Pathology: lab testing

Question 1

Characteristics of lab tests

Answer 1

-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)

Question 2

Discovery test

Answer 2

• Used to discover, or screen for a disease

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

Question 3

Confirmatory test

Answer 3

• 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

Question 4

Exclusion test

Answer 4

• 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

Question 5

Coefficient of variation (CV)

Answer 5

• Used to determine the impreciseness of a test

- CV = (st. dev/mean) x100

Question 6

Isoenzymes

Answer 6

• 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

Question 7

Acute pancreatitis

Answer 7

• 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

Question 8

Acute myocardial infarct (AMI)

Answer 8

• 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

Question 9

Serologic tests for hepatitis

Answer 9

• 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)

Question 10

Tests for Hep A Virus (HAV)

Answer 10

• 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)

Question 11

Tests for Hep B Virus (HBV)

Answer 11

• 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+)

Question 12

Tests for Hep C Virus (HCV)

Answer 12

• 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

Question 13

How to go about testing for hepatitis

Answer 13

• 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)

Question 14

Applications of tumor markers

Answer 14

• 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

Question 15

Substances secreted by cancers

Answer 15

• 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

Question 16

CEA as a tumor marker

Answer 16

• 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

Question 17

AFP as a tumor marker

Answer 17

• 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

Question 18

PSA as a tumor marker

Answer 18

• 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

Question 19

Cancers causing increase in Ca and PO4

Answer 19

• 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

Question 20

Cancer Ags

Answer 20

• 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

Question 21

Tumors associated w/ hypercalcemia

Answer 21

• 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)

Question 22

Tumors secreting PTHrP

Answer 22

• 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)

Question 23

Metastatic CA to bone

Answer 23

• 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

Question 24

Cushing’s syndrome

Answer 24

• 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)

Question 25

Decision limits

Answer 25

- 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