Laboratory Diagnosis Flashcards

1
Q

What is a screening test for?

A

•A screening test identifies an asymptomatic individual who may have a particular disease

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2
Q

What is a diagnostic test for?

A

•A diagnostic test is used to confirm the presence of a disease when a subject shows signs or symptoms of the disease

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3
Q

When is a diagnostic test typically done?

A

After screening test is positive

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4
Q

Name eight examples of common screening tests.

A
  1. •Pap smear
  2. •Fasting blood cholesterol
  3. •Fasting blood sugar
  4. •Blood pressure
  5. •Fecal occult blood
  6. •Ocular pressure
  7. •PKU test
  8. •TSH
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5
Q

•History
–A 56 year-old man presents to the emergency department with constant, sub sternal chest pain of two hours duration. The pain began after lunch of spicy burritos in a local restaurant. The patient has a history of angina however his chest pain usually subsides with nitroglycerin. He has a history of peptic ulcer disease and takes an H2 blocker as needed.
•Physical Exam
–The patient is in some distress secondary to pain. BP-158/96 mm Hg, pulse is 112 bpm, respiration 20 bpm
–Auscultation of the heart reveals a regular rate and rhythm with a Grade II/VI harsh, systolic murmur best hear along the right sternal border.
–Abdomen is flat, soft and nontender on palpation. No masses or organomegaly was noted

What tests?

A

–Serum lactate dehydrogenase level
–Serum creatinine phosphokinase level
–Serum myoglobin levels
–Serum troponin levels

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6
Q

Lactate dehydrogenase is an enzyme that catalyzes the conversion of lactate to pyruvate. As cells die, their LDH is released and finds its way into the blood. What is one of the most important uses of separating LDH isoenzymes?

A

Diagnosis of MI

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7
Q

What is the gold standard test for MI?

A

Troponin

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8
Q

What are the troponins we look for in cardiac injury?

A

Troponins I and T cTnI and cTnT

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9
Q

What does sensitivity mean in regards to testing?

A
  • If the test is highly sensitive and the test result is negative you can be nearly certain that they don’t have disease.
  • A very sensitive test is likely to give a fair number of false-positive results, but almost no true positives will be missed.
  • A lower rate of true positives and a very high rate of true negatives
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10
Q

High sensitivity tests are used for what?

A
  • Tests with a high sensitivity are often used to screen for disease.
  • Screening tests tend to cast a wide net in order to pick up all cases of a disease and not miss anyone, but they often include some accidental positive results in people who don’t actually have the disease.
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11
Q

What does specificity mean in regards to testing?

A

•If the test result for a highly specific test is positive you can be nearly certain that they actually have the disease.

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12
Q

A test with high specificity will have what rates of true/false negatives and positives?

A

•A lower rate of true negatives and a very high rate of true positives

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13
Q

Patients that come up positive on a sensitive screening test but negative on a specific confirmatory test…

A

•People who came up positive on a very sensitive screening test may come up negative on a specific confirmatory test, which means the doctor can reassure them they do not actually have the disease.

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14
Q

What are tests with high specificty used for?

A

•Tests with a high specificity are used to confirm the results of sensitive, but less specific screening tests.

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15
Q

What is validity?

A

•Validity is a measure of the test’s ability to indicate which individuals have the disease and which do not

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16
Q

What is reliability?

A

•Reliability is another term for consistency. If the test is administered repeatedly , does it yield the same results.

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17
Q

How are specific and sensitive tests used for testing of HIV?

A
  • If 100 people were to be tested for HIV, one would start by testing them with ELISA, a test that is very sensitive but not very specific.
  • Then, all the people who had positive ELISA tests would be retested with a Western blot, which is so specific that it would almost never falsely show HIV.
  • The people with false-positive results could then be reassured that they almost certainly do not have HIV, because the very specific Western blot can accurately tell the difference.
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18
Q

What is incidence?

A
  • Incidence is calculated as the number of new cases of a disease or condition in a specified time period (usually a year) divided by the size of the population under consideration who were initially disease free.
  • For example, the incidence of meningitis in the US in 2010 could be calculated by finding the number of new meningitis cases registered during 2010 and dividing that number by the population of the US who didn’t have meningitis.
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19
Q

How is incidence often considered?

A

•As this incidence rate would be very small again we tend to consider number of cases per 100,000 people.

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20
Q

What is incidence a direct measure of?

A

•Incidence is a direct measure of disease risk—higher incidence implies higher risk

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21
Q

What is prevalence?

A
  • Prevalence is the actual number of cases alive with the disease either during a period of time (period prevalence) or at a particular date in time (point prevalence).
  • Prevalence is frequently reported as the number of cases as a fraction of the total population at risk.

Prevalence = ACTIVE TOTAL CASES, either per year or date in time

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22
Q

What kind of prevalence is the better measure of disease load?

A

•Period prevalence provides the better measure of the disease load since it includes all new cases and all deaths between two dates, whereas point prevalence only counts those alive on a particular date.

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23
Q

How are incidence and prevalence different?

A

•The prevalence of a condition means the number of people who have the condition at a given time, whereas “incidence” refers to the annual number of people who developed the condition during the time being measured.

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24
Q

What does the relationship between incidence and prevalence depend on?

A

•The relationship between incidence and prevalence depends greatly on the natural history of the disease state being reported.

  • highly fatal disease makes prevalence go down, as people that die from it aren’t figured into prevalence

•These two measures are very different. And are used for different purposes.

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25
Q

What can have a high incidence and a low prevalence?

A
  • A short-duration curable condition can have a high incidence but low prevalence, because many people get the flu each year, but few people actually have the flu at any given time.
  • A highly contagious, rapidly fatal disease can have a high incidence but low prevalence since very few people with the disease will be alive at any given time.
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26
Q

What can have a low incidence but a high prevalence?

A

•A chronic, incurable disease can have a low incidence but high prevalence, because the prevalence is the cumulative sum of the several past years’ incidences.

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27
Q

What is the limitation on prevalence growth?

A

mortality which occurs in the population

Prevalence will continue to grow until mortality equals or exceeds the incidence rate

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28
Q

What lab tests would you order for a workup of chest pain?

A

•Laboratory tests currently used in the workup of chest pain:

–Serum lactate dehydrogenase level

–Serum creatinine phosphokinase level

–Serum myoglobin levels

–Serum troponin levels

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29
Q

What do LDH levels do following an MI?

A

•The total LDH level rises within 24-48 hours after an MI, peaks in two to three days, and returns to normal in approximately five to ten days.

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30
Q

How accurate is an LDH test for an MI?

A

•Diagnostic sensitivity and specificity is more than 90% within 24 hours of an MI when LDH-1 > 40% of total however even slight hemolysis can cause non-diagnostic elevations in LDH-1

31
Q

What does CPK do?

A

•CPK catalyzes the reversible transfer of phosphate groups between creatinine and phosphocreatine as well as between ATP and ADP.

32
Q

Where does most of the CPK reside?

A

•Most of the CPK resides in skeletal muscle, cardiac muscle, and brain

33
Q

Why is CPK elevated after an MI? What also elevates it?

A

•CPK enters the blood rapidly following damage to muscle cells but CPK levels rise and fall rapidly with a variety of other circumstances including surgical procedures, vigorous exercise, a fall, or a deep intramuscular injection.

34
Q

When is peak sensitivity and specificity for CPK-MB? Why?

A
  • Sensitivity and specificity of CPK-MB for myocardial infarction are >90% within 7-18 hours; peak concentrations occur within 24 hours
  • CPK is a relatively small enzyme (MW = 86K), so it is filtered and cleared by the kidneys; levels return to normal after 2-3 days
35
Q

When is sensitivity and specificity poor for CPK?

A

•Sensitivity is poor when total CPK is very high, and specificity is poor when total CPK is low

36
Q

What is the CPK relative index?

A
  • This is a measure of the mass of the CPK-MB fraction/ Total CPK x 100.
  • The relative index is only used if the total CPK is elevated.
37
Q

What is a CPK relative index of 3 consistent with? 5?

A
  • A ratio of less than 3 is consistent with a skeletal muscle source
  • A ratio greater than 5 is indicative of a cardiac source.
38
Q

What is myoglobin?

A

•O2-binding protein found in all muscle tissue cells, it is the functional and structural analog of hemoglobin.

39
Q

When do myoglobin levels rise? Peak?

A
  • Low molecular weight so levels rise early after muscle damage
  • Elevations detected within 2-4 hours after symptoms; levels peak at 6-12 hours and return to normal after 24-36 hours
40
Q

How sensitive are myoglobin levels?

A

•Readily available but not sensitive enough to use for negative predictive value

41
Q

What is troponin?

A
  • A regulatory protein found in striated muscle
  • When calcium channels open, the calcium causes the troponin to change shape allowing actin and myosin to bind leading to contraction
  • Composed of three subunits

–TnC binds calcium ions

–TnT binds to tropomyosin

–TnI binds to actin myofilaments

42
Q

When are troponin levels peaking after an MI?

A

–Serum levels increase 3-12 hours after the onset of chest pain, peak at 24-48 hours and return to baseline in 5-14 days

–Now considered the criterion standard for diagnosing myocardial infarction by the American College of Cardiology and the American Heart Association

43
Q

Why are troponins considered the gold standard for dx of an MI?

A
  • Troponins I and T have cardiac-specific forms, cTnI and cTnT
  • Circulating concentrations of cTnI and cTnT are very low
  • cTnI and cTnT remain elevated for several days
  • Hence, Troponins would seem to have the specificity of CK-MB (or better), and the long-term sensitivity of LD-1
44
Q

•History

–A 78 year-old woman sees her primary care physician because she has felt weak and dizzy for the last month. She has a history of hypertension well-controlled with lisinopril but is otherwise healthy

•Physical Exam

–The patient is alert and oriented but appears somewhat lethargic. She is very pale. BP-102/66 mm Hg, pulse-112 bpm, respirations-12 bpm

–Her sclerae and conjunctival mucous membranes are pale.

–Heart-Auscultation reveals a early systolic, grade III/VI systolic murmur best heard at the 2nd intercostal space at the right sternal border

–Lungs-Clear with full breath sounds

–Abdomen-Soft and non tender. No masses or organomegaly

Dx?

A

anemia

45
Q

What are common causes of anemia? Most common etiology?

A

–Blood loss

–Decreased production of red blood cells

•Marrow failure

–Increased destruction of red blood cells

•Hemolysis

–Iron deficiency is the most common etiology

46
Q

What labs are helpful in figuring out the etiology of anemia?

A

–RBC count with indices

–Peripheral smear

–Serum iron

–Total iron binding capacity

–Serum ferritin

–Reticulocyte count

–Red cell distribution width

47
Q

How is a CBC helpful with anemia?

A

•The CBC documents the severity of the anemia. In chronic iron deficiency anemia, the cellular indices show a microcytic and hypochromic erythropoiesis—that is, both the mean corpuscular volume (MCV) and the mean corpuscular hemoglobin concentration (MCHC) have values below the normal range.

48
Q

Is a CBC helpful with anemia due to blood loss?

A

•If the CBC is obtained after blood loss, the cellular indices do not enter the abnormal range until most of the erythrocytes produced before the bleed are destroyed at the end of their normal lifespan (120 days).

49
Q

How is a peripheral smear helpful in identifying anemia?

A
  • Peripheral Smear
  • Examination of the erythrocytes shows microcytic and hypochromic red blood cells in chronic iron deficiency anemia. The microcytosis is apparent in the smear long before the MCV is decreased after an event producing iron deficiency.
50
Q

What would you see in a peripheral blood smear with anemia due to folate or Fe deficiency?

A

•Folate and iron deficiency are common in areas of the world with little fresh produce and meat. The peripheral smear reveals a population of macrocytes mixed among the microcytic hypochromic cells. This combination can normalize the MCV.

51
Q

What tests are helpful in dx’ing an Fe deficiency anemia? Why?

A
  • Serum Iron, Total Iron-Binding Capacity, and Serum Ferritin
  • Low serum iron and ferritin levels with an elevated TIBC are diagnostic of iron deficiency. While a low serum ferritin is virtually diagnostic of iron deficiency, a normal serum ferritin can be seen in patients who are deficient in iron and have coexistent diseases, e.g. hepatitis or anemia of chronic disorders.
52
Q

What are the most sensitive tests for Fe deficiency anemia? Are red blood cell indices helpful?

A
  • Serum ferritin and stainable iron in tissue stores are the most sensitive laboratory indicators of mild iron deficiency and are particularly useful in differentiating iron deficiency from the anemia of chronic disorders.
  • Red blood cell indices do not become abnormal for several months after tissue stores are depleted of iron.
53
Q

You suspect your patient has microcytic anemia. What tests would be helpful?

A
  • Hemoglobin electrophoresis and measurement of hemoglobin A2 and fetal hemoglobin
  • Hemoglobin electrophoresis and measurement of hemoglobin A2 and fetal hemoglobin are useful in establishing either beta-thalassemia or hemoglobin C or D as the etiology of the microcytic anemia.
54
Q

What is reticulocyte hemoglobin content testing good for?

A
  • Reticulocyte hemoglobin content
  • Reticulocyte hemoglobin content and serum iron are the only parameters that are independently associated with iron deficiency anemia.
55
Q

How is stool testing helpful in figuring out cause of anemia?

A
  • Stool testing
  • Testing stool for the presence of hemoglobin is useful in establishing gastrointestinal (GI) bleeding as the etiology of iron deficiency anemia.
56
Q

How is bone marrow aspiration helpful in figuring out anemia?

A

In the real world, only a sadist would do this. However…

  • Bone marrow aspiration
  • A bone marrow aspirate can be diagnostic of iron deficiency. The absence of stainable iron in a bone marrow aspirate permits establishment of a diagnosis of iron deficiency without other laboratory tests.
57
Q

What is oliguria?

A
  • A diminished capacity to form and pass urine-less than 500 mL in every 24 hours-so that the end products of metabolism cannot be excreted efficiently.
  • It is usually caused by an imbalance in body fluids and/or electrolytes, renal disease or urinary tract obstruction.
58
Q

What would you expect to see in urinalysis in prerenal failure?

A
  • In prerenal failure, a few hyaline and fine, granular casts may be observed with little protein, heme, or red cells.
  • In prerenal failure, the specific gravity of the urine is almost always increased.
59
Q

What would you expect to see in urinalysis with intrinsic renal failure?

A

•In intrinsic renal failure, hematuria and proteinuria are prominent. Broad, brown, granular casts are typically found in ischemic or toxic acute tubular necrosis, and red cell casts are characteristically observed in acute glomerulonephritis.

60
Q

What would you expect to see in urinalysis in acute interstitial nephritis?

A

•The urine in acute interstitial nephritis shows white cells, especially eosinophils and white cell casts.

61
Q

What urinary indices would you expect with pre renal failure?

A
  • Pre renal failure:
  • Urine specific gravity is high >1020
  • Ratio of urinary to plasma creatinine is >40
  • Ratio of urinary to plasma osmolality is >1.5
  • Urinary sodium concentration is low <20 mEq/L
  • Fractional excretion of sodium (FENa) <1%
62
Q

What urinary indices would you expect to see with renal failure?

A
  • Renal failure
  • Ratio of urinary to plasma creatinine is <20
  • Ratio of urinary to plasma osmolality is <1.1
  • Urinary sodium concentration is >40 mEq/L
  • Fractional excretion of sodium (FENa) >2%
63
Q

What is most often used to distinguish GFR from intrinsic renal disease?

A

fractional excretion of Na+

64
Q

What is the BUN/Cr ratios for prerenal and renal failure?

A
  • Pre renal failure-BUN/creatinine ratio >20/1
  • Renal failure-BUN/creatinine ration <20/1
65
Q

Serum creatinine is commonly used as an indicator of renal damage but is unreliable for what reasons?

A

–Serum creatinine can vary with age, lean muscle mass and hydration status

–Serum levels may not change until > 50% of kidney function has been lost

–At lower GFR increased tubular secretion of creatinine can lead to overestimation of renal function

66
Q

How is serum Na+ helpful in oliguria?

A

•Serum sodium is useful in diagnosing the cause of oliguria since urine output is influenced by the serum sodium.

67
Q

What is hyponatremia frequently caused by?

A

•Hyponatremia is usually dilutional secondary to fluid retention or administration of hypotonic fluids.

68
Q

What is hypernatremia frequently caused by?

A

•Hypernatremia is usually secondary to dehydration.

69
Q

What does oliguria do to K+ levels?

A

•Oliguria is frequently associated with decreased GFR→ Reduced tubular secretion→ metabolic acidosis→ Increased serum potassium

70
Q

What relationship does K+ have with pH?

A

•Each 0.1 reduction in arterial pH raises the serum potassium by 0.3 Meq/L

71
Q

What are the 4 legitimate reasons for ordering a lab test?

A

–Diagnosis (To rule in or rule out a diagnosis)

–Monitoring (To evaluate the effect of therapy)

–Screening (To discover disease not clinically apparent)

–Research (To understand the pathophysiology of a particular disease)

72
Q

What questions should you ask before ordering a lab test?

A

–Why is the test being ordered?

–What are the consequences of not ordering the test?

–How good is the test in discriminating between health versus disease?

–How are the test results interpreted?

–How will the test results influence patient management and outcome?

73
Q

What are the 2 approaches to ordering lab tests?

A
  • Shotgun-Ordering a large number of laboratory tests that may or may not have adequate diagnostic and predictive value in identifying a particular disease
  • Rifle-Ordering specific laboratory tests based on an assessment of their diagnostic accuracy and predictive value in identifying a particular disease