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PCP 301
Clinical interpretation of laboratory data
Pharm Wesley E. Hedima
Department of Clinical Pharmacy and Pharmacy Practice, Gombe State
University
1
Introduction
Laboratory tests are performed for multiple purposes, including
to:
• Discover a disease,
• Confirm or differentiate a diagnosis,
• Stage or classify a disease, and
• Monitor effectiveness of therapy.
2
Introduction
Laboratory tests are classified as screening or diagnostic.
• Screening tests are used in patients with no signs or symptoms of a disease (e.g., serum
cholesterol for assessing cardiovascular disease risk).
• Diagnostic tests are done in patients with signs and symptoms of disease or with an abnormal
screening test.
3
Intro cont’d
Pharmacists usually monitor laboratory tests to:
a. Assess the therapeutic and adverse effects of a drug (e.g., monitoring the serum uric
acid level after allopurinol is administered, checking for increased liver function test values
after administration of isoniazid)
b. Determine the proper drug dose (e.g., assessment of the serum creatinine or
creatinine clearance value before use of a renally excreted drug)
c. Assess the need for additional or alternate drug therapy (e.g., assessment of white
blood cell count after an antibiotic is administered)
d. Prevent test misinterpretation resulting from drug interference (e.g., determination
of a false-positive result for a urine glucose test after cephalosporin administration)
4
Introduction cont’d
• These tests can be expensive, and requests for them must be balanced
against potential benefits for patients and how the laboratory test will affect
your decision regarding therapy.
5
Definition of normal values
a. Normal limits may be defined somewhat arbitrarily; thus, values outside the normal range may
not necessarily indicate disease or the need for treatment (e.g., asymptomatic hyperuricemia).
b. Many factors (e.g., age, sex, time since last meal) must be taken into account when evaluating test
results.
c. Normal values also vary among institutions and may depend on the method used to perform the
test.
d. The goal is not to make all laboratory values normal; resist urges to do something in a clinically
stable patient.
e. Laboratory error must always be considered when test results do not correlate with expected
results for a given patient. If necessary, the test should be repeated.
f. Common sources of laboratory error include spoiled specimens, incomplete specimens, specimens
taken at the wrong time, faulty reagents, technical errors, incorrect procedures, and failure to take diet
or medication into account. 6
Types of test
1. Tests with normal values reported in ranges (i.e., 3.5 to 5.0 mEq/L) are called quantitative.
2. Tests with positive (+) or negative (-) outcomes are called qualitative.
3. Those with varying degrees of positivity (e.g., 1_, 2_, 3_ glucose in the urine) are termed
semiquantitative
accuracy (accuracy is defi ned as the extent to which the mean measurement is close to the true
value). Precision refers to the reproducibility of the assay.
7
HEMATOLOGICAL TESTS
• Blood contains three types of formed elements:
• red blood cells (RBCs),
• white blood cells (WBCs), and platelets.
• A CBC typically includes RBC count, total WBC count, hemoglobin (Hb), hematocrit (Hct), RBC
indices (mean cell volume [MCV], mean cell Hb [MCH], mean cell Hb concentration [MCHC]),
reticulocyte count, and platelet count.
8
A. RBCs (erythrocytes)
1. The RBC count, which reports the number of RBCs found in a given volume of blood, provides an
indirect estimate of the blood’s Hb content. Values are often reported in cells/microliter (µL) or
cells/liter and less commonly as cells/cubic millimeter (mm3).
Normal values are
• a. 4.3 to 5.9 × 1012 cells/L of blood for men
• b. 3.5 to 5.0 × 1012 cells/L of blood for women
2. The Hct or packed cell volume (PCV) measures the percentage by volume of packed RBCs in a
whole blood sample after centrifugation. The Hct value is usually three times the Hb value and is given
as a percent or fraction of 1 (42% to 52% or 0.42 to 0.52 for men; 37% to 47% or 0.37 to 0.47 for
women).
• a. Low Hct values indicate such conditions as anemia, overhydration, or blood loss.
• b. High Hct values indicate such conditions as polycythemia vera or dehydration.
HEMATOLOGICAL TESTS
9
HEMATOLOGICAL TESTS
3. The Hb test measures the grams of Hb contained in 100 mL (1 dL) or 1 L of whole blood and
provides an estimate of the oxygen-carrying capacity of the RBCs. Th e Hb value depends on the
• number of RBCs and the amount of Hb in each RBC.
• a. Normal values are 14 to 18 g/dL for men and 12 to 16 g/dL for women.
• b. Low Hb values indicate anemia.
4. RBC indices provide important information regarding RBC size, Hb concentration, and Hb weight.
They are used primarily to categorize anemias.
• Observations of a smear may show variation in RBC shape (poikilocytosis), as might occur in
sickle-cell anemia, or it may show a variation in RBC size (anisocytosis), as might occur in a mixed
anemia (folic acid and iron deficiency).
10
HEMATOLOGICAL TESTS
a. MCV is the ratio of the Hct to the RBC count. It essentially assesses average RBC size and reflects
any anisocytosis.
MCV =
Hct % ×10
RBC (Millions)
• (1) Low MCV indicates microcytic (undersize) RBCs, as occurs in iron deficiency.
• (2) High MCV indicates macrocytic (oversize) RBCs, as occurs in a vitamin B12 or folic acid
deficiency.
• (3) Normal range for MCV is 90 _+ 10.
b. Mean cell hemoglobin (MCH) assesses the amount of Hb in an average RBC.
• (1) MCH is defined as:
• MCH =
Hb ×10
RBC (Millions)
• (2) Normal range for MCH is 30 _ +4.
11
HEMATOLOGICAL TESTS
c. Mean cell hemoglobin concentration (MCHC) represents the average concentration of Hb in an
average RBC, defined as:
MCHC =
Hb ×100
Hct
• (1) Normal range for MCHC is 34 _ +3.
• (2) Low MCHC indicates hypochromia (pale RBCs resulting from decreased Hb content), as
occurs in iron deficiency.
• 5. The reticulocyte count provides a measure of immature RBCs (reticulocytes), Hence, this test
provides an index of bone marrow production of mature RBCs.
• a. Increased reticulocyte count occurs with such conditions as hemolytic anemia, acute blood
loss, and response to the treatment of a factor deficiency (e.g., an iron, vitamin B12, or folate
deficiency).
• b. Decreased reticulocyte count occurs with such conditions as drug-induced aplastic anemia.
12
HEMATOLOGICAL TESTS
• 6. The erythrocyte sedimentation rate (ESR) measures the rate of RBC settling of whole,
uncoagulated blood over time, and it primarily reflects plasma composition.
• a. Normal ESR rates range from 0 to 20 mm/hr for males and from 0 to 30 mm/hr for females.
• b. ESR values increase with acute or chronic infection, tissue necrosis or infarction, well
established malignancy, and rheumatoid collagen diseases.
• c. ESR values are used to
• (1) Follow the clinical course of a disease
• (2) Demonstrate the presence of occult organic disease
• (3) Differentiate conditions with similar symptomatology—for example, angina pectoris (no change
in ESR value) as opposed to a myocardial infarction (increase in ESR value)
13
HEMATOLOGICAL TESTS
• WBC Count
1. The WBC count reports the number of leukocytes in a given volume of whole blood.
a. Normal values range from 4,000 to 11,000 _ 103 cells/mm3 (or 109 cells/L)
b. Increased WBC count (leukocytosis) usually signals infection; it may also result from leukemia, tissue
necrosis, or administration of corticosteroids. It is most often found with bacterial infection.
c. Decreased WBC count (leukopenia) indicates bone marrow depression, which may result from metastatic
carcinoma, lymphoma, or toxic reactions to substances such as antineoplastic agents (anticancer agents).
2. The WBC differential evaluates the distribution and morphology of the five major types of WBCs: the
granulocytes (neutrophils, basophils, eosinophils) and the non-granulocytes (lymphocytes, monocytes).
A certain percentage of each type makes up the total WBC count.
• a. Neutrophils may be mature or immature. Mature neutrophils are polymorphonuclear leukocytes (PMNs),
also referred to as polys. A systemic bacterial infection, such as pneumonia can cause an increase in
neutrophils.
14
HEMATOLOGICAL TESTS
• Neutropenia, a decreased number of neutrophils, may occur with an overwhelming infection of any
type (bone marrow is unable to keep up with the demand). It may also occur with certain viral infections
(e.g., mumps, measles), with idiosyncratic drug reactions, and as a result of chemotherapy.
• Neutropenia is defined as an absolute neutrophil count (ANC) of < 1000 cells/mm3.
b. Basophils stain deeply with blue basic dye. Their function in the circulation is not clearly
• understood; in the tissues, they are referred to as mast cells.
• (1) Basophilia, an increased number of basophils, may occur with chronic myelogenous leukemia (CML)
as well as other conditions.
• (2) A decrease in basophils is generally not apparent because of the small numbers of these cells in the
blood.
15
c. Eosinophils stain deep red with acid dye and are classically associated with immune reactions.
• Eosinophilia, an increased number of eosinophils, may occur with such conditions as acute
allergic reactions (e.g., asthma, hay fever, drug allergy) and parasitic infestations (e.g.,
trichinosis, amebiasis).
• d. Lymphocytes play a dominant role in immunological activity and appear to produce antibodies.
They are classified as B lymphocytes or T lymphocytes; T lymphocytes are further divided into helper-
inducer cells (CD 4 T cells) and suppressor (cytotoxic) cells (CD 8 T cells).
• (1) Lymphocytosis, an increased number of lymphocytes, usually accompanies a normal or
decreased total WBC count and is most commonly caused by viral infection.
• 2) Lymphopenia, a decreased number of lymphocytes, may result from severe debilitating
• illness, immunodeficiency, or from AIDS, which has a propensity to attack TH4 cells.
HEMATOLOGICAL TESTS
16
HEMATOLOGICAL TESTS
e. Monocytes are phagocytic cells. Monocytosis, an increased number of monocytes, may occur with
tuberculosis (TB), subacute bacterial endocarditis, and during the recovery phase of some acute
infections.
C. Platelets (thrombocytes). These are the smallest formed elements in the blood, and they are involved in
blood clotting and vital to the formation of a hemostatic plug after vascular injury.
• 1. Normal values for a platelet count are 150,000 to 300,000/mm3 (1.5 to 3.0 _ 1011/L).
• 2. Thrombocytopenia, a decreased platelet count, can occur with a variety of conditions, such as
idiopathic thrombocytopenic purpura or, occasionally, from such drugs as quinidine and sulfonamides.
17
COMMON SERUM ENZYME TESTS.
• Small amounts of enzymes (catalysts) circulate in the blood at all times and are released into the
blood in larger quantities when tissue damage occurs. Thus, serum enzyme levels can be used to aid
in the diagnosis of certain diseases.
A. Creatine kinase (CK)
• 1. Creatine kinase—formerly known as creatine phosphokinase (CPK)—is found primarily in heart
• muscle, skeletal muscle, and brain tissue.
• 2. CK levels are used primarily to aid in the diagnosis of acute myocardial or skeletal muscle
damage. However, vigorous exercise, a fall, or deep intramuscular injections can cause
• significant increases in CK levels.
• 3. The isoenzymes of CK—CK-MM, found in skeletal muscle; CK-BB, found in brain tissue; and
• CK-MB, found in heart muscle—can be used to differentiate the source of damage. Increase in CK-
MB levels provides a sensitive indicator of myocardial necrosis.
18
COMMON SERUM ENZYME TESTS.
B. Lactate dehydrogenase (LDH)
Five individual isoenzymes make up the total LDH serum level.
• a. LDH1 and LDH2 appear primarily in the heart.
• b. LDH3 appears primarily in the lungs.
• c. LDH4 and LDH5 appear primarily in the liver and skeletal muscles.
C. Alkaline phosphatase (ALP)
• 1. ALP is produced primarily in the liver and bones.
• 2. Increased osteoblastic activity, as occurs in Paget disease, hyperparathyroidism,
osteomalacia,
• and others, also increases serum ALP levels.
19
COMMON SERUM ENZYME TESTS.
• D. Aspartate aminotransferase (AST)
• 1. Aspartate aminotransferase—formerly known as serum glutamic-oxaloacetic transaminase
(SGOT)—is found in a number of organs, primarily in heart and liver tissues.
• 2. Damage to the heart (e.g., from myocardial infarction) results in increased AST levels about 8
hrs aft er injury.
• Levels are also increased with passive congestion of the liver, such as occurs in congestive
heart failure (CHF).
20
COMMON SERUM ENZYME TESTS.
• E. Alanine aminotransferase (ALT)
• 1. Alanine aminotransferase—formerly known as serum glutamic-pyruvic transaminase
(SGPT)
—is found in the liver, with lesser amounts in the heart, skeletal muscles, and kidney.
• 2. Although ALT values are relatively specific for liver cell damage, ALT is less sensitive
than AST, and extensive or severe liver damage is necessary before abnormally increased
levels are produced.
• 3. ALT also increases less consistently and less markedly than AST after an acute
myocardial infarction.
21
COMMON SERUM ENZYME TESTS.
F. Cardiac troponins (I, T, and C)
• 1. Troponins assist in the diagnosis of acute myocardial infarction. These troponins may possess
superior specificity in situations in which false-positive elevations of CK-MB are likely.
• 2. Troponin T is found in cardiac and skeletal muscle, troponin I is found only in cardiac muscle, and
troponin C is present in two isoforms found in skeletal and cardiac muscle. Troponin T has shown
prognostic value in unstable angina and in detecting minor myocardial cell injury with greater
sensitivity than CK-MB.
• 3. The normal value for troponin T is < 0.1 ng/mL and I is <1.5 ng/mL.
22
LIVER FUNCTION TESTS
A. Liver enzymes
• 1. Levels of certain enzymes (e.g., LDH, ALP, AST, ALT) increase with liver dysfunction.
• 2. These enzyme tests indicate only that the liver has been damaged. They do not assess the
liver’s ability to function. Other tests provide indications of liver dysfunction.
B. Serum bilirubin
1. Bilirubin, a breakdown product of Hb, is the predominant pigment in bile. Effective bilirubin
conjugation and excretion depend on hepatobiliary function and on the rate of RBC turnover.
2. Serum bilirubin levels are reported as total bilirubin (conjugated and unconjugated) and as direct
bilirubin (conjugated only).
a. Bilirubin is released by Hb breakdown and is bound to albumin as water-insoluble indirect
bilirubin (unconjugated bilirubin), which is not filtered by the glomerulus.
23
LIVER FUNCTION TESTS
b. Unconjugated bilirubin travels to the liver, where it is separated from albumin, conjugated
• with diglucuronide, and then actively secreted into the bile as conjugated bilirubin (direct
• bilirubin), which is filtered by the glomerulus.
• 3. Normal values of total serum bilirubin are 0.1 to 1.0 mg/dL (2 to 18 mmol/L); of direct
bilirubin,
• 0.0 to 0.2 mg/dL (0 to 4 mmol/L).
• An increase in serum bilirubin results in jaundice from bilirubin deposition in the tissues. There
• are three major causes of increased serum bilirubin; Hemolysis, biliary obstruction, liver cell
necrosis.
24
LIVER FUNCTION TESTS
• C. Serum proteins
• 1. Primary serum proteins measured are albumin and the globulins (i.e.,α , β, γ ).
• a. Albumin (4 to 6 g/dL) maintains serum oncotic pressure and serves as a transport agent. Because it
is primarily manufactured by the liver, liver disease can decrease albumin levels. Albumin can also be used
to assess nutritional status.
• b. Globulin (23 to 35 g/L) relates to the total measurement of immunoglobins (antibodies) found in the
serum and function as transport agents and play a role in certain immunological mechanisms.
25
URINALYSIS
• Composed of chemical and microscopic tests of the urine used to provide basic information
regarding renal function, urinary tract disease, and the presence of certain systemic diseases.
Components of a standard urinalysis include:
• physical (color, turbidity, odor, specifi c gravity, and osmolality),
• chemical (pH, Hb, glucose, protein, glucose, ketone, leukocyte esterase, nitrites, bilirubin) and
• microscopic examination (RBC, WBC, epithelial cells, casts, bacteria).
A. Appearance. Normal urine is clear and ranges in color from pale yellow to deep gold. Changes
in color can result from drugs, diet, or disease.
1. A red color may indicate, among other things, the presence of blood.
2. A brownish yellow color may indicate the presence of conjugated bilirubin.
3. Other shades of red, orange, or brown may be caused by ingestion of various drugs (e.g.,
rifampin).
26
URINALYSIS
B. pH
• 1. Normal pH ranges from 4.5 to 9.0 but is typically acidic (around 6.0).
• 2. Alkaline pH may indicate such conditions as alkalosis.
C. Specific gravity
• Specific gravity provides a rough measure of urine concentration (osmolality). Normal range is 1.001 to
1.035; values may be low in the elderly or in patients with impaired renal function, who are less able to
concentrate urine.
• It is measured by hydrometer or refractometer or estimated with a dipstick. the test may be sufficient for
patients who have calculi and are advised to self-monitor urine concentration to maintain dilute urine.
27
URINALYSIS
D. Protein
• Under normal conditions, plasma proteins remain in the glomerular capillaries and thus do not cross the
glomerular basement membrane or enter the urinary space.
• Some of these proteins, such as albumin and globulins are not filtered by the glomerulus as a result of
charge and size selectivity (greater than 40 kDa) detected by standard dipstick tests, reflects mainly urinary
albumin concentration, classified as negative (< 10 mg/dL), trace (15 to 30 mg/dL), or 1+ (30 to 100 mg/dL)
through 4+ (> 500 mg/dL).
E. Glucose
• Glucose is usually not present in the urine because the kidney normally completely reabsorbs all the glucose
filtered at the glomerulus. When a patient’s blood glucose concentration exceeds the maximum threshold for
glucose reabsorption (~180 mg/dL [~10.0 mmol/L]), glucosuria will be present.
• Routine assessment of glucosuria to monitor diabetics has been replaced by newer methods of direct blood
glucose measurements. Urine glucose testing is now predominantly used as a screening tool for the detection of
diabetes.
28
URINALYSIS
F. Ketones
• Acetoacetate and acetone are not normally found in the urine; they are however excreted in
patients with diabetic ketoacidosis. They are also present under conditions of fasting or starvation.
• Typically, values of acetoacetate excretion are reported as small (less than 20 mg/dL [less than 2
mmol/L]), moderate (30-40 mg/dL [3-4 mmol/L]), and large (greater than 80 mg/dL [greater than 8
mmol/L]).
29
URINALYSIS
G. Evaluation. Microscopic examination: of centrifuged urine sediment normally reveals 0 to 1 RBC,
• 0 to 4 WBCs, and only an occasional cast per high-power field (HPF).
1. Hematuria (i.e., the presence of RBCs) may indicate such conditions as trauma, a tumor, or a systemic
bleeding disorder. In women, a significant number of squamous cells suggests vaginal contamination
(menstruation).
2. Casts (i.e., protein conglomerations outlining the shape of the renal tubules in which they were formed)
may or may not be significant. Excessive numbers of certain types of casts indicate renal disease.
3. Crystals, which are pH dependent, may occur normally in acid or alkaline urine. Uric acid crystals may
form in acid urine; phosphate crystals may form in alkaline urine.
4. Bacteria do not normally appear in urine. The finding of 50 or more bacteria per HPF may indicate a
urinary tract infection (UTI); smaller values may indicate urethral contamination.
30
COMMON RENAL FUNCTION TESTS
A. Introduction
• 1. Renal function may be assessed by measuring blood urea nitrogen (BUN) and serum
creatinine.
• Renal function decreases with age, which must be taken into account when interpreting test values.
• a. These tests primarily evaluate glomerular function by assessing the glomerular filtrationrate
(GFR).
• b. In many renal diseases, urea and creatinine accumulate in the blood because they are not
excreted properly.
• c. These tests also aid in determining drug dosage for drugs excreted through the kidneys.
31
COMMON RENAL FUNCTION TESTS
B. BUN
• 1. Urea, an end product of protein metabolism, is produced in the liver. From there, it travels through the
blood and is excreted by the kidneys.
• 2. Normal values for BUN range from 8 mg/dL to 18 mg/dL (3.0 to 6.5 mmol/L).
• a. Decreased BUN levels occur with significant liver disease.
• b. Increased BUN levels may indicate renal disease.
• C. Serum creatinine
• Creatinine clearance parallels the GFR within a range of - +10% and is a more sensitive indicator of
renal damage than BUN
• levels because renal impairment is almost the only cause of an increase in the serum creatinine level.
3. Normal values for serum creatinine range from 0.6 to 1.2 mg/dL (50 to 110 mmol/L).
• a. Values vary with the amount of muscle mass—a value of 1.2 mg/dL in a muscular athlete may
represent normal renal function, whereas the same value in a small, sedentary person with little muscle
mass may indicate significant renal impairment.
32
COMMON RENAL FUNCTION TESTS
• D. Creatinine clearance
• 1. Creatinine clearance, which represents the rate at which creatinine is removed from the
blood
• by the kidneys, roughly approximates the GFR.
• One estimation uses the method of Cockcroft and Gault, which is based on body weight, age, and
gender.
a. This formula provides an estimated value, calculated as:
•
•
•
140−𝑎𝑔𝑒 𝑎𝑔𝑒 (𝐵𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡 𝑘𝑔 )
72 ×𝑆𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 (
𝑚𝑔
𝑑𝐿
)
× 0.85 (𝑖𝑓 𝑓𝑒𝑚𝑎𝑙𝑒)
33
COMMON RENAL FUNCTION TESTS
• Determination of GFR. Th e modified diet in renal disease (MDRD) equation is considered
• a more accurate measurement of GFR than other equations used to estimate renal function
• (e.g., Cockcroft –Gault) in patients with reduced GFR and is used in staging renal disease. Patients
• must have a serum creatinine concentration.
• a. The MDRD equation for males is as follows:
• GFR 186 (Pcr)-1.154 age-0.203 where Pcr is serum creatinine. For females, multiply the result by 0.742; for
African Americans, multiply by 1.210.
34
Electrolytes
• Sodium (Na)
• Sodium is the major cation of the extracellular fluid. Sodium, along with chloride (Cl), potassium
• (K), and water, is important in the regulation of osmotic pressure and water balance between
• intracellular and extracellular fluids. Normal values are 135 to 147 mEq/L or mmol/L.
• An increase in sodium concentration (hypernatremia) may indicate impaired sodium excretion or
dehydration. A decrease in sodium concentration (hyponatremia) may reflect overhydration, abnormal
sodium loss, or decreased sodium intake.
• Patients with kidney, heart, or pulmonary disease may have difficulty with sodium and water balance. In
adults, changes in sodium concentrations most often reflect changes in water balance, not salt
imbalances. Therefore, sodium concentration is often used as an indicator of fluid status, rather than
salt imbalance.
• Control of sodium by the body is accomplished mainly through the hormones aldosterone and
antidiuretic hormone (ADH).
35
Electrolytes
• Hyponatremia is usually related to total body depletion of sodium—as in mineralocorticoid
deficiencies, sodium-wasting renal disease, replacement of fluid loss with non-saline solutions,
gastrointestinal (GI) losses, renal losses, or loss of sodium through the skin—or to dilution of serum
sodium—as in cirrhosis, CHF, nephrosis, renal failure, excess water intake, or syndrome of
inappropriate antidiuretic hormone (SIADH) secretion.
• Hypernatremia usually results from a loss of free water or hypotonic fluid or through excessive
sodium intake. Excess sodium intake can occur through the administration of hypertonic
intravenous (IV) solutions, mineralocorticoid excess, excessive sodium ingestion, or aft er
administration of drugs high in sodium content (e.g., ticarcillin, sodium bicarbonate [HCO3]).
36
Electrolytes
• Potassium (K)
• Potassium is the most abundant intracellular cation (intracellular fl uid potassium averages 141
mEq/L). Approximately 3500 mEq of potassium is contained in the body of a 70-kg adult.
• Only 10% of the body’s potassium is extracellular. Normal values are 3.5 to 5.0 mEq/L or mmol/L.
• The serum potassium concentration is not an adequate measure of the total body potassium
because most of the body’s potassium is intracellular.
• Fortunately, the clinical signs and symptoms of potassium deficiency—malaise, confusion,
dizziness, electrocardiogram (ECG) changes, muscle weakness, and pain—correlate well with
serum concentrations.
37
Electrolytes
• Hypokalemia can occur. Th e kidneys are responsible for approximately 90% of the daily
potassium loss. Other losses occur mainly through the GI system. Even in states of no potassium
intake, the
• kidneys still excrete up to 20 mEq of potassium daily.
• Therefore, prolonged periods of potassium deprivation can result in hypokalemia. Hypokalemia can
also result from potassium loss through vomiting or diarrhea, nasogastric suction, laxative abuse,
and by diuretic use ( mannitol, thiazides, or loop diuretics). Excessive mineralocorticoid activity and
glucosuria can also result in hypokalemia.
• Potassium can be shifted into cells with alkalemia and aft er administration of glucose and insulin.
• Hyperkalemia most commonly results from decreased renal elimination, excessive intake, or from
cellular breakdown (tissue damage, hemolysis, burns, infections).
38
Electrolytes
• Chloride (Cl)
• 1. Chloride is the major anion of the extracellular fluid and is important in the maintenance of acid–
base balance. Alterations in the serum chloride concentration are rarely a primary indicator of major
medical problems. Chloride itself is not of primary diagnostic significance. It is usually measured to
confirm the serum sodium concentration. The normal value for Cl is 95 to 105 mEq/L or mmol/L.
• 2. Hypochloremia is a decreased chloride concentration, and it is often accompanied by metabolic
alkalosis or acidosis caused by organic or other acids.
• Hyperchloremia is an increased chloride concentration that may indicate hyperchloremic metabolic
acidosis. Other causes include acute renal failure, dehydration, and excess chloride administration.
39
Electrolytes
• Bicarbonate (HCO3)/carbon dioxide (CO2) content
• The carbon dioxide (CO2) content represents the sum of the bicarbonate (HCO3) concentration and the
concentration of CO2 dissolved in the serum. Most disturbances of acid–base balance can be considered in
terms of this system. Normal values are 22 to 28 mEq/L or mmol/L.
• Hypobicarbonatemia is usually caused by metabolic acidosis, renal failure, hyperventilation, severe
diarrhea, drainage of intestinal fluid, and by drugs such as acetazolamide. Toxicity caused by salicylates,
methanol, and ethylene glycol can also decrease the HCO3 level.
• Hyperbicarbonatemia is usually caused by alkalosis, hypoventilation, pulmonary disease, persistent
vomiting, excess HCO3 intake with poor renal function, and diuretics.
40
MINERALS
• Calcium (Ca)
• Calcium plays an important role in nerve impulse transmission, muscle contraction, pancreatic insulin
release, and hydrogen ion release from the stomach, as a cofactor for some enzyme reactions and blood
coagulation and, most important, bone and tooth structural integrity. Normal total calcium values are 8.8 to
10.3 mg/dL or 2.20 to 2.56 mmol/L.
• Most laboratories measure the total calcium concentration; however, it is the free, ionized calcium that is
important physiologically. Ionized calcium levels may be obtained from the laboratory.
• Clinically, the most important determinant of ionized calcium is the amount of serum protein (albumin)
available for binding. The normal serum calcium range is for a serum albumin of 4.0 g/dL.
• Hypocalcemia usually implies a deficiency in either the production or response to parathyroid hormone (PTH)
or vitamin D.
41
MINERALS
• Calcium cont’d
• PTH abnormalities include hypoparathyroidism, pseudohypoparathyroidism, or hypomagnesemia.
• Vitamin D abnormalities can be caused by decreased nutritional intake, decreased absorption of
vitamin D, a decrease in production, or an increase in metabolism.
• Hypercalcemia is an increased calcium concentration, and it is usually associated with malignancy
or metastatic diseases. Other causes include hyperparathyroidism, Paget disease and drugs like
thiazides
42
MINERALS
• Phosphate (PO4)
• 1. Phosphate is a major intracellular anion and is the source of phosphate for adenosine
triphosphate (ATP) and phospholipid synthesis. Serum calcium and PO4 are influenced by many of
the same factors.
• It is useful to consider calcium and PO4 together when interpreting lab results. Normal PO4 values
are 2.5 to 5.0 mg/dL or 0.80 to 1.60 mmol/L.
• Hyperphosphatemia and hypophosphatemia: Hyperphosphatemia is usually caused by renal
insufficiency, although increased vitamin D or phosphate intake, hypoparathyroidism, and
hyperthyroidism are also causes.
• Hypophosphatemia can occur in malnutrition, especially when anabolism is induced, after
administration of aluminum-containing antacids or calcium acetate, in chronic alcoholics, and in
septic patients. Hyperparathyroidism and insufficient vitamin D intake can also induce
hypophosphatemia.
43
MINERALS
• Magnesium (Mg)
• Magnesium is the second most abundant intracellular and extracellular cation.
• Normal values are 1.6 to 2.4 mEq/L or 0.80 to 1.20 mmol/L.
• Hypomagnesemia and hypermagnesemia can occur. Hypomagnesemia is found more often than
hypermagnesemia.
• Depletion of magnesium usually results from excessive loss from the GI tract or the kidneys. Depletion
can occur from either poor intestinal absorption or excessive GI fluid loss. Signs and symptoms include
weakness, muscle fasciculations with tremor, tetany, and increased reflexes.
44
MINERALS
• Hypermagnesemia is most commonly caused by increased magnesium intake in the setting of
renal insufficiency. Other causes include excess magnesium intake, hepatitis, and Addison disease.
• Signs and symptoms of hypermagnesemia include bradycardia, flushing, sweating, nausea and
vomiting, decreased calcium level, decreased deep- tendon reflexes, flaccid paralysis, increased
pulse rate and QRS intervals, respiratory distress, and asystole.
45
Uric Acid
Uric Acid
Normal Range
• Male 3.4-8.5 mg/dL SI 202-506 μmol/L
• Females 2.3-6.6 mg/dL SI 137-393 μ mol/L
• Description
Uric acid is the main metabolic end product of the purine bases of DNA.
Clinical Significance
• Increased Uric Acid
• Increased uric acid (hyperuricemia) may be caused by excessive production of purines or inability of the
kidney to excrete urate. Common causes of hyperuricemia are renal dysfunction, metabolic acidosis, tumor
lysis syndrome, purine-rich diet, and use of furosemide, thiazide diuretics, and niacin.
• Hyperuricemia may be associated with the development of gouty arthritis, nephrolithiasis, and gouty tophi
46
Uric Acid
• Decreased Uric Acid
• Decreased uric acid levels (hypouricemia) are usually of little clinical significance but may occur
with a low-protein diet, deficiency of xanthine oxidase, or use of allopurinol, probenecid, or high
doses of aspirin or vitamin C.
47
LIPOPROTEIN PANEL
• LIPOPROTEIN PANEL
Total Serum Cholesterol
• Blood Levels
• Desirable level < 200 mg/dL SI < 5.17 mmol/L
• Borderline high 200-239 mg/dL SI 5.17-6.19 mmol/L
• High cholesterol >= 240 mg/dL SI > 6.20 mmol/L
Description
• Cholesterol is an important component of cell membranes and is necessary for the synthesis of
many hormones and bile acids.
• Elevated total serum cholesterol is well known to be associated with an increased risk of developing
coronary heart disease (CHD).
• Total serum cholesterol is a useful screening test to determine CHD risk
48
LIPOPROTEIN PANEL
• Clinical Significance
• Adults over 20 years of age should have a baseline fasting lipoprotein profile, and testing should be repeated
at least every 5 years thereafter. Cholesterol levels should be performed after the patient has fasted for at
least 9 to 12 hours.
• Increased Serum Cholesterol
• In cases of elevated cholesterol (hypercholesterolemia), the need for diet or drug therapy should be based on
the individual components of the lipid profile (LDL, HDL, and triglycerides [TG]) and the number of CHD risk
factors.
• Some causes of hypercholesterolemia include obesity, familial hypercholesterolemia, and cholestasis.
• Decreased Serum Cholesterol Decreased cholesterol levels may be seen in malabsorption, malnutrition,
hyperthyroidism, chronic anemia, or severe liver disease.
• However, low total serum cholesterol usually indicates good health.
49
Low-Density Lipoproteins
• Low-Density Lipoproteins
• Desired Range
• No CHD and < 2 CHD risk factors < 160 mg/dL (4.13 mmol/L)
• No CHD and >= 2 CHD risk factors < 130 mg/dL (3.36 mmol/L)
• With CHD or diabetes < 100 mg/dL (2.58 mmol/L) (optional < 70)
• Description
• Low-density lipoprotein (LDL) is a major cholesterol transport protein which comprises 60% to 70% of total
serum cholesterol. LDL is considered the “bad” cholesterol, and has been linked to atherosclerosis.
• Clinical Significance
• Low-density lipoprotein is not normally measured directly due to expense and time required. In addition to lipid
disorders, elevated LDL may also be associated with diabetes mellitus, diets high in cholesterol and saturated
fat, hypothyroidism, and nephrotic syndrome.
50
High-Density Lipoproteins
• Blood Levels
• Low < 40 mg/dL SI < 1.03 mmol/L
• High >= 60 mg/dL SI > 1.55 mmol/L
• Description
• High-density lipoproteins (HDL) are responsible for transport of 20% to 30% of serum cholesterol. HDL removes
excess cholesterol from peripheral tissues to the liver. It is considered the “good” cholesterol, and elevated HDL
levels are associated with a decreased risk for CHD.
• Clinical Significance
• Decreased HDL may be associated with cigarette smoking, poorly controlled diabetes mellitus, lack of exercise,
familial hypertriglyceridemia, and use of anabolic/androgenic steroids or b-blockers.
• It is estimated that CHD risk increases by 2% to 3% with each 1 mg/dL decrease in HDL.
• Elevated HDL may be seen with moderate alcohol intake or in patients taking estrogen, oral contraceptives, or
nicotinic acid.
51
Triglycerides
• Blood Levels
• Normal range < 150 mg/dL SI < 1.7 mmol/L
• Borderline high 150-199 mg/dL SI 1.7-2.26 mmol/L
• High 200-499 mg/dL SI 2.26-5.64 mmol/L
• Very high >= 500 mg/dL SI > 5.64 mmol/L
• Description
• Triglycerides are the main storage form of fatty acids, and they account for greater than 90% of
dietary fat intake.
• Clinical Significance
• Triglycerides may be significantly elevated in the non-fasting state and should be measured after a
fast of at least 12 to 14 hours.
52
Triglycerides
• In addition to lipid disorders, elevated triglycerides (hypertriglyceridemia) may be associated with a
non-fasting sample, poorly controlled diabetes mellitus, pancreatitis, nephrotic syndrome, chronic
renal failure, alcoholism, gout, and use of oral contraceptives or intravenous lipid infusion.
• Decreased triglycerides may be associated with malnutrition or brain infarction.
53
ENDOCRINE TESTS: THYROID FUNCTION
• Thyroid-Stimulating Hormone
• Normal Range
• 0.3-5 mU/mL SI 0.3-5 μU/L
• Description
• Thyroid-stimulating hormone (TSH) is a sensitive screening test used to detect hypothyroidism or
hyperthyroidism. An abnormal TSH level should be followed up with further thyroid testing, for
example, free thyroxine. TSH is also useful for monitoring therapy for hypothyroidism or
hyperthyroidism.
• Clinical Significance
• Elevated TSH
• Elevated TSH levels are indicative of hypothyroidism. In patients taking thyroid replacement
therapy, an elevated TSH suggests the need for an increase in the dose of thyroid medication.
54
ENDOCRINE TESTS: THYROID
FUNCTION
• Low TSH
• Abnormally low TSH levels (< 0.10) are associated with hyperthyroidism. In patients taking thyroid
replacement therapy, a decreased TSH indicates the need to reduce the dose of thyroid medication.
• Total Thyroxine
• Normal Range
• 4-12 mg/dL SI 51-154 nmol/L
• Description
• Thyroxine (T4) is the predominant circulating thyroid hormone. Total serum thyroxine measures both free
thyroxine and thyroxine bound to thyroxine binding globulin, albumin, and prealbumin.
• Only the unbound thyroxine is active. T4 levels are a measure of the functional status of the thyroid gland.
• T4 may also be used to monitor thyroid therapy.
• T4 levels may be affected by conditions that increase or decrease the thyroxine-binding proteins
55
ENDOCRINE TESTS: THYROID
FUNCTION
• Clinical Significance
• Increased T4
• T4 can be increased in hyperthyroidism, pregnancy, hepatitis, and with the use of estrogen
replacement therapy, oral contraceptives.
• Decreased T4
• Decreased T4 is most commonly seen in hypothyroidism, but may also be associated with renal
failure, malnutrition, liver disease, and use of medications that compete for T4-binding sites on T4-
binding proteins (eg, salicylates).
Free Thyroxine
• Normal Range
• 0.8-2.7 ng/dL SI 10-35 pmol/L
Description
• Because total T4 levels can be affected by conditions that alter the amount of thyroxine-binding
proteins, free T4 is a more accurate reflection of clinical thyroid status
56
• Free Thyroxine cont’d
• Clinical Significance
• Free T4 is a diagnostic test that may be used to confirm the diagnosis of hypothyroidism (decreased
free T4) or hyperthyroidism (increased free T4).
57
ENDOCRINE TESTS: THYROID
FUNCTION
• Total Triiodothyronine
• Normal Range
• 80-200 ng/dL SI 1.2-3.1 nmol/L
• The majority of T3 is formed from deiodination of T4 in the kidney and liver. Total T3 measures both
bound and unbound T3. T3 is usually used in the diagnosis of hyperthyroidism or T3 toxicosis, but
has little utility in the diagnosis of hypothyroidism.
• Clinical Significance
• Increased T3
• Increased T3 is seen in hyperthyroidism, T3 thyrotoxicosis (Grave disease), and with high doses of
levothyroxine. Pregnancy and use of estrogens or oral contraceptives may also be associated with
elevated T3.
58
ENDOCRINE TESTS: THYROID
FUNCTION
ENDOCRINE TESTS: THYROID
FUNCTION
• Total Triiodothyronine cont’d
• Decreased T3
• Decreased T3 may be associated with hypothyroidism, malnutrition, and
• anorexia. Corticosteroids and propranolol decrease peripheral conversion of
• T4 to T3 and may result in reduced T3 levels.
59
ENDOCRINE TESTS: DIABETES MELLITUS
• Glycosylated Hemoglobin (Hemoglobin A1c)
• Normal Range
• The normal range lies between 4% and 6%.
• Description
• The hemoglobin A1c (HbA1c) measures the percentage of hemoglobin A molecules that are glycosylated
(bound to glucose). During the life span of an RBC, glucose binds irreversibly to hemoglobin in the RBC. As
the serum glucose becomes more elevated, more glucose binds to the hemoglobin.
• Because the RBC has a life span of approximately 120 days, the HbA1c reflects average blood glucose for
the previous 2 to 3 months.
60
• Glycosylated Hemoglobin (Hemoglobin A1c) cont’d
• Clinical Significance
• The HbA1c may be used to assess glucose control over the 2 to 3 months
• preceding the test.
• The American Diabetes Association recommends a target HbA1c of less than 7% for most diabetic
patients. An HbA1c greater than 7% indicates the need for improved diabetic control through
adjustment of diet, exercise, or medication regimen.
61
ENDOCRINE TESTS: DIABETES MELLITUS
ENDOCRINE TESTS: DIABETES
MELLITUS
• Generally, the correlation between HbA1c and the estimated average blood glucose (eAG) can be
described by the following equation: eAG(mg/dL) = 28.7 × A1c - 46.7
62
A1c (%) Glucose (mg/dL) A1c (%) Glucose (mg/dL)
6 126
7 154
8 183
9 212
10 240
11 269
12 298
It is important to remember that the HbA1c does not provide
an indication of the variability in glucose levels, only an
estimate of the average. HbA1c may not be a reliable
indicator of the average glucose in patients with anemia,
hemolysis, or acute blood loss.
ENDOCRINE TESTS: ADRENAL
GLAND
• Cortisol
• Normal Range
• Morning 6-25 mg/dL 165-690 nmol/L
• Evening 3-16 mg/dL 83-441 nmol/L
Description
• Cortisol is a hormone produced by the adrenal cortex. It plays a critical role in carbohydrate metabolism
and response to stress.
Clinical Significance
• Increased Cortisol
• Increased cortisol levels are associated with Cushing syndrome, Cushing disease,
• hyperthyroidism, pregnancy, stress, and morbid obesity.2
• Decreased Cortisol
• Decreased cortisol may be secondary to Addison disease, hypothyroidism, or decreased pituitary function
63
ENDOCRINE TESTS: ADRENAL
GLAND
• Urine Free Cortisol
• Normal Range
• Cortisol level 24-108 mcg/24 hours (varies with assay).
• Description
• Urine free cortisol is a screening test for Cushing syndrome. Urine is collected for 24 hours, and
cortisol and creatinine levels are measured.8,14
• Clinical Significance
• Cortisol levels greater than 200-250 mcg/24 hours are highly suggestive of
• Cushing syndrome
64
ENDOCRINE TESTS: ADRENAL
GLAND
• Overnight Dexamethasone Suppression Test
• Normal Range
• Cortisol less than 5 mg/dL at 8:00 AM.
• Description
• In the overnight dexamethasone suppression test, 1 mg of dexamethasone is given at 11 PM, and plasma
cortisol levels are drawn at 8:00 AM. In a normal patient, the administration of exogenous steroid
(dexamethasone) should suppress the release of cortisol from the adrenal gland.
• The dexamethasone suppression test is useful in the diagnosis of Cushing syndrome.
• Clinical Significance
• A plasma cortisol level greater than 5 mg/dL suggests the diagnosis of Cushing syndrome
65
ENDOCRINE TESTS: ADRENAL
GLAND
• Adrenocorticotropic Hormone
• Normal Range
• < 60 pg/mL SI < 13.2 pmol/L
• Description
• ACTH is a hormone secreted from the anterior pituitary. It controls the release of cortisol from the
adrenal gland.
• Clinical Significance
• Increased ACTH
• Increased ACTH may be associated with Cushing disease, adrenal hyperplasia,
• Addison disease, or ectopic ACTH production.
66
ENDOCRINE TESTS: ADRENAL
GLAND
• Decreased ACTH
• Decreased ACTH may be seen in adrenal malignancy or states of pituitary insufficiency.
67
ENDOCRINE TESTS: ADRENAL
GLAND
• ACTH Stimulation Test (Cosyntropin)
68
ENDOCRINE TESTS: ADRENAL
GLAND
• ACTH Stimulation Test (Cosyntropin)
• Description
• The ACTH stimulation test is used to detect adrenal insufficiency. In the
• ACTH stimulation test, a baseline cortisol level is drawn. Then synthetic ACTH (cosyntropin) is administered,
and cortisol and aldosterone levels are collected 30 and 60 minutes post-administration.
• Clinical Significance
• Normal
• A normal response is a rise in cortisol greater than 10 mg/dL above baseline or a cortisol level greater than
20 mg/dL.2,8,14
• Abnormal If plasma cortisol remains low and fails to rise greater than 10 mg/dL above baseline, this is
indicative of adrenal insufficiency.
• The aldosterone level will help to determine if the adrenal insufficiency is related to failure of the adrenal
gland (primary adrenal insufficiency) or malfunction of the pituitary gland (secondary adrenal insufficiency)
69
Helicobacter pylori IgG
• Description
• Helicobacter pylori is a gram-negative rod that is responsible for the majority of cases of peptic ulcer
disease. H pylori can be detected in 90% to 100% of patients with duodenal ulcers and 70% to 80% of
patients with gastric ulcers. H pylori IgG is a serologic test that detects antibodies to H pylori.
• A positive test indicates the presence of H pylori. Normal value is negative.
• Clinical Significance
• A positive H pylori IgG in the presence of symptoms is highly suggestive of peptic ulcer disease, and a
course of antibiotic therapy is warranted.
• H pylori has been linked to some types of gastric lymphoma and gastric cancer.
70
Hemoccult
• Normal Value
• Normal value is negative.
• Description
• The hemoccult test is used to detect the presence of occult blood in the stool.
• Clinical Significance
• A positive hemoccult test indicates blood loss in the gastrointestinal tract and deserves further work-up.
• A false-positive result may be obtained if the patient has consumed red meat, broccoli, turnips, or radishes
within 3 days of the test.
• Aspirin (in doses > 325 mg daily), NSAIDs such as ibuprofen, and excess ETOH consumption have also
been associated with false positives. False negatives may occur in patients taking high doses of vitamin C
or consuming large amounts of citrus fruits or juices
71
COAGULATION TESTS
• Prothrombin Time
• Normal Range
• 10-13 seconds (varies with thromboplastin and test method used).
• Description
• The prothrombin test is sensitive to changes in the levels of clotting factors prothrombin (factor II),
factor VII, and factor X.
• It is performed by adding thromboplastin and calcium to a plasma sample. After addition of these
reagents, the time it takes for the blood to clot is measured.
• Clinical Significance
• The prothrombin time (PT) is used to monitor warfarin therapy. Because the PT may vary according
to the thromboplastin used to test the sample, the international normalized ratio (INR) is a better
monitoring tool.
72
COAGULATION TESTS
• Prothrombin Time cont’d
• The normal PT in a person not on anticoagulation therapy is 10 to
• 13 seconds. An increased PT may be seen with anticoagulation therapy, liver
• disease, vitamin K deficiency, and clotting factor deficiencies
73
COAGULATION TESTS
• International Normalized Ratio (INR)
• Desired Range
• Depends on indication for anticoagulation (see below).
• Description
• Because the PT may vary due to the thromboplastin used, the INR is used to standardize the PT.
• Clinical Significance
• An INR below the desired range indicates suboptimal anticoagulation and a need to increase
warfarin dosage. Conversely, an INR above the desired range indicates a need to omit and/or
reduce the warfarin dosage.
• Patients with elevated INRs and/or bleeding may require the administration of vitamin K, fresh
frozen plasma, or clotting factors
74
COAGULATION TESTS
• International Normalized Ratio (INR)
• To appropriately interpret an INR value and decide on the need for dosage adjustments, patients
should be questioned regarding dosage of warfarin, missed doses, dietary intake, alcohol intake,
and concomitant medications
75
COAGULATION TESTS
• Activated Partial Thromboplastin Time
• Normal Range
• The time varies between 20 and 35 seconds.
• Description
• It is used to monitor heparin therapy. Monitoring of the aPTT is usually not required for patients
receiving low molecular weight heparin.
• Clinical Significance
• The normal value above represents a control range for patients not on anticoagulation therapy.
Patients on heparin therapy will have an elevated aPTT.
76
• An aPTT below the desired therapeutic range indicates the need to rebolus and/or increase the
heparin infusion rate. An aPTT above the desired therapeutic indicates the need to hold and/or
reduce the dose of heparin.
• Patients with clinically significant bleeding may require reversal with protamine sulfate.
77
IMMUNOLOGIC TESTS
• Antinuclear Antibodies
• Normal Value
• Negative at 1:20 dilution (varies).
• Description
• Antinuclear antibodies (ANA) are antibodies directed against structures in the cell nucleus, for
example, nucleic acids.
• The ANA test is used as a diagnostic tool for autoimmune and connective tissue diseases,
particularly systemic lupus erythematosus (SLE).
• Clinical Significance
• High titers may be associated with SLE, rheumatoid arthritis, scleroderma, Sjogren syndrome,
polymyositis, dermatomyositis, and drug-induced lupus.
78
• Rheumatoid Factor
• Normal Value
• The normal value is either less than 1:20 or less than 20 IU/mL.
• Description
• Rheumatoid factor (RF) is an immunoglobulin whose activity is directed against IgG. Thus, a
positive RF test (titer > 1:20 or level > 20 IU/mL) is indicative of an autoimmune process.
• Clinical Significance
• A positive rheumatoid factor test is most commonly associated with rheumatoid arthritis but may
also be seen with SLE, Sjogren syndrome, scleroderma, malignancy, and infectious diseases such
as tuberculosis, syphilis, mononucleosis, and endocarditis.
79
IMMUNOLOGIC TESTS
INFECTIOUS DISEASE DIAGNOSTIC TESTS
• Enzyme Immunoassay for HIV
• Description
• The enzyme immunoassay (ELISA or EIA) for HIV detects antibodies to HIV. It is a highly sensitive
and specific test and is the most commonly used screening test for HIV.
• Positive tests should be repeated to assure positive results. Repeatedly positive samples should be
confirmed with the Western blot test or immunofluorescence assay.
• False Negative
• False negatives may be seen in early HIV infection and bone marrow transplant.
80
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• Western Blot
• Description
• The Western blot is a confirmatory test used following a positive ELISA result.
• It detects antibodies to specific proteins of the HIV virus.
• Clinical Significance
• Positive Result
• A positive result following a positive ELISA test confirms the diagnosis of HIV.
• Negative Result
• A negative result indicates no HIV antibodies. The ELISA in this case can be considered a false positive
81
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• Indeterminate Result
• Indeterminate results may occur if seroconversion is not complete (ie, it is too early in the disease process).
Individuals should be retested at a later date.
• Venereal Disease Research Laboratory Test
• Normal Value
• Normal value is nonreactive.
• Description
• The venereal disease research laboratory (VDRL) is a nontreponemal serologic test used to screen for
syphilis. It may also be used to assess response to syphilis therapy.
• Clinical Significance
• A positive VDRL titer is suggestive of syphilis.
82
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• HEPATITIS A
• Anti-HAV IgM
• Normal Value
• Normal value is negative.
• Description
• Hepatitis A IgM antibodies may be detected in the serum 4 to 6 weeks after exposure to hepatitis A
and often coincide with the onset of symptoms and jaundice.
• Clinical Significance
• The presence of anti-HAV IgM indicates acute or recent hepatitis A infection.
83
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• HEPATITIS B
• Hepatitis B Surface Antigen
• Normal Value
• Normal value is negative.
• Description
• Hepatitis B surface antigen (HBsAg) is an envelope protein on the surface of the hepatitis B virus. It
can be detected in the serum 4 to 12 weeks after infection.
• Clinical Significance
• A positive test for HBsAg indicates acute hepatitis B. Persistence of HBsAg for 6 months or more
after acute infection is indicative of chronic hepatitis B.
84
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• Hepatitis B “e” Antigen
• Normal Value
• Normal value is negative.
• Description
• Hepatitis B “e” antigen (HBeAg) is used to assess the degree of infectivity of patients with hepatitis
B.
• Clinical Significance
• Presence of HBeAg is associated with active viral replication and a high degree of infectivity.
HBeAg is usually present for 2 to 6 weeks after acute infection.
• Persistence of HBeAg is indicative of ongoing viral replication, that is, chronic hepatitis B.
85
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• Hepatitis B Core Antibody
• Normal Value
• Normal value is negative.
• Description
• Hepatitis B core antibody (anti-HBc) IgM and IgG may be detected in the blood a few weeks after
the appearance of HBsAg.
• Clinical Significance
• Positive anti-HBc IgM is a sensitive marker for acute hepatitis B infection.
86
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• Hepatitis B Surface Antibody
• Normal Value
• Normal value is negative.
• Description
• Hepatitis B surface antibody (anti-HBs) is usually detected in the blood 3 to 4 months after
infection.37
• Clinical Significance
• Presence of anti-HBs indicates recovery and immunity to hepatitis B.
• Individuals who have been vaccinated for hepatitis B will test positive for anti-HBs
87
INFECTIOUS DISEASE DIAGNOSTIC
TESTS
• HEPATITIS C
• Hepatitis C Antibody
• Normal Value
• Normal value is negative.
• Description
• Hepatitis C antibody (anti-HCV) is used as a screening test for hepatitis C virus.
• Clinical Significance
• Presence of anti-HCV indicates prior exposure to or chronic infection with hepatitis C. Unlike
antibodies to hepatitis A and B, antibodies to hepatitis C do not confer immunitysed as a screening
test for hepatitis C virus.
88
END
89

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Interpretation of clinical laboratory values.pptx

  • 1. PCP 301 Clinical interpretation of laboratory data Pharm Wesley E. Hedima Department of Clinical Pharmacy and Pharmacy Practice, Gombe State University 1
  • 2. Introduction Laboratory tests are performed for multiple purposes, including to: • Discover a disease, • Confirm or differentiate a diagnosis, • Stage or classify a disease, and • Monitor effectiveness of therapy. 2
  • 3. Introduction Laboratory tests are classified as screening or diagnostic. • Screening tests are used in patients with no signs or symptoms of a disease (e.g., serum cholesterol for assessing cardiovascular disease risk). • Diagnostic tests are done in patients with signs and symptoms of disease or with an abnormal screening test. 3
  • 4. Intro cont’d Pharmacists usually monitor laboratory tests to: a. Assess the therapeutic and adverse effects of a drug (e.g., monitoring the serum uric acid level after allopurinol is administered, checking for increased liver function test values after administration of isoniazid) b. Determine the proper drug dose (e.g., assessment of the serum creatinine or creatinine clearance value before use of a renally excreted drug) c. Assess the need for additional or alternate drug therapy (e.g., assessment of white blood cell count after an antibiotic is administered) d. Prevent test misinterpretation resulting from drug interference (e.g., determination of a false-positive result for a urine glucose test after cephalosporin administration) 4
  • 5. Introduction cont’d • These tests can be expensive, and requests for them must be balanced against potential benefits for patients and how the laboratory test will affect your decision regarding therapy. 5
  • 6. Definition of normal values a. Normal limits may be defined somewhat arbitrarily; thus, values outside the normal range may not necessarily indicate disease or the need for treatment (e.g., asymptomatic hyperuricemia). b. Many factors (e.g., age, sex, time since last meal) must be taken into account when evaluating test results. c. Normal values also vary among institutions and may depend on the method used to perform the test. d. The goal is not to make all laboratory values normal; resist urges to do something in a clinically stable patient. e. Laboratory error must always be considered when test results do not correlate with expected results for a given patient. If necessary, the test should be repeated. f. Common sources of laboratory error include spoiled specimens, incomplete specimens, specimens taken at the wrong time, faulty reagents, technical errors, incorrect procedures, and failure to take diet or medication into account. 6
  • 7. Types of test 1. Tests with normal values reported in ranges (i.e., 3.5 to 5.0 mEq/L) are called quantitative. 2. Tests with positive (+) or negative (-) outcomes are called qualitative. 3. Those with varying degrees of positivity (e.g., 1_, 2_, 3_ glucose in the urine) are termed semiquantitative accuracy (accuracy is defi ned as the extent to which the mean measurement is close to the true value). Precision refers to the reproducibility of the assay. 7
  • 8. HEMATOLOGICAL TESTS • Blood contains three types of formed elements: • red blood cells (RBCs), • white blood cells (WBCs), and platelets. • A CBC typically includes RBC count, total WBC count, hemoglobin (Hb), hematocrit (Hct), RBC indices (mean cell volume [MCV], mean cell Hb [MCH], mean cell Hb concentration [MCHC]), reticulocyte count, and platelet count. 8
  • 9. A. RBCs (erythrocytes) 1. The RBC count, which reports the number of RBCs found in a given volume of blood, provides an indirect estimate of the blood’s Hb content. Values are often reported in cells/microliter (µL) or cells/liter and less commonly as cells/cubic millimeter (mm3). Normal values are • a. 4.3 to 5.9 × 1012 cells/L of blood for men • b. 3.5 to 5.0 × 1012 cells/L of blood for women 2. The Hct or packed cell volume (PCV) measures the percentage by volume of packed RBCs in a whole blood sample after centrifugation. The Hct value is usually three times the Hb value and is given as a percent or fraction of 1 (42% to 52% or 0.42 to 0.52 for men; 37% to 47% or 0.37 to 0.47 for women). • a. Low Hct values indicate such conditions as anemia, overhydration, or blood loss. • b. High Hct values indicate such conditions as polycythemia vera or dehydration. HEMATOLOGICAL TESTS 9
  • 10. HEMATOLOGICAL TESTS 3. The Hb test measures the grams of Hb contained in 100 mL (1 dL) or 1 L of whole blood and provides an estimate of the oxygen-carrying capacity of the RBCs. Th e Hb value depends on the • number of RBCs and the amount of Hb in each RBC. • a. Normal values are 14 to 18 g/dL for men and 12 to 16 g/dL for women. • b. Low Hb values indicate anemia. 4. RBC indices provide important information regarding RBC size, Hb concentration, and Hb weight. They are used primarily to categorize anemias. • Observations of a smear may show variation in RBC shape (poikilocytosis), as might occur in sickle-cell anemia, or it may show a variation in RBC size (anisocytosis), as might occur in a mixed anemia (folic acid and iron deficiency). 10
  • 11. HEMATOLOGICAL TESTS a. MCV is the ratio of the Hct to the RBC count. It essentially assesses average RBC size and reflects any anisocytosis. MCV = Hct % ×10 RBC (Millions) • (1) Low MCV indicates microcytic (undersize) RBCs, as occurs in iron deficiency. • (2) High MCV indicates macrocytic (oversize) RBCs, as occurs in a vitamin B12 or folic acid deficiency. • (3) Normal range for MCV is 90 _+ 10. b. Mean cell hemoglobin (MCH) assesses the amount of Hb in an average RBC. • (1) MCH is defined as: • MCH = Hb ×10 RBC (Millions) • (2) Normal range for MCH is 30 _ +4. 11
  • 12. HEMATOLOGICAL TESTS c. Mean cell hemoglobin concentration (MCHC) represents the average concentration of Hb in an average RBC, defined as: MCHC = Hb ×100 Hct • (1) Normal range for MCHC is 34 _ +3. • (2) Low MCHC indicates hypochromia (pale RBCs resulting from decreased Hb content), as occurs in iron deficiency. • 5. The reticulocyte count provides a measure of immature RBCs (reticulocytes), Hence, this test provides an index of bone marrow production of mature RBCs. • a. Increased reticulocyte count occurs with such conditions as hemolytic anemia, acute blood loss, and response to the treatment of a factor deficiency (e.g., an iron, vitamin B12, or folate deficiency). • b. Decreased reticulocyte count occurs with such conditions as drug-induced aplastic anemia. 12
  • 13. HEMATOLOGICAL TESTS • 6. The erythrocyte sedimentation rate (ESR) measures the rate of RBC settling of whole, uncoagulated blood over time, and it primarily reflects plasma composition. • a. Normal ESR rates range from 0 to 20 mm/hr for males and from 0 to 30 mm/hr for females. • b. ESR values increase with acute or chronic infection, tissue necrosis or infarction, well established malignancy, and rheumatoid collagen diseases. • c. ESR values are used to • (1) Follow the clinical course of a disease • (2) Demonstrate the presence of occult organic disease • (3) Differentiate conditions with similar symptomatology—for example, angina pectoris (no change in ESR value) as opposed to a myocardial infarction (increase in ESR value) 13
  • 14. HEMATOLOGICAL TESTS • WBC Count 1. The WBC count reports the number of leukocytes in a given volume of whole blood. a. Normal values range from 4,000 to 11,000 _ 103 cells/mm3 (or 109 cells/L) b. Increased WBC count (leukocytosis) usually signals infection; it may also result from leukemia, tissue necrosis, or administration of corticosteroids. It is most often found with bacterial infection. c. Decreased WBC count (leukopenia) indicates bone marrow depression, which may result from metastatic carcinoma, lymphoma, or toxic reactions to substances such as antineoplastic agents (anticancer agents). 2. The WBC differential evaluates the distribution and morphology of the five major types of WBCs: the granulocytes (neutrophils, basophils, eosinophils) and the non-granulocytes (lymphocytes, monocytes). A certain percentage of each type makes up the total WBC count. • a. Neutrophils may be mature or immature. Mature neutrophils are polymorphonuclear leukocytes (PMNs), also referred to as polys. A systemic bacterial infection, such as pneumonia can cause an increase in neutrophils. 14
  • 15. HEMATOLOGICAL TESTS • Neutropenia, a decreased number of neutrophils, may occur with an overwhelming infection of any type (bone marrow is unable to keep up with the demand). It may also occur with certain viral infections (e.g., mumps, measles), with idiosyncratic drug reactions, and as a result of chemotherapy. • Neutropenia is defined as an absolute neutrophil count (ANC) of < 1000 cells/mm3. b. Basophils stain deeply with blue basic dye. Their function in the circulation is not clearly • understood; in the tissues, they are referred to as mast cells. • (1) Basophilia, an increased number of basophils, may occur with chronic myelogenous leukemia (CML) as well as other conditions. • (2) A decrease in basophils is generally not apparent because of the small numbers of these cells in the blood. 15
  • 16. c. Eosinophils stain deep red with acid dye and are classically associated with immune reactions. • Eosinophilia, an increased number of eosinophils, may occur with such conditions as acute allergic reactions (e.g., asthma, hay fever, drug allergy) and parasitic infestations (e.g., trichinosis, amebiasis). • d. Lymphocytes play a dominant role in immunological activity and appear to produce antibodies. They are classified as B lymphocytes or T lymphocytes; T lymphocytes are further divided into helper- inducer cells (CD 4 T cells) and suppressor (cytotoxic) cells (CD 8 T cells). • (1) Lymphocytosis, an increased number of lymphocytes, usually accompanies a normal or decreased total WBC count and is most commonly caused by viral infection. • 2) Lymphopenia, a decreased number of lymphocytes, may result from severe debilitating • illness, immunodeficiency, or from AIDS, which has a propensity to attack TH4 cells. HEMATOLOGICAL TESTS 16
  • 17. HEMATOLOGICAL TESTS e. Monocytes are phagocytic cells. Monocytosis, an increased number of monocytes, may occur with tuberculosis (TB), subacute bacterial endocarditis, and during the recovery phase of some acute infections. C. Platelets (thrombocytes). These are the smallest formed elements in the blood, and they are involved in blood clotting and vital to the formation of a hemostatic plug after vascular injury. • 1. Normal values for a platelet count are 150,000 to 300,000/mm3 (1.5 to 3.0 _ 1011/L). • 2. Thrombocytopenia, a decreased platelet count, can occur with a variety of conditions, such as idiopathic thrombocytopenic purpura or, occasionally, from such drugs as quinidine and sulfonamides. 17
  • 18. COMMON SERUM ENZYME TESTS. • Small amounts of enzymes (catalysts) circulate in the blood at all times and are released into the blood in larger quantities when tissue damage occurs. Thus, serum enzyme levels can be used to aid in the diagnosis of certain diseases. A. Creatine kinase (CK) • 1. Creatine kinase—formerly known as creatine phosphokinase (CPK)—is found primarily in heart • muscle, skeletal muscle, and brain tissue. • 2. CK levels are used primarily to aid in the diagnosis of acute myocardial or skeletal muscle damage. However, vigorous exercise, a fall, or deep intramuscular injections can cause • significant increases in CK levels. • 3. The isoenzymes of CK—CK-MM, found in skeletal muscle; CK-BB, found in brain tissue; and • CK-MB, found in heart muscle—can be used to differentiate the source of damage. Increase in CK- MB levels provides a sensitive indicator of myocardial necrosis. 18
  • 19. COMMON SERUM ENZYME TESTS. B. Lactate dehydrogenase (LDH) Five individual isoenzymes make up the total LDH serum level. • a. LDH1 and LDH2 appear primarily in the heart. • b. LDH3 appears primarily in the lungs. • c. LDH4 and LDH5 appear primarily in the liver and skeletal muscles. C. Alkaline phosphatase (ALP) • 1. ALP is produced primarily in the liver and bones. • 2. Increased osteoblastic activity, as occurs in Paget disease, hyperparathyroidism, osteomalacia, • and others, also increases serum ALP levels. 19
  • 20. COMMON SERUM ENZYME TESTS. • D. Aspartate aminotransferase (AST) • 1. Aspartate aminotransferase—formerly known as serum glutamic-oxaloacetic transaminase (SGOT)—is found in a number of organs, primarily in heart and liver tissues. • 2. Damage to the heart (e.g., from myocardial infarction) results in increased AST levels about 8 hrs aft er injury. • Levels are also increased with passive congestion of the liver, such as occurs in congestive heart failure (CHF). 20
  • 21. COMMON SERUM ENZYME TESTS. • E. Alanine aminotransferase (ALT) • 1. Alanine aminotransferase—formerly known as serum glutamic-pyruvic transaminase (SGPT) —is found in the liver, with lesser amounts in the heart, skeletal muscles, and kidney. • 2. Although ALT values are relatively specific for liver cell damage, ALT is less sensitive than AST, and extensive or severe liver damage is necessary before abnormally increased levels are produced. • 3. ALT also increases less consistently and less markedly than AST after an acute myocardial infarction. 21
  • 22. COMMON SERUM ENZYME TESTS. F. Cardiac troponins (I, T, and C) • 1. Troponins assist in the diagnosis of acute myocardial infarction. These troponins may possess superior specificity in situations in which false-positive elevations of CK-MB are likely. • 2. Troponin T is found in cardiac and skeletal muscle, troponin I is found only in cardiac muscle, and troponin C is present in two isoforms found in skeletal and cardiac muscle. Troponin T has shown prognostic value in unstable angina and in detecting minor myocardial cell injury with greater sensitivity than CK-MB. • 3. The normal value for troponin T is < 0.1 ng/mL and I is <1.5 ng/mL. 22
  • 23. LIVER FUNCTION TESTS A. Liver enzymes • 1. Levels of certain enzymes (e.g., LDH, ALP, AST, ALT) increase with liver dysfunction. • 2. These enzyme tests indicate only that the liver has been damaged. They do not assess the liver’s ability to function. Other tests provide indications of liver dysfunction. B. Serum bilirubin 1. Bilirubin, a breakdown product of Hb, is the predominant pigment in bile. Effective bilirubin conjugation and excretion depend on hepatobiliary function and on the rate of RBC turnover. 2. Serum bilirubin levels are reported as total bilirubin (conjugated and unconjugated) and as direct bilirubin (conjugated only). a. Bilirubin is released by Hb breakdown and is bound to albumin as water-insoluble indirect bilirubin (unconjugated bilirubin), which is not filtered by the glomerulus. 23
  • 24. LIVER FUNCTION TESTS b. Unconjugated bilirubin travels to the liver, where it is separated from albumin, conjugated • with diglucuronide, and then actively secreted into the bile as conjugated bilirubin (direct • bilirubin), which is filtered by the glomerulus. • 3. Normal values of total serum bilirubin are 0.1 to 1.0 mg/dL (2 to 18 mmol/L); of direct bilirubin, • 0.0 to 0.2 mg/dL (0 to 4 mmol/L). • An increase in serum bilirubin results in jaundice from bilirubin deposition in the tissues. There • are three major causes of increased serum bilirubin; Hemolysis, biliary obstruction, liver cell necrosis. 24
  • 25. LIVER FUNCTION TESTS • C. Serum proteins • 1. Primary serum proteins measured are albumin and the globulins (i.e.,α , β, γ ). • a. Albumin (4 to 6 g/dL) maintains serum oncotic pressure and serves as a transport agent. Because it is primarily manufactured by the liver, liver disease can decrease albumin levels. Albumin can also be used to assess nutritional status. • b. Globulin (23 to 35 g/L) relates to the total measurement of immunoglobins (antibodies) found in the serum and function as transport agents and play a role in certain immunological mechanisms. 25
  • 26. URINALYSIS • Composed of chemical and microscopic tests of the urine used to provide basic information regarding renal function, urinary tract disease, and the presence of certain systemic diseases. Components of a standard urinalysis include: • physical (color, turbidity, odor, specifi c gravity, and osmolality), • chemical (pH, Hb, glucose, protein, glucose, ketone, leukocyte esterase, nitrites, bilirubin) and • microscopic examination (RBC, WBC, epithelial cells, casts, bacteria). A. Appearance. Normal urine is clear and ranges in color from pale yellow to deep gold. Changes in color can result from drugs, diet, or disease. 1. A red color may indicate, among other things, the presence of blood. 2. A brownish yellow color may indicate the presence of conjugated bilirubin. 3. Other shades of red, orange, or brown may be caused by ingestion of various drugs (e.g., rifampin). 26
  • 27. URINALYSIS B. pH • 1. Normal pH ranges from 4.5 to 9.0 but is typically acidic (around 6.0). • 2. Alkaline pH may indicate such conditions as alkalosis. C. Specific gravity • Specific gravity provides a rough measure of urine concentration (osmolality). Normal range is 1.001 to 1.035; values may be low in the elderly or in patients with impaired renal function, who are less able to concentrate urine. • It is measured by hydrometer or refractometer or estimated with a dipstick. the test may be sufficient for patients who have calculi and are advised to self-monitor urine concentration to maintain dilute urine. 27
  • 28. URINALYSIS D. Protein • Under normal conditions, plasma proteins remain in the glomerular capillaries and thus do not cross the glomerular basement membrane or enter the urinary space. • Some of these proteins, such as albumin and globulins are not filtered by the glomerulus as a result of charge and size selectivity (greater than 40 kDa) detected by standard dipstick tests, reflects mainly urinary albumin concentration, classified as negative (< 10 mg/dL), trace (15 to 30 mg/dL), or 1+ (30 to 100 mg/dL) through 4+ (> 500 mg/dL). E. Glucose • Glucose is usually not present in the urine because the kidney normally completely reabsorbs all the glucose filtered at the glomerulus. When a patient’s blood glucose concentration exceeds the maximum threshold for glucose reabsorption (~180 mg/dL [~10.0 mmol/L]), glucosuria will be present. • Routine assessment of glucosuria to monitor diabetics has been replaced by newer methods of direct blood glucose measurements. Urine glucose testing is now predominantly used as a screening tool for the detection of diabetes. 28
  • 29. URINALYSIS F. Ketones • Acetoacetate and acetone are not normally found in the urine; they are however excreted in patients with diabetic ketoacidosis. They are also present under conditions of fasting or starvation. • Typically, values of acetoacetate excretion are reported as small (less than 20 mg/dL [less than 2 mmol/L]), moderate (30-40 mg/dL [3-4 mmol/L]), and large (greater than 80 mg/dL [greater than 8 mmol/L]). 29
  • 30. URINALYSIS G. Evaluation. Microscopic examination: of centrifuged urine sediment normally reveals 0 to 1 RBC, • 0 to 4 WBCs, and only an occasional cast per high-power field (HPF). 1. Hematuria (i.e., the presence of RBCs) may indicate such conditions as trauma, a tumor, or a systemic bleeding disorder. In women, a significant number of squamous cells suggests vaginal contamination (menstruation). 2. Casts (i.e., protein conglomerations outlining the shape of the renal tubules in which they were formed) may or may not be significant. Excessive numbers of certain types of casts indicate renal disease. 3. Crystals, which are pH dependent, may occur normally in acid or alkaline urine. Uric acid crystals may form in acid urine; phosphate crystals may form in alkaline urine. 4. Bacteria do not normally appear in urine. The finding of 50 or more bacteria per HPF may indicate a urinary tract infection (UTI); smaller values may indicate urethral contamination. 30
  • 31. COMMON RENAL FUNCTION TESTS A. Introduction • 1. Renal function may be assessed by measuring blood urea nitrogen (BUN) and serum creatinine. • Renal function decreases with age, which must be taken into account when interpreting test values. • a. These tests primarily evaluate glomerular function by assessing the glomerular filtrationrate (GFR). • b. In many renal diseases, urea and creatinine accumulate in the blood because they are not excreted properly. • c. These tests also aid in determining drug dosage for drugs excreted through the kidneys. 31
  • 32. COMMON RENAL FUNCTION TESTS B. BUN • 1. Urea, an end product of protein metabolism, is produced in the liver. From there, it travels through the blood and is excreted by the kidneys. • 2. Normal values for BUN range from 8 mg/dL to 18 mg/dL (3.0 to 6.5 mmol/L). • a. Decreased BUN levels occur with significant liver disease. • b. Increased BUN levels may indicate renal disease. • C. Serum creatinine • Creatinine clearance parallels the GFR within a range of - +10% and is a more sensitive indicator of renal damage than BUN • levels because renal impairment is almost the only cause of an increase in the serum creatinine level. 3. Normal values for serum creatinine range from 0.6 to 1.2 mg/dL (50 to 110 mmol/L). • a. Values vary with the amount of muscle mass—a value of 1.2 mg/dL in a muscular athlete may represent normal renal function, whereas the same value in a small, sedentary person with little muscle mass may indicate significant renal impairment. 32
  • 33. COMMON RENAL FUNCTION TESTS • D. Creatinine clearance • 1. Creatinine clearance, which represents the rate at which creatinine is removed from the blood • by the kidneys, roughly approximates the GFR. • One estimation uses the method of Cockcroft and Gault, which is based on body weight, age, and gender. a. This formula provides an estimated value, calculated as: • • • 140−𝑎𝑔𝑒 𝑎𝑔𝑒 (𝐵𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡 𝑘𝑔 ) 72 ×𝑆𝑒𝑟𝑢𝑚 𝑐𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒 ( 𝑚𝑔 𝑑𝐿 ) × 0.85 (𝑖𝑓 𝑓𝑒𝑚𝑎𝑙𝑒) 33
  • 34. COMMON RENAL FUNCTION TESTS • Determination of GFR. Th e modified diet in renal disease (MDRD) equation is considered • a more accurate measurement of GFR than other equations used to estimate renal function • (e.g., Cockcroft –Gault) in patients with reduced GFR and is used in staging renal disease. Patients • must have a serum creatinine concentration. • a. The MDRD equation for males is as follows: • GFR 186 (Pcr)-1.154 age-0.203 where Pcr is serum creatinine. For females, multiply the result by 0.742; for African Americans, multiply by 1.210. 34
  • 35. Electrolytes • Sodium (Na) • Sodium is the major cation of the extracellular fluid. Sodium, along with chloride (Cl), potassium • (K), and water, is important in the regulation of osmotic pressure and water balance between • intracellular and extracellular fluids. Normal values are 135 to 147 mEq/L or mmol/L. • An increase in sodium concentration (hypernatremia) may indicate impaired sodium excretion or dehydration. A decrease in sodium concentration (hyponatremia) may reflect overhydration, abnormal sodium loss, or decreased sodium intake. • Patients with kidney, heart, or pulmonary disease may have difficulty with sodium and water balance. In adults, changes in sodium concentrations most often reflect changes in water balance, not salt imbalances. Therefore, sodium concentration is often used as an indicator of fluid status, rather than salt imbalance. • Control of sodium by the body is accomplished mainly through the hormones aldosterone and antidiuretic hormone (ADH). 35
  • 36. Electrolytes • Hyponatremia is usually related to total body depletion of sodium—as in mineralocorticoid deficiencies, sodium-wasting renal disease, replacement of fluid loss with non-saline solutions, gastrointestinal (GI) losses, renal losses, or loss of sodium through the skin—or to dilution of serum sodium—as in cirrhosis, CHF, nephrosis, renal failure, excess water intake, or syndrome of inappropriate antidiuretic hormone (SIADH) secretion. • Hypernatremia usually results from a loss of free water or hypotonic fluid or through excessive sodium intake. Excess sodium intake can occur through the administration of hypertonic intravenous (IV) solutions, mineralocorticoid excess, excessive sodium ingestion, or aft er administration of drugs high in sodium content (e.g., ticarcillin, sodium bicarbonate [HCO3]). 36
  • 37. Electrolytes • Potassium (K) • Potassium is the most abundant intracellular cation (intracellular fl uid potassium averages 141 mEq/L). Approximately 3500 mEq of potassium is contained in the body of a 70-kg adult. • Only 10% of the body’s potassium is extracellular. Normal values are 3.5 to 5.0 mEq/L or mmol/L. • The serum potassium concentration is not an adequate measure of the total body potassium because most of the body’s potassium is intracellular. • Fortunately, the clinical signs and symptoms of potassium deficiency—malaise, confusion, dizziness, electrocardiogram (ECG) changes, muscle weakness, and pain—correlate well with serum concentrations. 37
  • 38. Electrolytes • Hypokalemia can occur. Th e kidneys are responsible for approximately 90% of the daily potassium loss. Other losses occur mainly through the GI system. Even in states of no potassium intake, the • kidneys still excrete up to 20 mEq of potassium daily. • Therefore, prolonged periods of potassium deprivation can result in hypokalemia. Hypokalemia can also result from potassium loss through vomiting or diarrhea, nasogastric suction, laxative abuse, and by diuretic use ( mannitol, thiazides, or loop diuretics). Excessive mineralocorticoid activity and glucosuria can also result in hypokalemia. • Potassium can be shifted into cells with alkalemia and aft er administration of glucose and insulin. • Hyperkalemia most commonly results from decreased renal elimination, excessive intake, or from cellular breakdown (tissue damage, hemolysis, burns, infections). 38
  • 39. Electrolytes • Chloride (Cl) • 1. Chloride is the major anion of the extracellular fluid and is important in the maintenance of acid– base balance. Alterations in the serum chloride concentration are rarely a primary indicator of major medical problems. Chloride itself is not of primary diagnostic significance. It is usually measured to confirm the serum sodium concentration. The normal value for Cl is 95 to 105 mEq/L or mmol/L. • 2. Hypochloremia is a decreased chloride concentration, and it is often accompanied by metabolic alkalosis or acidosis caused by organic or other acids. • Hyperchloremia is an increased chloride concentration that may indicate hyperchloremic metabolic acidosis. Other causes include acute renal failure, dehydration, and excess chloride administration. 39
  • 40. Electrolytes • Bicarbonate (HCO3)/carbon dioxide (CO2) content • The carbon dioxide (CO2) content represents the sum of the bicarbonate (HCO3) concentration and the concentration of CO2 dissolved in the serum. Most disturbances of acid–base balance can be considered in terms of this system. Normal values are 22 to 28 mEq/L or mmol/L. • Hypobicarbonatemia is usually caused by metabolic acidosis, renal failure, hyperventilation, severe diarrhea, drainage of intestinal fluid, and by drugs such as acetazolamide. Toxicity caused by salicylates, methanol, and ethylene glycol can also decrease the HCO3 level. • Hyperbicarbonatemia is usually caused by alkalosis, hypoventilation, pulmonary disease, persistent vomiting, excess HCO3 intake with poor renal function, and diuretics. 40
  • 41. MINERALS • Calcium (Ca) • Calcium plays an important role in nerve impulse transmission, muscle contraction, pancreatic insulin release, and hydrogen ion release from the stomach, as a cofactor for some enzyme reactions and blood coagulation and, most important, bone and tooth structural integrity. Normal total calcium values are 8.8 to 10.3 mg/dL or 2.20 to 2.56 mmol/L. • Most laboratories measure the total calcium concentration; however, it is the free, ionized calcium that is important physiologically. Ionized calcium levels may be obtained from the laboratory. • Clinically, the most important determinant of ionized calcium is the amount of serum protein (albumin) available for binding. The normal serum calcium range is for a serum albumin of 4.0 g/dL. • Hypocalcemia usually implies a deficiency in either the production or response to parathyroid hormone (PTH) or vitamin D. 41
  • 42. MINERALS • Calcium cont’d • PTH abnormalities include hypoparathyroidism, pseudohypoparathyroidism, or hypomagnesemia. • Vitamin D abnormalities can be caused by decreased nutritional intake, decreased absorption of vitamin D, a decrease in production, or an increase in metabolism. • Hypercalcemia is an increased calcium concentration, and it is usually associated with malignancy or metastatic diseases. Other causes include hyperparathyroidism, Paget disease and drugs like thiazides 42
  • 43. MINERALS • Phosphate (PO4) • 1. Phosphate is a major intracellular anion and is the source of phosphate for adenosine triphosphate (ATP) and phospholipid synthesis. Serum calcium and PO4 are influenced by many of the same factors. • It is useful to consider calcium and PO4 together when interpreting lab results. Normal PO4 values are 2.5 to 5.0 mg/dL or 0.80 to 1.60 mmol/L. • Hyperphosphatemia and hypophosphatemia: Hyperphosphatemia is usually caused by renal insufficiency, although increased vitamin D or phosphate intake, hypoparathyroidism, and hyperthyroidism are also causes. • Hypophosphatemia can occur in malnutrition, especially when anabolism is induced, after administration of aluminum-containing antacids or calcium acetate, in chronic alcoholics, and in septic patients. Hyperparathyroidism and insufficient vitamin D intake can also induce hypophosphatemia. 43
  • 44. MINERALS • Magnesium (Mg) • Magnesium is the second most abundant intracellular and extracellular cation. • Normal values are 1.6 to 2.4 mEq/L or 0.80 to 1.20 mmol/L. • Hypomagnesemia and hypermagnesemia can occur. Hypomagnesemia is found more often than hypermagnesemia. • Depletion of magnesium usually results from excessive loss from the GI tract or the kidneys. Depletion can occur from either poor intestinal absorption or excessive GI fluid loss. Signs and symptoms include weakness, muscle fasciculations with tremor, tetany, and increased reflexes. 44
  • 45. MINERALS • Hypermagnesemia is most commonly caused by increased magnesium intake in the setting of renal insufficiency. Other causes include excess magnesium intake, hepatitis, and Addison disease. • Signs and symptoms of hypermagnesemia include bradycardia, flushing, sweating, nausea and vomiting, decreased calcium level, decreased deep- tendon reflexes, flaccid paralysis, increased pulse rate and QRS intervals, respiratory distress, and asystole. 45
  • 46. Uric Acid Uric Acid Normal Range • Male 3.4-8.5 mg/dL SI 202-506 μmol/L • Females 2.3-6.6 mg/dL SI 137-393 μ mol/L • Description Uric acid is the main metabolic end product of the purine bases of DNA. Clinical Significance • Increased Uric Acid • Increased uric acid (hyperuricemia) may be caused by excessive production of purines or inability of the kidney to excrete urate. Common causes of hyperuricemia are renal dysfunction, metabolic acidosis, tumor lysis syndrome, purine-rich diet, and use of furosemide, thiazide diuretics, and niacin. • Hyperuricemia may be associated with the development of gouty arthritis, nephrolithiasis, and gouty tophi 46
  • 47. Uric Acid • Decreased Uric Acid • Decreased uric acid levels (hypouricemia) are usually of little clinical significance but may occur with a low-protein diet, deficiency of xanthine oxidase, or use of allopurinol, probenecid, or high doses of aspirin or vitamin C. 47
  • 48. LIPOPROTEIN PANEL • LIPOPROTEIN PANEL Total Serum Cholesterol • Blood Levels • Desirable level < 200 mg/dL SI < 5.17 mmol/L • Borderline high 200-239 mg/dL SI 5.17-6.19 mmol/L • High cholesterol >= 240 mg/dL SI > 6.20 mmol/L Description • Cholesterol is an important component of cell membranes and is necessary for the synthesis of many hormones and bile acids. • Elevated total serum cholesterol is well known to be associated with an increased risk of developing coronary heart disease (CHD). • Total serum cholesterol is a useful screening test to determine CHD risk 48
  • 49. LIPOPROTEIN PANEL • Clinical Significance • Adults over 20 years of age should have a baseline fasting lipoprotein profile, and testing should be repeated at least every 5 years thereafter. Cholesterol levels should be performed after the patient has fasted for at least 9 to 12 hours. • Increased Serum Cholesterol • In cases of elevated cholesterol (hypercholesterolemia), the need for diet or drug therapy should be based on the individual components of the lipid profile (LDL, HDL, and triglycerides [TG]) and the number of CHD risk factors. • Some causes of hypercholesterolemia include obesity, familial hypercholesterolemia, and cholestasis. • Decreased Serum Cholesterol Decreased cholesterol levels may be seen in malabsorption, malnutrition, hyperthyroidism, chronic anemia, or severe liver disease. • However, low total serum cholesterol usually indicates good health. 49
  • 50. Low-Density Lipoproteins • Low-Density Lipoproteins • Desired Range • No CHD and < 2 CHD risk factors < 160 mg/dL (4.13 mmol/L) • No CHD and >= 2 CHD risk factors < 130 mg/dL (3.36 mmol/L) • With CHD or diabetes < 100 mg/dL (2.58 mmol/L) (optional < 70) • Description • Low-density lipoprotein (LDL) is a major cholesterol transport protein which comprises 60% to 70% of total serum cholesterol. LDL is considered the “bad” cholesterol, and has been linked to atherosclerosis. • Clinical Significance • Low-density lipoprotein is not normally measured directly due to expense and time required. In addition to lipid disorders, elevated LDL may also be associated with diabetes mellitus, diets high in cholesterol and saturated fat, hypothyroidism, and nephrotic syndrome. 50
  • 51. High-Density Lipoproteins • Blood Levels • Low < 40 mg/dL SI < 1.03 mmol/L • High >= 60 mg/dL SI > 1.55 mmol/L • Description • High-density lipoproteins (HDL) are responsible for transport of 20% to 30% of serum cholesterol. HDL removes excess cholesterol from peripheral tissues to the liver. It is considered the “good” cholesterol, and elevated HDL levels are associated with a decreased risk for CHD. • Clinical Significance • Decreased HDL may be associated with cigarette smoking, poorly controlled diabetes mellitus, lack of exercise, familial hypertriglyceridemia, and use of anabolic/androgenic steroids or b-blockers. • It is estimated that CHD risk increases by 2% to 3% with each 1 mg/dL decrease in HDL. • Elevated HDL may be seen with moderate alcohol intake or in patients taking estrogen, oral contraceptives, or nicotinic acid. 51
  • 52. Triglycerides • Blood Levels • Normal range < 150 mg/dL SI < 1.7 mmol/L • Borderline high 150-199 mg/dL SI 1.7-2.26 mmol/L • High 200-499 mg/dL SI 2.26-5.64 mmol/L • Very high >= 500 mg/dL SI > 5.64 mmol/L • Description • Triglycerides are the main storage form of fatty acids, and they account for greater than 90% of dietary fat intake. • Clinical Significance • Triglycerides may be significantly elevated in the non-fasting state and should be measured after a fast of at least 12 to 14 hours. 52
  • 53. Triglycerides • In addition to lipid disorders, elevated triglycerides (hypertriglyceridemia) may be associated with a non-fasting sample, poorly controlled diabetes mellitus, pancreatitis, nephrotic syndrome, chronic renal failure, alcoholism, gout, and use of oral contraceptives or intravenous lipid infusion. • Decreased triglycerides may be associated with malnutrition or brain infarction. 53
  • 54. ENDOCRINE TESTS: THYROID FUNCTION • Thyroid-Stimulating Hormone • Normal Range • 0.3-5 mU/mL SI 0.3-5 μU/L • Description • Thyroid-stimulating hormone (TSH) is a sensitive screening test used to detect hypothyroidism or hyperthyroidism. An abnormal TSH level should be followed up with further thyroid testing, for example, free thyroxine. TSH is also useful for monitoring therapy for hypothyroidism or hyperthyroidism. • Clinical Significance • Elevated TSH • Elevated TSH levels are indicative of hypothyroidism. In patients taking thyroid replacement therapy, an elevated TSH suggests the need for an increase in the dose of thyroid medication. 54
  • 55. ENDOCRINE TESTS: THYROID FUNCTION • Low TSH • Abnormally low TSH levels (< 0.10) are associated with hyperthyroidism. In patients taking thyroid replacement therapy, a decreased TSH indicates the need to reduce the dose of thyroid medication. • Total Thyroxine • Normal Range • 4-12 mg/dL SI 51-154 nmol/L • Description • Thyroxine (T4) is the predominant circulating thyroid hormone. Total serum thyroxine measures both free thyroxine and thyroxine bound to thyroxine binding globulin, albumin, and prealbumin. • Only the unbound thyroxine is active. T4 levels are a measure of the functional status of the thyroid gland. • T4 may also be used to monitor thyroid therapy. • T4 levels may be affected by conditions that increase or decrease the thyroxine-binding proteins 55
  • 56. ENDOCRINE TESTS: THYROID FUNCTION • Clinical Significance • Increased T4 • T4 can be increased in hyperthyroidism, pregnancy, hepatitis, and with the use of estrogen replacement therapy, oral contraceptives. • Decreased T4 • Decreased T4 is most commonly seen in hypothyroidism, but may also be associated with renal failure, malnutrition, liver disease, and use of medications that compete for T4-binding sites on T4- binding proteins (eg, salicylates). Free Thyroxine • Normal Range • 0.8-2.7 ng/dL SI 10-35 pmol/L Description • Because total T4 levels can be affected by conditions that alter the amount of thyroxine-binding proteins, free T4 is a more accurate reflection of clinical thyroid status 56
  • 57. • Free Thyroxine cont’d • Clinical Significance • Free T4 is a diagnostic test that may be used to confirm the diagnosis of hypothyroidism (decreased free T4) or hyperthyroidism (increased free T4). 57 ENDOCRINE TESTS: THYROID FUNCTION
  • 58. • Total Triiodothyronine • Normal Range • 80-200 ng/dL SI 1.2-3.1 nmol/L • The majority of T3 is formed from deiodination of T4 in the kidney and liver. Total T3 measures both bound and unbound T3. T3 is usually used in the diagnosis of hyperthyroidism or T3 toxicosis, but has little utility in the diagnosis of hypothyroidism. • Clinical Significance • Increased T3 • Increased T3 is seen in hyperthyroidism, T3 thyrotoxicosis (Grave disease), and with high doses of levothyroxine. Pregnancy and use of estrogens or oral contraceptives may also be associated with elevated T3. 58 ENDOCRINE TESTS: THYROID FUNCTION
  • 59. ENDOCRINE TESTS: THYROID FUNCTION • Total Triiodothyronine cont’d • Decreased T3 • Decreased T3 may be associated with hypothyroidism, malnutrition, and • anorexia. Corticosteroids and propranolol decrease peripheral conversion of • T4 to T3 and may result in reduced T3 levels. 59
  • 60. ENDOCRINE TESTS: DIABETES MELLITUS • Glycosylated Hemoglobin (Hemoglobin A1c) • Normal Range • The normal range lies between 4% and 6%. • Description • The hemoglobin A1c (HbA1c) measures the percentage of hemoglobin A molecules that are glycosylated (bound to glucose). During the life span of an RBC, glucose binds irreversibly to hemoglobin in the RBC. As the serum glucose becomes more elevated, more glucose binds to the hemoglobin. • Because the RBC has a life span of approximately 120 days, the HbA1c reflects average blood glucose for the previous 2 to 3 months. 60
  • 61. • Glycosylated Hemoglobin (Hemoglobin A1c) cont’d • Clinical Significance • The HbA1c may be used to assess glucose control over the 2 to 3 months • preceding the test. • The American Diabetes Association recommends a target HbA1c of less than 7% for most diabetic patients. An HbA1c greater than 7% indicates the need for improved diabetic control through adjustment of diet, exercise, or medication regimen. 61 ENDOCRINE TESTS: DIABETES MELLITUS
  • 62. ENDOCRINE TESTS: DIABETES MELLITUS • Generally, the correlation between HbA1c and the estimated average blood glucose (eAG) can be described by the following equation: eAG(mg/dL) = 28.7 × A1c - 46.7 62 A1c (%) Glucose (mg/dL) A1c (%) Glucose (mg/dL) 6 126 7 154 8 183 9 212 10 240 11 269 12 298 It is important to remember that the HbA1c does not provide an indication of the variability in glucose levels, only an estimate of the average. HbA1c may not be a reliable indicator of the average glucose in patients with anemia, hemolysis, or acute blood loss.
  • 63. ENDOCRINE TESTS: ADRENAL GLAND • Cortisol • Normal Range • Morning 6-25 mg/dL 165-690 nmol/L • Evening 3-16 mg/dL 83-441 nmol/L Description • Cortisol is a hormone produced by the adrenal cortex. It plays a critical role in carbohydrate metabolism and response to stress. Clinical Significance • Increased Cortisol • Increased cortisol levels are associated with Cushing syndrome, Cushing disease, • hyperthyroidism, pregnancy, stress, and morbid obesity.2 • Decreased Cortisol • Decreased cortisol may be secondary to Addison disease, hypothyroidism, or decreased pituitary function 63
  • 64. ENDOCRINE TESTS: ADRENAL GLAND • Urine Free Cortisol • Normal Range • Cortisol level 24-108 mcg/24 hours (varies with assay). • Description • Urine free cortisol is a screening test for Cushing syndrome. Urine is collected for 24 hours, and cortisol and creatinine levels are measured.8,14 • Clinical Significance • Cortisol levels greater than 200-250 mcg/24 hours are highly suggestive of • Cushing syndrome 64
  • 65. ENDOCRINE TESTS: ADRENAL GLAND • Overnight Dexamethasone Suppression Test • Normal Range • Cortisol less than 5 mg/dL at 8:00 AM. • Description • In the overnight dexamethasone suppression test, 1 mg of dexamethasone is given at 11 PM, and plasma cortisol levels are drawn at 8:00 AM. In a normal patient, the administration of exogenous steroid (dexamethasone) should suppress the release of cortisol from the adrenal gland. • The dexamethasone suppression test is useful in the diagnosis of Cushing syndrome. • Clinical Significance • A plasma cortisol level greater than 5 mg/dL suggests the diagnosis of Cushing syndrome 65
  • 66. ENDOCRINE TESTS: ADRENAL GLAND • Adrenocorticotropic Hormone • Normal Range • < 60 pg/mL SI < 13.2 pmol/L • Description • ACTH is a hormone secreted from the anterior pituitary. It controls the release of cortisol from the adrenal gland. • Clinical Significance • Increased ACTH • Increased ACTH may be associated with Cushing disease, adrenal hyperplasia, • Addison disease, or ectopic ACTH production. 66
  • 67. ENDOCRINE TESTS: ADRENAL GLAND • Decreased ACTH • Decreased ACTH may be seen in adrenal malignancy or states of pituitary insufficiency. 67
  • 68. ENDOCRINE TESTS: ADRENAL GLAND • ACTH Stimulation Test (Cosyntropin) 68
  • 69. ENDOCRINE TESTS: ADRENAL GLAND • ACTH Stimulation Test (Cosyntropin) • Description • The ACTH stimulation test is used to detect adrenal insufficiency. In the • ACTH stimulation test, a baseline cortisol level is drawn. Then synthetic ACTH (cosyntropin) is administered, and cortisol and aldosterone levels are collected 30 and 60 minutes post-administration. • Clinical Significance • Normal • A normal response is a rise in cortisol greater than 10 mg/dL above baseline or a cortisol level greater than 20 mg/dL.2,8,14 • Abnormal If plasma cortisol remains low and fails to rise greater than 10 mg/dL above baseline, this is indicative of adrenal insufficiency. • The aldosterone level will help to determine if the adrenal insufficiency is related to failure of the adrenal gland (primary adrenal insufficiency) or malfunction of the pituitary gland (secondary adrenal insufficiency) 69
  • 70. Helicobacter pylori IgG • Description • Helicobacter pylori is a gram-negative rod that is responsible for the majority of cases of peptic ulcer disease. H pylori can be detected in 90% to 100% of patients with duodenal ulcers and 70% to 80% of patients with gastric ulcers. H pylori IgG is a serologic test that detects antibodies to H pylori. • A positive test indicates the presence of H pylori. Normal value is negative. • Clinical Significance • A positive H pylori IgG in the presence of symptoms is highly suggestive of peptic ulcer disease, and a course of antibiotic therapy is warranted. • H pylori has been linked to some types of gastric lymphoma and gastric cancer. 70
  • 71. Hemoccult • Normal Value • Normal value is negative. • Description • The hemoccult test is used to detect the presence of occult blood in the stool. • Clinical Significance • A positive hemoccult test indicates blood loss in the gastrointestinal tract and deserves further work-up. • A false-positive result may be obtained if the patient has consumed red meat, broccoli, turnips, or radishes within 3 days of the test. • Aspirin (in doses > 325 mg daily), NSAIDs such as ibuprofen, and excess ETOH consumption have also been associated with false positives. False negatives may occur in patients taking high doses of vitamin C or consuming large amounts of citrus fruits or juices 71
  • 72. COAGULATION TESTS • Prothrombin Time • Normal Range • 10-13 seconds (varies with thromboplastin and test method used). • Description • The prothrombin test is sensitive to changes in the levels of clotting factors prothrombin (factor II), factor VII, and factor X. • It is performed by adding thromboplastin and calcium to a plasma sample. After addition of these reagents, the time it takes for the blood to clot is measured. • Clinical Significance • The prothrombin time (PT) is used to monitor warfarin therapy. Because the PT may vary according to the thromboplastin used to test the sample, the international normalized ratio (INR) is a better monitoring tool. 72
  • 73. COAGULATION TESTS • Prothrombin Time cont’d • The normal PT in a person not on anticoagulation therapy is 10 to • 13 seconds. An increased PT may be seen with anticoagulation therapy, liver • disease, vitamin K deficiency, and clotting factor deficiencies 73
  • 74. COAGULATION TESTS • International Normalized Ratio (INR) • Desired Range • Depends on indication for anticoagulation (see below). • Description • Because the PT may vary due to the thromboplastin used, the INR is used to standardize the PT. • Clinical Significance • An INR below the desired range indicates suboptimal anticoagulation and a need to increase warfarin dosage. Conversely, an INR above the desired range indicates a need to omit and/or reduce the warfarin dosage. • Patients with elevated INRs and/or bleeding may require the administration of vitamin K, fresh frozen plasma, or clotting factors 74
  • 75. COAGULATION TESTS • International Normalized Ratio (INR) • To appropriately interpret an INR value and decide on the need for dosage adjustments, patients should be questioned regarding dosage of warfarin, missed doses, dietary intake, alcohol intake, and concomitant medications 75
  • 76. COAGULATION TESTS • Activated Partial Thromboplastin Time • Normal Range • The time varies between 20 and 35 seconds. • Description • It is used to monitor heparin therapy. Monitoring of the aPTT is usually not required for patients receiving low molecular weight heparin. • Clinical Significance • The normal value above represents a control range for patients not on anticoagulation therapy. Patients on heparin therapy will have an elevated aPTT. 76
  • 77. • An aPTT below the desired therapeutic range indicates the need to rebolus and/or increase the heparin infusion rate. An aPTT above the desired therapeutic indicates the need to hold and/or reduce the dose of heparin. • Patients with clinically significant bleeding may require reversal with protamine sulfate. 77
  • 78. IMMUNOLOGIC TESTS • Antinuclear Antibodies • Normal Value • Negative at 1:20 dilution (varies). • Description • Antinuclear antibodies (ANA) are antibodies directed against structures in the cell nucleus, for example, nucleic acids. • The ANA test is used as a diagnostic tool for autoimmune and connective tissue diseases, particularly systemic lupus erythematosus (SLE). • Clinical Significance • High titers may be associated with SLE, rheumatoid arthritis, scleroderma, Sjogren syndrome, polymyositis, dermatomyositis, and drug-induced lupus. 78
  • 79. • Rheumatoid Factor • Normal Value • The normal value is either less than 1:20 or less than 20 IU/mL. • Description • Rheumatoid factor (RF) is an immunoglobulin whose activity is directed against IgG. Thus, a positive RF test (titer > 1:20 or level > 20 IU/mL) is indicative of an autoimmune process. • Clinical Significance • A positive rheumatoid factor test is most commonly associated with rheumatoid arthritis but may also be seen with SLE, Sjogren syndrome, scleroderma, malignancy, and infectious diseases such as tuberculosis, syphilis, mononucleosis, and endocarditis. 79 IMMUNOLOGIC TESTS
  • 80. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Enzyme Immunoassay for HIV • Description • The enzyme immunoassay (ELISA or EIA) for HIV detects antibodies to HIV. It is a highly sensitive and specific test and is the most commonly used screening test for HIV. • Positive tests should be repeated to assure positive results. Repeatedly positive samples should be confirmed with the Western blot test or immunofluorescence assay. • False Negative • False negatives may be seen in early HIV infection and bone marrow transplant. 80
  • 81. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Western Blot • Description • The Western blot is a confirmatory test used following a positive ELISA result. • It detects antibodies to specific proteins of the HIV virus. • Clinical Significance • Positive Result • A positive result following a positive ELISA test confirms the diagnosis of HIV. • Negative Result • A negative result indicates no HIV antibodies. The ELISA in this case can be considered a false positive 81
  • 82. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Indeterminate Result • Indeterminate results may occur if seroconversion is not complete (ie, it is too early in the disease process). Individuals should be retested at a later date. • Venereal Disease Research Laboratory Test • Normal Value • Normal value is nonreactive. • Description • The venereal disease research laboratory (VDRL) is a nontreponemal serologic test used to screen for syphilis. It may also be used to assess response to syphilis therapy. • Clinical Significance • A positive VDRL titer is suggestive of syphilis. 82
  • 83. INFECTIOUS DISEASE DIAGNOSTIC TESTS • HEPATITIS A • Anti-HAV IgM • Normal Value • Normal value is negative. • Description • Hepatitis A IgM antibodies may be detected in the serum 4 to 6 weeks after exposure to hepatitis A and often coincide with the onset of symptoms and jaundice. • Clinical Significance • The presence of anti-HAV IgM indicates acute or recent hepatitis A infection. 83
  • 84. INFECTIOUS DISEASE DIAGNOSTIC TESTS • HEPATITIS B • Hepatitis B Surface Antigen • Normal Value • Normal value is negative. • Description • Hepatitis B surface antigen (HBsAg) is an envelope protein on the surface of the hepatitis B virus. It can be detected in the serum 4 to 12 weeks after infection. • Clinical Significance • A positive test for HBsAg indicates acute hepatitis B. Persistence of HBsAg for 6 months or more after acute infection is indicative of chronic hepatitis B. 84
  • 85. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Hepatitis B “e” Antigen • Normal Value • Normal value is negative. • Description • Hepatitis B “e” antigen (HBeAg) is used to assess the degree of infectivity of patients with hepatitis B. • Clinical Significance • Presence of HBeAg is associated with active viral replication and a high degree of infectivity. HBeAg is usually present for 2 to 6 weeks after acute infection. • Persistence of HBeAg is indicative of ongoing viral replication, that is, chronic hepatitis B. 85
  • 86. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Hepatitis B Core Antibody • Normal Value • Normal value is negative. • Description • Hepatitis B core antibody (anti-HBc) IgM and IgG may be detected in the blood a few weeks after the appearance of HBsAg. • Clinical Significance • Positive anti-HBc IgM is a sensitive marker for acute hepatitis B infection. 86
  • 87. INFECTIOUS DISEASE DIAGNOSTIC TESTS • Hepatitis B Surface Antibody • Normal Value • Normal value is negative. • Description • Hepatitis B surface antibody (anti-HBs) is usually detected in the blood 3 to 4 months after infection.37 • Clinical Significance • Presence of anti-HBs indicates recovery and immunity to hepatitis B. • Individuals who have been vaccinated for hepatitis B will test positive for anti-HBs 87
  • 88. INFECTIOUS DISEASE DIAGNOSTIC TESTS • HEPATITIS C • Hepatitis C Antibody • Normal Value • Normal value is negative. • Description • Hepatitis C antibody (anti-HCV) is used as a screening test for hepatitis C virus. • Clinical Significance • Presence of anti-HCV indicates prior exposure to or chronic infection with hepatitis C. Unlike antibodies to hepatitis A and B, antibodies to hepatitis C do not confer immunitysed as a screening test for hepatitis C virus. 88