Interpreting Clinical Lab Data

1. Interpreting Clinical Lab Data M.ABD ELAZIZ, PhD, MD Professor of clincal pharmacology Mansoura University

2. 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.

3. 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.

4. 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span a full 24-hour period); • 3- Errors also can arise due to faulty poor quality reagents (e.g., improperly prepared, outdated); • 4-due to technical errors (e.g., human error in reading result, computer-keying error); • 5- due to interference from medical procedures (e.g.,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.

6. 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.

7. Divisions of the Clinical Lab • Hematology • Complete blood count • WBC count • Platelets • RBC count • Chemistry • Electrolytes • Potassium • Sodium • Total CO2 • Chloride

8. Divisions of the Clinical Lab • Microbiology • Sputum gram stain • Sputum culture and sensitivity • Pleural fluid culture and sensitivity • Blood Bank - blood typing and storage

9. CELL MORPHOLOGY

10. 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

11. Cell Morhphology (neutrophil)

12. 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

14. 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

15. Cause of Neutrophilia • Pathologic • Bacterial infection • Certain viruses and fungi • Inflammatory responses to tissue death • Burns • Snake bites • Drugs • steroids • lithium

16. Causes of Neutrophilia (cont.) • Physiologic • Pseudoneutrophilia (shift of cells from the MP to CP) • Catecholamines • Acute stress • Other inflammatory responses • Neoplastic growth • Metabolic disorders

17. Pools of Neutrophils • Bone marrow: many banded forms are present; neutrophilia with lots of bands suggest bone marrow was source • Circulating Pool: used to deal with day to day invasion of the body by organisms • Marginated Pool: no bands; respond to physiologic stimulation

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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)

26. 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.

27. Lymphocyte Count: Decreased • Decreased • AIDS • Bone Marrow suppression • Aplastic Anemia • Steroids • Neurologic Disorders • Multiple Sclerosis • Myasthenia Gravis • Gullain Barre Syndrome

28. Lymphocyte count: Increased • Influenza • Pertussis • Tuberculosis • Mumps • Cytomegalovirus Infection • Infectious Mononucleosis • Infectious Hepatitis • Viral pneumonia

29. 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.

30. Interpreting the CBC

31. 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

32. 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.

33. 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

34. 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)

35. 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

36. 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

37. 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)

38. 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

39. Platelet

40. Platelet (Activated)

49. Red Blood Cells

50. 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