LFT, Enzymes, Tumor Markers

the following are the main functions of the ____:

• excretory and secretory

• metabolism

• detoxification (CYP450 system)

• storage

liver

the most important function of the liver is excretion of ____ in the bile.

bilirubin

bilirubin reference interval.

0.2-1.0 mg/dL

_____ bilirubin is described as:

• lipid soluble

• carried on albumin

• very small amount in plasma

• NOT in bile

• NOT filtered by glomeruli

• NOT excreted in urine

• HIGH affinity for brain tissue

unconjugated

_____ bilirubin is described as:

• water soluble

• normally present in bile

• not much in plasma

• small % filtered by kidney

• majority excreted through gut as urobilin (feces)

• LOW affinity for brain tissue

conjugated

what refers to yellow discoloration of the skin, eyes (sclera), and mucous membranes due to retention of bilirubin?

jaundice

jaundice will be overt at a bilirubin range of ____.

3.0-5.0 mg/dL

what laboratory term is used to refer to jaundice?

icterus

what classification of jaundice is caused by a problem prior to bilirubin metabolism?

pre-hepatic

what classification of jaundice is caused by intrinsic liver defects or diseases?

hepatic

what classification of jaundice is best described below:

• increased amount of bilirubin delivered to the liver

• most common cause is hemolytic anemia

• liver responds by functioning at maximum capacity

• total bilirubin rarely exceeds 5 mg/dL

• unconjugated hyperbilirubinemia

pre-hepatic

what classification of jaundice is best described below:

• disorders of bilirubin metabolism or transport: Crigler-Najjar syndrome, Gilbert’s disease, and neonatal physiological jaundice of the newborn, Dubin-Johnson syndrom, Rotor syndrome

• due to diseases resulting in hepatocellular injury or destruction

hepatic

what condition is described below:

• most common cause of unconjugated hyperbilirubinemia

• generally benign with no mortality/morbidity in affected people

• no risk of brain damage (kernicterus)

gilbert’s syndrome

gilbert’s syndrome AND crigler-najjar syndrome is caused by a mutation in the ____ gene with 20-30% normal function.

UGT1A1

what condition is described below:

• rare but serious condition

• similar to gilbert’s syndrome but with a more dangerous mutation in the UGT1A1 gene

• risk of brain damage (kernicterus) in infants

crigler-najjar syndrome

which type of crigler-najjar syndrome refers to a complete absence of the enzymatic conjugation system?

type I

which type of crigler-najjar syndrome refers to a severe deficiency in the enzyme activity?

type II

dubin-johnson syndrome and rotor syndrome are both characterized by _____ hyperbilirubinemia.

conjugated

what refers to a rare autosomal recessive condition with a deficiency of the canalicular multidrug resistance 2 (MDR2)?

dubin johnson syndrome

what condition is described below:

• bilirubin uptake is normal but excretion into the bile is defective, with an increase in delta bilirubin

• total bilirubin usually 2.0-5.0 mg/dL, >50% conjugated bilirubin

• dark granules on liver biopsy

dubin johnson syndrome

what refers to conjugated bilirubin bound to albumin?

delta bilirubin

what refers to the dark granules found on a liver biopsy of a patient with dubin johnson syndrome?

pigmented lysosomes

what condition is described below:

• clinically similar to dubin johnson syndrome

• cause is unknown, may be reduction in concentration of ligandin

• NO dark granules on liver biopsy

• relatively benign with excellent prognosis, no treatment required

rotor syndrome

physiologic jaundice of the newborn may be due to a deficiency in ____ where premature infants may not have it at all.

UDPGT

physiologic jaundice of the newborn has a rapid build up of _____ bilirubin (sometimes up to 20 mg/dL) and is life-threatening.

unconjugated

physiologic jaundice of the newborn is treated with _____ and monitored with daily measurement of bilirubin because of the cause of kernicterus (causes brain cell damage).

phototherapy

what classification of jaundice is caused by biliary obstructive disease, usually caused by physical obstructions (e.g., tumors, gallstones, etc.)?

post-hepatic

in post-hepatic jaundice, conjugation is effective but ____ is defective.

excretion

what classification of jaundice can cause clay colored stool?

post-hepatic

equation to calculate indirect bilirubin.

indirect = total - direct

which drug- and alcohol-related disorder is described below:

• mildest form

• slight increase in ALT, AST, GGT

• fatty infiltrates in vacuoles of liver cells on biopsies

• complete recovery 1 month after drug removal

alcoholic fatty liver

which drug- and alcohol-related disorder is described below:

• fever, ascites

• moderate increase in ALT, AST, GGT, ALP, total bilirubin >5 mg/dL

• AST/ALT ratio >2.0

• albumin reduced; INR increased

• threatening sign: increased creatinine (may precede hepatorenal syndrome and death)

alcoholic hepatitis

the AST/ALT ratio refers to the ____ ratio.

de ritis

which drug- and alcohol-related disorder is described below:

• last and most severe

• 5 year survival rate:

  • 60% if drinking is stopped

  • 30% if drinking goes on

• nonspecific symptoms: weight loss, weakness, hepatomegaly, splenomegaly, jaundice, ascites, fever, malnutrition, edema

• increase in liver function tests (ALT, AST, GGT, ALP, and total bilirubin

• decrease in albumin

• prolonged PT and PTT (liver → vit. K → factors 2, 7, 9, 10)

alcoholic cirrhosis

a definitive diagnosis of alcoholic cirrhosis can be made based on a ____.

liver biopsy

the most common drug toxic to the liver is _____.

acetaminophen

neonatal jaundice is usually noted between days 2 and 3 of neonatal life and peaks by day ____.

5

in neonatal jaundice, bilirubin concentration may rarely rise at a rate of greater than _____ mg/dL per day.

5

_____ is described below:

• may appear within the first 24 hours of life

• may persist beyond 10 days

• bilirubin rises quickly

• conjugated bilirubin >2mg/dL

• most common cause is HDFN

neonatal jaundice

the sample of choice for ____ measurement is serum/heparinized plasma and MUST be protected from light.

bilirubin

for bilirubin testing, ____ will interfere with the diazo reaction.

hemolysis

bilirubin samples must be protected from light as there is a _____% reduction in bilirubin per hour if left unprotected.

40-50%

which liver enzyme is greatly increased in obstructive jaundice?

ALP

which liver enzyme is greatly increased in cirrhosis?

GGT

which liver enzyme is greatly increased in hepatitis and also known as serum glutamic oxaloacetic transferase (SGOT)?

AST

which liver enzyme is greatly increased in hepatitis and also known as serum glutamic pyruvic transaminase (SGPT)?

ALT

what condition refers to inflammation of the liver by viral, bacterial, parasitic causes, also by chemicals, drugs, toxins, radiation, and autoimmune disease?

hepatitis

which hepatitis is described below:

• most common

• fecal-oral transmission route

• no chronic phase with a vaccine available

hepatitis A

IgM anti-HAV is undetectable after ____ months.

3-6

IgG anti-HAV appears soon after IgM and is stable for years. true or false?

true

RT-PCR is less sensitive to detect the viral genome in different source for hepatitis A (e.g., food, clinical specimens, etc.). true or false?

false

which hepatitis is described below:

• can cause acute and chronic hepatitis

• can be found in ALL body fluids

• very stable DNA virus

• groups at higher risk:

  • persons sharing body fluids (high risk sexual behaviors)

  • sharing drug injection needles

  • children born to (+) mothers

hepatitis B

which serologic marker for hepatitis B is initially present in the incubation stage?

HBsAg

which serologic marker for hepatitis B is most often a cause of spreading infection?

HBeAg

which serologic marker for hepatitis B is the first Ab made?

anti-HBc

which hepatitis is described below:

• transmitted parenterally, major route is blood transfusion of inappropriately screened blood products

• around 3% world population infected

• acute disease mild and symptomless, main concern is high rate of progress to chronic disease, cirrhosis, HCC

• leading cause of liver transplantation in the U.S.

hepatitis C

PSA is organ specific but NOT cancer specific and can be _____ in benign prostatic hyperplasia and prostatitis.

increased

only 30-40% of patients with elevated ____ (>4 ng/mL) have prostrate cancer, significant interindividual variation, and level varies with race (poor sensitivity: many people with prostate cancer have PSA <4.0 ng/dL).

PSA

_____ levels of free PSA correlates wtih prostate cancer.

decreased

which form of colorectal cancer screening is guaiac based where Hb has endogenous peroxidase that is capable of oxidizing guaiac in the presence of H2O2 to a blue product (false positive: causes of NSAID use or eating meat, turnip, or horseradish; false negative: excessive vitamin C consumption)?

fecal OB testing

which form of colorectal cancer screening is more specific and has no dietary restrictions?

immuno-chemical fecal testing (IFT)

what tumor marker is described below:

• markedly increased in some patients with colorectal carcinoma

• plays role in preoperative evaluation of patients with known colon cancer and in the postoperative monitoring of such patients

• higher levels implies a worse prognosis

• mildly increased in smoking, peptic ulcer, IBD, and cirrhosis

CEA

what tumor marker is described below:

• elevated in epithelial ovarian neoplasms

• may be elevated in pregnancy, benign ovarian cysts, pelvic inflammation

CA 125

what tumor markers is described below:

• measures different epitopes of the same antigen

  • protein encoded by breast cancer associated MUC1 gene

• elevated in advanced stage of breast cancer

CA 27-29; CA 15-3

what tumor marker is described below:

• marker for pancreatic adenocarcinoma

• elevated in 80% at presentation

CA 19-9

what tumor marker is described below:

• normally synthesized in the yolk sac, fetal liver, fetal GI

• elevated in normal pregnancy, cirrhosis, hepatitis

• elevated in most hepatocellular carcinomas

a1-fetoprotein (AFP)

what tumor marker is described below:

• independent prognostic factor for multiple myeloma

b2-microglobulin (b2M)

what tumor marker is described below:

• indication of osteoblastic activity

• elevated in osteogenic sarcoma or bone metastases

• sensitive test for hepatic metastases

• regan isoenzyme may be elevated in many advanced cancers

ALP

what enzyme is associated with prostatic carcinomas?

ACP

the following enzymes are associated with _____ carcinomas:

• ALT

• ALP

• AST

• GGT

• LD

hepatic

the following enzymes are associated with _____ carcinomas:

• ACP

prostatic

the following enzymes are associated with _____ disorders:

• ALD

• AST

• CK

skeletal muscle

what enzyme is associated with bone disorders?

ALP

the following enzymes are associated with _____:

• AST

• CK

• LD

myocardial infarction

what enzyme is associated with hemolysis and carcinoma?

LD

which marker of cardiac damage (MI) refers to:

• first marker identified

• high false negative rate, labor intensive, short window of elevation

• replaced by LD

AST

which marker of cardiac damage (MI) refers to:

• more sensitive than AST

• remains elevated up to 2 weeks post MI

• very low specificity in cardiac muscle

• 5 isoenzymes

LD

which LD isoenzyme is specific to myocardium?

LD1

in cases of a myocardial infarction, plasma ____ is higher than LD1.

LD2

in the MI ratio of LD1/LD2, it will peak at _____.

24-48 hours

in the MI ratio of LD1/LD2, it will return to baseline in _____.

10-14 days

which marker of cardiac damage (MI) refers to:

• highly upregulated in brain and (striated) muscle cells

• problem: ubiquitous expression in ALL muscle cells, low specificity (also elevated in stroke, pulmonary disease, chronic alcoholism, and after strenuous exercise)

CK

list the 3 isoenzymes of CK.

CK-BB, CK-MM, CK-MB

which CK isoenzyme has 15-30% activity in the cardiac muscle and only 1-3% in normal striated muscle?

CK-MB

which CK isoenzyme levels begin to rise within 4-8 hours post MI, peaks at 12-24 hours, and returns to normal levels within 48-72 hours (usually by 4 days maximum)?

CK-MB

what are the 3 proteins of cardiac troponins that regulate striated muscle contraction?

TnT, TnI, TnC

which cardiac troponins are very cardiac specific and can detect even small damage to cardiac tissue; immunoassays using moAbs against amino acids specific to cardiac isoenzymes?

cTnI; cTnT

which marker of cardiac damage (MI) refers to:

• rapidly increased post-MI (4-6 hours)

• return to baseline after 2-4 days (short window of time after a suspected MI)

CK-MB

which marker of cardiac damage (MI) refers to:

• levels remain elevated for up to 10 days

• not detectable until 24-48 hours post MI

• peak at 72 hours

LD

which marker of cardiac damage (MI) refers to:

• detectable in plasma at 3-12 hours after myocardial injury

• peaking at 12-24 hours and remaining elevated for more than 1 week

cardiac troponins

which cardiac troponin will remain elevated for 8-21 days?

TnT

which cardiac troponin will remain elevated for 7-14 days?

TnI

which marker of cardiac damage (MI) refers to:

• elevated in all MI patients within 6-10 hours

• peaks at 12th hour

• non-specific and has limited value in MI diagnosis

myoglobin