Ординатура / Офтальмология / Английские материалы / Clinical Medicine in Optometric Practice_Muchnick_2007
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38 DIAGNOSTIC PROCEDURES
To test the eleventh nerve, place your hands on the patient’s shoulders and press downward while the patient attempts to shrug the shoulders against your resistance (Figure 3-16, A). Another test involves having the patient attempt to turn his or her head against resistance. Place your hand on the left side of the patient’s face and push against the patient’s left cheek while he or she tries to turn his or her head to the left. Palpate the patient’s right sternomastoid muscle and feel it tighten while the patient attempts to turn his or her head to the left. Repeat the process with the patient attempting to turn his head to the right against resistance (Figure 3-16, B). Damage to the eleventh cranial nerve can occur as a result of radical nerve surgery or trauma.
FIGURE 3-17 ■ Testing the hypoglossal nerve. The patient sticks out his or her tongue and moves it laterally against resistance from a cotton-tipped applicator.
Twelfth Cranial Nerve—Hypoglossal Nerve
The twelfth cranial nerve supplies efferent motor fibers to all intrinsic and extrinsic muscles of the tongue (except the palatoglossus). Damage to the nerve results in paralysis of the tongue on the affected side. Therefore, when the patient sticks out his or her tongue, it will deviate to the side of the lesion (Figure 3-17).
To test the hypoglossal nerve, the examiner should ask the patient to stick out his or her tongue and move A it right and left against resistance offered by the examiner, who holds a cotton-tipped applicator to the lat-
eral aspect of the tongue.
B
FIGURE 3-16 ■ Testing the accessory nerve. A, The examiner pushes down on the shoulders of the patient, who tries to shrug against the resistance. B, The patient turns his or her head against the examiner’s hand while the sternomastoid muscle is palpated for tone. The patient then turns to the other side. The muscle tone on both sides is compared.
BIBLIOGRAPHY
Brazio PW, Masdeu JC, Biller J: Localization in clinical neurology, Boston, 1985, Little, Brown.
Campbell WW, ed: Dejong’s the neurological exam, ed 6, Lippincott Williams and Wilkins, 2005.
Prior JA, Silberstein JS, Stang JM: Chapter 18. In Physical diagnosis-the history and examination of the patient, ed 6, St. Louis, 1981, Mosby-Year Book.
Swartz Mark H: Chapter 18. In Textbook of physical diagnosis,
Philadelphia, 1989, WB Saunders.
Weiner WJ, Goetz CG, eds: Neurology for the non-neurologist,
Philadelphia, 1981, Harper and Row.
Wilson-Pauwels L, et al: Cranial nerves: anatomy and clinical comments, Toronto, 1988, BC Decker.
C H A P T E R 4
Laboratory Testing
C H A P T E R O U T L I N E
POINT-OF-CARE TESTING |
URINALYSIS |
THE LOCAL LABORATORY |
Macroscopic Evaluation |
THE LABORATORY STRUCTURE |
Microscopic Evaluation |
BLOOD ANALYSIS |
Urinalysis in Eye Care |
Blood Appropriation |
CLINICAL DIAGNOSIS BY LABORATORY METHODS |
HEMATOLOGY |
Inflammatory Disease |
Complete Blood Count |
Collagen-Vascular Disease |
BLOOD CHEMISTRY |
Sarcoidosis |
Biochemical Profile |
Thyroid Disorders |
INFLAMMATORY MARKERS |
Atherogenic Heart Disease |
Erythrocyte Sedimentation Rate |
Diabetes Mellitus |
C-Reactive Protein |
Infectious Diseases |
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or the most part, eye disease can be diagnosed |
ide levels determined by in-office tabletop instru- |
Ffrom a careful history, symptoms, clinical signs, |
ments. A battery of special hematology, chemistry, and |
and in-office procedures. The diagnosis of systemic |
immunology laboratory tests is used to evaluate sys- |
disease with ocular manifestations, however, man- |
temic disorders underlying recurrent uveitis. The pa- |
dates the use of laboratory medicine. The use of labo- |
tient who has the early signs of Graves’ thyroidopathy |
ratory testing can assist the optometrist in developing |
should have laboratory testing to evaluate endocrine |
a differential diagnosis and may help in the detection |
function. Infections such as gonorrhea, toxoplasmosis, |
or confirmation of a disorder. Once the diagnosis is |
and cytomegalovirus retinopathy are detected by se- |
established, laboratory testing may help the clinician |
rology testing. For the most part, the optometrist can |
in determining the prognosis of the disease and in |
diagnose eye disease using a careful history, symp- |
monitoring the effectiveness of therapy. In this regard, |
toms, clinical signs, and in-office procedures. The di- |
laboratory testing impacts heavily on modern eye |
agnosis of systemic disease with ocular manifestations, |
care. Routine blood testing and urinalysis are ordered |
however, mandates the use of laboratory medicine. |
for the preoperative medical evaluation of patients |
|
awaiting ocular surgery. The eye-care practitioner can |
POINT-OF-CARE TESTING |
use portable and relatively inexpensive instruments to |
|
monitor blood serum and urine glucose levels in a |
Point-of-care (POC) testing brings the laboratory to |
patient who has or who might have diabetes mellitus. |
the optometry office so that a patient may be tested at |
Patients who are seen with hypertensive retinopathy, |
the site of the examination. POC testing can be help- |
retinal arteriolar sclerotic changes, and retinal vascular |
ful in acute cases of sudden refractive shifts that are |
plaques can have their serum cholesterol and triglycer- |
possibly caused by undiscovered diabetes mellitus. |
39
40 DIAGNOSTIC PROCEDURES
Measurements of such a patient’s serum glucose level, which are obtained quickly, allow the optometrist to identify a critical systemic crisis and intervene in a timely and appropriate manner. Portable instrumentation has become available in recent years that permit the analysis of blood and urine in the optometry office. Although most relevant for the identification of diabetes, these portable chemistry analyzers provide results for a number of tests, including cholesterol and triglyceride levels. The optometrist who wishes to participate in such POC technology should be aware of some significant factors influencing inoffice lab testing, including cost, accuracy, training, safety, relevance, billing to the patient, and maintenance of equipment. The optometrist should check with his or her state optometry board to make sure that drawing blood in the office is legal. In some states, the drawing of blood without supervision of a pathologist or a medical doctor is considered practicing medicine without a license. In addition, the malpractice insurance carrier of the optometrist may feel that such POC procedures do not fall within the purview of optometry, and may not cover misdiagnosis or unexpected and unwanted incidents during blood or urine testing. In-office identification of the undiscovered diabetic is unlikely to be worth the time, effort and cost to the private practitioner. In cases of uveitis, in which a significant number of laboratory tests may be needed to find a systemic cause, POC has little if any relevance, and the local laboratory’s facilities are mandatory.
The Clinical Laboratories Improvement Act of 1988 (CLIA-88) prohibits a laboratory from accepting human specimens for analysis unless it holds a certificate issued by the Secretary of the Department of Health and Human Services (HHS) for each category of testing that is to be performed. Because a laboratory is defined as “a facility for the examination of materials derived from the human body for the diagnosis, prevention, or treatment of any disease or impairment of, or the assessment of the health of, human beings,” then in-office POC procedures may cause the private optometry office to be classified as a laboratory. In 1992, all laboratories, including in-office laboratories, were required to register with the federal government before performing any analysis used in patient care. In effect, CLIA-88 mandates that any laboratory that performs blood testing must be accredited by the federal government, pay a registration fee, document all laboratory procedures, submit to quality control and assurance monitoring and inspections, and pay fines if the office is found in violation of the law.
Devices used for at-home determination of blood glucose and total cholesterol and urinalysis, are considered under CLIA-88 to be “waived tests” and, as such, are exempt from quality assurance and profi-
ciency testing. Laboratories that perform only waived tests, as in the case of an optometry office that uses home-testing devices (i.e., the Accumeter, Accucheck, ChemTrak), however, must still register with the federal government, pay a biennial fee, and comply with their state board of optometry requirements for inoffice lab testing.
THE LOCAL LABORATORY
To gain familiarity with laboratory testing, the optometrist should meet with the laboratory manager of the local medical laboratory and tour the facilities. The practitioner should observe how the tests are actually performed. The laboratory will give instructions on how to order specific tests, what instructions the patient needs to follow (such as fasting before a procedure), what forms need to be filled out, where the patient is to report or where the sample needs to be sent, and the cost of the test. Be sure to get a laboratory user’s guide from the laboratory. This guide lists all the tests available, as well as information concerning each test, how the sample is collected, patient preparation, interpretation of results, and methodology. This guide and the laboratory manager are invaluable sources of information when laboratory testing is indicated.
THE LABORATORY STRUCTURE
The medical laboratory is composed of several sections. These sections include anatomic pathology to examine tissue biopsy and acid-fast stains, the blood bank for transfusions, the chemistry section to analyze myriad blood compounds, hematology to study the cells and plasma of the blood, immunology to detect infections and inflammation, microbiology to identify infectious agents, nuclear medicine to scan tissues and organs using injected radiopharmaceuticals, and urinalysis. The individual laboratory tests ordered on a given patient fall under one of these sections.
BLOOD ANALYSIS
The chemicals, solids, and plasma of the blood may be analyzed by a wide variety of laboratory techniques. The study of the formed elements of the blood and the blood-forming tissues is known as hematology. The biochemical make-up of the blood, which can reflect the presence of systemic disease, is analyzed in chemistry. Immunology serum testing analyzes diseases characterized by antibody-antigen reactions. Blood cultures to detect, isolate, and identify potentially pathogenic organisms causing bacteremia are studied by microbiology. Nuclear medicine makes use of radionuclides in the diagnosis and management of disorders, and in some cases blood must be sampled and analyzed.
Blood Appropriation
Blood may be obtained from capillaries, vein, or bone marrow for laboratory analysis. The wearing of gloves is mandatory for all laboratory workers handling bodily fluids. If a danger exists of sample splashing, then staff should wear a gown and goggles.
Fingerstick (Finger Puncture)
Blood taken from a finger capillary is of a small volume and is used when a larger amount of venous blood is not needed or cannot be obtained. Fingerstick is the method of choice for in-office POC procedures. This method is most useful for single chemical tests, such as glucose or cholesterol levels, and has the advantage of being an easy technique for patients to learn when personal sampling is necessary. Fingerstick is inexpensive and does not require trained personnel or a specialized environment, and is relatively painless. This method may not be as accurate as venous blood sampling, however, and may not provide enough volume to perform a blood chemistry profile.
To perform skin puncture, an appropriate puncture site must be selected. In adults, this is usually the palmar surface of the last digit of the second, third, or fourth finger. The earlobe is a good alternate site. In infants, the lateral or medial plantar heel surface is most appropriate. The chosen puncture site can be warmed with a moist towel to increase blood flow through the capillaries. The site is then cleansed with 70% aqueous isopropanol solution and dried. The puncture is made with a sterile lancet in a deliberate motion perpendicular to the skin surface.
To sample the blood, the first drop of blood should be wiped away. The site should not be “milked” because this may introduce excessive tissue fluid into the sample. The sample is collected into a suitable container by capillary action. Alternatively, the sample may be placed directly on a reagent strip for an in-office single analysis test with use of a portable analyzer. Collection tubes should then be sealed and marked with the patient’s demographics for shipment to the lab.
Venipuncture
Large samples of blood may be obtained from the superficial veins of the midarm, wrist, and back of the hand. These sample sizes are appropriate for blood chemistry profiles and special blood testing.
To obtain venous blood from the midarm, the patient must first be appropriately identified. If fasting is required, it must be confirmed that the patient did indeed fast. The patient is positioned properly, whether sitting or prone. The practitioner must wear gloves and a coat according to safety standards. The patient is instructed to make a fist and a suitable vein is identified; most often, one of the veins of the antecubital
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fossa is used. The area is cleansed with 70% isopropanol alcohol and then a tourniquet is applied several inches above the site of the needle insertion. The tourniquet should never be left on for longer than a minute. A needle is inserted into the vein and an evacuated container is connected to the needle for the blood collection. The tourniquet is then removed, the needle is withdrawn, and a gauze pad is placed over the site. The practitioner must never withdraw the needle without removing the tourniquet. After needle removal, the patient can be instructed to relax his or her fist. Anticoagulant agents can be added to the blood sample; these agents preserve blood cell morphology while preventing blood coagulation. Contaminated materials are disposed of in hard-cased containers (sharps container). The patient should be continuously monitored for a few minutes after blood sampling for possible syncope.
HEMATOLOGY Complete Blood Count
In general, the complete blood count (CBC) provides an overview of hematologic abnormalities that reflect systemic disease states. The CBC is particularly useful in the evaluation of anemia and leukemia, although hematologic changes may occur in infection and inflammation. Any patient who shows clinical signs of anemia (i.e., dilated retinal veins, retinal hemorrhaging, retinal edema, and exudates) or leukemia ( i.e., infiltration and hemorrhages of the lids and conjunctiva) needs a hematologic evaluation including a CBC.
The CBC includes the red blood cell (RBC) count, hemoglobin (Hb or Hgb) measurement, hematocrit (Hct), red blood cell indices, white blood cell (WBC) count and differential (diff) count, blood smear, and platelet count. Inexpensive, easy, and rapidly performed as a screening test, the CBC is ordered from the laboratory on a hematology order form. The blood is obtained by venipuncture or fingerstick, and results are available within a few hours.
Red Blood Cell Count
The RBCs, or erythrocytes, are created in the bone marrow and act to transport oxygen and carbon dioxide and help control the pH of the blood. The RBC count is the number of circulating RBCs in 1 mm3 of peripheral venous blood. Erythropoietic dysfunction or blood loss is indicated by results outside the normal range of 4.6 to 6.2 million/mm3. A decrease in RBCs occurs in drug use, tumors, anemia, hemorrhage, pregnancy, dietary deficiency, genetic disorders, and bone marrow failure. Ocular effects occur in severe cases of anemia and include hyphema, hard exudates, conjunctival pallor, flameshaped hemorrhages, and dot and blot hemorrhages.
42 DIAGNOSTIC PROCEDURES
Polycythemia is seen as an increase in RBCs and may be caused by high altitude, congenital heart disease, polycythemia vera, and dehydration. Polycythemia may have ocular manifestations, including markedly dilated and tortuous retinal veins as well as disc edema. The normal lifespan of a RBC is 120 days, and when age or cell membrane damage causes the RBC to be lysed, it will be removed from circulation by the spleen. A shortened lifespan of an RBC may be the result of artificial heart valves and peripheral vascular atherosclerotic plaques.
Hemoglobin
The Hgb concentration is the total amount of Hgb in the peripheral blood, and reflects the total number of RBCs in the blood. Hgb is the oxygen and carbon dioxidecarrying pigment of the red blood cell. Its level is reported as grams per 100 ml (dl) of blood. The normal hemoglobin level in men is 14 to 18 g/dl and in women is 12 to 16 g/dl.
Decreased levels of Hgb can indicate pregnancy, a reduced number of RBCs (anemia), and hemoglobinopathies such as sickle cell disease. Anemic retinopathy may occur in severe cases of a reduced Hgb level. Elevated Hgb is typical in patients living at high altitudes and in cases of polycythemia vera, chronic obstructive pulmonary disease and congestive heart failure, and may be seen in patients with typical polycythemia-type retinopathy. The Hgb measurement is ordered through hematology.
Hematocrit
The Hct is the packed red blood cell volume, and reflects the percentage of the total blood volume that is made up of red blood cells. This measurement closely reflects the Hgb and RBC values. The normal Hct is 42% to 52% in males and 37% to 47% in females. Reduced levels of Hct indicate anemia, and elevated levels may be caused by erythrocytosis, which is an absolute increase in red blood cell mass, and heart failure or chronic anoxia. The Hct and Hgb are most often ordered together as an “H and H” through the hematology lab.
Red Blood Cell Indices
These erythrocyte parameters help diagnose specific anemias. To correctly diagnose the various types of anemias, the relationship between the size, number, and Hgb content of the erythrocytes must be established. To this end, an examination of the stained peripheral blood (collected by venipuncture or fingerstick method) reveals the red blood cell characteristics. These indices include the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW).
Mean Corpuscular Volume
The MCV index provides information on the size of the RBC. Cell size may be normocytic (normal RBC size), microcytic (smaller than normal RBC size), or macrocytic (larger than normal RBC size). The MCV measures the average volume of a single erythrocyte, expressed as cubic micrometers per red blood cell. The normal value is 80 to 95 µm3, and the value may be increased in liver disease, alcoholism, and vitamin B12 and folic acid deficiency (megaloblastic anemia). The value is decreased in anemia because of iron deficiency and thalassemia.
Mean Corpuscular Hemoglobin
The MCH index provides information on the amount, or weight, of hemoglobin in an individual RBC. This value closely resembles the MCV number because macrocytic RBCs tend to have more Hgb, and microcytic RBCs are smaller and so have less Hgb. The normal MCH value is 27 to 31 pg.
Mean Corpuscular Hemoglobin Concentration
The MCHC is a measurement of the average concentration of hemoglobin within a single RBC. The normal values are 32 to 36 g/dl (or 32% to 36%). A low value indicates lower hemoglobin concentration, a pale RBC, and is described as hypochromic. A normal hemoglobin concentration produces a normal-appearing RBC color and is normochromic. Elevation of hemoglobin concentration above 37 g/dl is impossible because of size constraints. Therefore, a hyperchromic condition does not exist. Low levels are seen in iron deficiency and thalassemia. Anemias that are normochromic and normocytic in nature are most often caused by tumor, iron deficiency, acute blood loss, and aplastic anemia (caused by, for example, chloramphenicol toxicosis). Microcytic, normochromic anemia is most commonly caused by renal disease. Microcytic, hypochromic anemia is commonly caused by thalassemia, lead poisoning, and iron deficiency. Finally, macrocytic, normochromic anemia can be secondary to a vitamin B12 or folic acid deficiency and chemotherapy.
Red Blood Cell Distribution Width
The RDW is a measurement of variation in RBC size. Anisocytosis is a type of anemia characterized by a wide range of RBC sizes. An increase in RDW can occur in iron-deficiency and B12-deficiency anemia, sickle cell disease, and posthemorrhagic anemia.
White Blood Cell Count
The WBC count measures the total number of leukocytes, or WBCs, in 1 µl of peripheral venous blood. The normal WBC count is between 4500 and 10,000 cells/ mm3. An elevation in the number of WBCs is known as
leukocytosis and is most often caused by infection involving a bacterial cause. Other causes of leukocytosis include trauma, stress, neoplasm, and inflammation. A decrease in the WBC count is called leukopenia and may arise from bone marrow failure after chemotherapy or radiation therapy, acute viral infections, starvation, drugs, and stress. The WBC count gives only the total number of leukocytes and is of limited value in diagnosis. Significant additional information is provided when a differential count of the various leukocyte types is performed. Collection of a WBC count is by venipuncture or fingerstick and is ordered through hematology, usually as part of a CBC.
Differential
The differential count identifies and measures the percentages of the various types of leukocytes. Because the WBC count yields only the total number of WBCs, it may have limited value in the differential diagnosis of anemias, leukemias, infections, and inflammations. To this end, the various types of leukocytes are differentiated and counted. The leukocytes include the granulocytes, or polymorphonuclear leukocytes (neutrophils, basophils, and eosinophils), and the nongranulocytes (the lymphocytes and monocytes). Changes in each of these leukocytes may indicate certain disease states and are of great value in the differential diagnosis. The function of the various types of leukocytes is usually to fight infection and to react against foreign antigens. Elevated levels of one particular leukocyte will cause a drop in levels of other types of WBCs. The test is ordered through hematology and the sample is collected by fingerstick or venipuncture.
Neutrophils. These granulomatous leukocytes compose 56% of the total WBC and are the most abundant of all the cells seen. A reduction in the number of neutrophils can occur in acute viral infections and starvation. An elevation in the number of neutrophils can be caused by bacterial infection, trauma, inflammation, tumors, and drugs. Neutrophils are produced in 1-2 weeks within the bone marrow from stem cells and exist for approximately 6 hours. These leukocytes act to destroy bacterial microorganisms by phagocytosis.
Basophils. These granulomatous mast cells compose 1.5% of the total number of leukocytes and are involved in allergic reactions. Basophils do not react to bacterial or viral infections but are involved in anti- body-antigen reactions by releasing heparin. Parasitic infestation may cause a rise in the basophil level.
Eosinophils. Composing as much as 8% of the total number of WBCs, these granulomatous leukocytes are elevated in allergic reactions or parasitic disease. A reduction in eosinophils is seen when the allergic response abates and in stress reactions.
Lymphocytes. These nongranuloctyes, or agranulocytes, compose 19% to 48% of the WBCs and are formed
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in the lymph nodes and thymus gland. Lymphocytes mediate chronic bacterial infections and acute viral infections. The two types of lymphocytes are T cells and B cells. The T cells participate in cellular-type immune reactions, and the B cells are primarily involved with antibody production (humoral immunity). The differential counts the T cells and B cells as a total number of lymphocytes and does not differentiate them. Elevations in the lymphocyte level may occur in chronic lymphocytic leukemia and in viral infections, such as measles, chickenpox, and mononucleosis.
Monocytes. These phagocytic nongranulocytes fight bacteria much like neutrophils but are produced more rapidly and circulate for a longer period of time. Monocytes compose from 3.4% to 9% of the total WBCs.
Platelet Count
Because the platelets, or thrombocytes, are necessary for blood coagulation, the platelet count helps in the evaluation of bleeding disorders. The platelet count is the number of thrombocytes in a cubic milliliter of blood. The normal platelet count is between 150,000 and 400,000/mm3. A low platelet count is referred to as thrombocytopenia, and may be caused by immunologic response, drugs, transfusion, or infection. A rise in thrombocytes, or thrombocytosis, may be the result of iron deficiency, malignant disease, or myeloproliferative syndromes.
BLOOD CHEMISTRY
Biochemical Profile
Any variety of blood chemicals may be analyzed to help in the diagnosis and management of disease states. Twelve of the most common and meaningful of these chemistry tests can be performed by ordering a chemistry panel, also known as the sequential (or simultaneous) multiple analysis (SMA-12). With the advent of sophisticated instrumentation, the physician is encouraged to order the most appropriate tests necessary to profile the patient. The SMA-12, on the other hand, is useful as a multiple organ system survey. The test may include the following general screenings: enzymes [usually alkaline phosphatase (ALP), lactic dehyrogenase (LD), and serum glutamic-pyruvic transaminase], waste products [usually bilirubin, blood urea nitrogen (BUN), creatinine, and uric acid], nutritional components (albumin and total protein) and miscellaneous chemicals (most often calcium, phosphorous, total cholesterol, and serum glucose).
Clinical Enzymology
Enzymes are protein catalysts that help to speed most of the chemical reactions of the body. Enzymes are found in all tissues and are found in elevated amounts in the blood when tissue or organ injury exists. When
44 DIAGNOSTIC PROCEDURES
damaged or stressed, certain tissues will release specific enzymes into the serum, and the detection of these elevated levels pinpoints the organ system involved in the disease.
Alkaline Phosphatase
Critical in the study of bone diseases, elevations in ALP are seen in patients with healing fractures and bone tumors. In addition, elevated levels of ALP may be seen in liver problems such as jaundice or spaceoccupying lesions. ALP can be elevated in pregnancy, in some cases of sarcoidosis, and in childhood because of bone growth.
Aminotransferases (Transaminases)
Aspartate aminotransferase (AST, formerly glutamate oxaloacetate transaminase), and alanine aminotransferase (ALT, formerly serum glutamate pyruvate transaminase), are both most often markedly elevated in liver disease. Elevations are seen in viral hepatitis, cirrhosis, and metastatic carcinoma to the liver. Persistent elevation in ALT is useful in the diagnosis of hepatitis C. In a patient with acute myocardial infarction, the level of AST may be elevated within 12 hours of the time of infarction, and peaks on the second day. Normal levels return by the fifth day. In such patients, the level of ALT remains typically normal, because ALT is elevated primarily in liver disease.
Lactate Dehydrogenase
LD is found throughout the tissues of the body, particularly in the heart, kidney, liver and muscle. Most often, elevations in LD are used to diagnose myocardial infarction and kidney and liver dysfunction. In patients with myocardial infarction, LD elevates within 24 hours of the onset of the heart attack, peaks in 3 days (as compared with AST which peaks 2 days postinfarction), and persists for a week or two.
Creatine Kinase
Also known as creatine phospokinase, or CPK, CK is concentrated in high levels in the skeletal muscle, heart, and brain. It is not found in the liver, so high amounts may indicate myocardial infarction but not liver disease. After myocardial infarction, CK rises quickly (within 6 hours) and peaks in 24 hours, so it is most useful in the acute diagnosis of heart attack. AST then peaks in 48 hours, and LD peaks in 72 hours postinfarction. CK is the main cardiac enzyme studied in possible heart attack. Myoglobin is an oxygen-binding protein that, when elevated, indicates damage to the myocardium three hours after myocardial infarction. It is not considered part of SMA testing, but it is more specific than and elevates earlier than the CK test. New and promising lab studies into muscle proteins called troponins have revealed them to be a valuable asset in estab-
lishing the diagnosis of myocardial infarction and in predicting future cardiac events. This test is used on patients with chest pain and unstable angina to establish true myocardial damage. The cardiac-specific troponin test is more specific than the CK test in the determination of cardiac muscle injury.
Angiotensin-converting Enzyme
Angiotensin-converting enzyme (ACE) is found mainly in the lung and liver. Serum elevations of ACE are found in patients with sarcoidosis, and significant levels are achieved in pulmonary sarcoid. Inactive sarcoid rarely produces elevated ACE levels. Active tuberculosis infection of the lung does not produce elevated ACE levels. Cirrhosis of the liver may produce elevated ACE levels.
Waste Products
Screening for renal function using levels of blood urea nitrogen (BUN) and nonprotein nitrogenous compounds (creatine, creatinine, and uric acid) is a quick and inexpensive way to detect renal failure. In addition, BUN can be used to detect liver disease. Bilirubin is a pigment and is used as a test of liver function.
Blood Urea Nitrogen
The BUN test measures the amount of urea nitrogen in the blood. Ingested proteins are broken down into amino acids, which are metabolized in the liver-forming urea, which is then transported by the blood to the kidney for excretion. Because urea is inadequately excreted, elevated BUN (azotemia) can indicate renal disease, a high-protein diet, and dehydration. Low levels of BUN occur in liver disease because the synthesis of urea depends on the liver. The BUN is used with the creatinine test to determine renal function.
Creatinine
Creatinine is excreted entirely by the kidneys; therefore, its level reflects renal function. Abnormal elevations indicate impairment of renal excretion, as would occur in glomerulonephritis and urinary obstruction. The creatinine level is not influenced heavily by the liver. In addition, creatinine elevation tends to indicate chronic kidney disease, and elevated BUN indicates acute renal disease.
Uric Acid
Uric acid is a major product of purine catabolism. Uric acid is mostly excreted by the kidneys, although a smaller amount is excreted in the intestinal tract. If uric acid is overproduced or excretion is decreased, a state of hyperuricemia will exist, with an elevated serum uric acid level. Overproduction can be a result of cancer or a catabolic enzyme deficiency. A decrease in excretion is a result of renal failure. Elevated serum
uric acid levels can result in gout and may be associated with diabetes mellitus, hypertension, atherosclerosis, and myocardial infarction. Gout may be associated with deposits of uric acid crystals in the anterior stroma of the cornea resulting in reduced visual acuity. Low levels of serum uric acid occur in Wilson’s disease.
Bilirubin
Bilirubin is a bile pigment, the breakdown product of erythrocyte hemoglobin. This substance forms in the liver and may circulate in the plasma bound to albumin. Bilirubin is a waste product and must be eliminated from the liver into the bowel. Elevated bilirubin can occur in hepatitis, cirrhosis, alcoholism, and some anemias. Patients who are seen with jaundice, with possible yellowing of the conjunctiva, have high concentrations of bilirubin. The most common clinical disorder associated with jaundice is hepatitis, which causes obstruction of the bile ducts because of gallstones or a tumor. Jaundice may produce yellowing of the conjunctiva.
Miscellaneous Tests
These tests analyze four chemical constituents of the sera that reflect the general health of the patient and screen for systemic diseases. These tests include calcium, phosphorus, glucose, and total cholesterol.
Calcium
Calcium is essential for heart, muscle, and nerve function, and blood coagulation. Calcium is used to test parathyroid function, monitor renal failure, and assess calcium metabolism. Elevated calcium levels occur in carcinoma, alcoholic dehydration, sarcoidosis, tuberculosis, histoplasmosis, leukemia, and hyperthyroidism. In fact, about 25% of individuals with sarcoidosis have elevated calcium levels. Low calcium levels are seen in malnutrition and low protein levels, because calcium is bound to serum albumin. For this reason, serum calcium and serum albumin should always be measured at the same time. Hypercalcemia is confirmed when calcium levels are elevated on three consecutive tests. Eye patients who are seen with corneal band keratopathy, lithiasis of the conjunctiva, juvenile xanthelasma of the lids, and corneal arcus juvenilis may have abnormal calcium levels and should have a serum test.
Phosphorus
Phosphorus, an inorganic blood compound in the form of phosphate, is found mostly in the human skeleton bound to calcium. The remainder is in the serum as a phosphate salt. Elevated levels of phosphorus may be found in some patients with sarcoidosis and diabetic ketosis. Decreased levels are found
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in acute alcoholism and malabsorption syndrome. The phosphorus level is often evaluated relative to the calcium level, and as the level of one goes up the other goes down.
Total Cholesterol
No longer considered an adequate evaluation of serum lipid levels, elevated total cholesterol levels are nonetheless associated with increased risk of coronary artery disease in middle-aged men. Recent studies support the observation that elevated total cholesterol in both men and women is linked to an increased risk of a vascular event. It is the most significant lipid related to arteriosclerotic disease. For appropriate determination of relevant cholesterol levels, it is recommended that low density and high-density lipoprotein cholesterol also be determined as part of a lipid profile. Eye patients with pronounced arcus juvenilis and retinal Hollenhorst plaques should have cholesterol levels measured in an effort to determine the risk of coronary artery disease and other vascular diseases in these patients. Cholesterol is both ingested and synthesized in the liver. It is used for fat transport, cell membrane formation, and steroid and sex hormone formation. The clinician should corroborate elevated cholesterol levels by averaging the results of multiple studies when determining the risk assessment for a vascular event. Low cholesterol is rare and is an indicator of severe liver disease.
Glucose
Glucose is a sugar that is metabolized within cells to produce glycogen, amino acids, and fatty acids. Glucose enters the cells from the surrounding blood by binding to the hormone insulin. This process occurs after a meal, when serum glucose rises. In the fasting state, serum glucose levels are low, which stimulates the production of glucagon. Glucagon is a hormone that raises serum glucose levels; thus an elaborate feedback mechanism exists that controls the level of glucose in the blood. A low serum level of glucose is undesirable, because it means that cells cannot get the nutrition they need for metabolism. A high serum level of glucose is also undesirable, because it means that glucose is not entering the cells. To achieve the appropriate blood glucose level, an inverse relationship exists between the amount of secreted insulin and glucagon. For the fasting blood glucose level, the patient should be instructed to fast for 8 hours before the test. Serum glucose is useful in the diagnosis of diabetes mellitus. Patients with an unexplained retinopathy, and any patient with a sudden shift in refractive error, increase in hunger (polyphagia), increase in thirst (polydipsia), or increase in urination (polyurea), should be given a fasting blood glucose test. Elevated serum glucose can also occur during
46 DIAGNOSTIC PROCEDURES
anesthesia, cerebrovascular accident, myocardial infarction, pregnancy and certain medications.
Nutritional Status
Total serum protein and serum albumin are the most common SMA-12 tests used to monitor the nutritional status of the patient.
Total Serum Protein
Proteins are used as co-transporters and buffers in the blood, and they are constituents of muscles, enzymes, and hormones. The protein level and the albumin level are used to evaluate a patient’s nutritional status, liver function, and nephrotic syndromes. Patients who are seen with nutritional-type amblyopia, alcoholism, or anorexia warrant a protein level determination.
Serum Albumin
A specific protein, albumin is formed in the liver and makes up the majority of the total protein. Its major function in the blood is to maintain colloidal osmotic pressure. A good indicator of nutritional status, albumin is also useful in the evaluation of burns, liver disease, kidney disease, heart disease, and chronic alcoholism.
INFLAMMATORY MARKERS Erythrocyte Sedimentation Rate
The protein content of the plasma, mostly fibrinogen, increases in response to acute and chronic inflammation. This process causes the erythrocytes, or red blood cells, to bind to each other in clumps and settle out of solution in a container. The erythrocyte sedimentation rate (ESR) measures the rate at which the RBCs settle out of solution during a specified period of time. The causes of an increased ESR include some infections, collagen-vascular diseases, inflammatory diseases, and tissue damage from myocardial infarction. The ESR occurs as a reaction to an existing inflammatory disorder, and so it is considered an “acute-phase” protein. It is fairly sensitive, but very nonspecific, and so it is not diagnostic for any particular disorder. ESR is, however, a reliable indicator of therapy and can be used to measure the effectiveness of treatment. ESR is especially useful in the diagnosis of temporal arteritis (giant-cell arteritis) and the uveitis-related systemic diseases.
C-Reactive Protein
Like the ESR, the C-reactive protein (CRP) is an acutephase protein. CRP is, however, more sensitive than the ESR rate, and so responds more quickly to the presence of inflammation, and disappears faster on resolution of the inflammation. The high-sensitivity
CRP (hsCRP) test measures small amounts of CRP in the blood. The hsCRP is useful in assessing the risk for cardiac disease. CRP is useful in the diagnosis of inflammatory diseases such as rheumatoid arthritis, Reiter’s syndrome, and Crohn’s disease. Recent research points to the effectiveness of measuring CRP to help predict the likelihood of a major vascular event. Elevated CRP is nonspecific and thus does not indicate any particular disorder. A positive result does, however, indicate the presence of an inflammatory disease. A protein formed by antigen-immune complexes, CRP is found in tissue damaged by trauma and is produced when pathogens, such as bacteria and viruses, initiate an immune response. CRP has been shown to be useful in the evaluation of myocardial infarction, peaking later than CK, and if values remain high, it may indicate chronic heart-tissue damage.
URINALYSIS
The normal patient excretes about 1 L of urine daily. Waste products of metabolism are carried out of the body in the urine, as is important information related to the presence of disease. To this end, urinalysis provides a technique for the urine to help in the evaluation and management of disorders.
Urinalysis actually encompasses several tests that can be performed in the laboratory, office, or home. Urinalysis is divided into macroscopic testing and microscopic testing. Macroscopic testing includes an evaluation of the sample’s appearance, specific gravity, color, and pH. Also included are tests to detect the presence of protein, glucose, ketone bodies, bilirubin, nitrite, occult blood, leukocyte esterase, and urobilinogen. Microscopic studies include tests of the urine sediment following centrifugation of the sample to look for red or white blood cells, bacterial colonies, casts, and crystals.
A total urinalysis is obtained on a clean-catch, midstream specimen. The urine sample is then split into two parts, with one sent to the laboratory for analysis and the other for culturing
Macroscopic Evaluation
Appearance
The macroscopic evaluation begins with the appearance of the urine. Because a wide range of urine constituent concentrations exists, urine specimens have a wide variety of characteristic colors, from pale yellow (dilute urine) to dark amber (concentrated urine). The normal color of urine is a result of metabolic breakdown products such as bile, as well as pigments found in the patient’s diet. Evaluation of the appearance of urine includes not only color but also an inspection for stringy mucus, which may be the result of infection.
Blood in the urine is called hematuria and is a significant finding necessitating a medical evaluation. Dark red urine indicates bleeding from the kidney, and bright red urine results from bleeding in the lower urinary tract. Dark brown urine may occur in jaundice, indicating possible liver disease.
Odor
Volatile acids cause the typical urine scent. A strong, sweet-smelling urine can occur in diabetic ketoacidosis. A urinary tract infection may produce a pungent and rancid smell.
Specific Gravity
The specific gravity of the urine sample may reflect the degree of hydration present. It is an indicator of renal function and is dependent on the urine volume and presence of excreted solids. Normal urine-specific gravity is approximately 1.020.
Urine Volume
The volume of urine typically increases in uncontrolled diabetes mellitus. Patients with a complaint of polyuria should be evaluated for diabetes.
Dipstick Testing
Urine must be collected in clean, usually disposable, containers. The patient is asked to void into the container after following any specific instructions, such as fasting, or collecting multiple samples for 24 hours.
The use of dipsticks containing a number of tests on each stick expedites macroscopic urinalysis. These tests include glucose, protein, ketones, blood, pH, bile, bilirubin, nitrite, leukocyte esterase, and urobilinogen.
Glucose
Normal urine does not contain enough glucose to yield a positive result on a dipstick. A positive urine glucose finding should therefore be treated as an abnormality, and an evaluation to rule out diabetes mellitus is mandatory. Because a positive urine glucose test does not confirm the presence of the disease, serum glucose remains a more meaningful test than urine glucose testing alone. This is a significant fact when a clinician is considering in-office glucose testing of patients with diabetic retinopathy or neuropathy.
Protein
Protein found in the urine (proteinuria) is an important indicator of renal disease. The protein, when found in the urine, is usually albumin. The list of disorders that cause proteinuria includes renal failure, glomerulonephritis, systemic lupus erythematosus, and many others. Proteinuria appears early in renal disease and may be the only clinical sign of the abnormality.
LABORATORY TESTING |
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Ketone Bodies
Ketone bodies are intermediates of fat metabolism formed in the liver. Testing for ketone bodies is important in diabetics, children, pregnancy, all hospital admissions, and presurgical evaluations. Large amounts (ketonuria) occur in diabetic ketoacidosis. Ketones occur when fat instead of carbohydrate is used for energy. The presence of ketone bodies in the urine of a patient with diabetes indicates that the patient is not adequately controlled.
Blood
Blood in the urine (hematuria) may be detected visually as a smoky brown-appearing sample, chemically by a dipstick, or microscopically. Hematuria is usually caused by urinary tract disease, and occult (hidden) blood may be the result of any number of renal disorders.
pH
Although it can vary widely, the normal pH of urine is usually between 5.0 and 8.5. Changes in the pH value may be caused, for example, by a urinary tract infection, which can cause an alkaline shift (e.g., 9.0).
Bile
Bilirubin is formed from hemoglobin, bound to serum protein, and carried to the liver for processing. Bile is then produced and excreted into the intestine. An increase in bilirubin occurs when chemicals or viruses interfere with liver function.
Urine Urobilinogen and Bilirubin
Urobilinogen and bilirubin form from hemoglobin metabolism and are both considered bile pigments. Both are tested by dipstick. Bilirubin can appear in the urine in hepatitis, bile duct obstruction, and chemical injury to the liver. Elevated urobilinogen occurs in jaundice and cirrhosis.
Leukocyte Esterase (WBC Esterase)
A positive test indicates white blood cells in the urine, which is an indicator of urinary tract infection.
Nitrites
The nitrite test is positive in cases of urinary tract infection. Bacteria produce an enzyme called reductase, which reduces urinary nitrates to nitrites that are subsequently detected by this test.
Microscopic Evaluation
Urine can be centrifuged and the sediment examined for casts, cells, crystals, and bacteria. Casts usually indicate renal disease. Red and white blood cells indicate
