Review of Laboratory and

Diagnostic Tests
 Provide important information
• The response to drug therapy
• The ability of patients to metabolize
• Eliminate specific therapeutic agents
• The diagnosis of disease
• Progression of disease
• Regression of disease
 Laboratory and diagnostic tests
• Invasive tests
– Require penetration of the skin or insertion of instruments or
device into a body orifice
– Risk: pain, bleeding, bruising, death
– Exp: collection of blood, insertion of a central venous catheter,
collection of cerebrospinal fluid
• Noninvasive test
– Do not penetrate the skin or involve insertion of instruments into
body orifices
– Risk: little
– Exp: chest radiograph, analysis of spontaneously voided urine, stool
occult blood analysis
 Normal Values Lab Test
• Inside the range  “normal”
• Outside the range  “abnormal”
• Helpful in assesing clinical disorders,
establishing a diagnosis, assesing drug
theraphy, evaluating disease progression
• Unit of measures
– SI Units
– Conventional Units
 Laboratory Error
• Patient-related factors (e.g., age, gender, weight, height, time since last meal)
• Laboratory-based issues
– improper handling or processing (e.g., hyperkalemia due to hydrolysis of a blood
specimen);
– it was taken at a wrong time (e.g., fasting blood glucose level taken shortly after a meal);
– collection was incomplete (e.g., 24-hour urine collection that does not span a full 24-hour
period);
– faulty or poor quality reagents (e.g., improperly prepared, outdated);
– technical errors (e.g., human error in reading result, computer-keying error);
– interference from medical procedures (e.g., cardioconversion increases creatine kinase
[CK] serum concentrations);
– dietary effects (e.g., rare meat ingestion can cause a false-positive guaiac test);
– medications can interfere either with the testing procedure or by their pharmacologic
effects (e.g., thiazides can increase the serum uric acid concentration, β-agonists can
reduce serum potassium concentrations).
Laboratory tests and diagnostic procedures

• Angiography: radiographic test used to evaluate blood

vessels and the circulation
• Biopsy: involves removal and evaluation of tissue
• Computed tomography: (CT, CAT scan) uses
computerized x-ray system to produce detailed
sectional x-ray images
• Doppler echography: uses ultrasound technology to
measure shifts in frequency from moving images
• Endoscopy: is used to examine the interior of hollow
viscus or canal
Angiography
CT Scan
Echocardiography
Laboratory tests and diagnostic procedures

• Magnetic Resonance Imaging (MRI): uses an

externally applied magnetic field to align the
axis of nuclear spin of cellular nuclei
• Standard radiography: (plain film, X-Ray Films)
produces images on photographic plates by
passing rontgen rays through the body .
• Ultrasonography (Echography): uses ultrasound
to create images of organs and vessels. Ex: it is
used to visualize the fetus in utero
Chest X-Ray
MRI
 Cardiovascular system
• CARDIAC ENZYMES
– The pattern and time course of the appearance of enzymes in the
blood after cardiac muscle cell damage are used to diagnose MI
• Creatine kinase
– CK-MB is detected in the blood within 3 to 5 hours after MI; level
peak in about 10 to 20 hours and normalize within about 3 days
• Lactic Dehydrogenase (LDH)
– After MI, the rise in LDH1 concentration exceeds the rise in LDH2
concentration (the LDH 1 to LDH2 ratio is > 1). LDH increases within
12 hours after MI, peaks between 24 and 48 hours, and normalizes
by about day 10
 Cardiovascular system
• C-Reactive Protein
– Is a biological marker of systemic inflammation
– CRP naikrisiko tinggi MI, stroke
• Troponin
– Are a complex of proteins (Troponin I, C and T)
– Troponin I and T concentrations increase within a
few hours of cardiac muscle injury and remain
elevated for 5 to 7 days
 Cardiovascular System
• Electrocardiogram (ECG): records the electrical
activity of the heart
Index Reference Range
Creatinine kinase
Female 40-150 U/L
Male 60-400 U/l
CK-MB 0-7.5 ng/ml
C-reactive protein <8µg/ml
Lactic dehydrogenase 110-210 U/L
Lactic dehydrogenase isoenzymes
LDH1 17-27%
LDH2 28-38%
LDH3 18-28%
LDH4 5-15%
LDH5 5-15%
Troponins
Troponin I <0.35 ng/ml
Troponin T <0.2 µg/L
 Electrolyte
• Sodium
• Potassium
• Chloride
• BUN
• Creatinine
• Glucose (fasting)
• Uric Acid
Index Reference Range (covent) Reference Range (SI unit)
Sodium 135-145 mEq/L 135-145 mmol/L
Potassium 3.5-5 mEq/L 3.5-5 mEq/L
Chloride 95-105 mEq/L 95-105 mEq/L
BUN 8-18 mg/dL 2.8-6.4 mmol/L
Creatinine 0.6-1.2 mg/dL 50-110 µmol/L
Glucose (fasting) 70-110 mg/dL 3.9-6.1 mmol/L
Uric acid 2-7 mg/dL 0.12-0.42 mmol/L
 Sodium
• Sodium is the predominant cation of extracellular fluid (ECF)
• Dietary intake of sodium is balanced by renal excretion of sodium
• An increase in the serum sodium concentration could suggest
either impaired sodium excretion or volume contraction
• Conversely, a decrease in the serum sodium concentration to less-
than-normal values could reflect hypervolemia, abnormal sodium
losses, or sodium starvation.
• Although healthy individuals are able to maintain sodium
homeostasis without difficulty, patients with kidney failure, heart
failure, or pulmonary disease often encounter sodium and water
imbalance.
•
 Potassium
• Sodium is the major cation in the ECF, and
potassium is the major intracellular cation in
the body
• The clinical manifestations of potassium
deficiency (e.g., fatigue, drowsiness, dizziness,
confusion, electrocardiographic changes,
muscle weakness, muscle pain) correlate well
with serum concentrations.
 Chloride
• Chloride is the principal inorganic anion of the
ECF; changes in chloride concentration are
usually related to sodium concentration in an
effort to maintain a neutral charge
 Blood Urea Nitrogen
• Urea nitrogen is an end product of protein metabolism
• It is produced solely by the liver, is transported in the
blood, and is excreted by the kidneys. T
•
• Acute or chronic renal failure is the most common
cause of an elevated BUN.
• Although the BUN is an excellent screening test for
renal dysfunction, it does not sufficiently quantify the
extent of renal disease.
 Case Study
• 1. M.C., a 61-year-old woman with no known drug allergies (NKDA) is
hospitalized with a chief complaint of increasing shortness of breath
(SOB) and orthopnea over the past week. She has been treated
previously for heart failure and has not taken any medication over the
past 2 weeks. M.C. has severe (4+) pedal edema and is in respiratory
distress. Laboratory tests were ordered and reported back as follows:
sodium (Na), 123 mEq/L (normal, 135–145); potassium (K), 4.1 mEq/L
(normal, 3.5–5.0); chloride (Cl), 90 mEq/L (normal, 95–105); carbon
dioxide (CO2), 28 mEq/L (normal, 22 to 28); blood urea nitrogen
(BUN), 30 mg/dL (normal, 8–18); serum creatinine (SCr), 1.3 mg/dL
(normal, 0.6–1.2); and fasting glucose, 100 mg/dL (normal, 70–110).
Why should M.C. not be given sodium chloride to return her serum
sodium concentration to a normal value?
• All body fluids are in osmotic equilibrium, and changes in
serum sodium concentration are associated with shifts of
water into and out of cells. M.C. has 4+ pedal edema and
heart failure; her serum concentration of sodium is
probably low because her plasma volume is increased
relative to sodium. The serum sodium concentration in
this case does not reflect total body sodium content. The
usual treatment for this type of hyponatremia is salt and
water restriction combined with diuresis in an attempt to
remove the excess fluid associated with M.C.'s heart
failure
• 2. Why is the BUN abnormal for M.C. (from
question 1)?
• The BUN serum concentration in M.C. is
somewhat increased, perhaps because of
inadequate renal perfusion secondary to her
heart failure. Her renal function could also be
more severely compromised than one would
anticipate from her slightly increased BUN
value because of dilution by increased ECF
volume. Therefore, M.C.'s renal status should
be further evaluated.
 Creatinine
• Creatinine is derived from creatine and phosphocreatine,
major constituents of muscle. Its rate of formation for a given
individual is remarkably constant and is determined primarily
by an individual's muscle mass or lean body weight.
• Once creatinine is released from muscle into plasma, it is
excreted renally almost exclusively by glomerular filtration.
• A decrease in the glomerular filtration rate (GFR) results in an
increase in the SCr concentration.
• Thus, careful interpretation of the SCr concentration is used
widely in the clinical evaluation of patients with suspected
renal disease
• M.C. was given digoxin 0.125 mg/day, and a
SCr was ordered to further assess her renal
function. The clinical laboratory determined
her SCr was 1.2 mg/dL. Although this
laboratory test result is within normal limits,
why does it not clearly indicate normal renal
function for M.C.?
• A SCr of 1.2 mg/dL in M.C. does not necessarily reflect
normal renal function. As patients become older,
muscle mass represents a smaller proportion of total
weight, and creatinine production is decreased.
Furthermore, the SCr concentration in female patients
is generally 0.2 to 0.4 mg/dL (85%–90%) less than for
males because females have relatively smaller
kidneys. Because M.C. is a 61-year-old woman, a
creatinine clearance (CrCl) determination would more
accurately reflect her renal function status.
 Glucose
• The fasting glucose concentration in the ECF is regulated
closely by homeostatic mechanisms to provide body tissues
with a ready source of energy.
• Insulin and glucagon play a critical role in this complex process.
• Generally, normal glucose values refer to the plasma glucose
concentration in the fasting state
• Glucose testing using whole blood from capillary finger sticks is
used in conjunction with blood glucose metering devices for
patients with diabetes.
• Whole blood measurements using these devices are typically
15% lower than corresponding plasma glucose levels.
• T.C., a 68-year-old male, visits his endocrinologist to
assess control of his type 2 diabetes. His average
blood sugar over the past 90 days recorded via his
blood glucose monitor is 217 mg/dL. However, T.C.'s
Hgb A1c was 9%, which correlates with an average
glucose concentration of roughly 240 mg/dL. T.C. is
confused that these values are different because he
routinely ensures his blood glucose machine is
calibrated and coded properly. Why is the laboratory
average different?
• T.C. should not be alarmed with the difference in these values. His blood
glucose monitor is probably working properly and adequately measuring
fluctuations in his plasma glucose concentrations. However, the monitor may
be reflecting a lower average glucose concentration due to the timing of his
daily testing for glucose. For example, measuring blood glucose in a fasting
state more frequently than after mealtime could contribute to lower average
concentrations because fasting values are typically lower than postprandial
concentrations. The A1c is more indicative of his average blood sugar control
over the past 90 days than the 90-day average recorded by his blood glucose
monitor. A higher concentration of glucose in the blood positively correlates to
a higher glycosylated Hgb. This value is typically reported as a percentage, with
approximately 5% (100 mg/dL) considered as normal in a person without
diabetes. As the A1c percentage increases, each point raises thecorresponding
blood glucose value by about 35 mg/dL (e.g., 8% = 205 mg/dL, 9% = 240
mg/dL).
 Uric Acid
• Uric acid is an end product of purine metabolism.
• It serves no biological function, is not metabolized, and
must be excreted renally.
• Gout is usually associated with increased serum
concentrations of uric acid and deposits of monosodium
urate.
• Increased serum uric acid concentrations can result from
either a decrease in urate excretion (e.g., renal
dysfunction) or excessive urate production (e.g., increased
purine metabolism resulting from cytotoxic therapy of
neoplastic or myeloproliferative disorders).
 Liver Function Tests
• Aspartate Aminotransferase
– Normal: 0 to 35 units/L or 0 to 0.58 µkat/L
– The AST enzyme, formerly called “serum glutamic oxaloacetic
transaminase,” is abundant in heart and liver tissue and
moderately present in skeletal muscle, the kidney, and the
pancreas.
– In cases of acute cellular injury to the heart or liver, the
enzyme is released into the blood from the damaged cells
– In clinical practice, AST determinations have been used to
evaluate myocardial injury and to diagnose and assess the
prognosis of liver disease resulting from hepatocellular injury
 Liver Function Tests
• Alanine Aminotransferase
– Normal: 0 to 35 units/L or 0 to 0.58 µkat/L
– The ALT enzyme, formerly called “serum glutamic pyruvic transaminase,” is
found in essentially the same tissues that have high concentrations of AST
– In cases of acute cellular injury to the heart or liver, the enzyme is released
into the blood from the damaged cells
– However, elevations in serum ALT are more specific for liver-related injuries or
diseases.
– Evaluating the ratio of ALT to AST can be potentially useful, particularly in the
diagnosis of viral hepatitis.
– The ALT/AST ratio frequently exceeds 1.0 with alcoholic cirrhosis, chronic liver
disease, or hepatic cancer.
– However, ratios <1.0 tend to be observed with viral hepatitis or acute
hepatitis, which can be useful when diagnosing liver disease.
• L.M., a 59-year-old female currently taking atorvastatin 40 mg daily
for hypercholesterolemia, complains of fatigue and myalgia over
the past week since her last prescription refill. On assessment, her
primary care provider determines she has been taking an incorrect
dose. Instead of cutting an 80-mg tablet in half, she has been taking
the entire tablet, thereby effectively doubling her dose. The
physician orders liver function tests (LFTs), CK, and SCr to evaluate
her myalgia. Laboratory results indicate the following: AST, 51
units/L (normal, <35); ALT, 72 units/L (normal, <35); ALP, 82 units/L
(normal, 30–120); CK, 216 units/L (normal, <150); and SCr, 1.4
mg/dL (normal, 0.6–1.2). Why are these laboratory results of
sufficient concern to warrant discontinuation of atorvastatin?
• L.M.'s LFTs are elevated and are of concern, particularly in light of her other
signs and symptoms. Statins have been implicated in causing elevations in
LFTs on initiation of therapy and with dose increases. LFTs can be increased
by up to three times the upper limit of normal. In the absence of jaundice
or other clinical signs and symptoms, reduction of her atorvastatin dose
will generally be sufficient in returning LFTS to normal values without
adverse sequelae. L.M.'s values will likely return to baseline when her
atorvastatin dose is reduced to 40 mg or discontinued. Additional
monitoring after intervention would be indicated to confirm whether her
LFTs stabilize or whether a trend of elevations is noted on multiple
occasions. CK serum concentrations can also be increased in response to
muscle injury or myalgia. When CK increases ten times the upper limit of
normal, myopathy should be suspected. L.M.'s CK is mildly increased at this
time, but not at an alarming value.
 Cholesterol and Triglycerides
• Cholesterol total
– Normal <200 mg/dL or <5.2 mmol/L
– Desirable = Total <200; LDL 70–160 (depends on
risk factors); HDL >45 mg/dL; ↑ LDL or ↓ HDL are
risk factors for cardiovascular disease.
• Triglycerides (fasting)
– Normal <160 mg/dL or <1.80 mmol/L
– ↑ by alcohol, saturated fats, drugs (propranolol,
diuretics, oral contraceptives). Obtain fasting level.
 Complete Blood Count
• A CBC measures the RBCs, Hgb, Hct, mean cell volume (MCV), mean
cell Hgb concentration (MCHC), and total white blood cells (WBCs)
• Red Blood Cells (Erythrocytes)
– Males—Normal: 4.3 to 5.9 × 106/mm3 or 4.3 to 5.9 × 1012/L
– Females—Normal: 3.5 to 5.0 × 106/mm3 or 3.5 to 5.0 × 1012/L
– Erythrocytes or RBCs are produced in the bone marrow, released into the
peripheral blood, circulated for approximately 120 days, and cleared by the
reticuloendothelial system.
– The primary function of RBCs is to transport oxygen to tissues.
– The concentration of RBCs in the blood can be measured to detect anemia,
calculate RBC indices, or calculate the Hct.
– Hct and Hgb concentrations are generally used to monitor quantitative
changes in RBCs.
• Hematocrit
– Males—Normal: 39% to 49% or 0.39 to 0.49 I
– Females—Normal: 33 to 43% or 0.33 to 0.43 I
– Hct (packed cell volume) is determined by centrifuging a capillary
tube of whole blood and comparing the height of the settled RBCs
to the height of the column of whole blood.
– The percentage of RBCs to the blood volume is the Hct.
– A decrease in Hct may result from bleeding, the bone marrow
suppressant effects of drugs, chronic diseases, genetic alterations
in RBC morphology, or hemolysis.
– An increase in Hct may result from hemoconcentration,
polycythemia vera, or polycythemia secondary to chronic hypoxia.
• Hemoglobin
– Males—Normal: 14 to 18 g/dL or 140 to 180 g/L
– Females—Normal: 12 to 16 g/dL or 120 to 160 g/L
– Hgb is the oxygen-carrying compound contained in RBCs.
– Therefore, total Hgb concentration primarily depends on
the number of RBCs in the blood sample.
– As mentioned with Hct, medical conditions that impact
the number of RBCs will also affect Hgb concentration.
– Glycosylated Hgb (A1c) is a related test used to monitor
diabetes mellitus.
• White Blood Cells
– Normal: 3.2 to 9.8 × 103/mm3 or 3.2 to 9.8 × 109/L
– Leukocytes or WBCs are comprised of five different types of cells.
– Neutrophils are the most abundant of the circulating WBCs, followed in order of
frequency by lymphocytes, monocytes, eosinophils, and basophils.
– The neutrophils, eosinophils, basophils, and monocytes are formed from stem cells
in the bone marrow.
– Lymphocytes are formed primarily in the lymph nodes, thymus, spleen, and, to a
lesser extent, bone marrow.
– Each WBCs has unique functions, and it is best to consider them independently
rather than collectively as “leukocytes.”
– Ultimately, all WBCs contribute to host defense mechanisms.
– A convenient mnemonic for remembering the various types of WBCs is “Never Let
Monkeys Eat Bananas” (N = neutrophils; L = lymphocytes; M = monocytes; E =
eosinophils; and B = basophils).
Index Reference Range (covent) Reference Range (SI unit)
Neutrophils 54%–62% 0.54–0.62
↑ in neutrophils suggests bacterial or fungal infection. ↑ in bands suggests bacterial
infection.
Lymphocytes 25%–33% 0.25–0.33
Monocytes 3%–7% 0.03–0.07
Eosinophils 1%–3% 0.01–0.03
Eosinophils ↑ with allergies and parasitic infections.
Basophils <1% <0.01
• R.L., a 45-year-old man, is hospitalized with a
sustained high fever of 39.4°C, SOB, and pleurisy.
His cough is productive of rusty sputum, and he
appears to be in acute distress. The results of the
CBC and leukocyte differential are as follows: total
WBC count, 18,000/mm3; neutrophils, 76%; bands,
13%; lymphocytes, 10%; monocytes, 0; eosinophils,
1%; and basophils, 0. On the basis of this laboratory
report and other findings, a diagnosis of
pneumococcal pneumonia is suspected. How is
R.L.'s laboratory report consistent with bacterial
infection?
• WBCs are the host's chief defense system, and the neutrophil
is the main component of that system. During bacterial
infections, the leukocyte count and the neutrophils are
generally increased, and a left shift (increase in bands) may
be noticeable. The percentage of other types of WBCs is
decreased proportionately because the number of
neutrophils is increased.
• As the infection progresses, the percentage of band cells may
decrease as a result of an increase in the number of
neutrophils that have a longer half-life. This decrease in bands
does not necessarily indicate improvement. A decrease in the
percentage of neutrophils with a decrease in the total WBC
count is characteristic of effective antibiotic therapy.
• S.Q., a 35-year-old woman, was treated for 7
days with dicloxacillin for cellulitis of the left
leg. On the eighth day, an allergic urticarial
rash developed. The CBC showed a total
leukocyte count of 10,000/mm3 with 6%
eosinophils. What is the significance of this
eosinophil count?
• In the clinical setting, absolute leukocyte counts may be used in
conjunction with normal reference values. Absolute counts are calculated
by multiplying the percentage of each individual cell by the total leukocyte
count. Eosinophils are usually increased in allergic reactions; therefore, a
drug-induced hypersensitivity reaction is a strong probability in S.Q., with
an absolute count of 600 eosinophils/mm3 (i.e., 6% of 10,000 leukocytes).
The clinician should be suspicious of an allergic drug reaction when
absolute eosinophil counts exceed 300 cells/mm3. Eosinophils may increase
before, after, or concurrent with other evidence of allergy (e.g., rash).
Eosinophilia without evidence of allergy is not sufficient cause to
discontinue a suspected medication unless the eosinophilia is significant
(i.e., >2,000 cells/mm3). In addition, the absence of eosinophilia certainly
does not rule out an allergic diagnosis in a patient exhibiting clear clinical
manifestations of an apparent allergic reaction.