Interpreting Clinical Lab Data M.ABD ELAZIZ, PhD, MD Professor of clincal pharmacology Mansoura University GENERAL PRINCIPLES Generally, laboratory tests should be ordered only 1-if the results of the test will affect decisions about the care of the patient. 2- The serum, urine, and other bodily fluids can be analyzed routinely; 3-however, the economic cost of obtaining these data must always be balanced by benefits to patient outcomes. Normal Values Clinical laboratory test results that appear within a predetermined range of values are referred to as “normal,” and those outside this range are typically referred to as “abnormal.” 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. Clinical laboratories can analyze sample specimens by different laboratory methods; therefore, each laboratory has its own set of normal values. Consequently, clinicians should rely on normal values listed by their own clinical laboratory facility when interpreting laboratory tests. Laboratory Error Avariety of factors can interfere with the accuracy of laboratorytests. 1- Patient-related factors (e.g., age, gender, weight,height, time since last meal) can affect the range of normal values for a given test. 2- Laboratory-based issues can also influence the accuracy of laboratory values. For example, a specimencan be spoiled A-because of improper handling or processing (e.g., hyperkalemia due to hydrolysis of a blood specimen); B-because it was taken at a wrong time (e.g., fasting blood glucoselevel taken shortly after a meal); C- because collection was incomplete (e.g., 24-hour urine collection that does not span a full 24-hour period); 3- Errors also can arise due to faulty poor quality reagents (e.g., improperly prepared, outdated); 4-due to technical errors (e.g., human error in reading result, computer-keying error); 5- due to interference from medical procedures (e.g., cardioconversion increases creatine kinase [CK] serum concentrations); 6-due to dietary effects (e.g., rare meat ingestion can cause a false-positive guaiac test); 7- because 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). 8-Clinicians might not be aware of when laboratory-related issues arise. As a result, laboratory findings must always be interpreted carefully, and the validity of a test result questioned when it does not seem to correlate with a patient’s clinical status. Side A Side B Side A Side B 1 aden/o . gland 11.carcin/o cancer 2 cardi/o . heart 12.chem/o chemical 3 cis/o . to cut 13.dermat/o skin 4 enter/o . small intestines 14.gastr/o stomach 5 gynec/o . female 15.hemat/o blood 6 hydr/o . water 16.immun/o immun 7 laryng/o . voice box 17.morph/o shape 8 nephr/o . kidney 18.neur/o nerve 9 ophthalm/o . eye 19.ot/o ear 1 0path/o . disease 20.pulmon/o lung Interpreting Clinical Lab Data Objectives: 1. Identify the characteristics and function of each type of leukocyte. 2. Identify the significance of comparing the WBC count to the neutrophil count in patients with pneumonia. 3. Identify common causes for increases and decreases in the neutrophil count. 4. State how the “rule of three” is useful for interpretation of the RBC count and indices. Divisions of the Clinical Lab Hematology – Complete blood count • WBC count • Platelets • RBC count Chemistry – Electrolytes • • • • Potassium Sodium Total CO2 Chloride Divisions of the Clinical Lab Microbiology – Sputum gram stain – Sputum culture and sensitivity – Pleural fluid culture and sensitivity Blood Bank - blood typing and storage CELL MORPHOLOGY Cell Morhphology (neutrophil) Segmented neutrophil (40-70% of WBCs) Life span of about 10 days Moves from bone marrow to blood to tissues Mature more quickly under stressful conditions Primary defense for bacterial infections Cell Morhphology (neutrophil) The Neutrophil Once in the peripheral blood, it can be in the circulating pool (CP) or the marginated pool (MP) (approx. 50%) cells in MP not counted in CBC Shift from the MP to the CP can occur with stress, trauma, catecholamines, etc. This results in a transient leukocytosis Such leukocytosis can last 4 to 6 hours The Neutrophil Present in band and segmented forms Bands make up < 5 % of circulating neutrophils normally “Left shift” is seen as an increase in the number of bands and is common with acute infection Main function is to locate, ingest, and kill bacteria and other foreign invaders Cause of Neutrophilia Pathologic – Bacterial infection – Certain viruses and fungi – Inflammatory responses to tissue death • Burns • Snake bites Drugs – steroids – lithium Causes of Neutrophilia (cont.) Physiologic – Pseudoneutrophilia (shift of cells from the MP to CP) • Catecholamines • Acute stress Other inflammatory responses – Neoplastic growth – Metabolic disorders Pools of Neutrophils 1. Bone marrow: many banded forms are present; neutrophilia with lots of bands suggest bone marrow was source 2. Circulating Pool: used to deal with day to day invasion of the body by organisms 3. Marginated Pool: no bands; respond to physiologic stimulation Causes of Neutropenia Decreased Production of WBCs – bone marrow diseases – malignancies that affect the bone marrow Increased Neutrophil Destruction – overwhelming infection – certain bacteria – immune reactions Pseudoneutropenia (shift of cells from CP to MP) – viral infections – hypothermia Cell morphology (Eosinophil) Segmented eosinophil Life span = 14 days Spends little time in the blood before it locates in the skin, GI tract, or respiratory tract Only 1% of mature cells are located in blood The Eosinophil Also function as phagocytes but appear to be less potent than neutrophil Drawn to sites of hypersensitivity reactions by mast cell chemotactic factors Often found in sputum of asthmatics May play a role in pathogenesis of lung dz Play a role in parasitic infections The Basophils Mature basophil Least common of WBCs (< 2%) Nucleus does not always segment Increase in response to same conditions that cause eosinophils to respond The Monocytes Also not common in circulating blood Stay in blood for about 70 hours Become macrophages in tissue and live for several months or longer The Monocytes Primary role is phagocytosis Play large role in ingesting cellular debris Become “activated” when direct contact with microorganisms occurs Activated cell has greater motility, enzyme activity and killing capacity (causes fever) Also play a role in immunity The Lymphocytes May mature into B or T cells Main function is antigen recognition and immune response Life span quite varied (up to two years) Can pass back and forth between blood and tissues Lymphocytes: B & T types B cells are not only produced in the bone marrow but also mature there. However, the precursors of T cells leave the bone marrow and mature in the thymus (which accounts for their designation) Types of Lymphocytes B lymphocytes (or B cells) are most effective against bacteria & their toxins plus a few viruses T lymphocytes (or T cells) recognize & destroy body cells gone awry, including virus-infected cells & cancer cells. T cells come in two types: helper cells and suppressor cells; normally the helper cells predominate. Lymphocyte Count: Decreased I. A. B. C. D. E. 1. 2. 3. Decreased AIDS Bone Marrow suppression Aplastic Anemia Steroids Neurologic Disorders Multiple Sclerosis Myasthenia Gravis Gullain Barre Syndrome Lymphocyte count: Increased a. Influenza b. Pertussis c. d. e. f. g. h. Tuberculosis Mumps Cytomegalovirus Infection Infectious Mononucleosis Infectious Hepatitis Viral pneumonia Interpreting the CBC What is total white cell count? If elevated (>11,000), what type of WBC is the culprit? Is it the neutrophils, eosinophils, lymphocytes, basophils, or monocytes? Marked leukocytosis is usually due to neutrophils or lymphocytes. Interpreting the CBC Normal Values Neutrophils % Absolute 40 – 70 1800 – 7500 Eosinophils 0–6 0 – 600 Basophils 0–1 0 – 100 20 – 45 900 – 4500 2–6 90 - 1000 Lymphocytes Monocytes Interpreting the CBC If the neutrophils are causing the leukocytosis, compare the neutrophil % to total WBC. The % neutrophils indicates the severity of the infection; the total WBC reflects the quality of the immune system Interpreting the CBC (Case # 1) 85 yr old female with pneumonia: Total WBC is: 11,500 Neutrophil % = 80% (9200) bands = 5% This indicates that a severe infection is present but the immune system is unable to respond appropriately. Prognosis poor. Interpreting the CBC (Case # 2) 5 yr old male with pneumonia WBC = 18,000 Neutrophils = 60% (10,800) Marked leukocytosis and normal range for neutrophils indicates moderate infection but excellent immune system response Excellent prognosis Interpreting the CBC (Case #3) 10 yr old male admitted for pneumonia: WBC: 16,000 neutrophils = 75% (12,000) (1800-7500) Bands = 5% (800) (0-100) Eosinophils = 1% (160) (0-600) Lymphocytes = 10% (1600) (900-4500) Basophils = 0% (0) (0-100) Monocytes = 3% (480) (90-1000) Interpreting the CBC (Case #3) Interpretation neutrophilia probably due to bacterial pneumonia left shift indicative of severe infection the source of the neutrophils is the bone marrow since many bands are present Case Study # 4 20 yr old male admitted following MVA WBC 14,500 75% neutrophils 1% bands Leukocytosis due to neutrophilia History and low per cent of bands suggest pseudoneutrophilia Due to liberation of marginated neutrophils in the intravascular system Interpreting the CBC What is indicated by leukopenia? 1. Bone marrow failure cancer e.g. leukemia, lymphoma 2. Overwhelming infection severe pneumonia pt who has poor immune system and can’t produce enough WBCs 3. Shift of neutrophils to MNP (viral infections and hypothermia) Platelet Count Normal count is 140,000 to 440,000/mm3 Life span of about 10 days Low platelet counts (thrombocytopenia) cause excessive bleeding Thrombycytopenia is common with the use of heparin, DIC, bone marrow disease, liver failure and sepsis Platelet Platelet (Activated) Side A 1 aden/o . 2 cardi/o . 3 cis/o . 4 enter/o . 5 gynec/o . 6 hydr/o . 7 laryng/o . 8 nephr/o . 9 ophthalm/o . 1 0path/o . Side B Side A Side B gland 11.carcin/o cancer heart 12.chem/o chemical to cut 13.dermat/o skin small intestines 14.gastr/o stomach female 15.hemat/o blood water 16.immun/o immun voice box 17.morph/o shape kidney 18.neur/o nerve eye 19.ot/o ear disease 20.pulmon/o lung 22.a , without, away from 27.an without 23.ante before, in front of 28. anti- , against 24.auto , self 29. brady slow 25.dys- painful, difficult 30. endo , within, inner Red Blood Cells Red Blood Cells (Erythrocytes) Produced in the bone marrow Life span of about 120 days Primary function is gas transport Immature version has nucleus and is called a reticulocyte Interpreting the RBC count 1. Normal values: Men: 4.2 – 5.4 million/mm3 Women: 3.6 – 5.0 million/mm3 2. Anemia – abnormal Decrease in RBC count - decreased production - increased destruction (hemolysis) - blood loss Interpreting the RBC count 3. Increased RBC count = Polycythemia A. Primary B. Secondary living at altitude chronic lung/heart disease tobacco use/carbon monoxide C. Relative Polycythemia dehydration Red Blood Cell Indices Mean Corpuscular Volume (MCV) – Volume occupied by a single RBC – Increase in MCV is known as Macrocytic anemia. – Decrease in MCV is known as Microcytic anemia. Mean Corpuscular Hemoglobin Concentration – (MCHC) – Measure of the concentration of hemoglobin in an average RBC – Decrease in MCHC is known as Hypochromic anemia – Normal is known as Normochromic anemia. Red Blood Cell Indices Normocytic anemias – Blood loss – Hemolytic anemia Microcytic anemias (<80 fL*) – Iron deficiency Macrocytic anemias (>100 fL) – Folic acid deficiency – Vitamin B12 deficiency – Some COPD patients *femtoliters Red Blood Cell Indices Hematocrit The RULE of Three Applies to normocytic, normochromic erythrocytes only Useful to detect laboratory error in measuring the Hb, HCT, and RBC count 3 times the RBC count should = Hb 3 times Hb should = Hct The RULE of Three RBC = 3.0 x 1012 3x3=9 Hb = 9.2 g/dL 3 x 9.2 = 27.6 Hct = 28% Interpreting the Red Blood Cells CBC: RBC (x1012/L) Hgb (g/dL) Hct MCV (m3) MCHC Results 4.2 10.6 34.9% 77.0 30.4% Normals 4.2-5.4 11.5-15.5 38%-47% 80-96 32-36% Interpretation: Microcytic, hypochromic anemia; rule of 3 does not apply Reticulocyte Count Normal values: – 0.5 – 1.5% of RBC Helpful to identify cause of Anemia Increase indicates Anemia is due to Blood loss Decrease indicates Anemia is due to Bone marrow disease Bibliography Steine-Martin: Clinical Hematology, 2nd edition, Lippincott, Philadelphia, 1998. Kaplan: Clinical Chemistry, 4th edition, Mosby, St. Louis, 2003. Wilkins: Clinical Assessment in Respiratory Care, 5th edition, Mosby, St. Louis, 2005.