Clinical Chemistry Flashcards
distance traveled by one complete wave cycle measured in nanometers
wavelength
particles of light
photon
measures light transmitted by the analyte in the solution
spectrophotometer
most common type of incandescent lamps used in visible and infrared regions
tungsten
type of incandescent lamp used in ultraviolet region
deuterium
part of spectrophotometer that isolates light of a specific wavelength
monochromator
monochromators used in photometers
glass filters and interference filters
monochromators used in spectrophotometers
diffraction graftings and prisms
range of wavelengths in nanometers that is transmitted by the monochromator and exit slit between two points of a spectral scan where the light transmitted is one half of the peak transmittance
bandpass/spectral bandwidth
detector converts the electromagnetic radiation transmitted by a solution into an electrical signal: the more light transmitted, the more energy and the greater the electrical signal that is measured
photodetectors
based on the principle that ground-state atoms absorb light at defined wavelength: the difference in the amount of light leaving the HCl and the amount of light measured by the detector is indirectly proportional to the concentration of the metal analyte in the sample
atomic absorption spectrophotometry
HCl contains an anode, a cylindrical cathode, made of metal being analyzed, and an inert gas such as helium or argon: applied voltage causes ionization of the gas and these excited ions are attracted to the cathode, where they collide with the metal coating on the cathode, knocking off atoms and causing atomic electrons to become excited
hollow cathode lamp
measurement of light scattered by a particulate solution: generally, scattered light is measured at an angle to the incident light when small particles are involved; for large particles, forward light scatter can be measured (the amount of scatter is directly proportional to the number and size of particles present in the solution)
nephelometry
measures light blocked as a decrease ion the light transmitted through the solution; dependent on the particle size and concentration, uses a spectrophotometer for measurement, and it is limited by the photometric accuracy and sensitivity of the instrument
turbidimetry
process where atoms absorb energy at a particular wavelength, electrons are raised to higher energy orbitals, and the electrons release energy as they return to ground state by emitting light energy of a longer wavelength than the exciting wavelength
fluorescence
UV light is used for excitation and is passed through a primary filter for proper wavelength selection for the analyte being measured. the excitation light is absorbed by the atoms of the analyte in the solution, which causes the electrons to move to higher energy orbitals. upon return to ground state, light is emitted from the fluorescing analyte and that light passes through a secondary filter. the secondary filter and the detector are placed a right angle to the light source to prevent incident light from being measured by the detector
fluorometry
emission of light produced by certain substances after they absorb energy, similar to fluorescence, except that the time delay is longer between absorption of radiant energy and release of energy as photons of light
phosphorescence
process where the chemical energy of a reaction produces excited atoms, and upon electron return to ground state, photons of light are emitted
chemiluminescence
process where an enzyme-catalyzed chemical reaction produces light emission
bioluminescence
technique where solutes in a sample are separated for identification based on physical differences that allow their differential distribution between a mobile phase and a stationary phase
chromatography
type of planar chromatography: stationary phase may be silica gel that is coated onto a solid surface such as glass plate of plastic sheet. the mobile phase is a solvent, where solvent polarity should be just enough to achieve clear separation of the solutes in the sample. used for urine drug screening
thin layer chromatography
interpretation of the chromatographic results is by comparing the rf of solutes in comparison to aqueous standards. rf values are affected by:
chamber solution
temperature
humidity
composition of solvent
technique used to separate volatile sources, components include a carrier gas with a flow control device to regulate the gas flow, a heated injector, chromatographic column to separate the solutes, heated column oven, detector and a computer to process data and control the operation of the system
gas-liquid chromatography
inert carrier gas (mobile phase) carries the vaporized sample into the column. the carrier gases commonly used in gas-liquid chromatography are:
hydrogen
helium
nitrogen
argon
type of liquid chromatography where the mobile phase is a liquid that is passed over the stationary phase of the column, components include solvent reservoir, one or more pumps to propel the solvents, injector, chromatographic column, detector and computer to process data and control the operation of the system
high performance liquid chromatography
solvents commonly used for the mobile phase in hplc:
acetonitrile
methanol
ethanol
isopropanol
water
strength of the solvent remains constant during separation
isocratic elution
strength of the solvent continually increased (% per min) during separation
gradient elution
organic material covalently bonded to silica that may be polar or nonpolar in composition in hplc
stationary phase
instrument that uses the principle of charged particles moving through a magnetic or electric field with ions being separated from other charged particles according to their mass to charge ratios
mass spectrometer
high quality technique for identifying drugs or drug metabolites amino acid composition of proteins and steroids. has applications in the filed of proteomics. components include ion source, vacuum system, analyzer, detector and computer
mass spectrometry
destructive process where ion pass through the analyzer one time and then strike the detector
beam type
beam type analyzer where mass-to-charge ratios are scanned during a prescribed time period to form a mass spectrum
quadrupole
employs an electrochemical cell by gradually increasing the voltage applied between two electrodes of the cell in contact with a solution containing the analyte, then the current measured voltage versus current plotted, voltage at which sharp rise in current occurs characteristics of the electrochemical reaction involved. amount of increase in current proportional to the concentration of analyte
polarography
used to assay heavy metals such as lead in blood and based on polarography
anodic stripping voltammetry
technique used to determine the concentration of substance in solution employing an eletrochemical cell that consists of two half-cell, where the potential difference between an indicator electrode and reference electrode is measured
potentiometry
most common type of reference electrode in potentiometry
silver-silver chrloride
employs a pH-sensitive glass electrode for measuring blood pH and it employs pCO2 and pO2 electrodes for measuring gases in blood
pH/blood gas analyzer
type of potentiometric ion-selective electrode, the membrane is made of inert solvent and ion-selective neutral carrier material
ion-exchange electrode
antibiotic used in K+ analysis because of its ability to bind K+ by acting as a neutral carrier
valinomycin
antibiotics used in NH4+ analysis as a neutral carrier membrane
nonactin, monactin
glass membrane used in sodium analysis is made from:
silicon dioxide
sodium oxide
aluminum oxide
electrochemical technique that measures the amount of current produced through oxidation or reduction of the substance to be measured at an electrode held at a fixed potential
amperometry
current in amperometry is _____ proportional to the pO2
directly
based on Faraday’s law, which states that in an electrochemical system, the number of equivalent weights of a reactant oxidized or reduced is directly proportional to the quantity of electricity used in the reaction
coulometry
used clinically to separate and identify proteins, including serum, urine, csf proteins, lipoproteins, isoenzymes through movement of charged molecules in a liquid medium when an electric field is supplied
electrophoresis
movement of charged molecules in a porous supporting medium where the molecules separate at distinct zones
zone electrophoresis
tetramer composed of four globin chains, four heme groups and four iron atoms
hemoglobin
hemoglobin that has two alpha and two beta chains
HbA1 (adult hemoglobin 1)
hemoglobin that has two alpha and two delta chains
HbA2 (adult hemoglobin 2)
hemoglobin that has two alpha and two gamma
HbF (fetal hemoglobin)
HbS is a hemoglobinopathy because of substitution of ____ for glutamic acid in position 6 of beta chain
valine
HbC is a hemoglobinopathy because of substitution of ___ for glutamic acid in position 6 of beta chain
lysine
arrange these Hb according to their speed to move towards the anode in cellulose acetate at pH 8.6: A1, A2, C, D, E, F, G, O, S
A2 = C = O = E < S = G = D < F < A1
arrange these Hb according to their speed to move towards the anode on agar gel at pH 6.2: A1, A2, C, D, E, F, G, S
F < A1 = A2 = D = E = G < C = S
centrifugal force moves samples and reagents into cuvet areas for simultaneous analysis
centrifugal analysis
each sample reaction is compartmentalized: may relate to an analyzer designed to assay only one analyte or an analyzer capable of performing multiple tests where the same sample and reagents are in a separate cuvet/reaction vessel for each test
discrete analysis
able to perform individual tests or panels, and allows for stat samples to be added to the run ahead of other specimens
random access
samples processed as a group
batch analysis
instruments from a single discipline with automated capability
sand alone
instrument from a single discipline with additional internal automated capabilities
automated stand alone
at least two instruments from a single discipline with one controller
modular work cell
instruments able to perform tests from at least two disciplines
multiple platform
at least two analytical modules supported by one sample and reagent processing and delivery system
integrated modular system
transports specimens quickly from one location to another
pneumatic tube system
maximum number of test generated per hour
throughput
amount of time to generate one result
turn around time
mechanism for patient/sample identification; used for identification by an instrument
bar coding
amount of serum that cannot be aspirated
dead volume
contamination of a sample by a previously aspirated sample
carry over
use of preliminary test results to determine if additional tests should be ordered or cancelled on a particular specimen; performed manually or automated
reflex testing
automated systems exists for laboratories where samples are received, centrifuged, distributed to particular instruments using a conveyor system and loaded into the analyzer without operator assistance
total laboratory automation
most common reaction temperatures
37degC
30degC
determination of sample concentration vs change in absorbance over time
kinetic assays
performing diagnostic tests outside the main laboratory and at near patient care areas
point of care testing
encompasses a number of imunnochemical techniques used to detect an extremely small amount of analyte by reacting it with an antibody to form an antigen-antibody complex; used to quantify hormones, tumor markers, drugs
immunoassay
antibodies produced in an animal from many cell clones in response to an immunogenic hetererogenous mixture of antibodies
polyclonal antiserum
antibodies produced from a single clone or plasma cell line; homogenous antibodies
monoclonal antiserum
based on competition between an unlabeled antigen and a labeled antigen for an antibody
competitive-binding immunoassays
require that the free labeled antigen be physically removed from the labeled antigen bound to antibody
heterogeneous assays
do not require physical removal of free labeled antigen from bound-labeled antigen
homogeneous assays
homogeneous immunoassay where the sample analyte competes with the enzyme labeled antigen for the binding sites on the antibody
enzyme multiplied immunoassay technique
based on measuring the degree to which fluorescence intensity is greater in one plan than in another
fluorescent polarization immunoassay
in FPIA, the amount of analyte in the sample is ____ proportional to the amount of fluorescence polarization
inversely
technique between antigen and antibody that employs a chemiluminescent indicator molecule such as isoluminol and acridinium ester as labels for antibodies and haptens
chemiluminescent immunoassay
in chemiluminiscent immunoassay, the signal is ____ proportional to the amount of analyte in the serum sample
directly
homogenous technique that is an adaptation of the chemiluminescent immunoassay
luminescent oxygen channeling immunoassay
uses an indicator label such as ruthenium in sandwich and competitive immunoassays, following a wash procedure to remove unbound label bound to magnetic beads at an electrode undergoes this reaction with the resulting light emission measured by photomultiplier tube
electrochemiluminescence immunoassay
formed when the carboxyl group of one amino acid links to the amino group of another amino acid with the loss of a water molecule
peptide bond
end of protein with a free amino group
n-terminal
end of protein structure with free carboxyl group
c-terminal
amino acids are linked to each other through covalent peptide bonding in a specific sequence to form a polypeptide chain
primary structure
polypeptide chain winds to form alpha helixes and beta sheets through the formation of hydrogen bonds between CO and NH groups of the peptide bonds
secondary structure
coiled polypeptide chain folds upon itself to form a 3d structure through the interactions of the R groups to form a functional protein
quaternary structure
polypeptides composed of only amino acids
simple proteins
symmetrical, compactly folded polypeptide chains (e.g. albumin)
globular proteins
elongated, asymmetrical polypeptide chains (troponin and collagen)
fibrous proteins
composed of protein (apoprotein) and non-protein (prosthetic group) components. prosthetic groups are commonly metal, lipid and carbohydrate in nature
conjugated protein
proteins with a metal prosthetic group (e.g. ceruloplasmin)
metalloproteins
proteins with a lipid prosthetic group (e.g. cholesterol, triglycerides)
lipoproteins
proteins with 10-40% carbohydrates attached (haptoglobin)
glycoproteins
protein with >40% carbohydrates attached (e.g. mucin)
mucoproteins
protein with dna or rna nucleic acids attached (e.g. chromatin)
nucleoproteins
functions of proteins
- energy production
- water distribution
- buffer
- transporter
- immunity
- cellular proteins
- structural proteins
- enzymes
protein function: proteins can be broken down into amino acids that can be used in the citric acid cycle to produce energy
energy productions
protein function: maintains colloidal osmotic pressure between different body compartments
water distribution
protein function: ionizable R groups of the individual amino acids of a protein provide buffering capacity by binding or releasing H+ ions as needed
buffer
protein function: binding of protein to hormone, free hemoglobin, lipids, drugs, calcium, unconjugated bilirubin, and so on, allows movement of these and other molecules in the circulation
transporter
protein function: proteins that protect the body against foreign invaders
antibodies
protein function: function as receptors for hormones so that the hormonal message can activate cellular components
cellular proteins
protein function: collagen is the fibrous component that maintains structure of body parts such as skin, bone, cartilage, and blood vessels
structural proteins
protein function: catalysts that accelerate chemical reactions
enzymes
protein regulation: synthesizes most of the plasma proteins
liver
protein regulation: synthesize the immunoglobulins
plasma cells
humoral antibodies produced in response in response to foreign antigens for the purpose of destroying them
immunoglobulins
reference ranges: total protein
6.5 - 8.3 g/dl
reference ranges: albumin
3.5 - 5.0 g/dl
causes of hypoproteinemia
- urinary loss
- gi tract inflammation
- liver disorders
- malnutrition
- inherited immunodeficiency disorders
- extensive burns
causes of hyperproteinemia
- dehydration
- increased protein production associated with monoclonal and polyclonal gammopathies
- chronic inflammatory diseases associated with paraprotein production
indicator of nutritional status and is one of the proteins that transport thyroid hormones (aka transthyretin)
prealbumin
prealbumin is decreased in what conditions:
liver disorders
inflammation
malignancy
poor nutrition
prealbumin is increased in these conditions:
steroid therapy
chronic renal failure
alcoholism
synthesized in the liver and has the highest concentration of all plasma proteins; binds many analytes for transport in the blood and significantly contributes to plasma osmotic pressure
albumin
acute phase reactant and a protease inhibitor that neutralizes trypsin type enzymes that can damage structural proteins
alpha-1-antitrypsin
alpha-1-antitrypsin is decreased in these following conditions:
emphysema-associated pulmonary disease
severe juvenile hepatic disorder
alpha-1-antitrypsin is increased in these following conditions
inflammatory disorders
synthesized during gestation in the yolk sac and liver of the fetus, peaking at 13 weeks and declining at 34 weeks
alpha 1 fetoprotein
measured between 15 and 20 weeks of gestation and is reported as multiples of emdiuan
maternal serum afp
causes of increased AFP level in maternal serum
neural tube defects
spina bifida
fetal distress
causes of decreased AFP level in maternal serum
down syndrome
trisomy 18
in adults, increased levels of AFP can be indicative of:
hepatocellular carcinoma
gonadal tumors
acute phase reactant; binds to basic drugs
alpha 1 acid glycoprotein (orosomucoid)
alpha 1 acid glycoprotein is increased in:
rheumatoid arthritis
pneumonia
conditions associated with cell proliferation
alpha 1 acid glycoprotein is decreased in:
nephrotic syndrome
alpha-2-globulin that binds free hemoglobin and is an acute phase reactant
haptoglobin
haptoglobin is increased in:
inflammatory conditions
burns
trauma
haptoglobin is decreased in:
intravascular hemolysis
acute phase reactant that is an alpha-2 globulin, copper-containing protein with enzymatic activity, approximately 90% of serum copper is bound to it
ceruloplasmin
ceruloplasmin is increased in:
pregnancy
inflammatory disorders
malignancies
oral estrogen
oral contraceptive
ceruloplasmin is decreased in:
Wilson’s disease
malnutrition
severe liver disease
proteolytic enzyme inhibitor that inhibits thrombin, trypsin and pepsin
alpha-2-macroglobulin
alpha-2-macroglobulin is increased in:
nephrotic syndrome
contraceptive use
pregnancy
estrogen therapy
alpha-2-macroglobulin is decreased in:
acute inflammatory disorders
prostatic cancer
acute pancreatitis
beta globulin that transports iron
transferrin
transferrin is decreased in:
infections
liver disease
nephrotic syndrome
transferrin is increased in:
iron deficiency anemia
pregnancy
beta-globulin that is an acute phase reactant
c-reactive protein
c-reactive protein is increased in:
tissue necrosis
rheumatic fever
infections
myocardial infarction
rheumatoid arthritis
gout
antibodies; synthesized in plasma cells as an immune response
immunoglobulins
Ig major classes
IgA
IgD
IgE
IgG
IgM
Ig that can cross the placenta
IgG
IgG is increased in:
liver disorders
infections
collagen disease
IgG that increases after birth
IgA
IgA is increased in:
liver disorders
infections
autoimmune diseases
IgA is decreased in:
inhibited protein synthesis
hereditary immune disorder
Ig that cannot cross the placenta; it is made by the fetus
IgM
IgM is increased in:
infections
Waldenstrom macroglobulinemia
IgM is decreased in:
renal diseases associated with protein loss
immunodeficiency disorders
IgD is increased in:
liver disorders
infections
connective tissue disorders
IgE is increased in:
allergies
asthma
hay fever
parasitic infections
used to predict the risk of premature birth; normal constituent in the placenta and amniotic fluid
fibronectin
based on the change in velocity of light as light passes through the boundary between air and water, which function as two transparent layers
refractometry
in refractometry, light is bent and such change is _____ to the concentration of the solute present in the water
proportional
based on cupric ions complexing with peptide bonds in an alkaline medium to produce a purple-colored complex
Biuret method
in biuret method, amount of purple complex produced is _____ proportional to the number of peptide bonds present and reflects the protein concentration
directly
allows protein to bind to a dye, forming a protein-dye complex that result in a shift of maximum absorbance of the dye
dye binding techniques
in dye binding techniques, the increase in absorbance is ____ proportional to protein concentration
directly
considered the reference method of choice to validate materials with the Biuret method; based on the quantification of the nitrogen content of protein
Kjeldahl technique
serum is applied in the cathode region of an agarose gel or cellulose acetate plate saturated with a buffer of pH 8.6
serum protein electrophoresis
in serum protein electrophoresis, serum proteins have a net _____ charge and migrate towards the ____
negative
anode
in serum protein electrophoresis, the order of the proteins from farthest to nearest
albumin
alpha 1
alpha 2
beta
gamma
modified technique that uses agarose gel a higher voltage, a cooling system, and a more concentrated buffer to separate proteins into as many as 12 zones
high resolution protein electrophoresis
type of zone electrophoresis in which protein separation is based on the isoelectric point of the proteins
isoelectric focusing
immunochemical methods
homogeneous and heterogeneous immunoassays
immunonephelometry
immunoelectrophoresis
radial immunodiffusion
electroimmunodiffusion
immunofixation
test methodology for albumin using these dyes
bromocresol green
bromocresol purple
true or false: direct measurement of total globulin is not generally performed
true
how to calculate the concentration of globulin
globulin = total protein - albumin
quantification of urinary proteins is performed on a ______
24-hour urine specimen
test methods for urinary proteins
sulfosalicylic acid
trichloroacetic acid
benzenthonium chloride (turbidimetric)
coomassie brilliant blue (spectrophtometric)
reference range of urine total protein
1-14 mg/dl
<100 mg/day
increased protein in urine may result from:
tubular or glomerular damage of dysfunction
multiple myeloma
waldenstrom macroglobulinemia
nephrotic syndrome
may be found in urine of patients with multiple myeloma
bence jones protein
glomerular membrane can be damaged in:
diabetes
amyloidosis
collagen disease
condition where the quantity of albumin in the urine is greater than normal yet is not able to be detected by the urine dipstick method
microalbumineria
glomerular dysfunction can be detected in its early stages by measuring ______ in urine
microalbumin
methods for quantification of microalbumin in the urine
enzyme immunoassays
immunonephelometric assays
reference range for urine albumin
<30mg/day
ultrafiltrate of plasma formed in the ventricles of the brain
cerebrospinal fluid
test methods for csf
sulfosalicylic acid
trichloroacetic acid
benzenthonium chloride (turbidimetric)
coomassie brilliant blue (spectrophtometric)
csf reference range
15-45 mg/dl
csf proteins are increased in:
viral, bacterial, fungal meningitis
traumatic tap
multiple sclerosis
heniated disk
cerebral infarction
csf proteins are decreased in:
hyperthyroidism
central nervous leakage of csf
ideal characteristic of tumor markers
measured easily
high analytical sensitivity of assay method
high analytical specificity of assay method
cost effective
test results contribute to patient care and outcome
true or false: tumor markers are very useful in diagnosis
false
produced by the epithelial cells of the prostrate gland and secreted into the seminal plasma
glycoprotein protease that functions in liquefaction of seminal coagulum
prostate specific antigen (psa)
form of psa found in blood that lacks immunoreactivity
enveloped by protease inhibitor, alpha-2 macroglobulin
form of psa found in blood that is immunologically detectable
complexed to another protease inhibitor, alpha-1-antichymotrypsin
free psa
serum level of psa is caused by:
benign prostrate hypertrophy
adenocarcinoma of the prostrate
this should be performed for psa >2.5 mg/ml
biopsy
measurement of the rate of change per year of serum psa
psa velocity
cutoff of psa velocity recommended to undergo biopsy
0.75ng/ml/year
true or false: men with prostrate cancer tend to have higher % free psa (free psa/total psa) than men with benign disease
false
lower %free psa is associated with high risk of ___
prostrate cancer
methods used to measure serum levels of psa
fluorescence
immunoassay
enzyme immunoassay
chemiluminescence immunoassay
oncofetal glycoprotein antigen; synthesized from the liver, yolk sac, and GI of fetus; useful in monitoring therapeutic response of cancer patients to treatment protocols
alpha fetoprotein (AFP)
fetal serum AFP peaks at 12-15 weeks of gestation with levels of ____
2-3 mg/ml
adult levels of AFP
<20ng/ml
increased levels of AFP in adults are associated with what conditions
hepatocellualr carcinoma
testicular and ovarian teratocarcinomas
pancreatic carcinoma
gastric and colonic carcinoma
viral hepatitis
chronic active hepatitis
increased levels of AFP in pregnancy are associated with what conditions
spina bifida
neural tube defects
fetal distress
decreased levels of AFP in pregnancy are associated with what conditions
Down syndrome
increased levels of CEA are associated with what conditions
adenocarcinoma of digestive tract
colorectal carcinoma
oncofetal glycoprotein antigen that is normally found in epithelial cells of the fetal GI tract, useful in monitoring therapeutic response of cancer patients to treatment protocols
carcinoembryonic antigen (CEA)
glycoprotein composed of alpha (common in other hormones) and beta subunit, which is unique and not common to other hormones) normally secreted by trophoblast cells of the placenta
human chorionic gonadotropin (hCG)
increased hCG secretion is associated with what conditions
trophoblastic tumors
choriocarcinoma
non seminmatous testicular tumors
ovarian tumors
mucin gp ag
useful for monitoring therapeutic response and for detecting recurrence of breast cancer in patients previously treated
CA 15-3
elevated CA 15-3 are observed in nonmalignant diseases such as what
chronic hepatitis
tuberculosis
systemic lupus erythemathosus
mucin gp ag
marker for ovarian and endometrial cancer, particularly for monitoring the progress of patients
CA 125
gp blood group antigen-related marker, sialylated derivative of the Lewis blood grou system
marker for pancreatic, colorectal, lung and gastric carcinomas
CA 19-9
major nitrogen-containing compound in the blood that results from protein catabolism and is synthesized in the liver from the deamination of amino acids
urea
causes of increased serum level of urea
renal failure
glomerular nephritis
urinary tract obstruction
congestive heart failure
dehydration
increased protein catabolism
causes of decreased serum level of urea
severe liver disease
vomiting
diarrhea
malnutrition
older term that is based on previous methodology where nitrogen was measured
blood urea nitrogen
conversion factor for BUN to urea
2.14
reference range of urea
6-20mg/dl
waste product of muscle construction that is formed from phosphocreatine, a high energy compound
regulated by kidney/excretion and measurements are used to assess the gfr
creatinine
test methodologies for creatinine level
jaffe method
enzymatic method
in jaffe method, creatinine reacts with picric acid (an alkaline solution) will form ___ which is color ____
creatinine picrate
red
reference range of serum creatinine for male
0.9-1.3 mg/dl
reference range of serum creatinine for female
0.6-1.1 mg/dl
used to assess the gfr, requires plasma sample and a 24-hour urine collection
creatinine clearance
creatinine clearance formula (ml/min)
(U x V x 1.73) / (P x SA)
cc for male
105 +- 20 ml/min/1.73m2
cc for female
95 +- 20 ml/min/1.73m2
uses only a blood creatinine and the modification of diet in renal disease (mdrd) formula which requires correction for gender and race
estimated glomerular filtration rate
major waste product of purine (adenosine and guanine) catabolism
synthesized in the liver
elimination from the blood is regulated by the kidneys through glomerular filtration and some uric acid is excreted through the GI tract
uric acid
increased serum uric acid level is caused by:
gout
renal disorders
treatment of myeloproliferative disorders
lead poisoning
lactic acidosis
toxemia of pregnancy
Lesch Nyhan syndrome
decreased serum uric acid level is caused by:
severe liver disease
tubular reabsorption disorders
drug-induced
reference range of serum uric acid for male:
3.5-7.2 mg/dl
reference range of serum uric acid for female:
2.6-6.0 mg/dl
produced from the deamination of amino acids
hepatocytes convert this to urea for excretion
ammonia
increased plasma ammonia levels are seen in:
hepatic failure
Reye’s syndrome
type of specimen for ammonia
venous blood free of hemolysis
reference range for serum ammonia
11-32 micromol/L
during a fast, the blood glucose level is kept constant by mobilizing the ____ stores in the liver
glycogen
during long fasts, _____ is required to maintain blood glucose levels because glycogen stores are used up in about 24-48 hours
gluconeogenesis
hyperglycemic range for fasting blood glucose
> 100mg/dl
hypoglycemic range for fasting blood glucose
<50mg/dl
metabolism of glucose molecule to pyruvate or lactate for production of energy
glycolysis
formation of glucose-6-phosphate from non-carbohydrate sources
gluconeogenesis
breakdown of glycogen to glucose for use as energy
glycogenolysis
conversion of glucose to glycogen for storage
glycogenesis
conversion of carbohydrates to fatty acids
lipogenesis
decomposition of fats
lipolysis
produced by the beta cells of the pancreatic islets of Langerhans
promotes the entry of glucose into liver, muscle and adipose tissue to be stored as glycogen and fat
inhibits the release of glucose from the liver
insulin
synthesized by the delta cells of pancreatic islet of Langerhans
inhibits secretion of insulin, glucagon and growth hormone, resulting in an increase in plasma glucose level
somatostatin
hormones secreted by the anterior pituitary gland that raise blood glucose levels
growth hormone
adrenocorticotropic hormone (ACTH)
secreted by the adrenal glands
stimulates glycogenolysis, lipolysis and gluconeogenesis
cortisol
secreted by the medulla of the adrenal glands
stimulates glycogenolysis and lipolysis
inhibits secretion of insulin
causing an increase in blood glucose levels
epinephrine
secreted by the alpha cells of the pancreatic islets of Langerhans
increases blood glucose by stimulating glycogenolysis and gluconeogenesis
glucagon
secreted by the thyroid gland
stimulates glycogenolysis and gluconeogenesis
increase glucose absorption from the intestines
thyroxine
condition caused by increase in blood glucose level and glucose appears in the urine
glucosuria
renal threshold for glucose
160-180mg/dl
pathogenesis of type 1 diabetes
destruction of pancreatic beta cells
pathogenesis of type 2 diabetes
insulin resistance and progressive insulin deficiency
c-peptide levels in type 1 diabetes
very low
c-peptide levels in type 2 diabetes
detectable
onset of diabetes mellitus during pregnancy
gestational diabetes mellitus
inherited diseases involving the deficiency of particular enzymes that cause defects in the normal metabolism of glycogen
glycogen storage diseases
identify the enzyme deficient in this glycogen storage disease: Ia - Von Gierke
glucose 6 phosphatase
identify the enzyme deficient in this glycogen storage disease: II - Pompe
amylo - 1,4 glucosidase
acid maltase
identify the enzyme deficient in this glycogen storage disease: III - Cori-Forbes
amylo - 1,6 glucosidase
debrancher enzyme
identify the enzyme deficient in this glycogen storage disease: IV - Andersen
amylopectinase
glycogen branching enzyme
identify the enzyme deficient in this glycogen storage disease: V - McArdle
muscle phosphorylase
identify the enzyme deficient in this glycogen storage disease: VI - Hers
liver glycogen phosphorylase
identify the enzyme deficient in this glycogen storage disease: VII - Tarui
phosphofructokinase
identify the enzyme deficient in this glycogen storage disease: XI - Fanconi-Bickel
glycogen transporter 2
identify the enzyme deficient in this glycogen storage disease: 0
glycogen synthetase
characterized by a deficiency or absence of galactokinase, galactose 1-phosphate uridyl transferase or uridyl disphosphate glucose-4-eprimase
galactosemia
what enzyme deficiency leads to excessive galactose in blood and excretion in urine
galactose-1-phosphate uridyl transferase
normal fasting plasma glucose
< 100mg/dl
impaired fasting glucose
100-125mg/dl
what level of fasting plasma glucose so that provisional diagnosis of diabetes mellitus can be made
> 126mg/dl
confirmation tests for dm: individual having physical symptoms and a random plasma glucose level of ______
> 200mg/dl
confirmation tests for dm: fasting plasma glucose level
> 126mg/dl
confirmation tests for dm: plasma glucose level of ____ at 2-hour point of an OGTT
> 200mg/dl
if a pregnant woman is not found to have gdm during the initial screening, she should be retested at ____ of gestation
24-28 weeks
diagnosis of gdm using 50-g OGTT
> 140mg/dl at 1 hour
diagnosis of gdm using 100-g OGTT
fasting plasma glucose >95mg/dl
plasma glucose >180mg/dl at 1 hour; >155mg/dl at 2-hour or 120mg/dl at 3-hour
diagnosis of gdm using 75-g OGTT
> 155mg/dl at 2 hour
for OGTT plasma glucose specimen is collected fasting at _____ before glucose load and at ____ after ingestion of glucose
10 min
120 min
impaired fasting glucose in OGTT
fpg 110-125mg/dl
2-h pg 140-199mg/dl
diabetes mellitus in OGTT
fpg >126mg/dl
2-h pg >200mg/dl
hemoglobin A is composed of three forms which are referred to as ____
formed from the nonenzymatic irreversible attachment of glucose to HbA
reflects blood glucose levels for the past 2-3 months
useful in monitoring effectiveness of treatment and compliance of diabetic individual to treatment protocol
glycated or glycosylated hemoglobin
specimen collection to measure HbA1c
non fasting blood drawn in EDTA tubes
reference range for HbA1c
4-6%
a stable ketoamine, formed by the reaction between glucose and the amino group of protein (predominantly albumin, but also including globulins and lipoprotein)
measurement of which reflects blood glucose levels for 2-3 weeks before sampling
fructosamine
reference range for fructosamine
205-285micromol/l
measurement of albumin excretion is useful for patients with renal complications of dm and abnormal values will be ____
> 30mg albumin/creatinine
methods for measuring plasma glucose (reactions)
glucose oxidase method
hexokinase method
reference range for blood glucose levels in adult
70-110mg/dl
normal end product of glucose metabolism
pyruvate
end product of glucose metabolism produced under condition of oxygen deficit (anaerobic metabolism)
used in assessing the degree of oxygen deprivation
lactate
caused by depressed oxygen levels that may occur in acute myocardial infarction, congestive heart failure, shock, pulmonary edema
type A lactic acidosis
caused by metabolic processes that may occur in dm, renal disorders, liver disease, ingestion of toxins (salicylate overdose and excess ethanol)
type B lactic acidosis
reference range (venous) for lactate
0.3-1.3mmol/l
formed from one glycerol molecule with three fatty acid molecules attached via ester bonds
comprise 95% of all fats stored in adipose tissues
triglycerides
triglycerides are transported through the body by ____ and _____
chylomicrons
VLDL
what can break down triglycerides
lipase
lipoprotein lipase
epinephrine
cortisol
unsaturated steroid alcohol
exists in the esterified form where a fatty acid forms an ester bond at carbon-3 and the free (unesterified) form
precursor for the synthesis of bile acids, steroid hormones and vitamin D
cholesterol
primary carrier of cholesterol
low density lipoprotein
composed of one glycerol molecule and two fatty acid molecules attached via ester bonds
focused on the surface of lipid layers, they are major constituents of cell membranes and outer shells of lipoprotein molecules
phospholipid
molecules that combine water insoluble dietary lipids and water-soluble proteins so that the lipids can be transported throughout the body
lipoproteins
spherical lipoproteins that have an inner core of neutral fat
micelles
largest lipoproteins and have the lowest density
formed in the intestines and transport triglycerides after a meal, giving serum a turbid appearance
composed of 80-95% triglyceride, 5% cholesterol, 7% phospholipids and 2% apolipoprotein
enter the circulation and are metabolized to remnant particles for uptake and further modification by the liver
chylomicrons
carries endogenous triglycerides synthesized in the liver
composed of 55% triglycerides, 19% cholesterol, 18% phospholipids, 8% apolipoproteins and have apoliproteins B-100 mainly, and C-I, C-II, C-III and E on their surface
secreted into the blood by the liver for metabolism in peripheral tissues
very low density lipoprotein
transitional form, as it is formed from VLDL and then further modified in the liver to form LDL
carry endogenous triglycerides and cholesterol esters
composed of 23% triglycerides , 38% cholesterol, 19% phospholipids, 19% apolipoprotein and have apolipoproteins B-199, mainly and some E on their surface
intermediate-density lipoprotein
body’s major cholesterol carrier and transports a large amount of endogenous cholesterol
easily taken up by cells, so elevated levels are associated with increased risk for atherosclerosis
composed of 50% cholesterol, 22% phospholipids, 6% triglycerides, 22% protein and have apoprotein B-100 on their surface
brings cholesterol to peripheral cells for membrane synthesis and formation of adrenal and reproductive hormones
low density lipoproteins
synthesized in the intestine and liver cells
recycled chylomicrons and VLDL molecules
composed of 50% protein, 28% phospholipids, 19% cholesterol and 3% triglycerides
has apoprotein A-I, mainly, and A-II on its surface
removes excess cholesterol from the peripheral tissues and transport it other catabolic sites
anti-atherogenic effect
high density lipoprotein
composed primarily of cholesterol esters, phospholipids and apolipoprotein(a) and B-100
form of LDL
elevated levels associated with increased risk for coronary heart disease, myocardial infarction, and cerebrovascular disease
lipoprotein (a)
desirable total cholesterol reference range
<200
borderline high total cholesterol reference range
200-239
high total cholesterol reference range
≥240
hdl cholesterol reference range that is protective against heart disease
<200
hdl cholesterol reference range that is major risk factor heart disease
≥240
optimal ldl cholesterol reference range
<100
near optimal ldl cholesterol reference range
100-129
borderline high ldl cholesterol reference range
130-159
high ldl cholesterol reference range
160-189
very high ldl cholesterol reference range
≥190
normal triglycerides reference range
<150
borderline high triglycerides reference range
150-199
high triglycerides reference range
200-499
very high triglycerides reference range
≥500
hyperlipoproteinemias have been using this classification system
Fredrickson-Levy
Fredrickson-Levy classification: elevated chylomicrons
serum appearance: creamy layer of chylomicrons over clear serum
normal to moderately elevated total cholesterol, extremely elevated triglyceride, Apo B-48 increased, Apo A-IV increased
Type I hyperlipoproteinemia
Fredrickson-Levy classification: increased LDL
clear serum appearance
generally elevated total cholesterol, normal triglycerides, Apo-B 100 increased
Type IIa hyperlipoproteinemia
Fredrickson-Levy classification: increased LDL and VLDL
clear or slightly turbid serum appearance
elevated total cholesterol, elevated triglyceride, Apo-B-100 increased
Type IIb hyperlipoproteinemia
Fredrickson-Levy classification: increased IDL
creamy layer sometimes present over a turbid layer serum
elevated total cholesterol, elevated triglycerides, Apo E-II increased, Apo E-III decreased and Apo E-IV decreased
Type III hyperlipoproteinemia
Fredrickson-Levy classification: increased VLDL
turbid serum appearance
normal to slightly elevated total cholesterol, moderately to severely elevated triglyceride
Apo C-II either increased or decreased, and Apo B-100 increased
Type IV hyperlipoproteinemia
Fredrickson-Levy classification: increased VLDL with increased chylomicrons
turbid with creamy layer serum appearance
slightly to moderately elevated total cholesterol, severely elevated triglycerides
Apo C-II increased or decreased, Apo B-48 increased and Apo B-100 increased
Type V hyperlipoproteinemia
Fredrickson-Levy classification: Type I
increased TAG, CM
Familial lipoprotein lipase deficiency
Fredrickson-Levy classification: Type IIa
increased chole and LDL
Familial hypercholesterolemia
Fredrickson-Levy classification: Type IIb
increased TAG, chole, LDL & VLDL
Familial combined hyperlipidemia
Fredrickson-Levy classification: Type III
increased TAG, chole & VLDL
Familial dysbetalipoproteinemia
Fredrickson-Levy classification: Type IV
increased TAG & VLDL
Familial hypertriglyceridemia
Fredrickson-Levy classification: Type V
increased TAG, CM, chole & VLDL
Familial hyperlipoproteinemia
most common familial form characterized by increased plasma levels of total and LDL cholesterol or triglyceride, or a combination of both
Apo B-100 is increased, level of HDL cholesterol may be decreased
familial combined hyperlipidemia
associated with VLDL and apo B-100 overproduction in the liver
characterized by normal or moderate elevation of LDL cholesterol with an elevated apo B-100
total cholesterol and triglyceride are generally elevated but may be normal
HDL cholesterol and apo A-I levels are decreased
hyperapobetalipoproteinemia
characterized by a moderate elevation of triglyceride with excess production of VLDL
both triglyceride and cholesterol are present in higher concentrations than normal in VLDL, LDL, cholesterol and apo B-100 are within their reference ranges
HDL cholesterol is decreased
familial hypertriglyceridemia
characterized by increased VLDL and chylomicrons
type V hyperlipoproteinemia
characterized by increased LDL cholesterol
plasma triglyceride level may be normal or slightly increased, and the plasma HDL cholesterol level is slightly decreased
familial hypercholesterolemia
hyperlipoproteinemia: total cholesterol level very low, triglyceride level nearly undetectable, LDL and apo B-100 absent
abetalipoproteinemia
hyperlipoproteinemia: unable to synthesize apo B-100 and apo B-48, low total cholesterol level and normal to low triglyceride level
hypobetalipoproteinemia
hyperlipoproteinemia: severely elevated triglyceride level and low HDL level
hypoalphalipoproteinemia
hyperlipoproteinemia: HDL absent, apo A-1 and apo A-II very low levels, LDL low, total cholesterol level low, triglyceride level normal to slightly increased
Tangier disease
elevated cholesterol concentrations have been linked to these conditions
atherosclerosis
coronary artery disease
myocardial infarction
decreased cholesterol concentrations have been linked to these conditions
liver diseases
alcoholic cirrhosis
chemical methodology for lipid test: end product for Liebermann-Burchardt reaction and end color
cholestedienyl monosulfonic acid
green
chemical methodology for lipid test: end product for Salkowski reaction and end color
cholestedienyl disulfonic acid
red
Friedewald formula for LDL cholesterol test methodology
ldl = total chole - (hdl + TAG/5)
major protein found in hdl that activates lecithin-cholesterol acyltransferase and removes free cholesterol from extrahepatic tissues
apo A-1
major protein found in LDL
associated with increased risk of coronary artery disease
apo B-100
independent risk factor associated with impaired plasminogen activation and thus decreased fibrinolysis
high level suggests increased risk for coronary heart disease and stroke
lp (a)
apo-a, apo-b and lp (a) are measured by immunochemical methods such as ___ and ___
immunoturbidimetric
immunonephelometric
reference range for apo-a
120-160mg/dl
reference range for apo-b
<120mg/dl
lp(a)
<30mg/dl
proteins that function as biological catalysts and neither consumed or permanently altered during a chemical reaction
enzymes
different forms of the same enzyme capable of the same catalytic function in the body
may be differentiated based on electrophoretic mobility and resistance to heat denaturation
isoenzyme
non-protein compound that may be required for enzyme activity
cofactor
inorganic cofactors needed for enzymatic activity such ass magnesium, zinc, and chloride
activators
organic cofactors such as NAD+
coenzyme
organic cofactor tightly bound to an enzyme
prosthetic group
location on an enzyme where the three-dimensional arrangement of amino acid residues allowing binding of substrate
active site
causes change in enzyme structure that results in loss of activity may be caused by elevated temperature, extreme changes in pH and certain chemicals
denaturation
oxidoreductases
lactate dehydrogenase
glucose-6-phospate dehydrogenase
malate dehydrogenase
isocitrate dehydrogenase
cytochrome oxidase
transferases
creatine kinase
aspartate aminotransferase (SGOT)
alanine aminotransferase (SGPT)
gamma glutamyl transferase (GGT)
hexokinase
hydrolases
esterase
peptidase
glycosidase
