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Flashcards in Pathology: lab testing Deck (25):
1

Characteristics of lab tests

-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)

2

Discovery test

-Used to discover, or screen for a disease
-Should have high sensitivity (low FN) because you want to catch every person w/ the disease

3

Confirmatory test

-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

4

Exclusion test

-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

5

Coefficient of variation (CV)

-Used to determine the impreciseness of a test
-CV = (st. dev/mean) x100

6

Isoenzymes

-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

7

Acute pancreatitis

-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

8

Acute myocardial infarct (AMI)

-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

9

Serologic tests for hepatitis

-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)

10

Tests for Hep A Virus (HAV)

-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)

11

Tests for Hep B Virus (HBV)

-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+)

12

Tests for Hep C Virus (HCV)

-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

13

How to go about testing for hepatitis

-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)

14

Applications of tumor markers

-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

15

Substances secreted by cancers

-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

16

CEA as a tumor marker

-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

AFP as a tumor marker

-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

PSA as a tumor marker

-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

Cancers causing increase in Ca and PO4

-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

Cancer Ags

-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

Tumors associated w/ hypercalcemia

-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

Tumors secreting PTHrP

-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

Metastatic CA to bone

-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

Cushing's syndrome

-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

Decision limits

-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