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2 Interpreting Clinical Laboratory Data

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Interpreting Clinical Laboratory Data
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Out line
• Introduction
• Diagnostic tests (General principle)
– Electrolytes ,
– Renal Function tests , Liver function tests
– Hematology
– Urine analysis
– Cardiovascular tests, Endocrine function test , Lipid panels
– Diagnostic imaging
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Why Bother?
• Pharmacist is a member of the health care team and
must ensure safe and effective drug therapy
• Need for information
– Patients details
 Disease History,
 Medication History,
 Laboratory data
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As a pharmacist
• You should be able to:
- Recognize normal ranges for common lab results in adults and
children
- Identify causes for abnormal values and interpret their clinical
significance
- Identify circumstances for false negative and false positive
- Utilize laboratory data to monitor disease states
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Introduction
Laboratory findings, both normal and abnormal,
can be helpful in assessing clinical disorders,
establishing a diagnosis, assessing drug
therapy, or evaluating disease progression.
In addition, baseline laboratory tests are often
necessary to evaluate disease progression
and response to therapy or to monitor the
development of toxicities associated with
therapy.
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Uses of lab data for pharmacist
 Ensure drug and dose is appropriate for each patient
 Monitor Adverse drug reactions
 Assess need for additional or alternative therapy
 Monitor response to therapy
 Prevent misinterpretation from drug interference
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General Principles: Reference ranges
• Reference ranges: aka “normal ranges”.
– Fall inside pre-determined values
• Abnormal ranges
 Fall outside pre-determined ranges
 Various factors affect lab results: age, disease state, lab
factors, drugs etc
 Not all abnormal values need to be treated
Remember: ALWAYS TREAT THE PATIENT NOT THE LAB VALUE!!
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Factors affecting Lab results
• Patient-related factors
– e.g., age, gender, weight, time since last meal
• Laboratory based issues
Spoiled specimen
Taken at wrong time
Incomplete collection
Technical error
Faulty reagents
• Dietary effect
• Medication
– e.g., thiazides can increase the serum uric acid concentration
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Electrolytes
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Sodium (Normal: 135–145 mEq/L)
• Sodium is the predominant cation of extracellular fluid (ECF).
• Only a small amount of sodium (∼5 mEq/L) is in intracellular
fluid (ICF).
• Along with chloride, potassium, and water, sodium is important
in establishing serum osmolarity and osmotic pressure
relationships between ICF and ECF.
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Sodium (Normal: 135–145 mEq/L)
• Extracellular cation (95% in ECF)
• Na+ balance is regulated by renal:
Aldostrone (Na+ reabsorption)
Natriuretic hormone (Na+ excretion)
Antidiuretic hormone (reabsorption of free water)
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Hyponatremia
• can result from dilution of the sodium concentration in serum or
from a total body depletion of sodium.
• Some clinical conditions (e.g., cirrhosis, congestive heart failure, renal
impairment), as well as the administration of osmotically active
solutes (e.g., albumin, mannitol), are commonly associated with
dilutional hyponatremia.
• Sodium-depletion hyponatremia can be caused by mineralocorticoid
deficiencies, sodium-wasting renal disease, or replacement of
sodium-containing fluid losses with non saline solutions.
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Hypernatremia
• can be caused by the loss of free water, loss of hypotonic fluid, or
excessive sodium intake.
• Free water loss is uncommon, except in the presence of diabetes
insipidus.
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Case 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
during the past week. She has been treated previously for heart failure and has
not taken any medication during 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
Potassium (K), 4.1 mEq/L
Chloride (Cl), 90 mEq/L
Carbon dioxide (CO2), 28 mEq/L
Blood urea nitrogen (BUN), 30 mg/dL
Serum creatinine (SCr), 1.3 mg/dL
Fasting glucose, 260 mg/dL
Should M.C. be given sodium chloride to return her serum sodium concentration to a
normal value?
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Potassium (Normal: 3.5–5.0 mEq/L)
• Potassium is the major intracellular cation in the body.
• Because the majority of potassium is sequestered within cells, a serum potassium
concentration is not a good measure of total body potassium
• The clinical manifestations of potassium deficiency (e.g., fatigue, drowsiness,
dizziness, confusion, electrocardiographic changes, muscle weakness, muscle pain)
correlate well with serum concentrations.
• During depletion K+ moves from the ICF into the ECF to maintain serum
concentration
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Potassium
• Serum potassium concentrations, therefore, can be misleading when interpreted
in isolation from other considerations, and assumptions should not be made as to
the status of total body potassium concentration based solely on a serum
concentration measurement.
• When the serum concentration decreases by a mere 0.3 mEq/L, the total body
potassium deficit is approximately 100 mEq
– ↓ 0.3 mEq/L =100 mEq the total body K+ deficit
• The kidneys are responsible for about 90%of daily potassium loss (∼40–90
mEq/day), and the remaining 10% of potassium excretion each day is managed by
the gastrointestinal (GI) system and the dermatologic system (i.e., sweating).
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Causes for Hypokalemia
• Prolonged intravenous therapy with potassium-free solutions in a
patient unable to obtain potassium in foods (e.g., nothing by mouth
[NPO] patient).
• Patients who are on thiazide or loop diuretics
• Vomiting and Severe diarrhea,
• Insulin and stimulation of β2-adrenergic receptors
• Treatment - replacement (IV or PO)
– KCl (IV)
– KCl, phosphate, or acetate (PO)
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Causes for Hyperkalemia
• decreased renal excretion of potassium,
• excessive exogenous potassium administration (especially when
combined with a potassium-sparing diuretic), or
• excessive cellular breakdown (e.g., hemolysis, burns, crush injuries,
surgery, infections).
• Metabolic acidosis also can induce hyperkalemia as hydrogen ions
move into cells in exchange for potassium and sodium.
– During Metabolic acidosis, for every 0.1 decrease in pH from 7.4, the serum potassium
concentration will be falsely elevated by about 0.6 mEq/L
• Use of ACE inhibitors, and K-sparing diuretics
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Treatment for Hyperkalemia
o Check ECG
o Na+ polystyrene sulfonate (Kayexalate) PO or rectal
o Loop diuretics
o Hemodialysis (if severe)
o IV calcium (to antagonize cardiac effect of K)
o regular insulin (shift) + dextrose (for insulin)
o Albuterol
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Case 2
• M.C. also has type 1 diabetes mellitus, and is
hospitalized a couple of months later for ketoacidosis.
Her fasting blood glucose is 802 mg/dL, her urine output
is 140 mL/hour, and her urine is positive (4+) for glucose
and ketones. M.C.’s blood pH is 7.1, and her serum
potassium concentration is 4.1 mEq/L.
• Although M.C.’s serum potassium concentration is
normal, why is her serum potassium of concern?
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Chloride (Normal: 96 – 106 mEq/L)
•Major anion involved in extracellular fluid balance and makes up
about two-thirds of the inorganic anion in plasma.
• Chloride is measured routinely along with other electrolytes,
sodium, potassium, and carbon dioxide and results are used to
calculate the anion gap.
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Chloride Con’t …
• When chloride is selectively depleted, most common seen in
vomiting, nasogastric suction, and in patients who developed a
metabolic alkalosis.
• The anion gap is much increased.
• Cl- exchanged with bicarbonate to maintain acid/base balance
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Bicarbonate
• HCO3 - Reference range (2- 28 mEq/L)
• Bicarbonate ions are controlled by kidney
 Increase in Bicarbonate concentration of the serum
–Metabolic alkalosis
exchange with chlorine
 Decrease in serum bicarbonate
–Metabolic acidosis
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Anion Gap
• Reference range : 5 - 12 mEq/mL , or < 16 mEq/mL
• represents the contribution of unmeasured acids like
lactate, phosphates, sulfates, and proteins
• Anion gap = (Primary cation – primary anion)
• Elevated anion gap shows metabolic acidosis
• Low anion gap
E.g - Hypoalbuminemia, Hyperviscosity of multiple myeloma
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Magnesium (Normal: 1.5–2.4 mEq/L)
• Magnesium is primarily an intracellular electrolyte
• metabolic role in the phosphorylation of adenosine triphosphate (ATP)
• Hypomagnesemia
– Primary cause is Malnourishment
– Should be corrected before attempting to correct hypokalemia or hypocalcemia
• Hypermagnesemia
– Causes
• Excessive ingestion of magnesium-containing antacids
• reduced renal function
– can slow conduction in the heart, prolong PT intervals, and widen the QRS
complex
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Calcium
• Normal reference; CaT = 8.5–10.5 mg/dL , Cai = 4.5 to 5.6mg/dL
• Resides primarily in the bone (99%)
• 40% is bound to plasma proteins (especially albumin)
• 5% to 15% is complexed with phosphate and citrate,
• 45% to 55% is in the unbound, ionized form
• The total serum calcium will decrease by 0.8 mg/dL for each decrease
of 1.0 g/dl in serum albumin concentration (4.0g/dl)
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Calcium
Hypercalcemia
• Metastasis
• Hyperparathyroidism
• Meds - Lithium, Thiazides
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Hypocalcaemia
• Vit D deficiency,
• Pancreatitis,
• Loop diuretics and
• Alcoholism
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Glucose (Normal: 70–110 mg/dL)
 Glucose level is controlled by homeostatic mechanisms
 FBG can fluctuate acutely based on either meals or insulin use
 Hgb A1c is an average blood glucose concentration over the life span
of circulating RBCs.
 Every 1% reduction in the elevated A1c reduced the risk of
microvascular complications
• Hyperglycemia - Diabetes mellitus
• Hypoglycemia - Missed meal in a patient receiving insulin
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Uric Acid (Normal: 2.0 to 7.0 mg/dL)
• 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.
• Increased uric acid (Leads to Gout)
– decrease in excretion
– excessive urate production - Diuretics (thiazides, loops), Neoplastic
therapy
• Low serum uric acid concentrations
– hypouricemic drugs (e.g., high dosages of salicylates)
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Albumin (3.5 – 5 g/dl)
• Synthesized by the liver
• Hypoalbuminema associated with Edema
• Causes
 malnutrition,
 malabsorption,
 impaired synthesis by the liver
 Direct loss from the blood
• Used for therapeutic monitoring of drugs and electrolytes that
are highly protein bound
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Renal function test
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Blood Urea Nitrogen (BUN)
(Normal: 8–18 mg/dL)
• 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.
• Causes of elevated BUN
– renal failure
– high protein intake
– increased protein catabolism
– hydration status
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BUN : SCr (normal=15:1)
>20:1
If - decreased blood flow to the kidney (dehydration)
- increased protein in the blood
<15:1
if -
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renal failure
significant malnourishment
severe liver disease
muscular individuals, renal dialysis
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Case 1
• Why is the BUN abnormal for M.C. (from question 1)?
– Blood urea nitrogen (BUN), 30 mg/dL
– Serum creatinine (SCr), 1.3 mg/dL
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Creatinine (Normal: 0.6–1.2 mg/dL)
• Creatinine is derived from creatine and phosphocreatine (major
constituents of muscle).
• Less affected by exogenous factor
• determined primarily by an individual's muscle mass or lean
body weight
• A doubling of the SCr level roughly corresponds to a 50%
reduction in the GFR.
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Creatinine Clearance
(Normal: 90- 130 mL/min)
• measure of a patient's GFR (glomerular filtration rate)
• Important for dose adjustment
• To calculate measured CrCl - 24-hour urine is collected
[Urine conc.(mg/dL)] × [Total urine volume(mL/min)] / SCr(mg/dL)
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Cockcroft-Gault method – Estimated CrCl
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Case 2
• A 24-hour CrCl determination was ordered for E.S., a 63-yearold, 60-kg man. The following data were returned from the
clinical laboratory: total collection time was 24 hours; total urine
volume, 1,000 mL; urine creatinine concentration, 42 mg/dL;
and SCr, 1.7 mg/dL. Determine both the measured and the
estimated CrCl for E.S. based on the given data, and compare
and contrast these results.
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Aspartate Aminotransferase (AST)
(Reference Range: 0–35 units/L)
• The AST enzyme, formerly called “serum glutamic oxaloacetic
transaminase (SGOT),” is abundant in heart and liver tissue and moderately
present in skeletal muscle, the kidney, and the pancreas.
• useful for identifying inflammation and necrosis of the liver
• AST level is increased in more than 95% of patients after an MI
• Peak AST ~ extent of myocardial damage
• Alcoholic hepatitis: AST exceeds ALT (> 2:1 ratio)
• Drugs also may increase AST (Acetaminophen, Erythromycin, Levlodopa,
phenytoin, Niacin, Valproic acid)
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Con’t …
• Acute hepatic necrosis - both AST and ALT will be increased,
even before the appearance of clinical symptoms
• Parenchymal liver disease - 100 times greater than the usual
upper limits of AST and ALT
• AST serum concentration is usually higher than that of ALT in
patients with cirrhosis
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Alanine Aminotransferase (ALT)
(Reference range 0 – 35U/L)
• The ALT enzyme, formerly called “serum glutamic pyruvic
transaminase (SGPT),” is found in essentially the same
tissues that have high concentrations of AST.
• Elevations in serum ALT are more specific for liver-related
injuries
• The ALT/AST ratio frequently exceeds 1.0 with
– chronic liver disease, or
– hepatic cancer.
• ratios <1.0 tend to be observed with
– viral hepatitis or acute hepatitis
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Alkaline phosphatase (AP)
(Reference range : 30 – 120 u/L)
 derived primarily from liver and bone
 elevated ALP
–
–
–
–
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mild intrahepatic or extra hepatic biliary obstruction.
Drug-induced cholestatic jaundice (e.g Sulfonamides)
conditions of pronounced osteoblastic activity
periods of rapid bone growth
during pregnancy
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Bilirubin
• Total Bilirubin= 0.1–1.0 mg/dL Direct Bilirubin = 0–0.2
mg/dL
• Bilirubin is a breakdown product of Hgb
• Unconjugated (indirect) bilirubin is water insoluble and
is highly bound to serum albumin
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Bilirubin
Hyperbilirubinemia
• liver disease
• Hemolysis or increased breakdown of red blood cells
• Drugs
- Antipsychotic
- Sulfonamides (Infants) - kernicterus
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Jaundice
- Yellow discoloration secondary to accumulation of bile
- may be noticeable
• in the sclera (white) of the eyes at levels of about 2 to 3
mg/dL and
• in the skin at higher levels.
- Jaundice is classified conjugated jaundice or
unconjugated jaundice depending upon whether the
bilirubin is free or conjugated to glucuronic acid
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HEMATOLOGY
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Hematogenesis
• All blood cells are produced in the bone marrow
• Hematopoietic stem cell differentiates into:
o Lymphoid progenitor cell that matures into lymphocytes in the
lymphoid organs
o Myeloid progenitor cells that mature into:
- Neutrophils, Eosinophils, Basophils, Monocytes,
- Reticulocytes and erythrocytes
- Platelets
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Complete Blood Count
•
•
•
•
•
•
•
•
•
Red blood cells (RBCs),
Hemoglobin (Hgb),
Hematocrit (Hct),
Mean cell volume (MCV),
Mean cell Hgb concentration (MCHC),
Total white blood cells (WBCs)
Platelets,
Reticulocytes,
Leukocyte differential.
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Red Blood Cells (Erythrocytes)
Males—Normal: 4.3 - 5.9 × 106/mm3
Females—Normal: 3.5 - 5.0 × 106/mm3
• RBCs are produced in the bone marrow and circulate in
peripheral blood for about 120 days.
• Primary function of RBCs is to transport oxygen to tissues
• RBCs useful to detect anaemia
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Con’t …
•Causes of decrease in RBC count
-Decreased production
-Increased destruction (hemolysis)
-Blood loss
•Increased RBC count
–living at altitude
–chronic lung/heart disease
–tobacco use/carbon monoxide
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Hematocrit (Packed cell volume)
Males—Normal: 39% to 49%
Females—Normal: 33 to 43%
• The percentage of RBCs to the blood volume
• Hct are 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
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Con’t …
A decrease in Hct may result from
• bone marrow suppressant drugs,
• chronic diseases,
• genetic alterations in RBC morphology
• Hemolysis,
• bleeding,
An increase in Hct may result from
• COPD, high altitude,
• Dehydration,
• polycythemia vera or polycythemia secondary to chronic hypoxia
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Hemoglobin
(Males— 14 to 18 g/dL,
Females—12 to 16 g/dL)
• Hgb is the oxygen-carrier
• conditions that impact the number of RBCs will also affect Hgb
concentration.
• glycosylated Hgb (A1c) is used to monitor diabetes mellitus
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RBC Indices
• Are useful in classification of anaemia
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Mean Cell Volume (MCV)
• It is Volume occupied by a single RBC and detects changes in cell
size
• Microcytic anemia - Decreased MCV indicates a microcytic cell
(<80 fL*) , usually due to iron deficiency anemia.
• Macrocytic anemia (>100 fL) - A large MCV indicates a
macrocytic cell, which can be due to:
 Vitamin B12 or folic acid deficiency
 Underlying disease states (e.g., habitual alcohol ingestion, chronic liver
disease, anorexia nervosa, hypothyroidism, reticulocytosis, hematologic
disorders).
• MCV can be normal (Normocytic anemia) in a patient with a “mixed”
(microcytic and macrocytic) anemia.
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Mean cell hemoglobin (MCH) and Mean corpuscular
hemoglobin concentration (MCHC)
MCH - the weight of Hgb, while MCHC - the concentration of Hgb
• The MCHC is a more reliable index of RBC Hgb than MCH.
• Changes in Hgb content of RBCs alter their color, so:
– Hypochromic: decrease in RBC Hgb, reflected by reduced MCHC, and
may indicate iron-deficiency anemia.
– Hyperchromic: elevated MCHC due to presence of greater amounts of
Hgb. These are not commonly encountered.
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Summary
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Reticulocytes
(Adults—Normal: 0.1% to 2.4% of RBCs)
• immature erythrocytes
• An increase in the number of reticulocytes implies an increased
number of erythrocytes are being released into the blood in
response to a stimulus.
• BCs regenerate rapidly, so reticulocytosis is noted within 3-5 days
after hemolysis or after a hemorrhagic episode
• Helpful to identify cause of Anemia
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Con’t …
• Increase Retic count
–Increase RBC production
–Haemorrhage, sickle cell disease
• Decrease count
–Infection, alcoholism, renal disease
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Erythrocyte Sedimentation Rate(ESR)
(Males—Normal: 0 to 20 mm/hour, Females—Normal: 0 to 30
mm/hour)
 ESR: rate at which RBCs settle to bottom of a test tube by gravity
and due to fibrinogen levels in the blood
 The ESR may be increased abnormally in
 acute and chronic inflammatory processes,
 acute and chronic infections,
 neoplasms,
 tissue necrosis,
 rheumatoid-collagen disease,
 dysproteinemias, nephritis, and
 pregnancy
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White Blood Cells
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White Blood Cells
• White Blood Cells (Normal: 4–11 × 10*3/μL or 4–11 × 10*9/L)
• five different types of cells
formed from
 stem cells in the bone marrow - Neutrophils, Monocytes,
Eosinophils, Basophils
 lymph nodes, thymus, or spleen - Lymphocytes
“Never Let Monkeys Eat Bananas”
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Neutrophils
 (Normal: 40% to 70% of WBC)
 “polys, segs, PMNs (polymorphonuclear
neutrophils), granulocytes”
 essential in killing invading microorganisms
 Immature neutrophils (bands) also
Cause of Neutrophilia
•Pathologic (Bacterial
infection, fungi,
Inflammatory responses to
tissue death)
•Burns
•Drugs (steroids, lithium)
• Physiologic
• Acute stress
increase in blood during bacterial
infection; this is known as “left shift”
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Agranulocytosis and Absolute Neutrophil Count
• Neutropenia is when <2,000 cells/mm3
• Agranulocytosis is severe neutropenia
 The % neutrophils indicates the severity of the infection
 the total WBC reflects the quality of the immune system
ANC =WBC × (% neutrophils + % bands)/100
• ANC exceeds 1,000/mm3 - low risk of infection;
• ANC is <500/mm3 - increased risk of infection
• ANC <100/mm3 - “profound neutropenia”
• The most common causes of neutropenia are metastatic carcinoma,
lymphoma, and chemotherapeutic agents.
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Lymphocytes: 20% to 40% of WBC
•
•
•
•
Main function -antigen recognition and immune response
T lymphocytes - cell-mediated immune responses
B lymphocytes - Humoral antibody responses
Therefore, diseases affecting lymphocytes manifest as immune
deficiency disorders (e.g. HIV) or as autoimmune diseases.
– elevated lymphocytes - lymphoma and viral infections
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Con’t
Lymphocytosis
- Hepatitis,
- viral infection (chickenpox, herpes)
Lymphocytopenia
• Acute infection
• Burns,
• trauma,
• HIV
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Monocytes: (0% to 11% of WBC)
• Monocytes are formed in the bone marrow and are the precursors to
macrophages and antigen-presenting cells (dendritic cells), which are
found in the body's tissues.
• Primary role is phagocytosis
Monocytosis occurs if
• subacute bacterial endocarditis,
• malaria,
• tuberculosis,
• recovery phase of some infections
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Eosinophils: 0% to 8% of WBC)
Eosinophilia is commonly associated with
• allergic reactions to drugs,
• allergic disorders (e.g., hay fever, asthma, eczema),
• invasive parasitic infections (e.g., hookworm, schistosomiasis,
trichinosis),
• collagen vascular diseases (e.g., rheumatoid arthritis), and
• Malignancies (e.g., Hodgkin disease)
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Basophils (Normal: 0 -3% of WBC)
During infection or inflammation, basophils leave the blood and
mobilize as mast cells to the affected site and release granules.
These granules contain histamine, serotonin, prostaglandins, and
leukotrienes
An increase in basophils
• allergic and anaphylactic responses,
• chronic myeloid leukemia,
• myelofibrosis, and
• polycythemia vera.
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Platelets (Thrombocytes)
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Platelets
• Thrombocytes (Normal: 150 to 450
× 103/mm3)
• (<50,000) may lead to spontaneous
hemorrhage
Thrombocytopenia
• decreased platelet production,
• accelerated destruction,
• dilution of blood samples secondary
to blood transfusion
• heparin
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• Thrombocytosis
 Malignancy,
 rheumatoid
arthritis,
 iron-deficiency
anemia,
 polycythemia vera,
and
 Post splenectomy
syndromes
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Coagulation Studies
• Tests below used to diagnose coagulation abnormalities or to
monitor the effectiveness of anticoagulation therapy.
 Prothrombin time (PT)
 International normalized ratio (INR), and
 Activated partial thromboplastin time (aPTT)
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Activated partial thromboplastin time (APTT)
Reference Range: 20–39 seconds
measures the intrinsic clotting system
- factors VIII, IX, XI, and XII and the factors involved in the final common
pathway of the clotting cascade (factors II, X, and V)
used to monitor unfractionated heparin
therapy
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Prothrombin Time (PT)
• Reference Range: 10–14 seconds
• Prothrombin is synthesized in liver and converted to thrombin during
the blood clotting process.
• measures the activity of clotting factors VII, X, prothrombin (factor II),
and fibrinogen
• PT measured by recording the time required for the blood to clot
after tissue thromboplastin is added to the patient’s blood sample
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International Normalized Ratio (INR)
• During initiation and maintenance of anticoagulant therapy
(warfarin)
• Reference range: 1.1 or less. Therapeutic goal 2-3
• variability observed between different laboratories
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Urinalysis
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Gross Appearance of the Specimen
- A standard urinalysis begins with simple observation of the colour
and the gross general appearance of the urine specimen.
- First-morning urine specimen
 Normal - Clear and slightly yellow
• Red - blood, phenolphthalein, beet root
• Brown- blood, Primaquine, Metronidazole, Chloroquine,
• Dark orange - Excessive excretion of urobilinogen ,rifampin or
phenazopyridine
• A blue to blue-green - methylene blue
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Specimen pH (pH 4.6 – 8)
Alkaline urine may indicate
• an aged specimen,
• systemic alkalosis,
• failure of renal acidifying mechanisms, or
• infection in the urinary tract
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Specific Gravity (1.002 to 1.025)
• Shows concentrating ability and hydration status
• water intake should be restricted
•Low specific gravity
– CRF (concentration ability) or
– Diabetes Insipidus (dilutional)
•Elevated specific gravity seen with elevated protein levels (100 to
750 m g/dL)
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Protein
- Sign of renal injury
a dipstick method
–
–
–
–
–
0 (<30 mg/dL),
1+ (30–100 mg/dL),
2+ (100–300 mg/dL),
3+ (300–1,000 mg/dL), and
4+ (>1,000 mg/dL)
• Protein > 150 mg/dL - refers to renal diseases
• Greater than 300 mg/dL is clinically significant
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Glucose
- Urinary threshold - > 180 mg/dL
- If glucose present
(1) hyperglycemia that exceeds the renal threshold for plasma glucose
(diabetes mellitus) or
(2) defective renal tubular reabsorption - congenital defects
•Drugs - thiazides, steroids, oral contraceptives
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Nitrite
• Gram –ve bacteria are capable of converting dietary nitrates into
nitrites
• If bacteria are present in the urine, there will be reduction of the
normally occurring nitrates to nitrites.
• Specific to presence of bacteria
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Bilirubin
–Normally no Bilirubin is detected in urine.
–Even trace amounts are clinically significant.
–Presence associated with liver diseases (hepatitis, obstructive
biliary tract diseases)
Drugs = phenazopyridine, phenothiazines
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Ketones
• Normal urine - negative with this test.
• Detectable levels seen during
–physiological stress such as fasting,
–pregnancy, and
–frequent strenuous exercise
• Large amounts with ketoacidosis due to starvation and abnormal
carbohydrate or lipid metabolism.
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ENDOCRINE TESTS
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Glucose
• Normal: 70–110 mg/dL (fasting)
• Hypoglycemia
Too much insulin
Not enough food
Increased physical activity
Illness
Injury
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Hypoglycemia
• Early signs: headache, hunger, mild agitation
• Blood sugar below 50 – 70 mg/dL
 Hallucinations or nervousness or outright hostility
 Cold sweat and tachycardia common but not required
• Blood sugar below 20 – 50 mg/dL
 Convulsions and loss of consciousness
 As sugar drops the convulsions stop but coma persists
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Hyperglycemic syndromes
• Diabetic ketoacidosis (DKA)
• Hyperglycemic hyperosmolar state (HHS)
• Manifestations – dehydration, polyuria/polydipsia, altered
mental status, nausea, emesis, abdominal pain
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Medications that affect glucose
• Beta blockers:
 Glycogenolysis & gluconeogenesis
Also mask hypoglycemic symptoms
• Phenytoin: suppress insulin secretion
• Diuretics: cause hyperglycemia
• Estrogen: contraceptives cause 43-61% increase; Progestrone
only – no effect
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Glucose Lab assessment
Initial diagnosis and short-term monitoring
– Fasting blood glucose
– Two hrs Post Prandial
– Oral Glucose Tolerance Test (OGTT)
Long-term monitoring
- Glycosylated hemoglobin (A1C)
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Fasting Plasma Glucose
• Normal: 80 – 110 mg/dl
• Prediabetes (impaired fasting glucose)
 110 < FPG < 126 mg/dl
• Diagnosis of DM:
 FPG > 126 mg/dl (at two occasions)
• FPG done after 8 hrs of fasting
• ADA recommend Q3 years screening (>30 yrs of age if have risk factors)
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Oral glucose tolerance test
• Normal: < 140 mg/dL
• Pre-diabetes : 2-hr post prandial glucose 140 – 200 mg/dL
• DM: 2-hr post prandial glucose ≥200 mg/Dl
– Commonly used to diagnosis gestational DM (pregnancy)
– 75 G glucose solution given over 5 min following overnight fasting
and blood drown at 0, 0-2 hr, and at 2 hrs.
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Thyroid Function Test
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TFT
• Secretion of the thyroid hormones T4
(thyroxine (tetra-iodothyronine)) and
T3 (tri-iodothyronine) is regulated by
pituitary thyrotropin (TSH).
• TSH secretion, in turn, is controlled
through negative feedback by thyroid
hormones.
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TFT con’t …
• Laboratory tests used to assess thyroid function:
 Serum TSH concentration - 0.5 to 5 μU/mL or mU/L
 Serum total T4 concentration - 4.6 to 11.2 mcg/dL
 Serum total T3 concentration - 75 to 195 ng/dL
 Serum free T4 concentration - Only 0.03 percent of serum
total T4
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Clinical use of TFT
Screening:
• Serum TSH normal: no further testing performed
• Serum TSH high: free T4 added to determine the degree of
hypothyroidism
• Serum TSH low: free T4 and T3 added to determine the degree
of hyperthyroidism
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Clinical use of TFT Con’t …
• Monitoring thyroxine therapy:
 Patients with primary hypothyroidism taking
levothyroxine replacement therapy: serum TSH
 If serum TSH is high, the dose needs to be increased;
 If it is low, the dose needs to be reduced
• Monitoring hyperthyroid patients
 Serum free T4 and T3 measurements (early)
 TSH (later)
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Cardiac Function Tests
• Cardiac biomarkers: useful for the evaluation, diagnosis, and
monitoring of patients with suspected heart injury
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Creatinine Kinase - 0 to 150 units/L
• In tissues that use high energy (skeletal muscle, myocardium,
brain)
• The serum concentration of CK can be increased by:
– Strenuous exercise,
– IM injections of drugs that are irritating to tissue (e.g., diazepam,
phenytoin)
– Acute psychotic episodes
– Crush injuries
– Myocardial damage
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Creatinine Kinase Con’t …
• CK is composed of M and B subunits, which are further divided
into three isoenzymes: MM, BB, and MB.
CK – MM predominantly in skeletal muscle,
CK – BB predominantly in the brain, and
CK – MB predominantly in the myocardium.
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Creatinine Kinase Con’t …
• CK-MB = 0-1 units/L
• Myocardial damage appears to correlate with the amount of CKMB released into the serum
The higher the amount of CK-MB, the more extensive the
myocardial injury
• CK-MB typically begins to increase 3 to 6 hours after an acute
myocardial infarction (MI), peaks at 12 to 24 hours
Remains elevated only for 2 to 3-days
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Troponin
• Troponins are proteins that mediate the calcium-mediated interaction of
actin and myosin within muscles.
• There are two cardiac-specific troponins, cardiac troponin I (cTnI) and
cardiac troponin T (cTnT).
• Whereas, cTnT is present in cardiac and skeletal muscle cells, cTnI is present
only in cardiac muscle
• cTnI - < 1.5 ng/Ml or < 1.5 mcg/L
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Troponin
• Compared with the detection of CK-MB, the presence of troponin I is a more
specific and sensitive indicator of myocardial damage
• The concentration of cTnI increases within 2 to 4 hours of an acute MI,
enabling clinicians to quickly initiate appropriate therapy.
• Troponin also remains elevated for about 10 days compared to the 2- to 3day elevation typically observed with CK-MB
• The use of troponin as a primary diagnostic test for acute MI is becoming
widely accepted as a standard
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Lipid Profile
• Also known as lipid panel or cholesterol
• Screen for abnormalities in lipids (dyslipidemia), a risk factor for
cardiovascular disease
• Tests for:




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Total cholesterol
High density lipoprotein
Low density lipoprotein
Triglycerides
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Lipid Profile
• Total cholesterol
– Ref values: < 200 mg/dL or 5.2 mmol/L
– Consider other risk factors to interpret
• Low density lipoprotein: bad lipid
– Ref values: 70–160 mg/dL
• High density lipoprotein: good lipid
– Ref values: 40 mg/dL
• Note: ↑ LDL or ↓ HDL are risk factors for
cardiovascular disease.
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Lipid Profile
• Triglycerides - Ref values: <150mg/dL
• ↑ by alcohol, saturated fats, drugs e.g., propranolol, diuretics,
oral contraceptives
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Thank you.
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Diagnostic Imaging
EKG
• Electrocardiography obtains a tracing of the electrical
activity of the heart.
–
–
–
–
sinus node of the right atrium
atrioventricular node
bundle of His
ventricles.
• Prominent parts of the ECG:
– P wave- atrial depolarization;
– QRS complex- ventricular depolarization; and
– T wave- ventricular repolarization.
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One normal cardiac cycle
113
P-Q interval … 0.16 s
Q-T interval 0.35 s
interval between two successive QRS complexes …. 0.83 s
114
Conventional radiography (x-rays)
• X-rays are a form of electromagnetic radiation,
able to pass through the human body and
produce an image of internal structures
• The common terms ‘chest X-ray’ and ‘abdomen
X-ray’
• As a beam of X-rays passes through the human
body, some of the X-rays are absorbed or
scattered producing reduction or attenuation of
the beam
1. Air/gas: black,
2. Fat: dark grey,
3. Soft tissues/water: light grey,
4. Bone: off-white
5. Contrast material/metal: bright white.
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CT scan
• CT is an imaging technique whereby cross-sectional
images are obtained with the use of X-rays.
• In CT, water is assigned an attenuation value of 0 HU
(Hounsfield units).
• fat and air, have negative values
• substances of greater density have positive values.
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Ultra sound (US)
• US imaging uses ultra-high-frequency sound waves to
produce cross-sectional images of the body.
• Solid organs, fluid-filled structures and tissue interfaces
produce varying degrees of sound wave reflection and
are said to be of different echogenicity.
• In an US image, hyper echoic tissues are shown as white
or light grey and hypo echoic tissues are seen as dark
grey
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Ultra sound (US)… con’t
• Advantages of US over other imaging modalities include:
– Lack of ionizing radiation, a particular advantage in pregnancy
and paediatrics
– Relatively low cost
– Portability of equipment.
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Ultra sound (US)… con’t
Disadvantages and limitations of US
- US is highly operator dependent.
- US cannot penetrate gas or bone.
- Bowel gas may obscure structures deep in the abdomen,
such as the pancreas or renal arteries.
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MRI
• MRI uses the magnetic properties of spinning hydrogen
atoms to produce images.
• patient is placed within a large powerful magnet
• white or light grey areas are referred to as ‘high signal’;
dark grey or black areas are referred to as ‘low signal’.
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Applications
• Imaging modality of choice for most brain and spine disorders
• Musculoskeletal disorders, including internal derangements of
joints and staging of musculoskeletal tumours
• Cardiac MR is an established technique in specific applications
including assessment of congenital heart disease and aortic
disorders
• MR of the abdomen is used in adults for visualization of the biliary
system, and for characterization of hepatic, renal, adrenal and
pancreatic tumours
• In children, MR of the abdomen is increasingly replacing CT for the
diagnosis and staging of abdominal tumours
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Hazards associated with medical imaging
• Exposure to ionizing radiation
• Anaphylactic reactions to iodinated contrast media
• Contrast-induced nephropathy (CIN)
• MRI safety issues
• Nephrogenic systemic sclerosis (NSF)
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Thank you.
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