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– faulty or poor quality reagents (e.g., improperly prepared, outdated);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.
• In adults, changes in serum sodium concentrations most often
represent water imbalances rather than sodium imbalances. .
 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.
• The serum concentration of urea nitrogen (i.e., BUN) is
reflective of renal function because the urea nitrogen in
blood is filtered completely at the glomerulus of the kidney,
and then reabsorbed and tubularly secreted within
nephrons.
• 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 1
• 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?
 Case 2
• 2. Why is the BUN abnormal for M.C. (from
question 1)?
 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
 Case 3
• M.C., 61-year-old woman, 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.?
 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.
 Case 4
• 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?
 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.
 Case 5
• 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?
 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
 Case 6
• 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?
 Case 7
• 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?