Pathology: lab testing Flashcards

1
Q

Characteristics of lab tests

A

-A result may be skewed to outside the normal range based on a variety of factors: age, gender, race, fasting, menstrual cycle, time of day
-Diseases w/ low prevalence will have fewer TP and more FP
-Pre-test probability (prevalence) is the number of people who have the disease over the total population studied: TP+FN/total
-Predictive value negative is how many people studied that were negative truly are negative: TN/TN+FN (total negatives)
-Predictive value positive is how many people studied that were positive truly are positive:
TP/TP+FP (total positives)
-Sensitivity is how well the test can detect someone w/ the disease: TP/TP+FN (total w/ disease)
-Specificity is how well the test can detect someone w/out the disease: TN/TN+FP (total w/out disease)

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2
Q

Discovery test

A
  • Used to discover, or screen for a disease

- Should have high sensitivity (low FN) because you want to catch every person w/ the disease

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3
Q

Confirmatory test

A
  • Used to confirm a Dx

- Should have 0 FP (100% specificity) b/c want to make sure every positive test is truly positive for confirmation

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4
Q

Exclusion test

A
  • Used to exclude a Dx

- Should have 0 FN (100% sensitivity) b/c want to make sure every negative test is truly negative for exclusion

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5
Q

Coefficient of variation (CV)

A
  • Used to determine the impreciseness of a test

- CV = (st. dev/mean) x100

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6
Q

Isoenzymes

A
  • Forms of nzs that are catalytically similar but are different based on some physiochemical properties
  • Various isonzs are expressed differently in different tissues, making them useful in identifying the source of tissue damage
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7
Q

Acute pancreatitis

A
  • Main symptoms are abdominal pain, nausea, vomiting, tachychardia, fever
  • Destruction + autodigestion of pancreas
  • Mostly caused by alcoholism and cholelithiasis (gal stones), can also be due to trauma, infection, duodenal ulcer, hypercalcemia, drugs, hyperlipoproteinemia, heritable defects
  • Can lead to hyperglycemia/lipemia, and hypocalcemia (formation of Ca soaps w/ peritoneal fat) or hypercalcemia
  • Often find elevated hematocrit and Hb levels due to dehydration or sequestering of fluid (concentrates blood)
  • High HCO3- and low Cl- due to vomiting
  • Elevated serum amylase to give Dx (rises @ 1-2 days after onset, falls @ 4-8 days), elevated serum lipase to confirm (amylase can be high due to renal failure)
  • Also use urine amylase (increased amylase clearance in pancreatitis), which may indicate elevated amylase even if blood levels are normal
  • Hyperlipidemia can give FN amylase levels
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8
Q

Acute myocardial infarct (AMI)

A
  • Main symptoms are chest pain, nausea, dyspnea, diaphoresis (perfuse sweating)
  • Dx requires rise and fall of cardiac troponin (cTn) plus one of the following: symptoms of ischemia, ECG w/ ischemic signs, imaging that shows loss of myocardium
  • cTnI and cTnT are expressed only in heart, elevated after AMI (starting 2 hrs after)
  • Must use multiple tests to confirm it is AMI (see rise and fall in cTn): t=0, 4hr and every 4-6 hrs after
  • Other sources of elevated cTn: myopericarditis, trauma, surgery, renal failure, infiltrative diseases of myocardium
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9
Q

Serologic tests for hepatitis

A
  • Nonspecific nzs released from liver during hepatitis: AST, ALT (Asp, Ala transferases), AP (alk phos)
  • Nonspecific symptoms: malaise, fever, fatigue, nausea, icterus (clay stool, dark urine, jaundice)
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10
Q

Tests for Hep A Virus (HAV)

A
  • Virus shed in stool, entry via fecal-oral route
  • Anti-HAV IgM detectable in blood @ onset of symptoms (15 days post infection)
  • After 4-6 weeks anti-HAV IgG replaces IgM (for life), positive IgG test indicated past exposure and immunity
  • Therefore Anti-HAV IgM is only clinically relevant test for acute HA (no chronic form)
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11
Q

Tests for Hep B Virus (HBV)

A
  • Caused by DNA virus, can test for many different proteins: HBsAg, HBcAG, anti-HBVs, anti-HBVc
  • Usually transmitted by blood, needles, sex (parenterally)
  • First detectable marker is HBsAg, but eventually anti-HBVs becomes detectable
  • Time btwn these to periods is the window period, and only anti-HBVc will be detected during this time
  • These Abs are IgG, and are life-long so not great indicators of acute. To test for acute use IgM form of anti-HBVc (but still can be raised in chronic flare ups, not a definitive Dx)
  • Many patients experience resolution of disease, some become chronic carriers. All have increased risk of cirrhosis and hepatocellular carcinoma
  • Hep D: requires prior or simultaneous infection w/ HBV (incomplete RNA virus). Look for anti-HDV IgM for acute, IgG for chronic (only if HB+)
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12
Q

Tests for Hep C Virus (HCV)

A
  • Similar incubation period as HBV, can cause similar complication too: massive hepatic necrosis
  • 85% develop chronic hepatitis
  • Transmitted parenterally (mother to fetus, blood, sex)
  • RNA virus, and can detect anti-HCV in blood (but doesn’t guarantee immunity), PCR test to confirm
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13
Q

How to go about testing for hepatitis

A
  • If ALT, AST, AP levels are high do serological testing
  • Usually is either A or B, so first test anti-HAV IgM
  • If negative test HBsAg and anti-HBVc IgM
  • If both are negative must consider HCV and test anti-HCV (though not always positive in acute HC)
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14
Q

Applications of tumor markers

A
  • Screening
  • Diagnosis
  • Prognosis
  • Monitoring tumor burden and therapy
  • Detecting recurrence
  • An ideal marker indicates the presence, site, type, and size of the tumor when it is localized, and reflects the status of the disease during therapy
  • None of these markers are useful for anything other than monitoring therapy and detecting recurrence
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15
Q

Substances secreted by cancers

A
  • Breast CA secrete CA-15-3
  • Pancreatic CA secrete CA-19-9
  • Ovarian CA secrete CA-125
  • HCC (hepatocellular CA) and nonseminomatous germ cell CA of testis secrete AFP
  • Prostate CA secrete PSA
  • Colon CA secrete CEA
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16
Q

CEA as a tumor marker

A
  • Usually indicates colon CA
  • Also elevated in breast, lung, gastric, pancreatic CA
  • Amount of CEA released by colon CA depends on the stage of cancer (later stages release more CEA)
  • Levels will fall after resection, if successful. If levels return that indicates the CA had metastasized
17
Q

AFP as a tumor marker

A
  • Normally indicates HCC or nonseminomatous germ cell CA
  • Also can be elevated from other CA: pancreas, gastric, colon, lung
  • Can be elevated from pregnancy or benign liver disease
  • Used to measure neural tube defects in fetus
  • AFP and hCG together are used for nonseminomatous germ cell CA
  • After tumor resection, AFP levels should fall if it was successful. If they rise it indicates metastasizes
18
Q

PSA as a tumor marker

A
  • Normally indicates prostate cancer, can also be from prostatitis, perineal trauma, sex
  • Is used in screening w/ DRE, but there are concerns about Rxing people w/ high PSA who do not need it
  • Men 55-69 should consider screening, or those w/ risk factors
  • PSA falls after prostectomy if successful. If it rises again that indicates metastasizes
19
Q

Cancers causing increase in Ca and PO4

A
  • Prostate and breast CA often metastasize to bone, leading to adenocarcinoma of the bone, leading to destruction of bone and release of Ca and PO4
  • Osteosarcoma (very rare in adults) can lead to the same thing
20
Q

Cancer Ags

A
  • CA 125 used primarily to monitor ovarian cancer (can also be elevated due to pregnancy, during menstrual cycle)
  • CA 19-9 used to monitor pancreatic cancer (people w/o lewis blood group Ag do not produce CA 19-9). Can be elevated from many other cancer and inflammatory disease. Pancreatic CA can lead to pancreatitis if tumor blocks outflow of pancreatic duct
  • CA 15-3 used to monitor breast cancer (can also be elevated in pancreatic, lung, ovarian, and other CA
21
Q

Tumors associated w/ hypercalcemia

A
  • Solid tumors w/o metastasis (producing PTHrP, parathyroid hormone related protein), this is usually from lung
  • Hematologic malignancies (multiple myeloma and T cell lymphoma)
  • Metastasis to bone (often from breast and prostate)
22
Q

Tumors secreting PTHrP

A
  • Solid tumors (usually lung, SCC)
  • Activates the PTH receptor on kidneys and produces PTH-like effects: increase in bone resorption, renal resorption of Ca, decreasing renal resorption of PO4
  • Difficult to distinguish from hyperthyroidism, except that the levels of PTH are not elevated, instead they are low (Ca feedback inhibition on the parathyroid)
23
Q

Metastatic CA to bone

A
  • Destruction of bone leads to both Ca and PO4 release, w/o increase in PTH or PTHrP
  • Thus no communication w/ kidney to decrease PO4 resorption
  • Net effect is same as tumor secreting PTHrP, except there will be high PO4, not low PO4, levels: more bone and renal Ca resorption (also more PO4 resorption, which is not seen in PTHrP tumors)
  • Will also have low PTH levels
24
Q

Cushing’s syndrome

A
  • Usually due to pituitary tumor releasing too much ACTH, causing elevated release of cortisol
  • Ectopic causes are usually from small (oat) cell CA, which turns propiomelanocortin (POMC) into ACTH
  • Classic symptoms of Cushing’s: moon facies, centripetal obesity, abdominal striae
  • Ectopic symptoms: acute onset of psychosis, hypokalemia, abnormal glc tolerance, or weakness (severe hypokalemia not a symptom of classic Cushing’s)
25
Q

Decision limits

A
  • Based on intersecting hyperbolic curves indicating the testing limits for those with and without a disease
  • Where the diseased graph meets the x-axis for the first time (lower limit of the test) is point B
  • A test measuring point B will have no FN (everyone below point B is negative and truly does not have the disease). Thus point B is 100% sensitivity (catches everyone w/ D) and used for exclusion tests
  • The next point up the x-axis is where the two graphs intersect (point C). This is the compromise point, where both the specificity and sensitivity are at maximums w/ each other
  • Point C is used for discovery tests, since you want highest possible sensitivity and specificity for discovery
  • The next point down the x-axis is point D, where the no disease graph intersects the X axis for the second time (upper limit of the test)
  • A test measuring point D will have no FP (everyone above point D is positive and truly does have the disease). Thus point D is 100% specific, and used for confirmation tests