Interpreting Clinical and Laboratory Data

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Chapter 16

Interpreting Clinical and Laboratory Data

Richard H. Kallet

Chapter Objectives

After reading this chapter you will be able to:

Describe what a critical value is, and state its importance in clinical practice.

Define the following terms related to clinical laboratory tests: leukocytosis, leukopenia, anemia, polycythemia, and thrombocytopenia.

Identify which electrolyte disturbances interfere with normal respiratory function.

Describe clinical tests used to identify cardiac stress and myocardial infarction.

Identify the three main tests used to diagnose coagulation disorders.

Describe how the sputum Gram stain and culture are used to diagnose pulmonary infections.

Interpreting Clinical Laboratory Tests

This chapter primarily discusses common blood tests performed on patients admitted to the hospital. These tests are done to evaluate the general health status of the patient, identify organ system dysfunction, detect the presence of infection, and determine the effects of therapy. The respiratory therapist (RT) must be familiar with these tests to understand the overall clinical status of patients under their care. The RT must be able to recognize how some abnormalities influence pulmonary function specifically. Sometimes the RT must alter his or her approach to practice based on abnormal laboratory test results.

This chapter also presents a brief review of fundamental physiologic concepts related to these tests. Comprehensive tables provide detailed information that can be used as a quick reference for each test. The chapter text provides a more general explanation on the significance of these tests and how they fit into an overall assessment of a patient’s status.

Introduction to Laboratory Medicine

Laboratory medicine involves the study of patient tissue and fluid specimens. It is divided into five major disciplines. Clinical biochemistry involves the analysis of blood, urine, and other bodily fluids primarily for electrolytes and proteins; hematology analyzes the cellular components of blood. The analysis of blood and other bodily fluids for the presence of infectious agents is the purview of clinical microbiology; this includes the subspecialties of identifying bacteria (bacteriology), viruses (virology), fungi (mycology), and parasites (parasitology). A closely related discipline involves the analysis of the immune system (immunology) focusing on autoimmune and immunodeficiency diseases. Finally, the analysis of tissue for diagnosing diseases is the purview of the anatomic pathology service.

Reference Range

Laboratory tests are employed to determine a patient’s health status and aid medical decisions. It is important to determine whether a specific test result falls within an expected range of values considered to be “normal.” The notion of normal is problematic, however. Early on in the history of laboratory medicine, tests to determine the normal range for blood chemistry and hematology were done primarily on small convenience samples of subjects who were not representative of the larger population in terms of age, gender, race, and ethnicity. An additional problem is that the term normal is not the same as healthy. The best example is cholesterol. A normal range of cholesterol found in most Americans puts them at risk of cardiovascular disease and cannot be considered healthy.

Beginning in the 1970s,¹ the term normal ranges was slowly replaced with more appropriate terms such as reference ranges, biologic reference intervals, and expected value.² This change in terminology acknowledged that what we consider normal must take into account variations related to age, gender, race, and ethnicity, which change over time as the demographic composition of society changes. A reference range sets the boundaries for any analyte (e.g., electrolyte, blood cell, protein, enzyme) that would likely be encountered in healthy subjects. This range would encompass the variability reflected in the larger, presumably healthy population.

Reference ranges vary from laboratory to laboratory for various reasons, including differences in measurement techniques, the populations of healthy individuals used to establish the reference intervals, or analytic imprecision when the intervals were constructed. Most differences in reference ranges are relatively small, with reasonably close agreement between most laboratories.² The reference ranges and critical values given in this chapter are from a single institution, and they serve as representative examples. RTs must become familiar with the reference ranges used at their institutions.

Critical Test Value

A critical test value is a result significantly outside the reference range and represents a pathophysiologic condition. A critical value may be potentially life-threatening unless corrective action is taken promptly. Critical values are reported in the hospital to alert caregivers as well to decrease medical errors and protect patients.

Typically, critical values are communicated by telephone from the clinical laboratory to the general ward or intensive care unit where the patient is situated. The nurse or RT who receives these results is required to read-back the critical value to the clinical laboratory. This requirement is to ensure that the correct information has been communicated. It is the responsibility of the nurse or RT to communicate the critical value in a timely fashion to the physician caring for the patient. The same read-back procedure is used. All communication of critical test values is documented in the medical record.

In this chapter, critical values are listed along with common pathophysiologic states with which they commonly occur. Not all clinical analytes have an associated critical value. For some tests, there is no general agreement on what a critical value would be. Others have only a one-sided value that exists below or above a critical threshold; this is true particularly for substances that do not normally appear in the blood. For example, certain enzymes and proteins are released only after extensive cellular damage following injury (see later section on enzyme tests). Under normal circumstances, these proteins or enzymes may be virtually undetectable in the serum or plasma.

When interpreting derangements for any test result, the clinician must consider the context of the change. In a patient with chronic renal disease, a serum creatinine of 3.0 mg/dl (approximately twice the upper limit of normal) would not be considered urgent. However, in a patient who presents with a bloodstream infection (i.e., sepsis) and hypotension, a sudden increase in serum creatinine to 3.0 mg/dl would be considered critical because it indicates acute kidney injury in the context of rapidly developing clinical instability.

Complete Blood Count

The complete blood count (CBC) provides a detailed description of the number of circulating white blood cells (WBCs), called leukocytes; red blood cells (RBCs), called erythrocytes; and platelets, called thrombocytes. The WBC count is made up of five different types of cells and is reported under the differential. RBCs are evaluated for size and hemoglobin content. The platelets are evaluated for number present. Table 16-1 lists the normal CBC results for adults.

TABLE 16-1

Reference Range Values for Complete Blood Count in an Adult

Test	Reference Range
Red blood cell count
Men	4.4-5.9 × 10⁶/mcl
Women	3.8-5.2 × 10⁶/mcl
Hemoglobin
Men	13.3-17.7 g/dl
Women	11.7-15.7 g/dl
Hematocrit
Men	40%-52%
Women	35%-47%
White blood cell count	3.9-11.7 × 10³/mcL
White blood cell differential
Segmented neutrophils	40%-75%
Bands	0%-6%
Eosinophils	0%-6%
Basophils	0%-1%
Lymphocytes	20%-45%
Monocytes	2%-10%
Platelet count	150-400 × 10³/mcL

Values for reference ranges and critical test results are from the University of California San Francisco Moffit-Long Hospital and San Francisco General Hospital. http://pathology.ucsf.edu/labmanual/mftlng-mtzn/test/test-index.html and http://pathology.ucsf.edu/sfghlab/test/ReferenceRanges.html. Accessed January 1, 2011.

Elevation of the WBC count is termed leukocytosis. It results from numerous problems, including stress, infection, and trauma. The degree of leukocytosis reflects the severity of infection. A significantly elevated WBC count (>20 × 10³/mcl) suggests the presence of a serious infection and that the patient’s immune system is generating a significant response. In contrast, leukopenia (or leukocytopenia) is a WBC count below normal that often occurs when the patient’s immune system is overwhelmed by infection. Other important causes of leukopenia include bone marrow diseases (e.g., leukemia, lymphoma), influenza, systemic lupus erythematosus, tuberculosis, and acquired immunodeficiency syndrome (AIDS). Also, chemotherapy and radiation therapy given to cancer patients frequently causes leukopenia.

White Blood Cell Count

White Blood Cell Count Differential

The differential of the WBC count determines the exact number of each type of WBC present in the circulating blood (Table 16-2). Most circulating WBCs are either neutrophils or lymphocytes. Because leukocytosis usually results from only one of the five cell types responding to a problem, significant elevation of the WBC count (>15 × 10³/mcl) occurs only when either neutrophils or lymphocytes are responding to an abnormality. Because basophils, eosinophils, and monocytes make up such a small proportion of the circulating WBCs, they are not likely to cause a major increase in the WBC count when responding to disease.

TABLE 16-2

Reference Range Values for White Blood Cell Count Differential and Common Causes for Abnormalities

Cell Type	Relative Value	Absolute Value	Causes for Abnormalities
Neutrophils	40%-75%	1.8-6.8 × 10⁹/L	Increased with bacterial infection and trauma; reduced with bone marrow diseases (critical value <1.0)
Lymphocytes	20%-45%	1.0-3.4 × 10⁹/L	Increased with viral and other infections; reduced with immunodeficiency problems
CD4 T lymphocytes	31%-60%*	410-1590 × 10⁶/L	HIV disease; diagnostic threshold <200
Eosinophils	0%-6%	0-0.4 × 10⁶/L	Increased with allergic reactions and parasitic infections
Basophils	0%-1%	0-0.1 × 10⁶/L	Increased with allergic reactions
Monocytes	2%-10%	0.2-0.8 × 10⁶/L	Increased with invasion of foreign material

^*Percentage of lymphocyte.

The WBC count differential is best interpreted by determining the absolute count of each WBC; this is calculated by multiplying the percentage of the WBCs under study by the total WBC count. This calculation prevents misinterpretation of the WBC count differential when any one cell type changes in absolute numbers and causes a relative change in the percentage of the other four cell types. For example, if the WBC count doubles because of an increase in neutrophils, the relative value of the other four cells would decrease by half, although their absolute value would not change. Many laboratories report the absolute value for each of the five WBCs to avoid this confusion.

The subanalysis of lymphocytes is important for identifying infection with HIV, the causative agent of AIDS. HIV targets and destroys CD4 T lymphocytes. Opportunistic infections, in particular, Pneumocystis jiroveci pneumonia, generally occur when these lymphocytes decrease to less than 200 × 10⁶/L, and this information is used in making the diagnosis of AIDS.

Elevation of the absolute value of neutrophils is termed neutrophilia. Immature neutrophils are known as bands because of the banded shape of the nucleus. Most bands are located in the bone marrow where they continue to mature. Mature neutrophils are known as segs because of the segmented shape of their nucleus. Severe infection causes the bone marrow to release stores of any available neutrophils, and both bands and segs enter the circulating blood volume. When bands and segs are elevated in the CBC, the patient is likely experiencing a more severe bacterial infection.

A reduced number of circulating neutrophils is termed neutropenia. Although uncommon, neutropenia is characteristic of patients with bone marrow disease (e.g., lymphoma, leukemia), patients undergoing treatment for cancer with chemotherapy or radiation or both, patients with some autoimmune disorders, and HIV-infected patients. Neutropenia puts the patient at risk for the development of infection.

Rule of Thumb

Elevation of the WBC count is usually caused by an increase in either neutrophils or lymphocytes in response to infection.

Rule of Thumb

When bacterial pneumonia is present, the severity of the infection can be assessed by evaluation of the degree of increase in neutrophils.

Red Blood Cell Count

The primary function of RBCs or erythrocytes is to supply oxygen to the tissues. The RBC count helps determine the ability of the blood to carry oxygen. An abnormally low RBC count is referred to as anemia and suggests that either RBC production by the bone marrow is inadequate or excessive blood loss has occurred. In either case, the oxygen-carrying capacity of the blood is reduced, and the patient is more likely to experience tissue hypoxia. There are several types of anemia with different causes. Some are related to dietary deficiencies in iron or vitamins (e.g., vitamin B₁₂ and folate). Other causes are related to chronic inflammatory diseases, such as Crohn disease, HIV/AIDS, lymphoma, and autoimmune diseases that result in the destruction of erythrocytes (hemolytic and aplastic anemia). A hereditary cause is sickle cell anemia, which is common in African-Americans. For most forms of anemia, a blood transfusion may be needed if the RBC count is too low. The trigger point for transfusion is based on the hemoglobin or hematocrit measurement rather than the RBC count.

Mini Clini

White Blood Cell Count Differential

Problem

A patient has been admitted to the hospital for acute shortness of breath. A chest x-ray reveals pneumonia, and the patient’s temperature is elevated. The CBC shows an increased WBC count of 15 × 10³/mcl with 75% neutrophils but only 10% lymphocytes. Given that the normal lymphocyte differential is 20% to 45%, does the value of 10% suggest a problem with lymphocyte production by the immune system? What type of pneumonia is probably present in this case?

Solution

The 10% differential for the lymphocytes represents a relative value. Because the total WBC count is markedly elevated, the 10% in relative terms represents 1500 lymphocytes in absolute value, which is well within normal range. If the total WBC count was reduced to less than normal and the differential showed a lymphocyte count of 10%, an abnormal absolute value would be present and would suggest an immunologic problem. This patient probably has bacterial pneumonia, given the elevated number of neutrophils.

An abnormally elevated RBC count is known as polycythemia. It occurs most often when the bone marrow is stimulated to produce extra RBCs in response to chronically low blood oxygen levels (secondary polycythemia). Polycythemia counteracts the negative side effects of reduced PO₂ in the blood by increasing the oxygen-carrying capacity of the blood. Patients who live at a high altitude and patients with chronic lung disease are most likely to experience chronic hypoxia and to develop secondary polycythemia.

In addition to the RBC count, the clinical laboratory reports hemoglobin and hematocrit levels. Hemoglobin is a protein substance with the unique ability to bind with oxygen. Each healthy RBC contains 200 million to 300 million molecules of hemoglobin, for a hemoglobin level of 12 to 17 g/dl in a healthy adult. Patients with an inadequate hemoglobin concentration have reduced oxygen-carrying capacity. In this condition, the RBCs are smaller than normal (microcytic anemia) and lack normal color (hypochromic anemia). The necessity for RBC transfusion depends on the cause of anemia and the patient’s overall condition. Usually a transfusion is triggered by a hemoglobin concentration of approximately 7.0 g/dl or a hematocrit of approximately 21%.

The hematocrit level is the ratio of RBC volume to whole blood. It is determined by spinning a blood sample in a centrifuge to separate the blood cells from the plasma. The proportion of the sample represented by the packed cells is the hematocrit. A low hematocrit reading occurs with anemia, and a high hematocrit reading is common with polycythemia. The hematocrit level is also a reflection of the hydration status of the patient. Dehydration causes the hematocrit to increase, whereas overhydration causes it to decrease.

Rule of Thumb

The threshold for blood transfusion typically is a hematocrit of 21% or a hemoglobin of 7.0 g/dl.

Electrolyte Tests

Basic Concepts for Understanding Electrolyte Balance

Normal cellular function depends on homeostasis of fluids, electrolytes, and acid-base balance. Homeostasis is the ability of complex organisms to maintain a dynamic balance or equilibrium in their internal environments by making constant adjustments. The guiding principle is that the total amount of water, electrolytes, acid, and base gained each day must be balanced by the total amount lost.

Electrolytes are positively or negatively charged ions that influence the functioning of enzymes. The concentration of any electrolyte is determined by the amount of water in which it is suspended. Electrolytes always must be interpreted within the context of fluid balance. Enzymes are proteins that regulate all chemical reactions occurring within cells, such as metabolism and protein synthesis. All cellular functions operate within very narrow parameters of electrolyte concentrations. Disturbances in electrolyte balance may disrupt normal cellular functioning.

Two important points must be kept in mind when interpreting these blood tests. First, blood samples provide a one-time “snapshot” of processes that are constantly in flux. These “snapshots” provide the clinician with valuable but time-limited insight into cellular processes. Often, the most important information comes from serial measurements, whereby both the degree of abnormalities and the directional changes can be assessed. Changes over time provide vital information about the severity and progression of disease as well as judging the effectiveness of therapy.

Second, the intravascular blood compartment is remote from the intracellular environment. Analyzing serum electrolyte levels gives the clinician only an indirect view of what might be occurring inside the cells of the body. The intracellular fluid compartment represents approximately two-thirds of total body fluid compared with approximately one-third that exists outside in the extracellular fluid compartment. Blood plasma is just a small component of the extracellular environment. Monitoring abnormalities in the extracellular fluid compartment via blood samples provides important but indirect information in assessing intracellular functioning.

Basic Chemistry Panel

The basic chemistry panel (BCP) or basic metabolic panel includes the predominant electrolytes sodium (Na⁺), potassium (K⁺), chloride (Cl⁻), and total carbon dioxide/bicarbonate (CO₂) and glucose. Because the body’s electrolyte balance is controlled by the kidneys, excretion of renal-mediated waste products is included in the panel: creatinine and blood urea nitrogen. A more comprehensive metabolic panel would include other important electrolytes, such as magnesium (Mg⁺⁺), phosphorus (PO₄⁻), and calcium (Ca⁺⁺). Each electrolyte plays a crucial role in maintaining normal cellular function. Specific information on the reference range and physiologic significance of each electrolyte and waste product can be found in Table 16-3. Information regarding the terminology used to describe abnormal test values for electrolytes, diseases associated with these disturbances, and sample critical test results are provided in Table 16-4.

TABLE 16-3

Components of Basic Metabolic Panel and Common Electrolyte Tests With Sample Reference Ranges and Physiologic Significance

Test	Reference Range*	Physiologic Importance
Sodium (Na⁺)	136-145 meq/L	Primary extracellular cation; crucial for maintaining fluid balance and nerve impulse conduction
Potassium (K⁺)	3.5-5.0 meq/L	Primary intracellular cation; crucial for maintaining normal heart and kidney function and acid-base balance
Chloride (Cl⁻)	98-106 meq/L	Primary extracellular anion; crucial for maintaining serum osmolarity and acid-base balance
Total carbon dioxide (CO₂)	22-29 meq/L	Primary metabolic end product of aerobic metabolism; crucial for maintaining acid-base balance
Calcium (Ca)	4.5-5.25 meq/L	Most abundant mineral in the body; essential for bone strength, muscular contraction, nerve impulse conduction, and coagulation
Ionized calcium (Ca⁺⁺)	2.2-2.7 meq/L	The approximately 50% of calcium not bound to circulating proteins; represents the biologically active portion
Glucose (Glu)	70-139 mg/dl	Primary cellular energy source
Creatinine (Cr)	0.7-1.3 mg/dl	Waste product from muscle catabolism excreted by the kidneys; one of the key markers of kidney function because it provides a gross estimation of glomerular filtration rate
Blood urea nitrogen (BUN)	8-23 mg/dl	Waste product from metabolism of amino acids; a key marker of kidney function
Magnesium (Mg⁺⁺)	1.7-2.1 meq/L	Essential for regulation of most biochemical processes; important for: normal muscle and neuronal functioning, regulating heart rate and blood pressure, glucose levels, bone strength, and immune function
Phosphorus (PO₄⁻)	1.2-2.3 meq/L	Main intracellular anion (phosphate), exists as phosphorus in serum; combined with calcium in teeth and bones; serum levels inversely related to serum calcium
Lactate	0.7-2.1 meq/L	End product of glucose metabolism under anaerobic conditions; clinically significant levels coincide with regional or systemic tissue hypoxia
Osmolarity	275-295 mOsm/kg	Tonicity or ability to attract water molecules; indicates overall ionic concentration in the serum

^*Reference ranges vary among clinical laboratories. See text for explanation.

TABLE 16-4

Sample Critical Test Results Reflecting Abnormalities in Electrolyte and Other Common Laboratory Tests

Test	Sample Critical Test Result*	Common Pathologic Conditions Associated With Abnormally High Levels	Common Pathologic Conditions Associated With Abnormally Low Levels
Sodium (Na⁺)	>155 meq/L; <125 meq/L	Hypernatremia: Dehydration from excessive water loss or fluid restriction; excessive administration of saline fluids or diuretics (usually ≥180 mmol)	Hyponatremia: Overhydration or abnormal secretion of antidiuretic hormone; severe vomiting or diarrhea; congestive heart failure, renal or hepatic failure, Addison disease
Potassium (K⁺)	>6.0 meq/L; <3.0 meq/L	Hyperkalemia: Acute or chronic kidney disease, Addison disease, severe alcoholism, rhabdomyolysis; values ≥6 mmol are life-threatening	Hypokalemia: Severe vomiting or diarrhea; chronic renal disease; high-dose beta-agonist therapy
Chloride (Cl⁻)	>120 meq/L; <70 meq/L	Hyperchloremia: Excessive chloride administration (usually saline resuscitation during shock); metabolic acidosis, diabetes insipidus	Hypochloremia: Severe vomiting or diarrhea; metabolic alkalosis, adrenal insufficiency, severe burns, excessive intravenous dextrose administration
Total carbon dioxide (CO₂)	>40 meq/L; <15 meq/L	Ventilatory failure	Metabolic acidosis; hyperventilation syndrome; severe diarrhea
Calcium (Ca)	>13.5 meq/L; <6.5 meq/L	Hypercalcemia: Hyperparathyroidism, lithium or thiazide diuretic therapy, metastatic cancer, multiple myeloma	Hypocalcemia: Hypoparathyroidism, blood transfusions, acute pancreatitis, vitamin D deficiency
Ionized calcium (Ca⁺⁺)	>1.5 meq/L; <0.8 meq/L
Glucose (Glu)	>500 mg/dl; <50 mg/dl	Hyperglycemia: Diabetes mellitus, severe sepsis	Hypoglycemia: Excessive insulin administration, inadequate dietary intake of carbohydrates
Creatinine (Cr)	>10 mg/dl	Acute kidney injury, chronic renal failure	Protein starvation, liver disease
Blood urea nitrogen (BUN)	>100 mg/dl	Acute kidney injury, chronic renal failure, dehydration	Liver disease, malnutrition
Magnesium (Mg⁺⁺)	>3.7 meq/L; <0.8 meq/L	Hypermagnesemia: Chronic renal failure, Addison disease, diabetic ketoacidosis, dehydration	Hypomagnesemia: Cirrhosis, pancreatitis, severe alcoholism, hemodialysis, toxemia of pregnancy, ulcerative colitis
Phosphorus (PO₄⁻)	<1.0 meq/L; >2.5 meq/L	Hyperphosphatemia: Commonly found in patients with renal failure, hepatic failure, bone metastasis, hypocalcemia, hypoparathyroidism	Hypophosphatemia: Most often seen in chronic hyperventilation syndrome; also caused by hypercalcemia, hyperparathyroidism, and malnutrition
Lactate	>4 meq/L		Primarily causes anaerobic metabolism; frequently found in patients with hemorrhagic or septic shock; may also be due to reduced hepatic clearance, dehydration, or trauma
Osmolarity	>320 mOsm/kg; <240 mOsm/kg

^*Reference ranges and critical test results vary among clinical laboratories. See text for explanation.

The respiratory therapist needs to be aware of subtle differences in how electrolytes are reported as this may cause confusion. The concentration of electrolytes in solution is reported either by the number of molecules (millimoles: mmol) or their associated valence or electrical charge (milliequivalents: mEq). Although customary practice has been to report electrolytes as mEq/L, many laboratories report electrolytes as mmol/L. In an electrolyte solution milliequivalents is simply millimoles per liter multiplied by the valence. For example, sodium possesses a valence of 1, so that the expression as either mmol/L or mEq/L is the same. For calcium and magnesium, which both possess a valence of 2, then the mEq value is twice the mmol value.

Glucose

The breakdown of carbohydrates results in the production of serum glucose, which is metabolized by the cells for energy. Insulin, which comes from the pancreas, is necessary for cells to use the glucose circulating in the blood. Abnormal elevation of blood glucose level is termed hyperglycemia and is most often the result of diabetes. An abnormally reduced serum glucose level is termed hypoglycemia and may be drug-induced or associated with digestive problems, inadequate dietary intake of carbohydrates, or overtreatment of diabetes with insulin.

Diabetes is diagnosed by measuring fasting blood glucose levels (i.e., a glucose measurement taken after 12 hours without food). A blood glucose level greater than 140 mg/dl on two occasions usually indicates diabetes. Severe hyperglycemia occurring with metabolic acidosis is consistent with diabetic ketoacidosis and represents a potentially life-threatening condition if not treated immediately.

In critically ill patients, insulin resistance and hyperglycemia are common. This condition is associated with a higher incidence of multiorgan failure and increased mortality. The condition can be ameliorated with a regimen of intensive insulin therapy to keep blood glucose levels at approximately 110 mg/dl.³ For intensive insulin therapy to be effective, blood glucose levels must be monitored frequently with a bedside (point-of-care) measuring device to facilitate rapid titration of insulin.

Anion Gap

As discussed in Chapter 13, metabolic acidosis is caused by either the addition of nonvolatile acids or a primary loss of HCO₃⁻. The anion gap provides a quick method for determining whether a decrease in HCO₃⁻ is caused by a disruption of normal anion balance or the presence of an abnormal acid anion. A balance normally exists between cations and anions in the serum. The normal anion gap occurs because sulfate, phosphate, and organic anions such as lactate are not routinely measured, whereas most cations are measured. The anion gap is calculated by adding the CO₂ and Cl⁻ values and then subtracting this total from the serum Na⁺. The normal anion gap is approximately 8 to 14 meq/L, and gap acidosis usually coincides with an anion gap of 16 mmol/L or greater. However, serum proteins are an important determinant of the anion gap. Hypoalbuminemia (decreased serum albumin) is a common finding in critically ill patients and significantly reduces the anion gap. As a rule, for every 1-g reduction in serum albumin below 4 g/dl, the anion gap is corrected upward by 3 meq/L.

Rule of Thumb

An anion gap greater than 16 is consistent with the presence of metabolic acidosis.

Lactate

Lactate is the end product of anaerobic glucose metabolism. Blood lactate concentration is dependent on the production of lactate in muscle cells and erythrocytes and the rate of metabolism by the liver. Lactic acidosis results from either overproduction of or insufficient metabolism of lactate. Abnormal levels of lactate can be found in diverse conditions such as diabetes mellitus; malignancies; and toxic ingestion of ethanol, methanol, or salicylates. However, the most common cause of lactic acidosis is anaerobic metabolism from tissue hypoxia associated with shock. Initial values of serum lactate greater than 4 meq/L are associated with higher mortality in patients with septic shock. Also, the inability to clear high lactate levels rapidly is associated with poorer outcomes in critically ill patients.

Rule of Thumb

In patients with septic shock, a serum lactate level greater than 4 meq/L is associated with higher mortality.

Mini Clini

Anion Gap

Problem 1

A patient in the intensive care unit is being treated for shock and acute renal failure. No ABGs have been drawn yet, but the RT suspects the respiratory system is involved because the patient has been breathing more rapidly over the past 12 hours. The electrolyte panel reveals a serum Na⁺ of 146 meq/L, a total CO₂ of 20 meq/L, and a serum Cl⁻ of 100 meq/L. Does the electrolyte panel suggest any problems, and what should be done if there are any?

Solution

The electrolytes are normal except for a decrease in the serum CO₂. The anion gap is calculated by subtracting the sum of CO₂ and Cl⁻ from the Na⁺ (146 − [100 + 20]). In this case, the anion gap is elevated (26 meq/L) and is consistent with a metabolic acidosis. An ABG analysis is needed to evaluate the acid-base status of the patient further. The patient’s rapid breathing probably is related to the metabolic acidosis because hyperventilation decreases CO₂ levels and promotes acid-base compensation.

Problem 2

A patient in the trauma intensive care unit is undergoing large fluid resuscitation with normal saline solution. The patient is in hemorrhagic and hypovolemic shock following a motor vehicle accident. An initial ABG reveals a pH of 7.25, PCO₂ of 25 mm Hg, and HCO₃⁻ of 10.6 with a base deficit of −14.9 meq/L. The trauma surgeons are debating increasing the amount of normal saline solution infused. They suspect their resuscitation efforts are inadequate, and metabolic acidosis is worsening from continued lactate accumulation. What additional information can be provided by obtaining a BCP to help guide therapy?

Solution

If the BCP reveals a Na⁺ of 140 meq/L, Cl⁻ of 95 meq/L, and CO₂ of 20 meq/L (anion gap of 25 meq/L), the surgeons would be correct in assuming that their resuscitation efforts were inadequate. The anion gap of 25 likely represents a worsening lactic acidosis. However, if the BCP reveals a Na⁺ of 150 meq/L, CO₂ of 20 meq/L, and Cl⁻ of 122 meq/L, the anion gap would be normal (8 meq/L). The metabolic acidosis would be caused by an abnormally high serum chloride concentration from excessive normal saline administration. This example represents a common problem in emergency and critical care practice: the overresuscitation of trauma patients from severe shock.

Enzyme Tests

TABLE 16-5

Liver Function and Other Enzymatic Tests

Test	Reference Range	Sample Critical Test Result*
Total bilirubin (T Bil)	0.1-1.1 mg/dl	≥15 mg/dl
Alanine aminotransferase (ALT)	7-56 U/L	^†
Aspartate aminotransferase (AST)	10-50 U/L	^†
Alkaline phosphatase (ALK)	40-125 U/L	^†
Total protein (TP)	15-45 mg/dl	^†
Albumin (ALB)	3.3-5.2 g/dl	^†
Ammonia	18-54 µmol/L	≥500 mcg/dl
Amylase (serum)	20-110 U/L	>330 U/L
Lipase	10-140 U/L	>420 U/L
Creatinine phosphokinase (CPK)	20-220 U/L	>10,000 U/L
Troponin I	0 ng/ml	>0.05 ng/ml
B-type natriuretic peptide	<100 pg/ml	^†
Lactate dehydrogenase (LDH)	110-220 U/L	>880 (moderate); >8800 (severe)

^*Critical test results vary among clinical laboratories based on instrumentation and calibration procedures. Not all tests have an associated critical result that can be reported.

^†No critical value established.

B-type natriuretic peptide (BNP) is a substance secreted by the heart in response to increased stretch in the cardiac muscle. The BNP test primarily is used to evaluate patients for heart failure, in particular, patients who present to the emergency department with dyspnea and pulmonary edema.⁴ Generally, values greater than 300 pg/ml indicate mild heart failure, whereas values greater than 600 pg/ml are found in patients with moderate heart failure, and values greater than 900 pg/ml are found in patients with severe heart failure.⁴ Other conditions such as acute respiratory distress syndrome and severe sepsis also cause increased stretch of the cardiac muscle. In these cases, the BNP levels typically are lower (300 to 500 pg/ml) than what is found commonly in critically ill patients with primary heart failure (700 to −1200 pg/ml).⁵

Sweat Chloride

Patients with cystic fibrosis have increased levels of Cl⁻ in their sweat because of an inability to reabsorb it. These patients have abnormally elevated sweat Cl⁻ levels of greater than 60 mmol/L. Values between 40 mmol/L and 60 mmol/L are considered borderline for cystic fibrosis, whereas values less than 40 mmol/L are considered unlikely to confirm the diagnosis. Although the sweat electrolyte test is an important tool for diagnosing cystic fibrosis, it must be combined with other tests.

Coagulation Studies

Coagulation is the process by which the blood and vascular tree form clots to stop bleeding and repair damage to the injured blood vessels. In brief, damage to the internal vascular wall (endothelium) exposes the blood to tissue factors that attract and activate platelets, which begin the clotting process. Thrombocytopenia (low platelets) and thrombasthenia (abnormal platelet functioning) lead to excessive bleeding, whereas thrombocytosis (excessive platelets) causes excessive clotting. In addition to direct measurement of platelets, the functionality of the entire process of coagulation is measured by the prothrombin time (PT) and partial thromboplastin time (PTT). These tests assess the two different pathways by which fibrin clots are formed.

PT is defined as the time in seconds required by plasma to form a fibrin clot after exposure to tissue factors. It assesses the extrinsic coagulation pathway and reflects the function of clotting factors I, II, V, VII, and X. In contrast, PTT primarily assesses the intrinsic coagulation pathway. It is used to evaluate abnormalities in blood clotting and to monitor the effects of anticoagulation therapy. Abnormalities in PTT are associated with clotting factors I through VI and factors VIII through XII. Clinically, abnormal increases in PT and PTT are found in patients with vitamin K deficiencies and patients receiving anticoagulation therapy such as warfarin or heparin. Increases in PT and PTT are also seen frequently in patients with disseminated intravascular coagulation (DIC) and patients with end-stage liver disease.

Because PT test results (Table 16-6) depend on manufactured animal tissue factors, which have unavoidable variability, PT is accompanied by an additional measurement known as the international normalized ratio (INR). The INR expresses PT relative to an established sample value. The reference range for INR is 0.9 to 1.3. INR values of approximately 5.0 indicate a high likelihood for bleeding. Values of 0.5 are associated with a tendency toward increased clotting.

TABLE 16-6

Coagulation Studies

Test	Reference Range	Critical Test Result
Prothrombin time (PT)	12-15 sec	>30 sec
Partial thromboplastin time (PTT)	25-39 sec	>50 sec
International normalized ratio (INR)	0.8-1.2	>5 sec
Fibrin D-dimer	<200 ng/ml	*
Platelet count	150,000-400,000/mm³	<25,000/mm³

^*No critical value established.

D-dimer is a small protein fragment found in the blood when fibrin clots are dissolving. It belongs to a larger group of substances generally referred to as fibrin degradation products. Clinically, D-dimer levels are measured to help diagnose the presence of deep vein thrombosis, pulmonary embolism, or disseminated intravascular coagulation. Unless significant clotting has occurred in the body, the D-dimer test is normal.

Protein C has an integral role in the regulation of coagulation. In its activated state (activated protein C), it inhibits coagulation and promotes the degradation of clots. Protein C levels are greatly reduced in patients with severe sepsis and acute respiratory distress syndrome. Low protein C promotes abnormal clot formation and damages blood vessels in the microcirculation throughout the body (disseminated intravascular coagulation). Significant deficiencies in protein C levels (<40% of normal) are associated with increased risk of death in patients with severe sepsis.⁶ Protein C levels are measured in patients with severe sepsis to assess the appropriateness of therapy with pharmacologic preparations of activated protein C.

Infection Monitoring

Procalcitonin (PCT) is an inactive protein of the hormone calcitonin that is released in response to bacterial infections. PCT levels are directly related with the severity of infection. Because PCT does not increase appreciably in response to viral infections, it is a unique marker for bacterial infections. PCT levels typically increase within 12 hours of infection and promptly decrease once the infection is controlled with appropriate antibiotic therapy. PCT inceasingly is being used to titrate antibiotic therapy. In general, a cutoff valure between 0.25-0.50 mcg/L is used to initiate antibiotic therapy. Measurements of PCT are repeated every 1-2 days to evaluate antibiotic therapy. When PCT decreases by approximately 90% from peak values antibiotic therapy is usually terminated.⁶

Sweat Chloride

Patients with cystic fibrosis have increased levels of Cl⁻ in sweat because of an inability to reabsorb it. These patients will have abnormally elevated sweat Cl⁻ levels of greater than 60 Eq/L. Values between 40-60 mEq/L are considered borderline for systic fibrosis, whereas values less than 40 mEq/L are considered unlikely to confirm the diagnosis. Although the sweat electrolyte test is an important tool for diagnosing systic fibrosis, it must be combined with other tests.

Microbiology Tests

Sputum Gram Stain

A patient who is suspected to have an infection in the lungs or airways may benefit from analysis of a sputum sample. The purpose of such an analysis is to determine the specific microorganism causing the infection, which indicates the most appropriate antibiotic to be given. The first step in evaluating the sputum sample is the Gram stain, which is performed in the clinical laboratory by a technician who smears the sputum sample on a glass slide, applies a staining solution, and examines it through a microscope.

Initially, the technician uses the Gram stain to determine the quality of the sputum sample. Some patients have difficulty producing an adequate sputum sample from the lung and may expectorate only saliva into the sputum cup. In such cases, the Gram stain shows few (<25 per low-power field) or no pus cells and numerous epithelial cells. This result indicates that the sample is merely saliva and should be discarded. A sample with numerous pus cells and few or no epithelial cells is most likely a true sample from the lung and is reflective of the infection source.

Rule of Thumb

A legitimate sputum sample has few epithelial cells and many pus cells (leukocytes).

After the sample has been verified, the laboratory technician identifies the Gram stain reaction (either positive or negative) and the shape of any bacteria present (rods vs. cocci). Such results are presumptive, and a definitive diagnosis is made only by isolation and culture of the specific organism present. Streptococcus pneumoniae, a common bacterium associated with pneumonia, stains as encapsulated, lancet-shaped, gram-positive diplococci. These results are consistent with the diagnosis of streptococcal pneumonia and allow the physician to begin an appropriate course of antibiotic therapy before the results of the sputum culture are available, perhaps days later.

Sputum Culture

If the Gram stain reveals an adequate sample, the technician prepares a portion of the sputum for culture. The sputum sample is placed in a medium consistent with growth of the organism. When the organism has matured, it is examined microscopically to determine its exact type and sensitivity to antibiotic therapy. This information allows the physician to prescribe the most effective antibiotic. These same procedures for Gram staining and culturing can be applied to samples of blood, pleural fluid, or any other body fluid involved in an infection.

Acid-Fast Testing

Pulmonary tuberculosis is caused by a mycobacterium (Mycobacterium tuberculosis) and is a highly communicable disease. The rapid identification and isolation of patients with suspected tuberculosis infection is an extremely important infection control measure to protect other patients and health care providers. A rapid and effective method for detecting tuberculosis infection is to perform a Gram stain of a slide containing a sample of sputum followed by an acid wash. A characteristic of all mycobacteria is that after staining, the subsequent acid wash does not weaken the cell wall sufficiently to remove the color dye. This resistance to decolorization classifies the organism as an acid-fast bacterium.

Clinical Application of Laboratory Data

The RT has a unique position in the health care team. Respiratory therapy is a highly specialized profession focused primarily on the pulmonary system. One disadvantage is that the day-to-day practice does not entail dealing directly with other organ systems, as nurses and physicians do. RTs normally do not have the integrated global perspective that these caregivers must have. However, it behooves the RT to have a general understanding of a patient’s overall condition and illness trajectory. This understanding can be gained by becoming familiar with laboratory tests and their implications. Disruption in other organ systems has a direct impact on the practice of respiratory care. The primary focus of the RT is on the oxygen-carrying capacity of the blood. Anemia and insufficient hemoglobin levels result in overall weakness that often stymies the ability of patients to participate effectively in respiratory care.

Coagulation Disorders

In patients requiring arterial blood gas (ABG) testing or nasotracheal suctioning, the RT must evaluate the clotting characteristics of the blood. For ABG testing, patients with an abnormally low platelet count or an elevated PT and INR need to have the puncture site compressed for a longer time after the arterial sample is obtained to prevent bleeding and hematoma development. Patients with an extremely low platelet count should have an arterial puncture performed (or undergo nasotracheal suctioning) only when it is essential because of the extremely high risk of bleeding.

In addition, RTs are intimately involved in assessing patients with suspected pulmonary embolism. Patients with pulmonary embolism present with some of the same symptoms as patients with myocardial infarction (e.g., dyspnea and chest pain), and it is important for the RT to be familiar with tests such as D-dimers, troponin I, CPK-1, and CPK-2, which help make the differential diagnosis.

Electrolyte Disorders

Severe electrolyte disorders have a profound impact on pulmonary function. The primary concern of the RT is the effect of electrolyte disorders on respiratory muscle function. Many electrolyte disorders cause generalized skeletal muscle weakness. This weakness may limit ambulation and increases the risk for patients developing pneumonia and venous thromboembolism that can lead to pulmonary embolism. In a patient with pulmonary disease, respiratory muscle weakness impairs the ability to sustain spontaneous ventilation and the ability to maintain pulmonary hygiene through deep breathing and adequate cough.

Primary electrolyte disorders causing respiratory muscle weakness include low serum levels of calcium, magnesium, and phosphate.7,8 A patient with hypoglycemia often complains of weakness, so that weaning from a ventilator is unlikely to be successful in the patient with hypoglycemia. In addition, abnormally high serum potassium levels, or hyperkalemia (>8.0 mmol/L), and abnormally low serum potassium, or hypokalemia (<2.0 mmol/L), or phosphorus, or hypophosphatemia (<1.0 mg /dl), can lead to respiratory muscle paralysis. In addition, severe hyperkalemia (>6.0 mmol/L) increases the likelihood of cardiac arrhythmias. Severe hypocalcemia (<6.5 mmol/L)sometimes leads to laryngeal stridor and dyspnea.

Electrolyte disorders and other toxins in the bloodstream can depress neurologic function. Pulmonary function is profoundly affected because decreased mental functioning may depress respiratory drive, prevent patients from cooperating with therapy, and suppress the ability of patients to protect their airway and clear secretions by depressing the cough mechanism. In severe cases, hypernatremia is a major cause of central nervous system depression, which can lead to lethargy, coma, and respiratory arrest.⁹ In patients with severe liver disease, elevated ammonia levels also depress neurologic function.

Lastly, laboratory tests are used by physicians to assess the overall likelihood of survival of a critically ill patient. RTs care for patients with primary pulmonary failure. Survival is intimately related to the prevention or amelioration of secondary organ failures. Following trends in creatinine, total bilirubin, and platelets is crucial in monitoring the development or progression of renal, hepatic, and hematologic failure. Patients with primary respiratory failure have less chance of survival with each additional organ system dysfunction that develops.

Summary Checklist

• The three formed elements of the blood are the WBCs (leukocytes), RBCs (erythrocytes), and platelets (thrombocytes).

• Elevation of the WBC count is known as leukocytosis. It often occurs with infection, stress, or trauma.

• A reduced WBC count is known as leukopenia. It puts the patient at risk for serious infection.

• Abnormal elevation of the RBC count is known as polycythemia, and an abnormal reduction in the RBC count is known as anemia.

• Anemia reduces the oxygen-carrying capacity of the blood and increases the risk of tissue hypoxia. It also contributes to weakness that prevents patients from participating effectively in respiratory therapy.

• Severe electrolyte abnormalities, including low calcium, magnesium, and phosphorus, cause respiratory muscle weakness. This weakness may limit the ability of the patient to breathe spontaneously or maintain adequate pulmonary hygiene.

• Severe hyperkalemia (>6 mmol/L) greatly increases the risk of cardiac arrhythmias.

• Troponin I and CPK-MM tests are used to help diagnose myocardial infarction.

• To minimize the risk of bleeding, respiratory care procedures such as arterial punctures and nasotracheal suctioning should be done with extreme caution in patients with thrombocytopenia, elevated PT, and increased INR.