Intrepretation of laboratory tests

Potassium K + • Measures serum potassium level – Majority of potassium is in cells intracellular, not in serum extracellular • Normal potassium value: 3.4 – 5.2 mmol/L • Critical potass

Intrepretation of Laboratory

Tests

Joseph S Bertino Jr., Pharm.D.

Bertino Consulting

Goals and Objectives

• Review common laboratory tests

– Chemistry

– Hematology

– Urinalysis

– Cerebral Spinal Fluid

– Microbiology and Serology

• Discuss how pharmacists can use information to assist in drug therapy

Specimen Types

• Serum: the fluid from blood after blood cells and clot are removed

• Plasma: fluid from blood centrifuged with anticoagulants

• Erythrocytes: red blood cells

• Leukocytes: white blood cells

• Urine: Random or “clean catch” (for microbiology)

• Feces

• Cerebral Spinal Fluid

• Joint Fluid

Normal values are specific to

a laboratory, I give general

normal ranges in this lecture

Chemistry

Sodium (Na + )

• Measures amount of serum sodium

– Major cation in the blood

– Balance depends on intake and renal excretion

• Normal: 136 – 146 mmol/L

• Critical values: < 120 or > 160 mmol/L

• ↑ Sodium (hypernatremia): ↑ Na+ intake, ↓ Na+ loss, Excessive free water loss

• ↓ Sodium (hyponatremia): ↓ Na+ intake, ↑ Na+ loss, ↑ free water intake

– If patient has low blood pressure use 0.9%

NaCl until BP is normal, then 0.45% NaCl IV

infusion

• Chronic hypernatremia

– Decrease serum sodium slowly (0.5 mmol/L

Use of 3% NaCl for Hyponatremia

• Choose desired correction rate of serum sodium (Example: correct at

Potassium (K + )

• Measures serum potassium level

– Majority of potassium is in cells

(intracellular), not in serum (extracellular)

• Normal potassium value: 3.4 – 5.2 mmol/L

• Critical potassium value: < 2.5 or > 6.5 mmol/L

• ↓ potassium (hypokalemia): insufficient K+ intake, burns, hyperaldosteronism,

Cushing syndrome, renal tubular acidosis, alkalosis, renal artery stenosis

– ↑ potassium (hyperkalemia): excessive K+ intake,

acidosis, acute/chronic renal failure, Addison

disease, hypoaldosteronism, infection,

dehydration

– if a specimen is hemolyzed (such as by traumatic venipuncture or drawing blood with a

needle that is too small) potassium value may be “falsely” high

– There are high concentrations of K in red blood

cells If RBCs are broken during phlebotomy, K is released into the serum resulting in elevated

measured K levels (falsely elevated)

Correction of Hypokalemia

• 1 mmol/L drop in K+ = 200-400 mmol K in body

• If K+ = 2.5-3.5 mmol/L with minor symptoms treat with oral potassium

• If K= < 2.5 mmol/L treat with IV potassium

• IV dose 10 mmol/hr, can also give oral K+ at the same time

• For higher amounts of K+ IV, need to use a central venous line

• Check Mg+2, if serum Mg+2 low, replace Mg also

Correction of Hyperkalemia

• Stop all potassium and diuretics that prevent renal excretion of potassium

• Insulin + glucose + sodium bicarbonate IV

• Furosemide IV

• Sodium polystyrene sulfonate by mouth to bind K+ in bowel (do not mix

with sorbitol)

• Inhaled beta 2 agonists (salbutamol 20 mg inhalation)

• Calcium IV to reduce cardiac effects

• Dialysis

Chloride (Cl - )

• Measures serum chloride level

– Major anion in extracellular space

– Helps maintain electrical neutrality;

Chloride follows sodium

• Normal: 98 – 108 mmol/L

• Critical: < 80 or > 115 mmol/L

• ↑ (Hyperchloremia): dehydration, metabolic acidosis, renal tubular acidosis,

Cushing syndrome, renal dysfunction, respiratory alkalosis,

hyperparathyroidism

• ↓ (Hypochloremia): overhydration, SIADH, CHF, chronic respiratory acidosis,

metabolic alkalosis, Addison disease, hyperaldosteronism,

vomiting/prolonged gastric suction, hypokalemia

Bicarbonate (HCO 3 - )

• Measures CO2 (carbon dioxide) content of blood

– Major anion important for acid-base balance

– Regulated by the kidneys

– Used to evaluate the pH status of patient

• Normal range: 22 – 32 mmol/L

• Critical range: < 6 mmol/L

• ↑ HCO3-: severe vomiting, high-volume gastric suction, hyperaldosteronism, COPD,

metabolic alkalosis

• ↓ HCO3-: chronic diarrhea, chronic loop diuretic use, renal failure, DKA, starvation,

metabolic acidosis, shock

Anion Gap (AG)

 The body must maintain equal numbers of cations (+) and anions(-)

 The AG measures the excess anions in the blood, a measure of excess acid

 AG = Na – Cl – HCO3 (normal AG =12 ± 2)

 AG corrected = AG + 2.5 [4 – albumin]

 If serum albumin is <4 correct AG

 Anion Gap indicates acidosis in a patient

• Direct measure of blood glucose

• Normal values: 3.8 – 6.7 mmol/L

• Critical: < 2.2 and > 22.2 mmol/L

• ↑ Glucose (hyperglycemia): Diabetes, acute stress response, Cushing syndrome,

pheochromocytoma, chronic renal failure, acute pancreatitis, acromegaly, corticosteroid

therapy

• ↓ Glucose (hypoglycemia): insulinoma, hypothyroidism, hypopituitarism, Addison disease, severe liver disease, insulin overdose, starvation

Diagnosing Diabetes

• The criteria for the diagnosis of diabetes:

– Fasting Plasma Glucose ≥7 mmol/L

– 2 hour Post-Prandial (eating) Glucose ≥11.1 mmol/L

– Random Plasma Glucose >11.1 mmol/L in the presence of

symptoms (increase urine, thirst, hunger)

– Any one of these tests should be repeated to confirm diagnosis

Blood Urea Nitrogen (BUN)

• Measures urea nitrogen in blood

– Urea nitrogen is end product of protein metabolism

(produced in liver)

– BUN is an indirect measure of renal function

– BUN is a poor measure of liver function

– BUN is usually interpreted along with serum creatinine (less

accurate than creatinine for measuring renal disease)

• Normal: 2.1 -7.5 mmol/L

• Critical: > 35.7 mmol/L

• ↑ BUN: prerenal causes (dehydration or drugs), renal disease

• ↓ BUN: liver failure, overhydration due to SIADH, pregnancy, nephrotic syndrome

Creatinine (Cr)

• Measures serum creatinine

– Catabolic product of creatine phosphate (from skeletal

muscle)

– Creatinine is excreted entirely by kidneys → direct measure

of renal function

– Minimally affected by liver function

– Elevation of creatinine occurs slower than BUN

• Normal Values: 35 – 106 umol/L

• ↑ Cr: diseases affecting renal function, rhabdomyolysis, acromegaly

• ↓ Cr: decreased muscle mass, corticosteroids

Calcium

• The total serum calcium is a measure of the total of:

– Free (ionized) calcium

– Protein bound (bound to albumin) calcium

• Therefore, the total serum calcium level is affected by changes in serum

albumin

– The total serum calcium level decreases by

approximately 0.2 mmol/L for every 1gram

decrease in the serum albumin level.

Calcium (Ca 2+ )

• Normal Values:

– Total Ca= 2.1 – 2.6 mmol/L

– Ionized Ca = 1.12 – 1.4 mmol/L

• Critical Values: Total Ca< 1.5 or > 3.25 mmol/L, Ionized Ca < 0.55 or > 1.75 mmol/L

• ↑ Ca (hypercalcemia): hyperparathyroidism, bone cancer, Paget disease of bone, prolonged

immobilization, milk-alkali syndrome, vitamin D intoxication, hyperthyroidism

• ↓ Ca (hypocalcemia): hypoparathyroidism, renal failure, rickets, vitamin D deficiency,

osteomalacia, pancreatitis, alkalosis, malabsorption, fat embolism, hypomagnesemia

Treatment of Calcium Disorders

• Hypercalcemia:

– Restrict calcium intake

– Restrict vitamin D intake

– IV fluids and diuretics (if severe)

• Hypocalcemia:

– Oral calcium if mild

– IV calcium if severe (tetany), 100-200 mg IV calcium gluconate

infused over 5-10 minutes

Serum Phosphorus

• Normal values: 0.97-1.45 mmol/L

• Serum phoshorus is a poor reflection of body stores because <1% is in serum

(extracellular fluid)

• Bones serve as a reservoir

Hypophosphatemia (<0.97

mmol/L): Causes

• Impaired absorption (diarrhea, Vitamin D deficiency, impaired metabolism)

• Medications: phosphate binding antacids [calcium and aluminum], sucralfate,

insulin, corticosteroids)

• Alcoholism, especially during alcohol withdrawal

• Intracellular shifts in alkalosis

• Refeeding syndrome in malnourished patients

• Increased body loss: hyperparathyroidism, renal tubular defects, DKA recovery,

hypomagnesemia, diuretic phase of acute tubular necrosis

Hypophosphatemia Treatment

• Administer 32-64 mmol/day of phosphate for 7-10 days to replenish body

• Give 1-3 mmol/hr phosphate intravenous infusion

• If using faster infusions, recheck serum phosphorus every 6 hours for first 24 hours

Hypophosphatemia Treatment

• Severe (<0.3 mmol/L): Give 0.08-0.16 mmol/kg IV, infuse over 2-6 hours

• Moderate, patient mechanically ventilated (0.3-0.8 mmol/L): Give 0.08-0.16 mmol/kg IV,

infused over 2-6 hours

• Moderate (no mechanical ventilation): Use oral therapy 1000 mg/day

• Mild: Use oral therapy 1000 mg/day

Hyperphosphatemia Causes (>1.45 mmol/L)

• Decreased renal excretion: acute or chronic renal failure (GFR<20-25 mL/min); hypoparathyroidism

• Increased cellular release: tissue necrosis, tumor lysis syndrome

• Increased exogenous phosphorus load or absorption, phosphorus containing laxatives or enemas, vitamin D excess

• Acidosis

Treatment of Hyperphosphatemia

• Reduce phosphorus in diet

• Stop phosphate containing drugs

• Calcium containing phosphorus binders (calcium acetate, citrate, chloride)

Magnesium (Mg)

• Normal values: 0.65-1.05 mmol/L

• Hypermagnesemia: Renal failure, excessive Mg intake (Mg is used in high

doses in pregnant women with eclampsia)

• Hypomagnesemia: Diarrhea, renal loss, alcoholism, refeeding syndrome in

malnutrition, vomiting, gastric suction, diabetes with glucosuria

Treatment of Magnesium Disorders

• Hypomagnesemia:

– Check serum calcium

– Check serum potassium

– Infuse 25 mmol magnesium IV in 8-24 hours once a day for 3-5

• Formed within liver and is 60% of total protein in blood

• Maintains colloidal osmotic pressure and transports blood constituents

• Measure of both hepatic function and nutritional state

• Normal Values: 3.5 – 5 g/dL

• ↑ albumin: dehydration

• ↓ albumin: malnutrition, pregnancy, liver disease, protein-losing from kidney and bowel, 3rd

space losses (ascites), overhydration, ↑ capillary permeability, trauma

Total Protein

• Measures total protein in blood

– Combination of albumin, other proteins and immunoglobulins

• Normal: 6.4 – 8.3 g/dL

Alkaline Phosphatase (ALP)

• ALP used to monitor liver and bone disease

• Normal Values: 30 -120 units/L

• ↑ALP: Primary cirrhosis, intrahepatic/extrahepatic biliary obstruction, Primary or metastatic liver tumor, hyperparathyroidism, Paget disease, metastatic cancer of

bones, rheumatoid arthritis, myocardial infarction

• ↓ALP: hypophosphatemia, malnutrition, milk-alkali syndrome, pernicious

anemia, scurvy

Alanine Aminotransferase (ALT)

• Found predominantly in liver

– Injury/disease to liver cells → ALT released into blood

• Normal: 4 – 36 international units/L

•

• HIgh ↑ ALT: hepatitis, hepatic necrosis, hepatic ischemia

• Mod ↑ ALT: cirrhosis, cholestasis, hepatic tumor, hepatotoxic drugs, obstructive jaundice, severe

burns, trauma to striated muscle

• Mild ↑ ALT: myositis, pancreatitis, mycardial infarction, infectious mononucleosis, shock

Aspartate Aminotransferase (AST)

• Found in cardiac & skeletal muscle, liver cells

– Disease/injury → cells break & release AST into

blood

• Normal: 0 – 35 units/L

• ↑AST: heart diseases, liver diseases, skeletal muscle diseases

• ↓ AST: acute renal disease, pregnancy, chronic renal dialysis

Gamma Glutamyl Transferase (GGT)

• Released from liver cells

• Used with ALP to determine if disease is liver or bone disease

• Normal values are dependent on sex

– Females > 1 year of age: 6-29 U/L

– Males: Range changes from age 1 to age 56, average range 12-48

u/L

• GGT elevated with alcohol use, phenytoin, carbamazepine, barbiturates

• End product of RBC, made in the liver

– Bilirubin is measured as unconjugated (indirect) and

conjugated (direct)

• Bilirubin is found in bile

• Used to evaluate liver function; hemolytic anemia in adults & jaundice in newborns

• Normal Values: 5.13–17.1 umol/L

• Jaundice occurs when total bilirubin > 43 umol/L

• Critical Value: > 205 umol/L

Hematology

Centrifuged blood (normal)

Red blood cells

Buffy coat (WBCs and Platelets) Plasma

Normal hematocrit in adult males

40-54%

Normal hematocrit in adult females

34-51%

Complete Blood Count (CBC)

• Provides information on cellular components of blood

• Includes red blood cell (RBC) count, Hemoglobin (Hgb), Hematocrit (Hct), RBC indices,

White blood cell (WBC) count and differential, Platelet count

Total WBCs (leukocytes)

• Measurement of total WBC count

– Consists of total # of WBCs/mm3 of peripheral venous blood

– Useful for evaluation of infection, tumor, allergy &

• ↓ WBC (leukopenia): drug toxicity, bone marrow failure, severe infection, congenital bone marrow

aplasia, bone marrow tumor, autoimmune disease, hypersplenism

Left Shift of Neutrophils

Less Mature More Mature

Erythrocyte count (Red Blood

• ↓ RBC: anemia, hemoglobinopathy, hemorrhage, bone marrow failure, renal disease, leukemia,

prosthetic heart valves, normal pregnancy, multiple myeloma, Hodgkins disease, lymphoma

Hemoglobin (Hgb)

• Measures total amount of Hgb in blood Hgb carries oxygen

• Normal Values: 12 – 15 g/dL

• Critical: < 5 or > 20 g/dL

Hematocrit (Hct)

• Measure of RBC percent of total blood volume

• Normal Values: 36 – 48%

• Critical Values: < 15% or > 60%

RBC indices

• Measures size and Hgb content of RBCs

• Used to classify anemia

• RBC indices includes:

– Mean corpuscular volume (MCV)

– Mean corpuscular hemoglobin (MCH)

– Mean corpuscular hemoglobin

concentration (MCHC)

– Red blood cell distribution width (RDW)

Mean Corpuscular Volume (MCV)

• Measure of average volume/size of a single RBC

• Normal Value: 80 – 100 femtoliters/cell

• ↑MCV (macrocytic anemia): pernicious anemia (vitamin B12 deficiency), folic acid

deficiency, alcoholism, chronic liver disease, hypothyroidism

• Normocytic Anemia (normal MCV): bone marrow failure/replacement, acute blood loss,

chronic disease, hemolytic anemia

• ↓MCV (microcytic anemia): Iron deficiency anemia, thalassemia, anemia of chronic illness

Macrocytic Red blood cells

Mean Corpuscular Hemoglobin (MCH)

• Measure of average amount of hemoglobin within a single RBC

– MCH = Hgb (g/dL) x 10/RBC (million/mm3)

– Provides little additional information compared to other indices

• Normal Value: 24 – 32 picograms/RBC

• ↑ MCH: macrocytic anemia

• ↓ MCH: microcytic anemia, hypochromic anemia

Mean Corpuscular Hemoblobin

Red Cell Distribution Width (RDW)

• Measure of variation of RBC size

– Useful in anemia classification

• Normal Value: variation of 11.5 – 16.9%

• ↑ RDW: Iron deficiency anemia, vitamin B12 or folate deficiency anemia,

hemoglobinopathies, hemolytic anemias, post hemorrhagic anemia

Platelet Count

• Measurement of number of platelets (thrombocytes)

– Used for evaluation of petechiae, spontaneous bleeding,

increasingly heavy menses or thrombocytopenia

– Used for monitoring the progression or the therapy of

thrombocytopenia/bone marrow failure

• Normal platelet count: 150,000 – 400,000/mm3

• Critical: < 50,000 or > 1,000,000/mm3

• ↑ Platelet count (thrombocytosis): malignant disorders, polycythemia vera, postsplenectomy syndrome,

rheumatoid arthritis, iron deficiency anemia

• ↓ Platelet count (thrombocytopenia): Hypersplenism, hemorrhage, immune thrombocytopenia, leukemia,

bone marrow failure, sepsis, lupus erythematosus, chemotherapy, pernicious anemia (vitamin B12

deficiency)