukemia, Hodgkin's disease, cirrhosis of the liver, and with The Use of oral contraceptives.

2. Decreased levels occur in Wilson's disease (in combination with increased urinary copper excretion), malabsorption, nephrosis, and copper deficiency associated with parenteral nutrition.

Serum and Plasma Chlorides

Normal values: 96–106 mEq/L (SI: 96–106 mmol/L).

A. Precautions. Determining this parameter in whole blood yields falsely low results compared to plasma or serum; only plasma or serum should be used for analysis. B. Physiological basis. Chloride is a major extracellular inorganic anion. It plays a vital role in maintaining acid-base balance, although it does not act as a buffer itself. Loss of chloride as HCl or NH₄Cl leads to alkalosis; chloride intake leads to acidosis. Chlorides (along with sodium) play a crucial role in regulating body fluid osmolarity.

C. Interpretation

1. Elevated levels occur in renal failure (when chloride intake exceeds excretion), nephrosis (occasionally), Renal Tubular Acidosis, hyperparathyroidism (occasionally), ureterosigmoidostomy (due to intestinal reabsorption from urine), dehydration (Water deficit), and salt solution overload.

2. Decreased levels occur in gastrointestinal disorders accompanied by the loss of gastric or intestinal contents (vomiting, diarrhea, impaired gastrointestinal absorption), renal failure (with salt-wasting), diuretic overdosage, chronic respiratory acidosis (emphysema), diabetic acidosis, excessive sweating, adrenal insufficiency (loss of NaCl), hyperadrenocorticism (chronic K⁺ loss), and metabolic alkalosis (NaHCO₃ intake, K⁺ deficiency).

Urinary Chlorides

Urinary chloride content varies depending on diet, acid-base balance, endocrine status, body stores of other electrolytes, and fluid balance. These interrelated factors are so diverse and complex that determining urinary chlorides has limited clinical significance.

Serum or Plasma Cholesterol

Normal values: 150–280 mg% (SI: 3.9–7.2 mmol/L). (See Table App. 1.)

A. Precautions. The test should be performed only in the fasting state.

Class="center">Table App. 1. Lipemia. Concentrations of serum cholesterol (C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). (Reproduced, with permission, from Krupp M. A. et al. Physician’s Handbook, 21st ed. Lange, 1985.)

B. Physiological basis. Cholesterol concentration depends on its metabolism, which is influenced by heredity, diet, Endocrine glands, and the condition of Internal Organs (liver, Kidneys). Cholesterol Metabolism is closely linked to Lipid Metabolism.

C. Interpretation

1. Elevated values occur in familial hypercholesterolemia (xanthomatosis), hypothyroidism, uncompensated Diabetes Mellitus, Nephrotic Syndrome, chronic hepatitis, biliary cirrhosis, obstructive jaundice, hypoproteinemia (idiopathic, secondary to nephrosis or chronic hepatitis), and lipidemia (idiopathic, familial).

2. Decreased values occur in acute hepatitis and Gaucher disease. In some cases, low cholesterol concentrations are observed with hyperthyroidism, acute infections, anemia, malnutrition, and apolipoprotein deficiencies.

Serum Creatine Phosphokinase (CPK)

Reference range: (varies by method) 10–50 IU/L at 30°C.

A. Precautions. The enzyme is unstable, and erythrocyte contents inhibit its activity. Serum must be promptly separated from the clot. If testing cannot be performed immediately, the serum must be frozen.

B. Physiological basis. CPK cleaves creatine phosphate (in the presence of ADP) to yield creatine and ATP. CPK is abundant in Skeletal Muscle, cardiac muscle, and the brain.

C. Interpretation

1. Elevated values occur in muscle damage (myocardial infarction, muscle trauma), muscular dystrophy, polymyositis, strenuous exercise (running), hypothyroidism, and stroke. Following a myocardial infarction, CPK rises rapidly (within 3–5 hours) and remains elevated for 2–3 days (i.e., a shorter duration than AST or LDH).

2. Values do not increase in pulmonary infarction or hepatic parenchymal disease.

Serum Creatine Phosphokinase Isoenzymes (see Table App. 2)

A. Precautions. Same as for CPK determination (see above).

B. Physiological basis. CPK exists as three isoenzymes that can be separated by Electrophoresis. Skeletal muscle is characterized by the MM isoenzyme, myocardium by MB, and brain by BB.

Table App. 2. Creatine Kinase Isoenzymes

C. Interpretation. CPK-MM levels increase in serum with skeletal muscle, heart muscle, and brain injury; in muscle disorders (dystrophy, hypothyroidism, dermatomyositis, polymyositis); in rhabdomyolysis; and following heavy physical exertion. CPK-MB levels rise shortly after myocardial infarction (within 2–4 hours) and remain elevated for up to 72 hours (prolonged elevations persist with myocardial infarction extension or reinfarction), in severe rhabdomyolysis or muscle trauma, severe myopathy, Reye syndrome, and Rocky Mountain spotted fever. CPK-BB levels occasionally increase in severe Shock, certain carcinomas (especially oat-Cell carcinoma, as well as ovarian, breast, or prostate carcinoma), or biliary atresia.

Urine Creatine (24-hour)

Reference range: see Table App. 3.

A. Precautions. Urine must be collected over an exact 24-hour period. The sample should be frozen or preserved with 10 mL of toluene or 10 mL of a 5% thymol-chloroform solution.

B. Physiological basis. Creatine is an important component of muscle, brain, and blood; as creatine phosphate, it serves as a high-energy phosphate reserve. Normally, small amounts of creatine are excreted in the urine, with excretion rates increasing during enhanced Catabolism and muscular dystrophy.

C. Interpretation

Table App. 3. Urine Creatine and Creatinine. Reference Values (24-hour)

1. Elevated values occur in muscular dystrophies (progressive muscular dystrophy, myotonia atrophica, myasthenia gravis), muscle hypotrophy (acute poliomyelitis, AMYOTROPHIC LATERAL SCLEROSIS, myositis presenting with muscle wasting), starvation and cachexia, hyperthyroidism, and febrile states.

2. Decreased values occur in hypothyroidism, congenital amyotonia, and renal failure.

Serum or Plasma Creatinine

Normal range: 0.7–1.5 mg% (SI: 60–132 µmol/L).

A. Precautions. None.

B. Physiological basis. Endogenous creatinine is excreted via Glomerular Filtration and tubular secretion, resulting in a clearance rate approximately 20% higher than that of inulin. The Jaffe reaction measures all plasma chromogens rather than creatinine alone. Because chromogens are not excreted in the urine, the determination of urinary creatinine yields a value about 20% lower than the total amount of creatinine plus plasma chromogens; however, this discrepancy is offset by the amount of creatinine secreted in the tubules. Thus, creatinine clearance is a standard method for assessing glomerular filtration, except in cases of progressive renal failure, where creatinine clearance exceeds inulin clearance due to creatinine secretion by the remaining renal tubules.

C. Interpretation. Elevated levels occur in acute or chronic renal failure, Urinary Tract obstruction, and renal impairment caused by certain medications. In addition to creatinine, other substances can react with picric acid in an alkaline environment (the Jaffe reaction), yielding falsely elevated results: acetoacetate, acetone, ß-hydroxybutyrate, a-ketoglutarate, Pyruvate, glucose, bilirubin, hemoglobin, urea, and uric acid. Values below 0.7 mg% currently have no established clinical explanation.

Urinary creatinine Normal range: See Table App. 3.

Serum or Plasma Glucose

Normal range: fasting "true" glucose — 65–110 mg% (SI: 3.5–6.1 mmol/L).

A. Precautions. If testing is delayed for more than an hour, sodium fluoride (3 mg/mL of blood) should be added to the sample. Filtrates can be stored frozen for up to 24 hours. Interpretation errors occur if the patient consumed sweets or received a parenteral glucose solution prior to blood collection, while the assay was evaluated as a fasting sample.

B. Physiological basis. Normally, the concentration of glucose in extracellular fluid is tightly regulated to ensure an adequate energy source for tissues while preventing urinary excretion. Nonspecific symptoms of impaired glucose metabolism include hypoglycemia and hyperglycemia.

C. Interpretation

1. Elevated levels occur in diabetes, hyperthyroidism, adrenocortical hyperfunction, hyperpituitarism, and occasionally in liver disease.

2. Decreased levels occur in hyperinsulinism, adrenal insufficiency, Hypopituitarism, liver disease (occasionally), functional hypoglycemia, and during the administration of hypoglycemic drugs.

Serum y-Glutamyltranspeptidase (Transferase)

Normal range: men — less than 30 mIU/mL at 30°C, women — 25 mIU/mL at 30°C, adolescents — 50 mIU/mL at 30°C.

A. Precautions. Hemolysis should be avoided. B. Physiological basis. y-Glutamyltransferase (GGT) is a highly sensitive indicator of liver disease. Its levels are frequently elevated even when transaminases and alkaline phosphatase are normal. For the Diagnosis of alcohol-induced liver dysfunction, GGT levels are more specific than the levels of the two aforementioned enzymes. GGT is located in the liver, kidneys, and pancreas; it transfers glutamic acid from Glutathione or another y-glutamyl peptide to an acceptor peptide or to L-Amino Acids. The enzyme is induced by alcohol.

C. Interpretation. Elevated levels occur in acute infectious or toxic hepatitis, chronic or subacute hepatitis, liver cirrhosis, intrahepatic or extrahepatic biliary obstruction, primary or metastatic hepatic tumors, and alcoholic liver disease. Elevated levels are occasionally observed in congestive heart failure, and rarely after myocardial infarction, in pancreatitis, or in pancreatic tumors.

Serum Iron

Normal range: 50–175 µg% (SI: 9–31.3 µmol/L).

A. Precautions. Syringes and needles must not leach iron into the solution. Hemolysis should be avoided. The serum must be free of hemoglobin.

B. Physiological basis. Blood testing for iron must be performed in the fasting state due to diurnal fluctuations in its levels, with peak values occurring in the morning. Plasma iron levels are determined by several factors, including intestinal absorption, storage in the intestine, liver, Spleen, and Bone Marrow, hemoglobin breakdown and loss, and the synthesis of new hemoglobin.

C. Interpretation

1. Elevated levels occur in hemochromatosis, hemosiderosis (resulting from multiple transfusions or iron overdoses), hemolytic anemias, pernicious anemia, and hypoplastic anemia. Elevated levels are also frequently found in Viral Hepatitis. False elevations may occur if the patient received parenteral iron therapy within 2–3 months prior to testing.

2. Decreased levels occur in iron deficiency, infections, nephrosis, chronic renal failure, and during periods of active hemopoiesis.

Iron-Binding Capacity of Serum

Normal range: total — 250–410 µg% (SI: 45–76 µmol/L), saturation percentage — 20–55%.

A. Precautions. None.

B. Physiological basis. Iron is transported as a complex with the metal-binding globulin transferrin (siderophilin). Typically, this protein carries an amount of iron corresponding to 30–40% of its total binding capacity.

C. Interpretation of total iron-binding capacity.

1. Elevated levels occur in iron deficiency anemia, during oral contraceptive use, in late pregnancy, in children, and occasionally in hepatitis.

2. Decreased levels occur in conditions associated with low plasma protein levels (nephrosis, starvation, Cancer), chronic infections, and hemosiderosis (resulting from transfusion or thalassemia).

D. Interpretation of transferrin saturation

1. Elevated levels occur in iron overload (iron poisoning, hemolytic disorders, thalassemia, hemochromatosis, pyridoxine deficiency, nephrosis, and occasionally hepatitis).

2. Decreased levels occur in iron deficiency, chronic infections, cancer, and late pregnancy.

Lactate dehydrogenase (LDH) in serum, serous fluids, CEREBROSPINAL FLUID, and urine

Normal range (varies by method): serum — 55–140 IU/L, 30° C. In serous fluids, levels are lower than in serum. In cerebrospinal fluid — 15–75 units (according to Wroblewski); 6.3–30 IU/L. In urine — less than 8300 units/8 h (according to Wroblewski).

A. Precautions. Hemolysis must be completely avoided, as the intracellular LDH concentration in erythrocytes is 100 times higher than in serum. Enzyme activity may be inhibited by heparin and oxalate. The clot should be separated from the serum promptly.

B. Physiological basis. LDH catalyzes the reversible reduction of pyruvic acid to lactic acid in the presence of NADH. LDH is found in all cells and body fluids.

C. Interpretation. Elevated levels occur in tissue necrosis, particularly in acute cardiac injury, erythrocyte damage, and lesions of the kidneys, skeletal Muscles, liver, Lungs, and Skin. Significant elevations accompany hemolytic anemias associated with vitamin B₁₂ and Folic acid deficiency, as well as polycythemia vera. A gradual increase over 3–4 days followed by a decline within 5–7 days may indicate myocardial infarction (though pulmonary infarction, tumors, and megaloblastic anemia must be ruled out). Elevated LDH levels are characteristic of the acute phase of infectious hepatitis, whereas in chronic liver diseases, enzyme activity is rarely increased.

Serum lactate dehydrogenase isoenzymes

Normal range: see Table App. 4.

A. Precautions. Same as for LDH (see above).

B. Physiological basis. There are 5 LDH isoenzymes, each of which is a tetramer composed of Two Types of subunits, H and M. The quantity of isoenzymes can be determined using kinetic, electrophoretic, immunologic Methods, or Chromatography. Upon electrophoretic Separation, the mobility of the isoenzymes corresponds to the Serum proteins a₁, a₂, ß, y₁, and y₂, and they are numbered as 1 (fastest migrating), 2, 3, 4, and 5 (slowest migrating). Isoenzyme 1 is present in high concentrations in heart muscle (HHHH tetramer), as well as in erythrocytes and the renal cortex; isoenzyme 5 is found in skeletal muscle (MMMM tetramer) and the liver.

Table App. 4. Lactate dehydrogenase isoenzymes

C. Interpretation. In myocardial infarction, the proportion of a-isoenzymes is elevated, particularly LDH 1, which increases the LDH 1 / LDH 2 ratio (rising above 1). A similar increase is observed in infarction of the renal cortex and in hemolytic anemia.

Relative elevations of LDH 4 and 5 occur in acute hepatitis, severe muscle injury, dermatomyositis, and muscular dystrophy.

Serum lipase

Normal range: 0.2–0.5 units.

A. Precautions. None. The sample may be stored frozen for up to 24 hours prior to analysis.

B. Physiological basis. The concentration of this fat-splitting enzyme in the circulating blood is low. In pancreatitis, pancreatic lipase enters the bloodstream, and elevated blood levels of lipase persist longer than elevated levels of amylase.

B. Interpretation. Serum lipase is elevated in acute or acute exacerbations of Chronic Pancreatitis and in obstruction of the pancreatic duct by a stone or tumor.

Serum Magnesium

Normal range: 1.8—3 mg% or 1.5—2.5 mEq/L (SI: 0.75–1.25 mmol/L).

A. Precautions. None.

B. Physiological basis. Magnesium is primarily an intracellular electrolyte. Extracellularly, it promotes neuromuscular excitability. Magnesium deficiency may occur with normal or slightly decreased levels in extracellular fluids. Low plasma magnesium levels lead to tetany, weakness, lethargy, and disorientation.

C. Interpretation

1. Elevated levels occur in renal failure and upon overdose of magnesium solutions.

2. Decreased levels occur in chronic diarrhea, acute intestinal fluid loss, starvation, chronic alcoholism, chronic hepatitis, hepatic failure, increased diuresis (diuretics), and inadequate parenteral nutrition. Magnesium deficiency may be observed in hypocalcemia and, furthermore, may sustain it in patients with hypoparathyroidism.

Serum Acid Phosphatase

Normal range (varies depending on the method): 0.1—0.63 Sigma units.

A. Precautions. Do not draw blood for testing within 24 hours following a prostate massage or instrumental examination. The assay must be performed promptly, as enzyme activity drops rapidly. Avoid hemolysis. For immunological testing, serum can be stored frozen for up to 3—4 days.

B. Physiological basis. Phosphatase active at pH 4.9 is present in high concentrations in the Prostate Gland, erythrocytes, platelets, Cells of the reticuloendothelial system, liver, spleen, and kidneys. Several isoenzyme forms have been identified, differing in their activity toward various substrates.

C. Interpretation. In prostate carcinoma, the "prostatic fraction" of acid phosphatase increases in the serum, especially if the tumor has broken through the capsule or metastasized. Palpation of the prostate leads to a temporary elevation of this value. Acid phosphatase activity may be elevated in Gaucher's disease, malignant bone disease, renal disorders, hepatobiliary diseases, reticuloendothelial system disorders, and thromboembolism. A febrile state can lead to a false elevation of the value.

Serum Alkaline Phosphatase

Normal range (varies across methods): Bessey-Lowry Method — children: 2.8—6.7 units; adults: 0.8—2.3 units; King-Armstrong method — adults: 5—13 units, 24—71 IU/L at 30° C.

A. Precautions. Serum can be stored in the refrigerator for no more than 48 hours, though values may increase slightly (up to 10%). Activity drops upon thawing. Do not use fluoride compounds or oxalate.

B. Physiological basis. Alkaline phosphatase is present in high concentrations in growing bones, bile, and the Placenta. In serum, alkaline phosphatase occurs as a mixture of isoenzymes that have not yet been fully identified. Isoenzymes can be separated by electrophoresis; liver alkaline phosphatase migrates faster than bone and placental enzymes, which travel together.

C. Interpretation

1. Elevated levels occur:

a) in children (normal bone growth);

b) in bone DISEASES ASSOCIATED WITH increased osteoblast activity — hyperparathyroidism, rickets, osteomalacia, Bone tumors (osteosarcoma, tumor metastases), ossification such as in myositis ossificans, Paget's disease (osteitis deformans), and Boeck's sarcoidosis;

c) in obstruction of the bile ducts (intrahepatic and extrahepatic) by stones, adhesions, or tumors;

d) in drug-induced liver diseases, such as those caused by chlorpromazine or methyltestosterone;

e) during pregnancy.

2. Decreased levels occur in hypothyroidism and in children with delayed growth.

Serum inorganic phosphorus

Normal values: children — 4–7 mg% (SI: 1.3–2.3 mmol/L); adults — 3–4.5 mg% (SI: 1–1.5 mmol/L).

A. Precautions. Glassware washed with phosphate-containing detergents should be rinsed thoroughly. Blood samples must be drawn in the fasting state to rule out postprandial decreases in phosphate associated with glucose Transport and Metabolism.

B. Physiological basis. The concentration of inorganic phosphate in circulating plasma is influenced by parathyroid gland function, vitamin D, intestinal absorption, renal function, bone metabolism, and nutrition.

C. Interpretation

1. Elevated levels occur in renal failure, hypoparathyroidism, and hypervitaminosis D.

2. Decreased levels occur in hyperparathyroidism, hypovitaminosis D (rickets, osteomalacia), malabsorption syndrome (steatorrhea), use of antacids that bind phosphates in the intestine, starvation or cachexia, chronic alcoholism (especially with liver damage), overdose of phosphate-poor solutions, administration of CARBOHYDRATES (especially intravenously), renal tubular dysfunction, use of thiazide diuretics, acid-base disorders, diabetic ketoacidosis (especially during recovery), and hereditary hypophosphatemia; occasionally during pregnancy and hypothyroidism.

Serum or plasma potassium

Normal values: 3.5–5 mEq/L (SI: 3.5–5 mmol/L).

A. Precautions. Hemolysis, which releases erythrocyte K⁺, must be avoided; serum should be promptly separated from the clot, or plasma from erythrocytes, to prevent potassium diffusion from red blood cells. Platelets and leukocytes are rich in potassium; if these cells are elevated (in thrombocytosis or leukemia), potassium released from them during blood clotting will increase its serum concentration. To prevent potential errors, it is preferable to use heparinized plasma.

B. Physiological basis. Plasma potassium concentration regulates neuromuscular and muscular excitability. An increase or decrease in potassium concentration impairs the contractile capacity of Muscle tissue.

C. Interpretation (see "Precautions" above).

1. Elevated levels occur in renal failure (especially with increased protein or cellular breakdown), adrenocortical insufficiency (especially hypoaldosteronism), hyporeninemic hypoaldosteronism, administration of spironolactone, excessively rapid administration of saline solutions (especially intravenously), and use of triamterene and phenformin.

2. Decreased levels occur:

a) in inadequate nutrition (starvation);

b) in inadequate absorption or acute loss of intestinal fluid (vomiting, diarrhea, malabsorption syndrome), or with the use of polystyrene sulfonate resin;

c) in increased renal loss — secondary to hyperadrenocorticism (especially hyperaldosteronism) and corticosteroid therapy; metabolic alkalosis; use of diuretics such as chlorothiazide and its derivatives, and mercurial diuretics; renal tubular defects (Fanconi Syndrome) and renal tubular acidosis; treatment with anion-excreting Antibiotics (carbenicillin, ticarcillin); and use of phenothiazines, amphotericin B, high-sodium preparations, and degraded tetracycline;

d) in abnormal potassium distribution between intracellular and extracellular fluid — hereditary periodic paralysis and testosterone administration.

Serum or plasma proteins (including fibrinogen)

Normal values: see "Interpretation"

A. Precautions. Serum or plasma showing signs of hemolysis must not be used. Because fibrinogen is removed during blood clotting, its determination in serum is not possible.

B. Physiological basis. Protein concentration determines the colloid-Osmotic Pressure of plasma. Plasma protein concentration is affected by nutrition, renal and liver function, A number of diseases (multiple myeloma), and Metabolic Disorders. Changes in the ratio of protein fractions may indicate specific pathologies.

C. Interpretation

1. Total serum protein. Normal values: 6–8 g% (SI: 60–80 g/L). See "Albumin and Globulin Fractions" below and Table App. 5.

Table App. 5. Protein fractions determined by electrophoresis

2. Serum or plasma albumin. Reference range: 3.5—5.5 g% (SI: 33—55 g/L):

a) elevated levels occur in dehydration, shock, hemoconcentration, and intravenous administration of large quantities of concentrated albumin solutions;

b) decreased levels occur in malnutrition, malabsorption syndrome, acute and Chronic Glomerulonephritis, nephrosis, acute and chronic liver failure, tumors, and leukemias.

3. Serum or plasma globulin. Reference range: 2—3.6 g% (SI: 20—36 g/L) (see Tables App.6 and App.7):

a) elevated levels occur in liver disease, infectious hepatitis, liver cirrhosis, biliary cirrhosis, hemochromatosis, systemic lupus erythematosus, plasma cell myeloma, lymphoproliferative disorders, sarcoidosis, and acute and chronic infections, particularly lymphogranuloma venereum, typhoid fever, leishmaniasis, Schistosomiasis, and malaria; b) decreased levels occur in malnutrition, congenital agammaglobulinemia, acquired hypogammaglobulinemia, and Lymphocytic Leukemia.

Table App.6. Gamma globulin fractions determined by Immunoelectrophoresis

Table App.7. Selected proteins of the globulin fraction

4. Plasma fibrinogen. Reference range: 0.2—0.6 g% (SI: 2–6 g/L):

a) elevated levels occur in glomerulonephritis, nephrosis (occasionally), and infections;

b) decreased levels occur in disseminated intravascular coagulation (cases of pregnancy with placental abruption, Amniotic Fluid Embolism, rapid labor), Meningococcal meningitis, metastatic prostate cancer, leukemias, acute and chronic liver failure, and congenital fibrinogenopenia.

Serum or plasma sodium

Reference range: 136—145 mEq/L (SI: 136—145 mmol/L). A. Precautions. Laboratory glassware must be meticulously washed.

B. Physiological basis. Sodium accounts for approximately 140 of the 155 mEq of plasma cations. Together with its associated anions, it is the primary osmotically active component of plasma, playing a crucial role in body water distribution. The shift of sodium into cells or the loss of sodium from the body leads to a decrease in extracellular fluid volume, affecting circulation, renal function, and The Nervous system.

C. Interpretation

1. Elevated levels occur in dehydration (water deficit), trauma or nervous system disorders, and hyperadrenocorticism with hyperaldosteronism or corticosteroid excess.

2. Decreased levels occur in adrenal insufficiency, renal failure (especially when combined with inadequate sodium intake), renal tubular acidosis, as a physiological response to trauma or Burns (cellular shift of sodium), gastrointestinal losses or acute and chronic diarrhea, intestinal obstruction or fistula, and excessive sweating with inadequate sodium replacement. In a number of patients with edema associated with cardiac or renal disease, serum sodium concentration is low, although total body sodium is higher than normal. This paradoxical situation is caused by water retention (elevated antidiuretic hormone, ADH) and abnormal redistribution of sodium between the intracellular and extracellular fluids. Hyperglycemia sometimes leads to a fluid shift from the intracellular to the extracellular space, causing dilutional hyponatremia. Artifact: When measured using a flame photometer, serum or plasma sodium will appear falsely decreased in the presence of hyperlipidemia or hyperglobulinemia; in these disorders, the volume normally occupied by water is displaced by other substances, resulting in spuriously low values for water and electrolytes in serum and plasma. In hyperglycemia, serum sodium concentration decreases by 1.6 mEq/L for every 100 mg% increase in glucose (above a total concentration of 200 mg%) due to the osmotic shift of water into the extracellular space.

Thyroxine (T₄), total serum T₄

Reference range: radioimmunoassay — 5—12 µg% (SI: 65—156 nmol/L); competitive protein binding (Murphy-Pattee method) — 4—11 µg% (SI: 51—142 nmol/L).

A. Precautions. None.

B. Physiological basis. Total thyroxine levels are not directly correlated with the physiological hormonal effects of thyroxine. Thyroxine levels fluctuate with changes in the concentrations of carrier proteins (thyroxine-binding globulin and prealbumin), which readily vary depending on physiological states such as pregnancy, various diseases, and medication use. The interpretation of total thyroxine values depends on carrier protein concentration, which can be estimated from erythrocyte or resin triiodothyronine (T₃) uptake values (see below). It is the concentrations of free T₃ and T₄ that determine hormonal activity.

C. Interpretation

1. Elevated levels occur in hyperthyroidism (along with elevated thyroxine-binding protein) and occasionally in cases of acute thyroiditis or acromegaly.

2. Decreased levels occur in hypothyroidism (Primary and secondary) and with a drop in thyroxine-binding protein concentration.

Serum Free Thyroxine

Normal range (equilibrium dialysis): 0.8–2.4 ng% (SI: 0.01–0.03 nmol/L). It can be determined from total thyroxine and T₃ resin uptake data.

A. Precautions. None.

Б. Физиологическая основа. Метаболическая активность Т₄ зависит от концентрации свободного Т₄.Т₄, по-видимому, в периферических тканях превращается, в основном, в Т₃ (который также секретируется щитовидной железой). Т₃ и Т₄ являются активными гормонами.

B. Интерпретация

1. Повышение показателя имеет место при гипертиреозе, иногда при активном тиреоидите.

2. Снижение показателя имеет место при гипотиреозе.

Serum Thyroxine-Binding Globulin (TBG)

Normal range (radioimmunoassay): 2–4.8 mg%.

A. Precautions. None.

Б. Физиологическая основа. ТСГ — главный белок- носитель Т₃ и Т₄ в плазме. Колебания концентрации ТСГ сопровождаются соответствующими колебаниями концентрации Т₄, т. е. осуществляется регуляция, позволяющая поддерживать такой уровень физиологически активных свободных гормонов, который обеспечивает эутиреоидную функцию. Наследственные дефекты, детерминирующие аномальные концентрации ТСГ, сцеплены с Х-хромосомой.

B. Интерпретация

1. Повышение показателя имеет место при беременности, инфекционном гепатите, врожденном повышении уровня ТСГ.

2. Снижение показателя имеет место при заболеваниях, сопровождающихся снижением содержания белков (глобулина), нефротическом синдроме, циррозе печени, активной акромегалии, дефиците эстрогенов, врожденном дефиците ТСГ.

Serum Triiodothyronine (T₃) Binding, Thyroxine Resin Uptake (TRU) Test, or Thyroxine-Binding Globulin Capacity (TBG Estimate)

Normal: TRU, expressed as the percentage of ¹²⁵I-T₃ uptake by an ion-exchange resin, is 25–36%; the TRU ratio (TBG estimate) is calculated as The ratio of ¹²⁵I-T₃ resin uptake in the test serum to that of a pooled normal serum: 0.85–1.15.

A. Precautions. None.

Б. Физиологическая основа. Если уровень тироксин-связывающих белков в сыворотке нормальный, то при гипертиреозе типа Т₄ большая часть ТСГ-связывающих сайтов будет занята Т₄, а при гипотереозе — сравнительно меньшая часть. Т₃, меченный ¹²⁵I и добавленный к сыворотке вместе со связывающим веществом (ионообменная смола, древесный уголь, тальк и т. д.), распределяется между ним и ТСГ. Затем связывающее вещество выделяют из сыворотки и определяют его радиоактивность (тест СТ₃С). Поскольку смола захватывает не связанный с ТСГ радиоактивный Т₃, её активность меняется в обратной зависимости от числа свободных сайтов на ТСГ, т. е. СТ₃С повышается, если ТСГ насыщен Т₄, и понижается, если насыщение ТСГ невелико.

B. Интерпретация

1. СТ₃С и СТ3С-отношение повышаются, когда число свободных сайтов связывания снижено, как при гипертиреозе, акромегалии, нефротическом синдроме, тяжелом циррозе печени, наследственном дефиците ТСГ.

2. СТ₃С и Т₃С-отношение снижаются, когда число свободных сайтов связывания увеличено, как при гипотиреозе, беременности, у новорожденных, инфекционном гепатите, наследственном повышении ТСГ.

Transaminases

See under "Aminotransferases" above

Serum Triglycerides

Normal range: less than 165 mg% (SI: 1.65 g/L) (see also Table App. 1).

A. Precautions. The test should be performed on an empty stomach (ideally after at least 16 hours of fasting). If serum is separated from the clot and frozen, the assay can be delayed.

B. Physiological basis. Dietary fat is hydrolyzed in the Small Intestine, and its breakdown products are absorbed. Subsequently, triglycerides are resynthesized within mucosal cells and secreted into the lacteals as chylomicrons. Chylomicron triglycerides are hydrolyzed by lipoprotein lipase (primarily in adipose tissue); the resulting products are absorbed and stored. Free Fatty acids, derived mainly from adipose tissue, serve as precursors for endogenous triglycerides synthesized in the liver. Endogenous triglycerides are transported along with β-Lipoproteins and very-low-density lipoproteins. For accurate determination of endogenous triglycerides, the sample must be drawn in the postabsorptive state.

C. Interpretation. The concentrations of triglycerides, cholesterol, and lipoprotein fractions (very-low-density, low-density, and high-density) are evaluated together. Alterations in the ratios of these lipid components can be primary or secondary.

1. Increased values — hyperlipoproteinemia:

a) primary — type I hyperlipoproteinemia (exogenous hyperlipidemia), type II hyperbetalipoproteinemia, type III "broad-beta" disease, type IV hyperlipoproteinemia (endogenous hyperlipidemia), and type V hyperlipoproteinemia (mixed hyperlipidemia);

b) secondary — hypothyroidism, diabetes mellitus, nephrotic syndrome, chronic alcoholism with fatty liver infiltration, contraceptive steroid therapy, bile duct obstruction, and stress.

2. Decreased values — hypolipoproteinemia:

a) primary — Tangier disease (α-lipoprotein deficiency), abetalipoproteinemia, and several rare, difficult-to-diagnose syndromes;

b) secondary — malnutrition, malabsorption, and (occasionally) parenchymal liver disease.

Blood urea nitrogen (BUN) and urea in blood, plasma, and serum

Normal range: blood urea nitrogen — 8–25 mg% (SI: 2.9–8.9 mmol/L); urea — 21–53 mg% (SI: 3.5–9 mmol/L).

A. Precautions. Neither ammonium oxalate nor "double oxalate" should be used as anticoagulants, as ammonia will be measured concurrently with urea in this case.

B. Physiological basis. Urea, the end product of protein metabolism, is excreted by the kidneys. Its concentration in the glomerular filtrate is identical to that in plasma. Tubular reabsorption of urea varies inversely with urine flow rate. Therefore, urea excretion is a less reliable indicator of glomerular filtration than The excretion of creatinine, which is not reabsorbed. There is a direct correlation between blood urea nitrogen and protein intake, and an inverse correlation between The rate of urea excretion and blood urea nitrogen.

C. Interpretation.

1. Elevated levels occur in:

a) renal failure — acute and chronic nephritis, acute tubular necrosis, and urinary tract obstruction;

b) enhanced Nitrogen metabolism accompanied by reduced renal blood flow or impaired renal function — dehydration of any etiology, as well as upper gastrointestinal bleeding (resulting from the combination of increased intestinal absorption of blood proteins and reduced renal blood flow);

c) decreased renal blood flow — shock, adrenocortical insufficiency, and occasionally congestive heart failure.

2. Decreased levels occur in hepatic failure, nephrosis (uncomplicated by renal failure), and cachexia.

Serum and plasma uric acid

Normal range: males — 3–9 mg% (SI: 0.18–0.53 mmol/L); females — 2.5–7.5 mg% (SI: 0.15–0.45 mmol/L).

A. Precautions. Lithium oxalate should be used as the anticoagulant when analyzing plasma; potassium oxalate may distort the results.

B. Physiological basis. Uric acid, the end product of nucleoprotein metabolism, is excreted by the kidneys. Gout, an inherited metabolic disorder, is characterized by elevated plasma and serum uric acid concentrations, an increase in total body uric acid, and tissue deposition of uric acid. Elevated plasma or serum uric acid levels may accompany accelerated nucleoprotein catabolism (hematologic disorders, antileukemic therapy); uric acid levels also rise during thiazide diuretic therapy and when renal excretion is impaired.

C. Interpretation

1. Elevated levels occur in gout, Preeclampsia, Eclampsia, leukemia, polycythemia, treatment with antileukemic and many other drugs, renal failure, Glycogen storage disease (type I), Lesch—Nyhan syndrome (X-linked hypoxanthine-guanine phosphoribosyltransferase deficiency), and Down syndrome. High blood uric acid levels are characteristic of the Filipino population.

2. Decreased levels occur in acute hepatitis (occasionally), and during treatment with allopurinol or probenecid.

Urine Uric Acid

Normal range: 350–600 mg/24 h on a standard purine-free diet (SI: 2.1–3.6 mmol/24 h). The urinary uric acid-to-creatinine ratio is 0.21–0.59 for adults, with a maximum of 0.75 for a 24-hour urine collection on a purine-free diet.

A. Precautions. Exclude purine-rich foods from the diet prior to testing and throughout the 24-hour urine collection period. Strenuous physical activity may lead to increased urinary purine excretion.

B. Physiological basis. Elevated serum uric acid levels may result from either increased production or decreased excretion.

C. Interpretation.

1. Elevated levels occur in 25–30% of gout cases and are attributed to increased uric acid synthesis. Increased synthesis and excretion of uric acid are characteristic of myeloproliferative disorders. Lesch—Nyhan syndrome (hypoxanthine-guanine phosphoribosyltransferase deficiency) and Glycogen Storage Diseases may also present with uricosuria.

2. Decreased levels occur in renal failure, in certain cases of glycogen storage disease (type I), and in any metabolic disorder associated with elevated blood levels of uric acid or ß-hydroxybutyric acid. Salicylates in doses under 2–3 g per day can cause renal retention of uric acid.