Basic Metabolic Panel Complete Blood Count Lipid Panel Thyroid Function

Basic Metabolic Panel

BASIC METABOLIC PANEL (BMP)- OVERVIEW BASIC METABOLIC PANEL- OBJECTIVES At the completion of this module the student will be able to: 1. Identify the key components of a BMP. 2. Identify normal values for each of these key components. 3. Identify the clinical indications for when to order a BMP. 4. Know how to interpret and develop differential diagnoses based on the laboratory findings. BASIC METABOLIC PANEL- LEARNING ACTIVITIES Key Concepts: Sodium (Na) Potassium (K) Chloride (Cl) Carbon Dioxide (CO2) Blood Urea Nitrogen (BUN) Creatinine (Cr) Glucose Activities: 1. 2. 3. Module: Work through the pages of the module. The contents of this module provide key concepts necessary for understanding and interpreting a BMP. Quiz: This quiz is to test your learned knowledge after review of the module. Basic Metabolic Panel Module Sodium o Normal Findings (Adult): 136-145 mEq/L o Critical Values: < 120 or > 160 mEq/L o Definition: Sodium is the major cation in the extracellular space, where there are serum levels of approximately 140 mEq/L. The concentration of sodium intracellularly is only 5 mEq/L. The serum sodium content is a result of a balance between dietary sodium intake and renal excretion. An average dietary intake for adults to maintain sodium balance is approximately 90-250 mEq per day. o Indications: Sodium analysis is part of the basic metabolic panel and is part of a routine laboratory evaluation. It is used to evaluate fluid and electrolyte status. o Differential Diagnoses

Increased Levels (hypernatremia)

Symptoms include dry mucous membranes, agitation, thirst, restlessness, mania, hyperreflexia, and convulsions. Dehydration and insufficient water intake Increased dietary intake of sodium Excessive diaphoresis Cushing's disease Hyperaldosteronism (aldosterone stimulates the kidneys to absorb sodium at the renal tubule) Diabetes insipidus (the deficiency of antidiuretic hormone (ADH) and the inability of the kidney to respond to ADH causes large free water losses, thus sodium becomes concentrated) Decreased Levels (hyponatremia) The first symptom is weakness. When levels fall below 115 mEq/L, confusion and lethargy occur and may progress to coma if levels continue to decline. Deficient dietary intake Severe diarrhea and vomiting (sodium loss occurs with the GI fluid loss) Administration of diuretics (many diuretics act by inhibiting sodium reabsorption by the kidney) Chronic renal insufficiency (Kidneys lose their reabsorptive capabilities, thus large amounts of sodium are lost in the urine) Syndrome of inappropriate antidiuretic hormone (SIADH) (oversecretion of ADH stimulates the kidney to reabsorb free water, thus sodium is diluted) Addison's disease (the kidneys do not reabsorb sodium adequately due to inadequate aldosterone and corticosteroid hormone levels, thus sodium is lost in the urine)

Basic Metabolic Panel Module - Potassium Normal Findings (Adult): 3.5-5.3 mEq/L Critical Values: < 2.5 or > 6.5 mEq/L Definition: Potassium is the major cation of intracellular fluid. Ninety percent of potassium is concentrated within the cell and

only very small amounts are contained in blood, thus minor changes have significant consequences. The kidneys do not reabsorb potassium, therefore if it is not supplied by the diet (80-200 mEq/day) or external means (intravenous therapy) serum levels can drop very quickly. Serum potassium concentration is dependent on aldosterone, sodium reabsorption and acid-base balance. It plays an important role in nerve conduction, muscle function, and osmotic pressure. Potassium, along with calcium and magnesium controls the rate and force of contraction myocardium.

Indications:Potassium is part of the basic metabolic panel. Due to the important role potassium plays in myocardial function, it is a part of all complete, routine laboratory evaluations, especially for those taking diuretics or cardiac medications. Differential Diagnoses

Increased Levels (hyperkalemia) Symptoms include nausea, vomiting, diarrhea, intestinal colic, and irritability. The EKG may reveal peaked T waves, a widened QRS complex, and a depressed ST segment. Excessive dietary /IV intake Acute or chronic renal failure (most common cause because K+excretion is diminished, thus serum levels rise) Cell damage, as in burns, surgery, chemotherapy, infection (damaged cells release potassium into the blood) Some diuretics (aldosterone inhibiting diuretics-Aldosterone, which enhances potassium excretion, is absent) Addison's disease (the kidneys do not excrete potassium adequately due to inadequate aldosterone) Metabolic acidosis (hydrogen enters the cell and to maintain a neutral state potassium is expelled) Decreased Levels (hypokalemia): Signs are related to a decrease in smooth, skeletal, and cardiac muscle contractility. This results in weakness, paralysis, hyporeflexia, ileus, and cardiac arrhythmias. The EKG may reveal dysrhythmias, flattened T waves, and prominent U waves. Deficient dietary/IV intake Some diuretics Excessive diarrhea, vomiting, and diaphoresis Hyperaldosteronism (aldosterone enhances the excretion of potassium) Respiratory alkalosis (hydrogen ions are driven out of the cell and to maintain neutrality, potassium is driven into the cell) Basic Metabolic Panel Module - Chloride Normal Findings (Adult): 98-106 mEq/L Critical Values: < 80 or > 115 mEq/L Definition: Chloride is the major extracellular anion. Its primary purpose is to maintain electrical neutrality. It follows sodium losses and accompanies sodium excess in an attempt to maintain its neutrality. When aldosterone directly causes an increase in the reabsorption of sodium (+ ion), the indirect effect is an increase in the absorption of chloride (- ion). Chloride also serves as a buffer in acid-base balance. When the bicarbonate level drops, as in metabolic acidosis, there is a reciprocal rise in chloride concentration. Indications: Chloride does not provide much information alone, but in combination with the other components of the basic metabolic panel, it can provide information about acid-base balance and hydration status. Differential Diagnoses *Increased Levels (hyperchloremia): Signs include lethargy, deep breathing, and weakness. Dehydration Metabolic acidosis Hyperventilation, which causes respiratory alkalosis Cushing's syndrome *Decreased Levels (hypochloridemia): Signs include hyperexcitability of the nervous system and muscles, hypotension, shallow breathing, and tetany. Vomiting or prolonged gastric suctioning Burns Overhydration Salt losing diseases (SIADH-chloride is diluted, nephritis) Aldosteronism (chloride excretion is increased) Metabolic alkalosis (chloride is driven into the cell to compensate for the bicarbonate that leaves the cell to maintain neutrality) Chronic respiratory acidosis BMP - Carbon Dioxide (CO2) Normal Findings (Adult): 23-30 mEq/L Critical Value: < 6 mEq/L Definition: In normal blood plasma, >95% of the total CO2 (TCO2) is contributed by bicarbonate ion, which is regulated by the kidneys. The other 5% is contributed by the dissolved CO2 gas and by carbonic acid. Dissolved CO2 gas is regulated by the lungs and contributes little to the TCO2, thus gives little information about lung status. Indications: This test is part of the basic metabolic panel and is used to assist in the evaluation of acid-base balance. Differential Diagnoses *Increased Levels: Severe vomiting High volume gastric suctioning Aldosteronism COPD (bicarbonate anions are increased to compensate for chronic hypoventilation, this is compensation for respiratory acidosis) Metabolic alkalosis (this is defined by an increased amount of bicarbonate anions in the blood) *Decreased Levels : Chronic diarrhea Starvation Diabetic ketoacidosis Shock (lactic acid builds up and is buffered by bicarbonate, therefore bicarbonate levels diminish)

BMP - Blood Urea Nitrogen (BUN) Normal Findings (Adult): 10-20 mg/dl Critical Value: > 100 mg/dl- - Indicates serious renal function impairment Definition: BUN measures the amount of urea nitrogen in the blood. Urea is formed in the liver from ammonia, which is an end product of protein metabolism. It is deposited in the blood stream and taken to the kidneys for excretion; therefore BUN serves as a measure of both the metabolic function of the liver and the excretory function of the kidney. Indications: It is part of the basic metabolic panel and it is an indirect measurement of renal function, glomerular filtration, and liver function. Differential Diagnoses *Increased Levels: Impaired renal function- Causes of impaired renal function include: congestive heart failure, salt and water depletion, shock, stress, acute MI (with reduced blood volume and cardiac function renal blood flow is diminished, thus renal excretion of BUN is decreased) Chronic renal disease (glomerulonephritis and pyelonephritis) Urinary tract obstruction (obstruction of the flow of urine causes reduced excretion of BUN) Excessive protein catabolism and starvation (as protein is broken down to amino acids at a higher rate, urea is formed at a higher rate and thus BUN rises) *Decreased Levels: Liver failure (BUN is formed in the liver from urea and reduce liver function is associated with reduced BUN levels) Malnutrition/Malabsorption (with protein depletion, urea production is reduced) Nephritic syndrome (this is associated with protein loss in the urine, thus BUN is reduced) Overhydration due to SIADH (BUN is diluted by the fluid overload) Basic Metabolic Panel Module - Creatinine Normal Findings (Adult) 0.4-1.5 mg/dl Critical Value: > 4 mg/dl Definition: Creatinine is a catabolic product of creatine phosphate, which is used in skeletal muscle contraction and is produced at a constant rate according to the muscle mass of the individual. It is easily excreted by the kidneys in healthy individuals and therefore is directly proportional to renal excretory function. Indications: It is part of the basic metabolic panel and is used to diagnose impaired renal function. Differential Diagnoses *Increased Levels: Diseased affecting renal function, such as glomerulonephritis, pyelonephritis, acute tubular necrosis, urinary tract obstruction, reduced renal blood flow (with these illnesses renal function is impaired and creatinine levels rise) Rhabdomyolysis (injury of the skeletal muscle causes large amounts of myoglobin to be released in the blood stream causing nephrotoxicity) Increased muscle mass (acromegalya and gigantism) *Decreased Levels: Decreased muscle mass (muscular dystrophy, myasthenia gravis, and debilitation) BMP - Glucose (fasting) Normal Findings (Adult): 65-110 mg/dl Critical Values: < 50 and > 400 mg/dl Definition: Glucose is formed from carbohydrate digestion and conversion of glycogen to glucose by the liver. Glucose is controlled by glucagon and insulin. Glucagon accelerates glycogen breakdown and thus causes blood glucose to rise. Insulin increases cell membrane permeability to glucose, transports glucose into cells for metabolism, stimulates glycogen formation, and thus reduces blood glucose levels. Adrenocorticotropic hormone (ACTH), epinephrine, thyroxine, and adrenocorticosteroids also play key roles in glucose metabolism. Indications: Glucose is part of the basic metabolic panel and is a direct measurement of the blood glucose level. It is frequently used in the evaluation of diabetic patients. According to the American Diabetic Association (2003) diagnosis of diabetes mellitus includes: 1. 1. Fasting plasma glucose (FPG) >/= 126 mg/dl and confirmed by a second test. 2. 2. Random glucose >/= 200 mg/dl with symptoms and confirmed by a second test. 3. 3. OGTT with the 2-hour values >/= 200 mg/dl confirmed by a second test. Differential Diagnoses *Increased Levels (hyperglycemia): Diabetes mellitus Cushing's disease (increased glucocorticoids cause elevated blood sugar levels) Acute stress response, including severe stress, infection, burns, and surgery (these stimulate catecholamine release, which in turn stimulates glucagon secretion causing hyperglycemia) Pancreatitis (the contents of the pancreatic cells, including glucagon, are spilled into the blood stream as the cells are injured during inflammation) Corticosteroid therapy (Cortisol causes hyperglycemia) *Decreased Levels (hypoglycemia): Insulin overdose (most common cause) Insulinoma (pancreatic islet cell carcinoma-too much insulin production) Addison's disease (Cortisol deficiency, thus hypoglycemia) Starvation (decreased carbohydrate ingestion causes hypoglycemia) Hypothyroidism and hypopituitarism (with decreased levels of these hormones, glucose levels fall)

BASIC METABOLIC PANEL- SUMMARY COMPLETE BLOOD COUNT (CBC)- Overview At the completion of this module the student will be able to: 1. Identify the key components of a CBC. 2. Identify normal values for each of these key components. 3. Identify the clinical indications for when to order a CBC. 4. Know how to interpret and develop differential diagnoses based on the laboratory findings. COMPLETE BLOOD COUNT- LEARNING ACTIVITIES Key Concepts: Red Blood Cell Count (RBC) Hemoglobin (Hb) Hematocrit (Hct) Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin (MCH) Mean Corpuscular Hemoglobin Concentration (MCHC) Red Cell Size Distribution Width (RDW) Platelet Count White Blood Cell Count (WBC) -Neutrophils -Lymphocytes -Monocytes -Eosinophils -Basophils Activities: Red Blood Cell (RBC) Count Normal Findings (Adult): Male- - 4.6-6.2 Female- - 4.2-5.4 Definition: The RBC determines the total number of red blood cells or erythrocytes found in a cubic millimeter of blood. Erythrocytes are formed in bone marrow and have a life span of 120 days. Maturation takes 3-5 days and the last stages of maturation are reticulocytes and erythrocytes. Within each RBC are molecules of hemoglobin that permit the transport and exchange of oxygen to the tissues and carbon dioxide from the tissues. Normal RBC values vary depending on age and gender. Women tend to have lower values than men and RBC counts tend to decrease with age. When the value is decreased more than 10% of the expected normal value, the patient is said to be anemic. Indications: The RBC count is part of the CBC. It is an important measurement in the determination of anemias Differential Diagnoses Increased Levels Erythrocytosis (RBC's are increased) Congenital heart disease (cyanotic heart disease's cause chronically low Po2 levels and in response the RBC's increase in number; therefore the hematocrit also increases) Polycythemia vera (the bone marrow inappropriately produces too many RBC's causing the hematocrit to increase) Severe dehydration (severe diarrhea, burns) Severe COPD Decreased Levels Anemia (this is a term given to the state associated with reduced number of RBC's) Hemoglobinopathies (with hemoglobin disorders and other blood dyscrasias there is a reduced number and survival of RBC's; therefore a reduced hematocrit as well) Hemorrhage Hemolytic reactions (such as transfusions with incompatible blood, reactions to chemicals and drugs, reactions to infectious agents) Various systemic diseases (leukemia, lymphoma, hodgkin's disease, sarcoidosis) CBC - Hemoglobin Normal Findings (Adult): Male- - 13.5-18 g/dl Female- - 12-16 g/dl Definition: Hemoglobin is the main component of erythrocytes and serves as the vehicle for the transportation of oxygen and carbon dioxide. It is composed of amino acids that form a single protein called globin and a compound called heme, which contains iron atoms and the red pigment porphyrin. The oxygen combining capacity of the blood is directly proportional to the hemoglobin concentration rather than to the RBC count. Each gram of hemoglobin can carry 1.34 ml of oxygen. Indications: Hemoglobin is part of the CBC. It is used to screen for disease associated with anemia, determine the severity of anemia, follow the response to treatment for anemia, and to evaluate polycythemia Differential Diagnoses Increased Levels Erythrocytosis (RBC's are increased) Congenital heart disease (cyanotic heart disease's cause chronically low Po2 levels and in response the RBC's increase in number; therefore the hematocrit also increases) Polycythemia vera (the bone marrow inappropriately produces too many RBC's causing the hematocrit to increase) Severe dehydration (severe diarrhea, burns) Severe COPD Decreased Levels Anemia (this is a term given to the state associated with reduced number of RBC's)

Hemoglobinopathy (with hemoglobin disorders and other blood dyscrasias there is a reduced number and survival of RBC's; therefore a reduced hematocrit as well) Hemorrhage Hemolytic reactions (such as transfusions with incompatible blood, reactions to chemicals and drugs, reactions to infectious agents) Various systemic diseases (leukemia, lymphoma, hodgkin's disease, sarcoidosis) CBC - Hematocrit Normal Findings (Adult): Male- - 40-54% Female- -38-47% Definition: The hematocrit is a measure of the percentage of the total blood volume that is made up by the RBC's. It is usually approximately three times the hemoglobin concentration when RBC's are of normal size and contain normal amounts of hemoglobin. Normal values vary according to age and gender. Women tend to have lower values than men and hematocrit values tend to decrease with age. Indications: Hematocrit is included in a CBC. It is the indirect measurement of the red blood cell number and volume. It is used as a rapid measurement of RBC count. It is an integral part of the evaluation of anemic patients. Differential Diagnoses Increased Levels Erythrocytosis (RBC's are increased) Congenital heart disease (cyanotic heart diseases cause chronically low Po2 levels and in response the RBC's increase in number; therefore the hematocrit also increases) Polycythemia vera (the bone marrow inappropriately produces too many RBC's causing the hematocrit to increase) Severe dehydration (severe diarrhea, burns) Severe COPD Decreased Levels Anemia (this is a term given to the state associated with reduced number of RBC's) Hemoglobinopathy (with hemoglobin disorders and other blood dyscrasias there is a reduced number and survival of RBC's; therefore a reduced hematocrit as well) Hemorrhage CBC - Mean Corpuscular Volume (MCV) Normal Findings (Adult): 80-95 fl Definition: The MCV is a measure of the average volume, or size, of a single RBC and therefore it used to classify anemias. Normal values vary according to age and gender. When the MCV value is increased, the RBC is abnormally large or macrocytic. This is most frequently seen with megaloblastic anemias, such as vitamin B12 or folic acid deficiency. When the MCV value is decreased, the RBC is abnormally small or microcytic. This is associated with iron deficiency anemia or thalassemia. Indications: The MCV is part of the CBC and is used to aid with classification of anemias. Differential Diagnoses Increased Levels (Macrocytosis) Pernicious anemia (vitamin B12 deficiency) and Folic acid deficiency (these are the most common causes of microcytic anemia) Alcoholism (this is probably more related to malnutrition) Chronic liver disease Decreased Levels (Microcytosis) Iron deficiency anemia Thalassemia Anemia of chronic illness CBC - Mean Corpuscular Hemoglobin (MCH) Normal Findings (Adult): 27-31 pg Definition: The MCH is the measure of the average amount or weight of hemoglobin within a RBC. Due to the fact that microcytic cells have less hemoglobin and microcytic cells tend to have more hemoglobin, the causes for these values tend to closely resemble those for MCV values Indications: The MCH is part of the CBC, but adds very little information to the other measures Differential Diagnoses Increased Levels Microcytic anemias (B12 and folic acid deficiency) Decreased Levels Microcytic anemias (iron-deficiency anemia, thalassemia, and anemia of chronic illness) CBC- Red Cell Size Distribution Width (RDW) Normal Findings (Adult): 11-14.5% Definition: The RDW is an indication of the variation in RBC size. It is calculated by a machine using the MCV and RBC values. Normally all RBC's are about the same size, but certain disease may alter the sizes. The RDW indicates the degree of this alteration in size. Indications: The RDW is part of the CBC and aids in classification of certain anemias. Differential Diagnoses Increased Levels Iron deficiency anemia B12 and folate deficiency anemias Sickle cell anemia Decreased Levels

None Anemia Type Table

CBC -Platelet Count (thrombocyte count) Normal Findings (Adult): 150,000-400,000 Definition: Platelets are formed in the bone marrow from megakaryocytes. Their main role is the maintenance of vascular integrity and they are essential to blood clotting. Most of the platelets exist in the blood stream (75%) and a smaller percentage in the liver and spleen (25%). Platelets survive an average of 7-9 days. Indications: The platelet count is part of the CBC. The platelet count is an actual number of platelets or thrombocytes per cubic milliliter of blood. It is typically performed on patients with petechiae, spontaneous bleeding, increasingly heavy menses, or thrombocytopenia. It is also used to monitor the course of bone marrow failure. Differential Diagnoses Increased Levels (thrombocytosis) Malignant disorders (leukemia, lymphoma, solid tumors) Postsplenectomy syndrome (the spleen normally extracts aging platelets from the bloodstream, but in it's absence it is done less effectively by other organs) Rheumatoid arthritis (the mechanism is unknown) Iron deficiency anemia (iron is not needed for platelet production, so in the presence of anemia marrow is stimulated) Polycythemia vera (this is a hyperplasia of all marrow cell lines) Decreased Levels (thrombocytopenia) Hypersplenism (an enlarged spleen extracts more platelets, both aging and new) Hemorrhage (they are lost in the bleeding process) Grave's disease (occurs in a small number of these patient's and the mechanism is unknown) Pernicious anemia (vitamin B12 is necessary for platelet production) Hemolytic anemia (usually the same process that produces the hemolysis also destroys the platelets) Infection (especially when patient is immunocompromised) CBC -White Blood Cell Count (WBC) or leukocytes Normal Findings (Adult): 5,000-10,000 Definition: The major function of WBC's is to fight infection and react against foreign bodies or tissues. There are five types of WBC's identified on a routine blood smear and they are neutrophils, lymphocytes, monocytes, eosinophils, and basophils. These will be discussed individually. WBC's are divided into granulocytes (neutrophils, basophils, eosinophils) and nongranulocytes (monocytes and lymphocytes). Granulocytes have granules in their cytoplasm that stain when examined on routine smear and they are sometimes referred to as polymorphonuclear leukocytes or PMN's. Indications: The WBC count is part of the CBC and is a count of the total number of white blood cells or leukocytes in 1 mm of peripheral venous blood. It is helpful in evaluation of patients with infection, neoplasms, allergies, or immunosuppression. Differential Diagnoses Increased Levels (leukocytosis) Infection (WBC's are integral to initiating and maintaining the body's defense against infection) Inflammation Trauma, stress, or hemorrhage (under hormonal influence the WBC's are increased) Malignancy (advanced nonmarrow cancers) Dehydration (it is a stress on the body and also through hemoconcentration)

Thyroid storm (the WBC count is influenced by thyroid hormones) Steroid use (glucocorticoids stimulate WBC production) Decreased Levels (leukopenia) Drug toxicity (chemotherapy) Bone marrow failure Overwhelming infections Dietary deficiencies, such as B12 or iron Hypersplenism (the spleen more aggressively extracts WBC's) Bone marrow infiltration CBC -Neutrophils Normal Findings (Adult): 55-70% and absolute 2500-8000 Definition: Neutrophils are the most common granulocyte. They are produced in 10-14 days and remain in circulation for only 6 hours. Its primary function is phagocytosis. Acute bacterial infections and trauma stimulate neutrophil production, resulting in an increased WBC count. When neutrophil production is significantly stimulated, early immature forms of neutrophils are released into circulation and this is referred to as a "shift to the left". These immature neutrophils are called bands or stab cells. Indications: The neutrophil count is part of the WBC differential included in a CBC. Differential Diagnoses Increased Levels (neutrophilia) Physical or emotional stress Acute infection Trauma Inflammatory disorders Myelocytic leukemia Cushing's syndrome Decreased Levels (neutropenia) Dietary deficiency Overwhelming bacterial infection (especially in the elderly) Viral infection (hepatitis, influenza, measles) Addison's disease CBC -Lymphocytes Normal Findings (Adult): 20-40% and absolute 1000-4000 Definition: There are two types of lymphocytes (T cells and B cells). T cells mature in the thymus and are involved with cellulartype immunity reactions. B cells mature in the bone marrow and they are involved with humoral immunity (antibody production). The primary function of lymphocytes is to fight chronic bacterial infections and acute viral infections. Indications: The lymphocyte count is part of the WBC differential included in a CBC. Differential Diagnoses Increased Levels (lymphocytosis) Physical or emotional stress Acute infection Trauma Inflammatory disorders Myelocytic leukemia Cushing's syndrome Decreased Levels (lymphocytopenia) Leukemia Sepsis Immunodeficiency diseases Lupus erythematosus Radiation therapy Medications, such as adrenocorticosteroids and antineoplastics CBC -Monocytes Normal Findings (Adult): 2-8% and absolute 100-700 Definition: Monocytes are phagocytic cells capable of fighting bacteria similar to the way neutrophils fight bacteria, however monocytes can be produced more rapidly and can stay in circulation longer than neutrophils Indications: The monocyte count is part of the WBC differential included in a CBC. Differential Diagnoses Increased Levels (Monocytosis) Chronic inflammatory disorders Infectious mononucleosis Tuberculosis Chronic ulcerative colitis Parasites Decreased Levels (Monocytopenia) Drug therapy with prednisone

COMPLETE BLOOD COUNT MODULE -Eosinophils Normal Findings (Adult): 1-4% and absolute 50-500 Definition: Eosinophils are involved in the allergic reaction to a greater degree than basophils and are capable of phagocytosis of antigen-antibody complexes. As the allergic reaction response diminishes, the eosinophil count decreases. They do not respond to bacterial or viral infections. Parasitic infestations are also capable of stimulating production of eosinophils. Indications: The eosinophil count is part of the WBC differential included in a CBC. Differential Diagnoses Increased Levels (eosinophilia) Allergic reactions Parasitic infections Eczema Leukemia Decreased Levels (Eosinopenia) Increased adrenosteroid production CBC -Basophils Normal Findings (Adult): 0.5-1.0% and absolute 25-100 Definition: Basophils are also called mast cells. They are involved in the allergic reaction to a lesser degree than eosinophils. The cytoplasm of basophils contains heparin, histamine, and serotonin. These cells infiltrate the tissue involved in the allergic reaction and serve to further the inflammatory response. Indications: The basophil count is part of the WBC differential included in a CBC Differential Diagnoses Increased Levels (basophilia) Myeloproliferative disease (myelofibrosis, polycythemia rubra vera) Leukemia Decreased Levels (basopenia) Acute allergic reaction Hyperthyroidism Stress reactions LIPID PANEL- OBJECTIVES At the completion of this module the student will be able to: 1. Identify the key components of a lipid panel. 2. Identify normal values for each of these key components. 3. Understand the National Cholesterol Education Program (NCEP) guidelines for screening individuals for dyslipidemia. 4. Identify the clinical indications for when to order a lipid panel. 5. Know how to interpret and develop differential diagnoses based on the laboratory findings. LIPID PANEL- LEARNING ACTIVITIES Key Concepts: Total Cholesterol (TC) High-Density Lipoprotein (HDL) Low-Density Lipoprotein (LDL) Triglycerides (TG) Cholesterol/HDL ratio LIPID PANEL MODULE -Total Cholesterol Normal Findings (Adult): < 200 mg/dl Definition: Cholesterol is required for the production of sex hormones, bile acids, steroids, and cellular membranes. It is metabolized by the liver and about seventy-five percent is bound to low-density lipoproteins (LDL). The other twenty-five percent is bound to high-density lipoproteins (HDL). It is the main lipid associated with atherosclerosis and increased risk of coronary heart disease. Indications: The purpose of cholesterol testing is to identify patients at risk for developing atherosclerosis, but by itself it is not a totally accurate predictor of heart disease. For this reason it is included as part of the lipid panel. Differential Diagnoses Increased Levels Atherosclerosis Hypothyroidism Pregnancy Pancreatic disease (uncontrolled diabetes mellitus) Hypertension Biliary obstruction Nephrotic syndrome High-cholesterol diet Drug use (progestins, anabolic steroids, corticosteroids, and some diuretics) Decreased Levels Hyperthyroidism

Malnutrition/Malabsorption Chronic anemias (pernicious and hemolytic) Severe liver cell damage due to chemicals, drugs, or hepatitis Conditions of acute illness/Infection Inflammation

LIPID PANEL MODULE -High-Density Lipoproteins (HDL) good cholesterol Normal Findings (Adult): Male- >45 mg/dl Female- >55 mg/dl Definition: HDL's are predominantly produced in the liver and to a smaller extent in the intestines. They are carriers of cholesterol and their main purpose is to remove cholesterol from the peripheral tissues and take it to the liver for excretion. HDL's (good cholesterol) may have a protective role in the prevention of coronary artery disease (CAD) by preventing the cellular uptake of cholesterol and lipids. Indications: HDL cholesterol is an independent inverse risk factor for coronary artery disease; therefore it is performed to identify those at risk for developing coronary artery disease. It is also used to monitor therapy once the abnormality has been identified. Differential Diagnoses Increased Levels Long-term vigorous exercise Chronic liver disease (cirrhosis, hepatitis, alcoholism) Oral estrogen use Familial HDL lipoproteinemia Decreased Levels Increased risk for CAD (for every 1 mg/dl decrease in HDL, risk for CAD increases by 2-3%) Familial low HDL Hepatocellular disease Hypoproteinemia (nephrotic syndrome and malnutrition) Interfering factors (cigarette smoking, obesity, lack of exercise, stress, acute illness, anorexia, and use of beta-blockers, thiazides, and steroids) LIPID PANEL MODULE -Low-Density Lipoproteins (LDL) Bad cholesterol Normal Findings (see NCEP guidelines at end of module) Definition: LDL's are the cholesterol-rich remnants of very-low-density lipoproteins (VLDL), but because LDL has a longer half-life and is easier to measure than VLDL, it is the test of choice. LDL is derived by subtracting the HDL plus one-fifth of the triglycerides from the total cholesterol. [LDL = Total Cholesterol (HDL + Triglycerides/5)] Indications: LDL is performed as part of the lipid panel to identify those at risk for developing coronary artery disease. It is also used to monitor therapy once the abnormality has been identified. Differential Diagnoses Increased Levels Familial lipoproteinemia Increased risk of CAD Diabetes mellitus Hypothyroidism Chronic renal failure High-cholesterol diet Anorexia Excessive alcohol consumption Decreased Levels Familial hypolipoproteinemia Hypoproteinemia (severe burns, malabsorption, malnutrition) Oral estrogen use Severe illness Hyperthyroidism LIPID PANEL MODULE -Triglycerides Normal Findings (Adult): < 150 mg/dl Definition: Triglycerides are produced in the liver and act as a storage source for energy. They are not a strong predictor of atherosclerosis or CAD and may not an independent risk factor. Indications: Triglycerides identify the risk of developing CAD and therefore are included as part of the lipid panel. Differential Diagnoses Increased Levels Hyperlipoproteinemia Poorly controlled diabetes mellitus Pancreatitis Chronic renal failure Gout Acute illness Hypothyroidism Nephrotic syndrome

Decreased Levels Hyperthyroidism Malnutrition/Malabsorption Recent weight loss Certain drugs including Metformin LIPID PANEL MODULE - Cholesterol/HDL Ratio The higher the cholesterol/HDL ratio, the greater the possible risk of developing atherosclerosis. Third Report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) The third report of the national cholesterol education program constitutes the national cholesterol education program's updated national clinical guidelines for cholesterol testing and management. This document is evidenced-based and provides scientific rationale for its recommendations. >Risk Category >LDL Goal >LDL Level to initiate therapeutic lifestyle changes (TLC) >LDL Level to consider drug therapy CHD or CHD risk equivalent <100 mg/dl >/= 100 mg/dl >/=130 mg/dl (100-129 mg/dl-LDL lowering drug is optional) 2+ risk factors <130 mg/dl >/= 130 mg/dl >/=190 mg/dl 0-1 risk factors <160 mg/dl >/=160 mg/dl >/=190 mg/dl (160-189 mg/dl-LDL lowering drug is optional) >Risk factors that modify LDL Goals Cigarette smoking Hypertension (BP > or = 140/90 mm/Hg or on an antihypertensive medication) Low HDL cholesterol (< 40 mg/dl) Family history of premature coronary heart disease (CHD) o CHD in male 1st degree relative < 55 y/o o CHD in female 1st degree relative < 65 y/o Age o Male > or = 45 y/o o Female > or = 55 y/o Coronary Heart Disease and Diabetes = separate risk category Therapeutic Lifestyle Changes (TLC) Reduced intakes of saturated fats (< 7% of total calories) and cholesterol (<200 mg per day) Therapeutic options for enhancing LDL lowering, such as plant stanols/sterols (2 g/day) and increased viscous (soluble) fiber (1025 g/day) Weight reduction Increased physical activity Thyroid Function Tests Module - TSH Normal Findings (Adult): 0.2-5.4 mU/L Definition: Thyroid activity is regulated by the body's perceived need for hormone. The hypothalamic release of thyroid releasing hormone (TRH) stimulates the anterior pituitary to release TSH, which in turn stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4). Both of these hormones feed back to the pituitary to inhibit TSH secretion. This is referred to as negative feedback. Hypothalamus (TRH) Anterior Pituitary Gland (TSH) Thyroid Gland (T3 and T4) Indications: TSH is the most sensitive marker of thyroid hormone action, thus it is used as a screening test for thyroid status. Differential Diagnoses Increased Levels Primary hypothyroidism (diagnosed by increased TSH) Hypothyroid patients receiving inadequate doses of thyroid replacement hormone Surgical ablation of the thyroid gland Hashimoto's thyroiditis TSH-producing tumors (pituitary, lung, or breast) Decreased Levels Secondary hypothyroidism caused by pituitary or hypothalamic dysfunction (dysfunction of the hypothalamus diminishes its capability to

secrete TRH. Dysfunction of the pituitary diminishes its capability to secrete TSH) Primary hyperthyroidism (increased levels of thyroid hormone inhibits the release of TSH) Overreplacement of thyroid hormone in the treatment of hypothyroidism >Thyroid Function Tests Module - Free Thyroxine (FT4)

Normal Findings (Adult): 0.8-2.8 ng/dl Definition: Free thyroxine comprises a small amount (about 5%) of total thyroxine. FT4 is the metabolically active form of this hormone and is unbound to protein and thus available to the tissues. Most of T4 is converted to T3 by peripheral nonthyroidal tissues. T3 exerts the majority of thyroidal hormone effects. Indications: This test is part of the evaluation of thyroid function and is especially useful in individuals with protein binding abnormalities. Differential Diagnoses

Increased Levels Primary hyperthyroidism (Grave's disease)- despite the lack of TSH stimulation, the thyroid gland produces increased T4. Hashimoto's thyroiditis (the thyroid secretes T4 during the acute inflammatory stages of thyroiditis, however in the latter stages the thyroid may become burned out, thus developing hypothyroidism) Hypothyroidism treated with thyroxine Decreased Levels Hypothyroid states, such as myxedema, surgical ablation, cretinism. (with these diseases the thyroid cannot produce adequate amounts of T4) Secondary hypothyroidism (pituitary dysfunction) Tertiary hypothyroidism (hypothalamic dysfunction)>Thyroid Function Tests Module - Triiodothyronine Normal Findings: Age > 24 years: 80-200 ng/dl Age 15-23 years: 100-220 ng/dl Age 1-14 years: 125-250 ng/dl Definition: T3 is more metabolically active than T4, but it is much less stable because it is much less tightly bound to serum proteins than T4. Thyroid hormones influence oxygen consumption, carbohydrate and protein metabolism, the mobilization of electrolytes, and the conversion of carotene to vitamin A. Indications: This is a quantitative measurement of T3 concentration of the blood. It is the test of choice in the diagnosis of T3 thyrotoxicosis, which is a variant of hyperthyroidism in which a thyrotoxic patient has elevated T3 values and normal T4 values. It is also useful in the diagnosis of hyperthyroidism, however it has limited value in diagnosing hypothyroidism. Differential Diagnoses Increased Levels Primary hyperthyroidism (Grave's disease) Acute thyroiditis (the thyroid secretes increased T3 during the acute inflammatory stages of thyroiditis, however in the latter stages the thyroid may become burned out, thus developing hypothyroidism) T3 thyrotoxicosis Factitious hyperthyroidism (patients who self administer T3 will have elevated levels) Thyroid binding globulin (TBG) from any cause (because total T3 assay measures total bound and unbound T3, any condition associated with an increased TBG will cause an elevation of T3) Decreased Levels Hypothyroidism Pituitary insufficiency Hypothalamic dysfunction Starvation, protein deficiency (with a decreased protein intake, TBG and albumin decrease. The T3 assay measures hormones bound to these proteins, thus T3 can be expected to decrease)