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4.10 Lab dx of liver and GI disease part II
by Dr. Ruiz
100
Pathology
Professional
04/11/2012

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Term
What is in the HBV vaccine?
Definition
recombinant HBsAg
Term
What is the serology of a patient who has had the hep B vaccine?
Definition
anti-HBsAg antibodies are positive (Anti-HBcAg= negative)
Term
HDV requires coinfection with ____ becaue it is _____.
Definition
hepatitis B, replication defective
Term
What HDV test are commercially available?
Definition
total anti-HDV antibodies
Term
What is the course of disease with hepatitis D coinfection with hepatitis B?
Definition
anti-HDV together with markers of acute HBV infection; low risk of chronicity
Term
What is the course of disease with super-infection with hepatitis B?
Definition
anti-HDV together with markers of chronic HBV infection; high risk of chronicity
Term
How can you tell whether a patient has recovered from their hep D?
Definition
anti-HDV antibodies disappear with recovery; anti-HDV antibodies remain positive with chronic infection
Term
What is another way to test for hepatitis D other than serology?
Definition
hepatitis D RNA
Term
Why is hepatitis C so likely to become chronic?
Definition
the virus mutates frequently
Term
T/F It is difficult to differentiate acute from chronic HCV infection.
Definition
true
Term
Why is it difficult to distinguish acute versus chronic hep C infection?
Definition
IgM anti-HCV is frequently present in chronic infections; most accutely infected individuals (8 out of 10) remain asymptomatic
Term
How do you measure total anti-HCV antibodies (EIA)?
Definition
measured by enzyme-linked immunoassay (EIA)
Term
How long does it take for anti-HCV antibodies to become positive?
Definition
6-8 weeks (do not identify early infections)
Term
In what situation would anti-HCV antibodies be falsely negative?
Definition
immunocompromised
Term
What happens to anti-HCV antibodies overcourse of disease/with recovery?
Definition
nothing; they persist positive for life and do not distinguish between acute, chronic, or past infections
Term
What is the positive predictive value for total anti-HCV antibodies?
Definition
in high risk populations=99%; in low risk populations= 25%
Term
How do you confirm a positive anti-HCV (EIA)?
Definition
RIBA= recombinant immunoblot assay; measures antibodies against four recombinent HCV proteins, antibodies to two or more is positive; antibodies to one protein is indeterminant
Term
Which HCV RNA test is more sensitive?
Definition
the qualitative is more sensitive than the quantitative
Term
What is the quantitative HCV RNA test used for?
Definition
confirm the presence/absence of infection; predict response to therapy (>800,000 IU/mL associated with poor response), monitor response to therapy
Term
What is the qualitative HCV RNA test used for?
Definition
to confirm the presence/absence of infection
Term
Which confirmatory HCV test is more commonly used: quantitative or qualitative?
Definition
quantitative because in most infections HCV RNA is in the range of quantitative assays (however some prefer qualitative assay for confirmation as it is more sensitive and less expensive)
Term
What test is useful in patients with positive HCV antibodies and negative HCV RNA?
Definition
RIBA
Term
What do positive HCV antibodies with negative HCV RNA mean?
Definition
may indicate that HCV infection has resolved, may be due to a false positive anti-HCV antibody test, may be due to a false negative HCV RNA test (use RIBA to rule out a false-positive HCV antibody result; HCV RNA test may be repeated in 6 months to rule out a false-negative RNA test result)
Term
What might cause a false negative HCV antibody test/
Definition
acute HCV infection, immunocompromised state
Term
How long after infection does it take for HCV RNA to be detectable?
Definition
2-14 days
Term
How do you determine the genotype of HCV infection?
Definition
determined by sequencing of regions of the genome or by hybridization of a PCR amplicon to nitrocellulose strips coated with genotype-specific probes
Term
What is the most common HCV genotype in the US?
Definition
genotype 1
Term
What is the response of the different HCV genotypes to treatment?
Definition
2 and 3 are more responsive; 1 is less responsive
Term
What are the noninvasive tests for H pylori infection?
Definition
serum antibodies to helicobacter, H pylori stool antigen (HPSA), urea breath test
Term
What is the downside to using serum antibodies to test for helicobacter infection?
Definition
serum antibodies remain positive after infection eradication; do not differentiate between current and past infections
Term
Describe how the HPSA test is performed.
Definition
A stool sample is transferred into a diluent vial and agitated, few diluent drops are transferred into a reading plate; H. pylori is detected by an antibody tagged with an enzyme that acts on a substrate eliciting a color change
Term
How does the urea breath test work?
Definition
urea labeled with a carbon isotope is given orally, helicobacter produces urease which hydrolyzes the urea producing isotope labeled CO2 which is measured in exhaled air
Term
What are the invasive tests used to dx helicobacterpylori?
Definition
rapid urease test, special stains on biopsy, cultures
Term
What is a rapid urease test?
Definition
biopsy placed in a fluid or gel containing urea; the urease produced by helicobacter hydrolyzes urea releasing ammonia and bicarbonate, a pH change occurs revealed by a color change
Term
What special stains are used to detect helicobacter pylori infection?
Definition
warthin-starry (steiner), giemsa, immunohistochemistry
Term
Why would you want to culture someone's helicobacter pylori infection?
Definition
in order to test for sensitivity to antibiotics
Term
Which cells produce gastrin?
Definition
G cells of the gastric antrum
Term
Why might you order a test for serum gastrin levels?
Definition
to diagnose either Zollinger-Ellison syndrome or autoimmune gastritis
Term
What is zollinger-ellison syndrome?
Definition
gastrin-secreting tumor, most commonly located in the pancreas
Term
What parameters can be used to diagnose zollinger ellison syndrome?
Definition
fasting serum gastrin more than 10x the upper limit of normal, gastric pH less than or equal to 2, for equivocal cases the secretin test is used
Term
What is the secretin test?
Definition
when secretin is given intravenously and serial determinations of serum gastrin are measured; if serum gastrin does not decline, ZES is likely (a paradoxical increase may occur)
Term
What tests can be used to diagnose autoimmune gastritis?
Definition
gastrin levels, serum B12/CBC/PBS, put pts serum on gastric mucosa for immunoflourescence, schilling test
Term
What is the schilling test?
Definition
give pt radioactive B12 po. If 24 hr urine has low radioactive B12, administer radioactive B12 + intrinsic factor. If 24 hour urine radioactive B12 is low, you have malabsorption, if normal you have autoimmune gastritis
Term
What are the main tests used to diagnose acute pancreatitis?
Definition
serum amylase, serum lipase, urine amylase, amylase/creatinine clearance ratio
Term
In general the diagnosis of acute pancreatitis relies on what lab findings?
Definition
at least 3x elevation of serum amylase or lipase
Term
What are the advantages/disadvantages to using serum amylase to diagnose pancreatitis?
Definition
quick and cheap; degree of elevation may not reflect the severity of acute pancreatitis, with fulminent pancreatitis levels may decline; extensive necrosis may cause enzyme exhaustion
Term
What is the time course of serum amylase rise during pancreatitis?
Definition
levels increase early (in 2-12 hours) then peak in about 48 hours; return to normal within 5 days
Term
Which organs are the major sources of amylase?
Definition
pancreas and salivary glands
Term
What percent of patients with acute pancreatitis have nearly normal serum amylase levels?
Definition
20%
Term
What kinds of pancreatitis are likely to have near normal amylase levels?
Definition
alcohol induced, relapsing pancreatitis, pancreatitis due to hypertriglyceridemia because it suppresses amylase activity
Term
Besides pancreatitis, serum amylase also is elevated d/t
Definition
cholecystitis, perforated ulcer, intestinal obstruction or ischemia,instrumentation (ERCP), after passing a gall stone, renal failure due to decreased clearance
Term
How do you determine whether serum amylase levels are due to pancreatitis or something?
Definition
values more than 3 x the upper limit of normal are highly suggestive of acute pancreatitis
Term
What's the difference between measureing urinary amylase and serum amylase?
Definition
urine amylase remains elevated longer than serum amylase (7-10 days)
Term
How do you calculate the amylase to creatinine clerance ratio (ACCR)?
Definition
100 x (urinary amylase x serum creatinine)/(serum amylase x urinary creatinine)
Term
What is the most specific test for acute pancreatitis?
Definition
ACCR
Term
What is the ACCR in acute pancreatitis?
Definition
>5%
Term
What kind of urine sample is needed for a ACCR?
Definition
2 hour or 24 hour urine
Term
What kind of disease process interferes with the results of a ACCR?
Definition
renal insufficiency
Term
What test is used to diagnose macroamylasemia?
Definition
ACCR
Term
What is macroamylasemia?
Definition
in some individuals amylase attaches to IgA or IgG which is too large to be excreted in the urine; persistent hyperamylassemia but no clinical consequences; Characteristically they show elevated serum amylase and decreased urinary amylase (low amylase clearance)
Term
What is the time frame of serum lipase elevation during acute pancreatitis?
Definition
levels increase 4-8 hours after onset, may peak earlier than amylase (24 hrs), remain elevated longer (7-14 days)
Term
How does the sensitivity of serum lipase vs. amylase compare?
Definition
serume lipase may be less sensitive than amylase (more acute pancreatitis patients fail to show lipase elevation)
Term
What are the advantages to measuring serum lipase over amylase?
Definition
elevated in alcohol induced acute pancreatitis, little lipase activity is found outside the pancreas, remains normal with macroamylasemia
Term
What are the disadvantages to measuring serum lipase to dx acute pancreatitis?
Definition
lipase may rise with some acute abdominal problems, other than acute pancreatitis, that elevate amylase; renal insufficiency may elevate lipase
Term
Besides increased amylase and lipase, what are other findings in acute pancreatitis?
Definition
hyperglycemia, hypocalcemia, hyperbilirubinemia, elevation of ALP, leukocytosis, electrolyte disturbances
Term
How do you test for chronic pancreatitis?
Definition
low pancreatic enzymes (lipase, trypsin) and bicarb in duodenal fluid after stimulation (secretion, CCK), low pancreatic enzymes (trypsinogen) in serum, low pancreatic enzymes (chymotrypsin, elastase) in stool, high fecal fat (>7 g/day) due to malabsorption, hyperglycemia, abnormal glucose tolerance test
Term
What liver disease can occur with cystic fibrosis?
Definition
biliary cirrhosis
Term
The sweat test is AKA the...
Definition
quantitative pilocarpine iontophoresis
Term
How is a chloride sweat test performed?
Definition
pilocarpine is carried into the skin with an electric current (iontophoresis), stimulates sweat gland secretion, sweat is collected, chloride concentration is measured, CF patients have high levels of chloride
Term
How many CFTR gene mutations are there?
Definition
more than 1500
Term
What is the ddx for secretory diarrhea?
Definition
small intestine pathogens, mostly viruses, also toxigenic bacteria or parasites, self limited
Term
What is the ddx for exudative diarrhea?
Definition
colonic pathogens, mostly bacteria (toxigenic or invasive), sometimes parasites
Term
What defines an exudative diarrhea?
Definition
fecal WBC (more than 10 WBC/10 high power fields)
Term
How do you test for WBC in feces?
Definition
tests for neutrophil products: calprotectin and lactoferrin
Term
What test is indicated for diarrhea if tehre is evidence of exudation or fever?
Definition
obtain stool culture for pathogenic bacteria
Term
What are the steps for evaluating chronic diarrhea?
Definition
rule out parasites, repeat bacterial cultures, rule out malabsorption, systemic diseae, functional causes, test fecal calprotectin and lactoferrin, endoscopy with mucosal biopsy
Term
How do you rule out a parasite infection in a patient with chronic diarrhea?
Definition
3 stool samples over 3 days for ova, cysts, and paracytes
Term
What systemic diseases can cause chronic diarrhea?
Definition
hyperthyroidism, diabetes, AIDS, tumor syndromes, other
Term
What is the IBD serology pannel?
Definition
anti-saccharomyces cerebesiae antibody (ASCA) IgG and IgA, atypical perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA)
Term
What is the typical serology of Crohn's disease?
Definition
p-ANCA-/ASCA+, IgG or IgA
Term
What is the typical serology of ulcerative colitis?
Definition
p-ANCA+/ASCA-
Term
How do you evaluate fat malabsorption?
Definition
fecal fat excretion (qualitative= microscopic, presence of fat globules, quantitative= grams/day), serum beta-carotene levels (fat soluble precursor of vitamin A that is adequately present in most diets)
Term
What tests detect small intestine dysfunction?
Definition
D-xylose test
Term
What is the D-xylose test?
Definition
D-xylose is normally absorbed in the jejunum and poorly metabolized and excreted in the urine; D-xylose is given orally to a fasting patient, over 20% should be excreted in the urine over a 5 horu period, an abnormal test indicates jejunal malabsorption
Term
A schilling test that does not correct with IF supplementation indicates...
Definition
terminal ileum dysfunction
Term
What causes lactose malabsorption?
Definition
lactase deficiency
Term
Where is lactase in the GI tract?
Definition
brush border of small intestine
Term
What is the function of lactase?
Definition
breaks down lactose into glucose and galactose which are then absorbed
Term
What is the lactose tolerance test?
Definition
administer lactose and plasma glucose is unchanged, then administer glucose and plasma glucose rises
Term
What is the hydrogen breath test?
Definition
detects malabsorption of carbohydrates, an oral dose of carbohydrates such as lactose or fructose is given. If not absorbed, the carbohydrate is metabolized by colonic bacteria releasing hydrogen. The hydrogen is absorbed in the colon and exhaled in the breath. A peak of hydrogen measured in exhaled air indicates malabsorption
Term
What is guaiac?
Definition
a natural resin extracted from the guaiacum tree wood
Term
What is the MOA of the guaiac test/
Definition
the heme in hemoglobin has peroxidase activity; when present in feces, heme catalyzes the oxidation of guaiac producing a color change.
Term
How many times should a guaiac test be administer before it is confirmed?
Definition
3 consecutive stools should be sampled
Term
What can cause a false negative FOBT?
Definition
vitamin C which supresses the peroxidase activity
Term
What can cause a false positive FOBT?
Definition
peroxidase activity in meat, peroxidase activity in some vegetables (horseradish, artichokes, turnips, cauliflower, broccoli, others), NSAIDS can cause gastric mucosal bleeding
Term
To avoid having skewed results, what should you tell patients to do before doing a guaiac test?
Definition
avoid red meats, peroxidase rich vegetables, and excess vitamin C for 3 days and NSAIDS for 7 days
Term
What is the MOA of an immunochemical FOBT?
Definition
detects specifically human hemoglobin protein by an immunochemical reaction
Term
How many stool samples are needed for the immunochemical FOBT?
Definition
3 consecutive stools
Term
Which is better immunochemical or guaiac FOBT?
Definition
immunochemical because it has superior specificity and does not require dietary restrictions; supreior sensitivity compared with guaiac test for colorectal lesions
Term
What are the downsides to immunochemical FOBT?
Definition
may detect only lower GI bleeding= hemoglobin from upper GI sources is generally degraded by digestive and bacterial enzymes and fails to react; more expensive and technically demanding than the guaiac test
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