Lecture 4: Intro to Lab Testing

Reasons to Order Lab Test

Screen

Diagnose

Manage Therapy

Prognosis

Osler’s Rule

If patient < 50 y/o, look for one etiology/one disease to explain all abnormal lab results

“Gold standard” test

Recognized best methodology against which new tests are compared

Test Accuracy

Test measures the true amount of a substance in a sample

Test Precision

Degree that result is consistently reproducible

Preanalytic events that compromise test results

Hemolysis #1 cause of rejection

Misidentification

Handling

Physiologic/biologic variation

Drugs & other interfering substances such as Biotin supplements (interfere with TSH, Troponin, T3-T4, Vit D levels, etc. in immunoassays)

Meals, hydration

Analytic events that compromise test results

Testing inaccuracies in the lab, e.g., bad reagents, bad instrument, etc.)

Rare

Postanalytic events that compromise test results

Errors in preparing or transmitting reports → result assigned to wrong patient or switched with another patient

Age-related variation in children

↑ Blood Lymphocyte count over adult range

↑ Alkaline phosphatase (ALP) in children & teens above adult from osteoblasts in active growth plates

Age-related variation in elderly

Albumin, total protein decrease starting mid-adult

GFR decreased

Creatinine decreased (lower muscle mass)

Muscle-related enzymes (AST, CPK) decreased (lower muscle mass)

Lymphocytes reduced

What common hormone shows a marked diurnal variation?

Cortisol highest in morning

Nicotine/tobacco smoke affects

↑ glucose, catecholamines, cortisol, free fatty acids; neutrophils; carboxyhemoglobin (Hb + CO due to carbon monoxide); ↑ CEA (Carcinoembryonic antigen)

Alcohol affects

↑ GGT (gamma glutamyl transferase) & Triglycerides

Caffeine affects

↑ catecholamines, glucose

Exercise/physical training/exertion affects

Strenuous exercise (post-marathon, etc.): ↑ muscle enzymes AST, CK, LD & ↑lactic acid

Well-trained athletes: ↓ glucose, WBCs, baseline CK

↑ bilirubin (hemolysis during exercise), ↑ BUN (due to high-protein diet; dehydration)

“Normal range”/Reference range

Values falling within 2 Standard Deviations from test mean

95% will have a result in the “normal range

2.5% will have a result above the “normal range” & 2.5% below

True positive (TP)

Positive result in patient with a certain disease/condition

True negative (TN)

Negative result in a patient who is without the disease

False positive (FP)

Positive result in a patient without disease

False negative (FN)

Negative result in a patient who has a disease

Ulysses Syndrome

The ill effects of extensive diagnostic

investigations conducted because of a false-positive result during routine laboratory screening

Sensitivity

True Positives/(True Positives + False Negatives)

Specificity

True Negatives/(True Negatives + False Positives")

Lower the prevalence

Higher the False positive rate

BUN (Blood Urea Nitrogen)

Made in Liver from Ammonia and excreted via Kidneys

Sensitive marker of decreased glomerular filtration (GFR)

↑ BUN & Creatinine = Azotemia (urea and nitrogen in blood

↑in renal disease & Poor renal perfusion (dehydration, shock, heart failure, etc.)

↑ in Catabolic states (fever, burns, diabetes, intense exercise)

↑ in GI bleeding due to digestion of blood into proteins & ↑BUN production

Creatinine

Catabolic end-product skeletal muscle Creatine (stores energy to make ATP)

Production is constant & proportional to muscle mass

Excreted by kidney: Indirect measurement of glomerular filtration (GFR)

Bilirubin

Waste product created from breakdown of Hemoglobin

Initially made in Unconjugated form (Indirect), then Conjugated in the liver (Direct bilirubin) & excreted via the bile ducts into GI tract

Prehepatic (unconjugated) hyperbilirubinemia is due to hemolysis

Intrahepatic (liver disease) as hepatitis, cirrhosis; liver failure: ↑ may be a mix of Unconjugated & Conjugated bilirubin

Posthepatic: due to large bile duct obstruction, as from gallstone (↑ Conjugated form)

AST (Aspartate aminotransferase)

Widely distributed; mitochondria & cytosol

Elevated in: Liver (hepatocyte) injury (“hepatitis”)

Skeletal muscle injury

ALT (Alanine aminotransferase)

In the cytosol

Elevated in: Liver injury

Alkaline Phosphatase (ALP)

Major source is from the Hepatobiliary system in cholestatic liver disease

Other from Bones of growing children & teenagers

Placenta (rises in pregnancy)

Minor sources: intestine, kidneys

Creatine Kinase (CK)/ Creatine Phosphokinase (CPK)

Total CK elevated in:

Skeletal muscle injury: trauma, intense exercise, Statin (drug) therapy; hypothyroidism; myositis; rhabdomyolysis

Myocardial infarction

Stroke/brain trauma

Globulins

Total Protein - Albumin

Albumin

Made in the Liver

Maintains oncotic pressure

Albumin decreased:

Impaired synthesis : malnutrition, malabsorption, hepatic disease

Increased loss: renal disease with proteinuria (particularly nephrotic syndrome), protein-losing gastroenteropathy

Polyclonal Gammopathy: chronic infection or inflammation

Decreased albumin

Polyclonal increase in γ globulins

Monoclonal Gammopathy: neoplastic plasma cell proliferation

“Monoclonal spike” potentially Malignant Multiple Myeloma

Hypogammaglobulinemia (or Agammaglobulinemia)

Indicative of B-cell immunodeficiency, congenital or acquired

Patient is at increased risk for pyogenic infections

Acute phase response

Inflammation (infectious or noninfectious, acute or chronic)

even if localized, if associated with significant production of inflammatory cell Cytokines (mainly TNF, IL-1, IL-6), may induce systemic reactions called Acute-phase response

Manifestations include Fever (>100°F; >38°C), production of acute-phase proteins (mainly by the Liver), Leukocytosis, & in cases of extreme cytokine production, Shock

Common Acute Phase Reactants (APR)

C-reactive protein

General scavenger molecule

Erythrocyte Sedimentation Rate (ESR)

Speed of fall of RBCs in a column of blood in mm/hr

ESR is a nonspecific indicator of inflammation

Procalcitonin

Mre severe the stimulus, the higher the elevations

Less than lower limit: bacterial infection is unlikely

Low level: localized infection or autoimmunity

High level: strongly favors severe bacterial infection

Also used to monitor effectiveness of Antibiotic Rx

An increase in what analyte implies systemic hypoperfusion?

Lactic Acid (Lactate) as an indicator of Shock

Lactate rises with all causes of systemic hypoperfusion