Clinical Chemistry Flashcards by KM Guntayon

distance traveled by one complete wave cycle measured in nanometers

wavelength

How well did you know this?

Not at all

Perfectly

particles of light

photon

How well did you know this?

Not at all

Perfectly

measures light transmitted by the analyte in the solution

spectrophotometer

How well did you know this?

Not at all

Perfectly

most common type of incandescent lamps used in visible and infrared regions

tungsten

How well did you know this?

Not at all

Perfectly

type of incandescent lamp used in ultraviolet region

deuterium

How well did you know this?

Not at all

Perfectly

part of spectrophotometer that isolates light of a specific wavelength

monochromator

How well did you know this?

Not at all

Perfectly

monochromators used in photometers

glass filters and interference filters

How well did you know this?

Not at all

Perfectly

monochromators used in spectrophotometers

diffraction graftings and prisms

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

process where the chemical energy of a reaction produces excited atoms, and upon electron return to ground state, photons of light are emitted

chemiluminescence

How well did you know this?

Not at all

Perfectly

process where an enzyme-catalyzed chemical reaction produces light emission

bioluminescence

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

1. energy production 2. water distribution 3. buffer 4. transporter 5. immunity 6. cellular proteins 7. structural proteins 8. 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

1. urinary loss 2. gi tract inflammation 3. liver disorders 4. malnutrition 5. inherited immunodeficiency disorders 6. extensive burns

causes of hyperproteinemia

1. dehydration 2. increased protein production associated with monoclonal and polyclonal gammopathies 3. 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

lyase

aldolase pyruvate decarboxylase glutamate decarboxylase tryptophan decarboxylase

isomerase

glucose phosphate isomerase ribose phosphate isomerase triosephosphate isomerase

ligase

glutathione synthetase

energy required to raise all molecules to the transition state in a chemical reaction so that products may be formed

activation energy

binds to free enzyme in an enzymatic reaction

substrate

rate of the reaction is directly proportional to substrate concentration

first-order kinetics

when substrate concentration is high enough to bind with all available enzyme, the reaction velocity is as its maximum. as product is formed, the enzyme becomes available to react with additional substrate

zero-order kinetics

the reaction velocity is proportional to the _____, provided that substrate concentration exceeds it

enzyme concentration

most enzymes of physiological interest function what range of pH

7.0-8.0

factors that influence enzyme reactions

substrate concentration enzyme concentration pH temperature inhibitors

substance that interferes with an enzyme-catalyzed reaction

inhibitors

competes with substrate for the active site and is reversible

competitive inhibitor

binds with the enzyme at a site different from the active site and prevents the enzyme-catalyzed reaction from taking place may be reversible or irreversible (if the active site is affected)

noncompetitive inhibitor

binds to the enzyme-substrate complex so that increasing the concentration of substrate leads to the formation of more enzyme-substrate complexes and more inhibition

uncompetitive inhibitor

two methods used to measure enzyme rections

endpoint kinetic

type of reaction combines reactants, stops the reaction at a fixed time and then measures the product formed activity of the enzyme is based on the final absorbance reading

endpoint

type of reaction combines reactants, then measures the change in absorbance at a specific time intervals (eg 60s) over a specific time period activity of the enzyme is based on the change in absorbance over time

kinetic

lactate dehydrogenase is found the highest concentrations in what organs/tissues

liver heart skeletal muscle kidney erythrocytes

elevated in cardiac disorders (acute myocardial infarction), hepatic disease (viral hepatitis, cirrhosis, infectious mononucleosis), skeletal muscle diseases, hemolytic and hematologic disorder (pernicious anemia) and neoplastic disorders (acute lymphoblastic leukemia)

lactate dehydrogenase

conditions affecting total lactate dehydrogenase: pronounced elevation (5 or more times normal)

megaloblastic anemia widespread carcinomatosis systemic shock and hypoxia hepatitis renal infarction

conditions affecting total lactate dehydrogenase: moderate elevation (3-5 times normal)

myocardial infarction pulmonary infarction hemolytic conditions leukemias infectious mononucleosis delirium tremens muscular dystrophy

conditions affecting total lactate dehydrogenase: slight elevation (up to 3 times normal)

liver diseases nephrotic syndrome hypothyroidism cholangitis

test methodology for lactate dehydrogenase: forward/direct reaction

Wacker method

test methodology for lactate dehydrogenase: reverse/indirect reaction

Wrobleuski La Due

reference range for lactate dehydrogenase

100-225 U/L

creatine kinase and isoenzymes are found the highest concentrations in what organs/tissues

skeletal muscle heart muscle brain tissue

CK isoenzymes consist of two subunits:

M (muscle) and B (brain)

LD isoenzyme consists of four subunits derived from two types of polypeptides designated

M (muscle/liver) and H (heart)

serum elevation level of what enzyme is associated with cardiac disorders, such as AML and skeletal muscle disorders, such as muscular dystrophy, and occasionally due to disorders of the central nervous system including seizures and cerebral vascular accidents

creatine kinase

conditions associated with creatinine kinase: pronounced elevation (5 or more times normal)

Duchenne's muscular dystrophy polymyositis dermatomyositis myocardial infarction

conditions associated with creatinine kinase: mild or moderate elevation (2-3 times normal)

severe exercise, trauma, surgical procedure, intramuscular injections delirium tremens, alcoholic myopathy myocardial infarction, severe ischemic injury pulmonary infarction pulmonary edema hypothyroidism acute agitated psychoses

test methodology for creatine kinase: forward/direct reaction

Tanzer Gilbarg method

test methodology for creatine kinase: reverse/indirect reaction

Rosalki and Hess

reference range for CK in males

15-160 U/L

reference range for CK in females

15-130 U/L

reference range for CK-MK

<6% of total CK 0-5ng/mL

aspartate aminotransferase is found at highest concentrations in what organs/tissue

heart liver skeletal muscle

used to evaluate hepatocellular disorders (up to 100 times upper reference limit in viral hepatitis up to 20 times URL in infectious mononucleosis and up to 4 times URL in cirrhosis), skeletal muscle disorders (up to 8 times URL) and pulmonary emboli (up to 3 times URL) and acute pancreatitis

aspartate aminotransferase

conditions affecting AST: pronounced elevation (5 or more times normal)

acute hepatocellular damage myocardial infarction circulatory collapse acute pancreatitis infectious mononucleosis

conditions affecting AST: moderate elevation (3-5 times normal)

biliary tract obstruction cardiac arrythmias congestive heart failure metastatic or primary tumor in liver muscular dystrophy

conditions affecting AST: slight elevation (up to 3 times normal)

pericarditis cirrhosis pulmonary infarction delirium tremens cerebrovascular accident

reference range for AST

5-30 U/L

alanine aminotransferase is found at highest concentrations in what organs/tissue

liver

hepatocellular disorders exhibit higher concentration of what enzymes more specific for liver diseases used to assess liver involvement with diagnosis of an AMI does not exhibit a significant increase in muscular dystrophy and is not affected in cases of pulmonary embolism or acute pancreatitis

alanine aminotransferase

reference range for ALT

6-37 U/L

increased serum levels are seen in hepatobiliary disease and bone disorders (with osteoblastic involvement) decreased serum levels are seen in hypophosphatasia, which is characterized by insufficient bone calcification

alkaline phosphatase

conditions affecting ALP: pronounced elevation (5 or more times normal)

bile duct obstruction biliary cirrhosis osteitis deformans (Paget's disease) Osteogenic sarcoma hyperparathyroidism

conditions affecting ALP: moderate elevation (3-5 times normal)

granulomatous or infiltrative diseases of liver infectious mononucleosis metastatic tumors in bone metabolic bone diseases (rickets, osteomalacia)

conditions affecting ALP: slight elevation (up to 3 times normal)

viral hepatitis cirrhosis healing fractures pregnancy

reference range for alkaline phosphatase in adults

50-115 U/L

reference range for alkaline phosphatase in children (4-15 years)

54-369 U/L

increased serum levels in prostate cancer, benign prostatic hypertrophy, bone disease, Paget disease, breast cancer with bone metastases, Gaucher disease, platelet damage, idiopathic thrombocytopenic purpura

acid phosphatase

acid phosphatase serum levels is found to be highest in what organ/tissue

prostrate gland

reference range of total ACP in male

2.5-11.7 U/L

reference range of total ACP in female

0.3-9.2 U/L

reference range of prostatic ACP in male

0.2-5.0 U/L

reference range of prostatic ACP in female

0.0-0.8 U/L

increased levels in all hepatobiliary diseases with levels increasing 2-5 times the URL (viral hepatitis, alcoholic cirrhosis), very sensitive indicator for these conditions higher levels observed in intra- and post-hepatobiliary tract obstruction with levels increasing to 5-30 times the URL increases before and remains elevated longer than ALP, AST, ALT

gamma glutamyl transferase

GGT concentration is found highest in what organ/tissue

liver kidneys pancreas intestines

reference range of GGT in male

up to 55 U/L

reference range of GGT in female

up to 38 U/L

increased serum levels in acute pancreatitis occur in 2-12 hours the onset of pain, with peak values in 24 hours, and return to normal in 3-4 days also increased in these conditions: mumps, perforated peptic ulcer, intestinal obstruction, cholecystitis, ruptured ectopic pregnancy, mesenteric infarction, acute appendicitis

amylase

amylase concentration is found to be highest in what organ/tissue

pancreas salivary glands small intestine fallopian tubes

salivary amylase migrates fastest to the anode

ptyalin

pancreatic amylase migrates slowest to the anode (cathodal)

asamylopsin amylopsin

test methodology for amylase: measures decrease in starch substrate

amyloclastic

test methodology for amylase: measures formation of the product produced from starch (maltose)

saccharogenic

test methodology for amylase: measures the formation of soluble starch fragments coupled with a chromogenic dye

chromogenic

test methodology for amylase: defined substrate used in coupled-enzymatic reactions

enzymatic

reference range for amylase

28-100 U/L

increased serum levels in acute pancreatitis occur in 4-8 hours after the onset of pain, with peak values in 24 hours and return to normal in 8-14 days increased also in perforated peptic ulcer, duodenal ulcers, intestinal obstruction, cholecystitis

lipase

lipase concentration is found to be highest in which organ/tissue

pancreas gastric mucosa intestinal mucosa adipose tisseu

source of error for testing amylase: triglycerides suppress AMS activity

hyperlipidemia

source of error for testing amylase: falsely elevated AMS levels

morphine and other opiates

source of error for testing lipase: hemolysis because ____ inhibits lipase activity

hemoglobin

reference range for lipase

up to 38 U/L

found in serum in decreased amount in hepatocellular disease due to decreased synthesis (hepatitis, cirrhosis) decreased also in insecticide poisonings testing this identifies individuals with atypical forms who are at risk of prolonged response to muscle relaxants used in surgery

pseudocholinesterase

found in red blood cells, lungs, spleens, nerve endings, gray matter of the brain

cholinesterase

true cholinesterase

acetylcholinesterase

reference range for PChE serum in male

40-78 U/L

reference range for PChE serum in female

33-76 U/L

inherited as a sex-linked trait drug-induced hemolytic anemia occurs when an individual is given antimalarial drugs (primaquine) hemolysis may also be caused by infections and ingestion of fava beans increased in megaloblastic anemias and AMI

G6PD deficiency

glucose-6-phosphate dehydrogenase concentration is found to be highest in what organs/tissues

erythrocytes adrenal glands thymus lymph nodes spleen

reference range for G6PD

8-14 U/g hemoglobin

used as an AMI indicator because of specificity and early rise in serum concentration following AMI

cardiac Troponin T or I

in cases of AMI, ___ increases ____ hours following infarction, peaks in ____ hours and returns to normal in ____ days. ___ increases in ____ hours following infarction, peaks in ____ hours and returns to normal in ___ days

cTnT, 3-4, 10-24, 10-14 cTnI, 3-6, 14-20, 5-10

form a complex of three proteins that bind to filaments of skeletal muscle and cardiac muscle to regulate muscle contractions

Troponins T, I and C

reference range for cTnT

<0.03ng/ml

reference range for cTnI

<0.40ng/ml

increased in skeletal muscle injuries, muscular dystrophy and AMI released early in cases of AMI rising in 1-3 hours and peaking in 5-12 hours and returns to normal in 18-30 hours not tissue specific and better used as a negative predictor in the first 2-4 hours following chest pain

myoglobin

myoglobin is found to be highest in which organs/tissues

skeletal and cardiac muscles

reference range for myoglobin in male

30-90ng/mL

reference range for myoglobin in female

<50ng/mL

function to promote of sodium and water by increasing the glomerular filtration rate and decreasing the tubular reabsorption of sodium by the kidneys

natriuretic peptides

synthesized in and secreted from myocardial ventricles in response to ventricular volume expansion and pressure overload causes dilation of blood vessels and promotes sodium and water loss, thus reducing fluid load on the heart to improve cardiac function increased in congestive heart failure

b-type natriuretic peptide

reference range for BNP

<100pg/mL

has longer half-life than BNP measurement shows no interference from nesiritide administration measured by electrochemiluminescence

NP-proBNP

human recombinant BNP used for treatment of CHF

nesiritide

beta globulin that is an acute phase reactant used as a predictor for cardiovascular risk increased levels seen in inflammation, infection, stress, trauma and AMI

c-reactive protein

refers to the sensitivity of the assay to determine low levels in serum for crp

high sensitivity crp

reference range for crp in males

0.3-8.6mg/L

reference range for crp in females

0.2-9.1mg/L

level of crp in cardiovascular risk classification: low risk

<1.0mg/L

level of crp in cardiovascular risk classification: average risk

1.0-3.0mg/L

level of crp in cardiovascular risk classification: high risk

>3.0mg/L

elevated levels cause damage to arterial walls that precedes formation of plaques indicator of arterial inflammation

homocysteine

reference range for homocysteine

5-15micromol/L

principal pigment in bile that is derived from hemoglobin breakdown

bilirubin

bilirubin is produced in the ___ from the breakdown of hemoglobin from senescent red blood cells

reticuloendothelial system

bilirubin is conjugated in the ___ and catalyzed by ___

hepatocyte endoplasmic reticulum uridine diphosphate glycuronyltransferase

orange brown pigment that gives stool its characteristic color

urobilin

yellow discoloration that occurs when the bilirubin concentration in the blood and bilirubin is deposited in the skin and sclera of the eyes

jaundice

bilirubin concentration in the blood in which jaundice will manifest

>2-3mg/dl

elevated bilirubin deposits in the brain tissues of infants, affecting the central nervous system and resulting in mental retardation

kernicterus

composition of bile salts

cholic acid chenodeoxycholic acid conjugated with glycine or taurine

occurs when there is excessive erythrocyte destruction characterized by an increased level of unconjugated bilirubin in the serum

prehepatic jaundice

occurs when the liver cells malfunction and cannot take up conjugate or secret bilirubin

hepatic jaundice

occurs when an obstruction blocks the flow of bile into the intestine characterized by a significantly increased level of conjugated bilirubin in the serum, increased conjugated bilirubin in the urine, decreased urine and fecal urobilinogen and stool that appears pale in color

post hepatic jaundice

may be caused by gallstones obstructing the common bile duct, neoplasms such as carcinoma of the Ampulla of Vater or carcinoma of the pancreas, and inflammatory conditions such as acute cholangitis or acute pancreatitis

extrahepatic cholestasis

result of chronic scarring of liver tissue turning it into nodules may be caused by excessive alcohol ingestion over a long period of time, hemochromatosis, complication of hepatitis

cirrhosis

primary cancer of the liver

hepatocellular carcinoma or hepatoma

cause is unknown but the symptoms include encephalopathy, neurologic abnormalities including seizures, and abnormal liver function tests due to hepatic destruction occurs mainly in children, usually after a viral infection (varicella or influenza) and aspirin therapy

reye syndrome

most specific for hepatocyte injury

ALT

markers for hepatocellular necrosis

ALT AST LD

less specific than ALT significant presence in other tissues

AST

least specific significant presence in other tissues

markers that reflect cholestasis

alkaline phosphatase gamma-glutamyl transferase

other tests to assess liver disorders

total bilirubin direct bilirubin indirect bilirubin albumin ammonia AFT

test methodology for total bilirubin green-blue azobilirubin (600nm)

Jendrassik-Grof test

for newborns, bilirubin concentration is read directly by spectrophotometry and concentration is proportional to absorbance at 455nm

direct spectrophotometric

reference range for total bilirubin in infants (0-1 day, full term)

2-6mg/dl

reference range for total bilirubin in adults

0.2-1.0mg/dl

reference range for indirect bilirubin

0.2-0.8mg/dl

reference range for direct bilirubin

0.0-0.2mg/dl

collective term for stereobilinogen, mesobilinogen and urobilinogen

urobilinogen

reference range for urine urobilinogen

0.1-1.0 Ehrlich Units/2hours

derived from a series of biochemical reactions that begin with the formation fo aminolevulinic acid from succinyl coenzyme A and glycine

heme

what chelates iron to form heme

protoporphyrin IX

types of porphyrias

plumbophorphyria acute intermittent porphyria congenital erythropoietic porphyria porphyria cutanea tarda hepatoerythropoietic porphyria hereditary coproporphyria variegate porphyria erythropoietic porphyria

overproduction or accumulation of porphyrins and precursors such as porphobilinogen in the bone marrow

erythropoietic porphyrias

overproduction or accumulation of porphyrins and precursors such as porphobilinogen in the liver

hepatic porphyrias

excess of early precursors such as ___ and ___, causes neuropsychiatric symptoms including abdominal pain, vomiting, constipation, tachycardia, hypertension and psychiatric symptoms

ALA PBG

porphyrias: excess of early precursors and later intermediates causes ____

neurocutaneous symptoms

for measurement of aminolevulinic acid, porphobilinogen, uroporphyrin, coproporphyrin, ____ should be collected

24-hour urine

porphyria: ____ more stable under alkaline conditions and ____ more stable under acid conditions hence sodium bicarbonate used as a compromise to maintain the pH near 7

porphobilinogen ALA

employs p-dimethylaminobenzaldehyde reagent (Ehrlich's aldehyde reagent) to form a red condensation product with porphobilinogen

Watson-Schwartz test

refer to the properties of a solution that are influenced by the number of molecules in solution but not their individual composition

colligative properties

4 types of colligative properties

boiling point freezing point osmotic pressure vapo pressure

measure of the number of dissolved particles in solution expressed as osmoles per kg of water

osmolality

osmolality is regulated by the hypothalamus through the sensation of thirst and the signaling to secretion of ___

antidiuretic hormone

posterior pituitary secretion of ADH will cause ___ and ____

renal absorption of water decrease the osmolarity

method used to measure all particles (molecules and ions) in solution; measure in osmolarity

osmometry

formulas used to calculate estimated osmolarity

1.86 Na + glucose/18 + BUN/2.8 + 9 = mOsm/kg 2Na + glucose/20 + BUN/3 = mOsm/kg

difference between the measured and calculated osmolarity should be <15 can exist for variety of reasons including excess production of beta-hydroxybutyrate, ingestion of toxin such as ethylene glycol, or ingestion of an excessive amount of alcohol

osmolal gap

particles in solution cause the freezing point of water to be decreased with the decrease in temperature being directly proportional to the total number of particles present

freezing point depression osmometry

water evaporation is decreased when solute is present in water, which is indicated by an inverse relationship between the osmolarity of the solution (amount of the particles present) and the vapor pressure

vapor pressure depression osmometry

charged ions found in intracellular fluid, extracellular fluid and intestinal fluid

electrolytes

positively charged ions

cations

major cations in the body

sodium potassium calcium magnesium

negatively charged ions

anions

major anions in the body

chloride bicarbonate phosphate sulfate organic acids proteins

major cation of extracellular fluid

sodium

due to sodium loss (thiazide diuretics and saline infusion) and to water retention <135mmol/L

hyponatremia

due to reduced water intake, increased water loss (water intake must be impaired), increased sodium content of the body >150mmol/L

hypernatremia

excessive water intake

primary polydipsia

reference range for Na

136-145mmol/L

sodium is excreted in the urine when the renal threshold for serum sodium exceeds ___

110-130mmol/L

hyponatremia: can be due to diuretics, hypoaldosteronism (Addison disease), diarrhea or vomiting and severe burns or trauma

depletional hyponatremia

hyponatremia: can be due to overhydration, syndrome of inappropriate anti-diuretic hormone (SIADH), congestive heart failure, cirrhosis and nephritic syndrome

dilutional hyponatremia

major intracellular cation

potassium

occurs when level is <3.0mmol/L results from decreased dietary intake, hyperaldosteronism, diuretics, vomiting, diarrhea, laxative abuse, and excess insulin which causes increased uptake of potassium

hypokalemia

occurs when level is >5.0mmol/L results from increased intake, renal failure, hypoaldosteronism, metabolic acidosis, increased red blood cell lysis, leukemia, chemotherapy

hyperkalemia

due to extracellular shift (acute acidosis, catabolic states, periodic paralysis, succinylcholine, muscle or cellular injury, chemotherapy, leukemia, cationic amino acids, exercise while using beta blocker, digitalis intoxication); excessive ingestion (rare); decreased renal excretion (hypoaldosteronism, tubular unresponsiveness to aldosterone, acute or chronic renal failure, potassium-sparing diuretics, antirejection medications, severe dehydration)

true hyperkalemia

caused by thrombocytosis, severe leukocytosis, use of torniquet with fist exercise, in vitro hemolysis

pseudohyperkalemia

reference range for potassium

3.4-5.0 mmol/L

major anion of extracellular fluid

chloride

reference range for chloride

98-107mmol/L

occurs when level is <98mmol/L results from excessive vomiting, use of diuretics, burns, aldosterone deficiency

hypochloremia

occurs when serum level is >107mmol/L results from prolonged diarrhea, renal tubular disease, dehydration, excess loss of bicarbonate

hyperchloremia

method using coulometric generation of silver ions which combine with chloride to quantitate chloride excess silver ions, which were not bound to chloride, is used to indicate chloride

amperometric-coulemetric titration Cotlove chloridometer

based on the reaction of chloride ions to mercuric ions to form mercuric chloride excess mercuric ions are then made to react with diphenylcarbazone in order to form violet blue color

meruric titration Schales and Schales method

uses mercuric thiocyanate and ferric nitrate to form ferric thiocyanate, which is a reddish colored complex with a peak absorbance at 480nm

colorimetric method

using a membrane selective for chloride ions membrane used is a combination of silver wire coated with AgCl

ion-selective electrode

second largest anion fraction of extracellular fluid

bicarbonate

reference range for bicarbonate

22-29mmol/L

decreased concentration of total carbon dioxide associated with what conditions

metabolic acidosis diabetic ketoacidosis salicylate toxicity

increased concentration of total carbon dioxide associated with what conditions

metabolic alkalosis emphysema severe vomiting

mathematical formula sued to demonstrate electroneutrality of body fluids represents the difference cations and anions that are not actually measured analytically when serum electrolytes are quantified

anion gap

unmeasured cations include ___ and ___, whereas the unmeasured anions include ___, ____, ____ and ____

calcium magnesium phosphate sulfate organic acids protein

_____ anion gap can be caused by uremia, lactic acidosis, ketoacidosis, hypernatremia, and ingestion of methanol, ethylene glycol or salicylate

increased

____ anion gap can be caused by hypoalbuminemia and hypercalcemia

decreased

calcium exists in plasma in three forms

50% free (ionized) 40% bound to protein 10% bound to anions

form of calcium that is biologically active

free (ionized)

decreased free (ionized) calcium levels cause muscle spasms or uncontrolled muscle contractions called ___

tetany

serum calcium is controlled by ___

parathyroid hormone vitamin D calcitonin

decrease in free calcium stimulates the release of ___

parathyroid hormone

in bone, PTH activated ___ to break down bone with the release of calcium

osteoclasts

in kidneys, PTH increases tubular reabsorption of calcium and stimulates _____ to the active form

hydroxylation of vitamin D

obtained by diet or exposure to sunlight

vitamin D

vitamin D is transported to the ____, where it is hydroxylated but still inactive, then is transported to ___ where it is converted to ___, active form

liver kidney 1,25-dihydroxycholecalciferol

released by the parafollicular cells of the thyroid gland when serum calcium level increases inhibits vitamin D and PTH activity, thus decreasing serum calcium

calcitonin

neoplasm of the parafollicular cells, resulting in ____ serum levels of calcitonin

medullary carcinoma of the thyroid gland

caused by primary hyperparathyroidism, other endocrine disorders such as hypothyroidism and acute adrenal insufficiency, malignancy involving bone and renal failure

hypercalcemia

caused by hypoparathyroidism, hypoalbuminemia, chronic renal failure, magnesium deficiency and vitamin D deficiency

hypocalcemia

reference range for total calcium in adults

8.6-10.3mg/dl

reference range for free calcium in adults

4.6-5.3mg/dl

PTH-mediated hypercalcemia

primary hyperparathyroidism familial hypocalciuric hypercalcemia ectopic secretion of PTH by neoplasm

most important regulatory hormone for phosphorus increases renal excretion of phosphate

PTH

regulates phosphate by causing intestinal absorption and renal reabsorption

vitamin D

causes of hyperphosphatemia

renal failure hypoparathyroidism pseudohypoparathyroidism neoplastic diseases lymphoblastic leukemia hypervitaminosis D cytolysis pyloric obstruction intense exercise

causes of hypophosphatemia

diabetic ketoacidosis primary hyperparathyroidism acute respiratory alkalosis myxedema steroids diuretic therapy renal tubular defects oncogenic phosphaturia asthma alcoholism malabsorption syndrome

test methodology for phosphate: colorless complex being read at 340nm

phosphomolybdate complex

test methodology for phosphate: use to reduce phosphomolybdate complex to form a colored product at 600-700nm

aminonaphtholsulfonic acid

reference range for phosphate

2.5-4.5 mg/dl

magnesium exists in plasma in three forms:

55% free (ionized) 30% bound to protein 15% complexed

magnesium level is regulated by the kidneys through reabsorption and excretion ___ enhances reabsorption by the kidneys and intestinal absorption and excretion

PTH

methods used to measure total serum magnesium

calmagite methylthymol blue atomic absoprtion spectrophotometry

reference range for magnesium (in adults)

1.7-2.4mg/dl

causes of hypermagnesemia

renal failure excess antacids

causes of hypomagnesemia

gastrointestinal disorders renal disease hyperparathyroidism drugs diabetes mellitus with glycosuria alcoholism

methodologies for total serum calcium

orthocresolphthalein complexone arsenazo III dye Clark Collip precipitation method Ferro Ham Chloroanilic acid precipitation method

methodologies for total serum magnesium

calmagite formazen dye methyl thymol blue titan yellow dye

methodologies for total serum phosphorus

fiske subbarow method (ammonium molybdate method)

iron stored form in blood and other cells

ferritin hemosiderin

transports iron in the blood

transferrin

reference range for transferrin

200-360mg/dl

reflects iron stores decreases early in iron-deficiency disorders, making it a sensitive early indicator of IDA increased in conditions of iron overload, hemochromatosis acute-phase protein measured directly by immunochemical methods

ferritin

reference range for ferritin in males

20-250ng/ml

reference range for ferritin in females

10-120ng/ml

decreased serum iron decreased % saturation increased total iron-binding capacity

iron deficiency anemia

decreased serum iron varied % saturation decreased total iron-binding capacity

malnutrition

increased serum iron increased % saturation decreased total iron-binding capacity

iron overdose hemochromatosis

measures serum ferric bound to transferrin by adding acid solution to release ferric ion. then reduced to ferrous ion and complexed with a chromogen reagent such as bathophenanthroline or ferrozine

total iron content (serum iron)

measures the quantity of iron bound to transferrin if all the binding sites on transferrin were occupied ferric is added to serum to saturate transferrin MgCO3 is added to remove unbound ferric then the mixture is centrifuged to measure the serum iron in the supernatant

total iron binding capacity

calculated value that represents the amount of iron that transferrin is capable of binding serum iron/TIBC x 100

% transferrin saturation

reference range for serum iron

45-160microgram/dl

reference range for TIBC

250-425microgram/dl

reference range for % saturation

15-55%

system that can resist change in pH composed of a weak acid or a weak base and its corresponding salt

buffer

four buffer systems of clinical importance exist in whole blood

bicarbonate-carbonic acid buffer system protein buffer system phosphate buffer system hemoglobin buffer system

most important buffer system in the plasma that minimizes pH changes in plasma and erythrocytes

bicarbonate-carbonic acid buffer system

uses plasma proteins to minimize pH changes in the blood

protein buffer system

uses HPO4 and H2PO4 to minimize pH changes in plasma and erythrocytes

phosphate buffer system

uses hemoglobin in red blood cells to minimize pH changes in the blood most important intracellular buffer

hemoglobin buffer system

process to supply cells with oxygen for metabolic processes and remove the carbon dioxide produced during metabolism

respiration

amount of pressure contributed by each glass to the total pressure exerted by the mixture

partial pressure

occurs when arterial blood pH<7.35

acidemia

occurs when arterial blood pH>7.45

alkalemia

increased blood PCO2

hypercapnia

decreased blood PCO2

hypocapnia

pH of plasma is a function of these two independent variables

PCO2 HCO3-

the variable crucial to maintain the plasma pH and being regulated by the lungs (respiratory mechanism)

PCO2

the variable crucial to maintain the plasma pH and being regulated by the kidneys (renal mechanism)

HCO3-

average normal ratio of cHO3- to cdCO2

20:1

reference ranges for arterial blood gas analysis: pH

7.35-7.45

reference ranges for arterial blood gas analysis: ctCO2

22-26mmol/L

reference ranges for arterial blood gas analysis: PCO2

35-45mmHg

primarily involve bicarbonate concentration

metabolic acid-base disorders

primarily involve carbon dioxide concentration

respiratory acid-base disorders

primary bicarbonate deficit bicarbonate concentration decreases causing a decrease in the 20:1 ratio

metabolic acidosis

acid-base disorder: diabetic ketoacidosis use to the production of acetoacetic acid and beta-hydroxybutyric acid

metabolic acidosis

acid-base disorder: lactic acidosis due to the production of lactic acid

metabolic acidosis

acid-base disorder: poisonings such as salicylate, ethylene glycol, and methyl alcohol

metabolic acidosis

acid-base disorder: reduced acid excretion due to renal failure or tubular acisodis

metabolic acidosis

acid-base disorder: loss of bicarbonate due to diarrhea or excessive renal excretion

metabolic acidosis

laboratory findings in metabolic acidosis

ctCO2 decreased PCO2 normal pH decreased

respiratory compensatory mechanism for metabolic acidosis: a decreased pH triggers ____ that lowers PCO2 and results in an increase in pH to increase the ratio between cHCO3- and cdCO2 to 20:1, which increases the blood pH

hyperventilation

laboratory findings in compensation for metabolic acidosis

ctCO2 decreased PCO2 decreased pH normal

primary bicarbonate bicarbonate concentration increases, causing an increase in the 20:1 ratio between cHCO3- and cdCO2, which results in an increase in the blood pH may be caused by ingestion of excess base, decreased elimination of base or loss of acidic fluids

metabolic alkalosis

acid-base disorder: ingestion of excess alkali (antacids)

metabolic alkalosis

acid-base disorder: intravenous administration of bicarbonate

metabolic alkalosis

acid-base disorder: renal bicarbonate retention

metabolic alkalosis

acid-base disorder: prolonged diuretic use

metabolic alkalosis

acid-base disorder: loss of hydrochloric acid from the stomach after vomiting

metabolic alkalosis

acid-base disorder: intestinal obstruction or gastric suction

metabolic alkalosis

acid-base disorder: glucocorticoid excess as in Cushing's syndrome and mineralocorticoid excess as hyperaldosteronism

metabolic alkalosis

laboratory findings in metabolic alkalosis

ctCO2 increased PCO2 normal pH increased

respiratory compensatory mechanism for metabolic acidosis: pH increase which triggers ____, thus increasing the amount of CO2 retained by lungs the increased CO2 retention causes an increase in H2CO3, which results in more dissolved CO2 in the blood. The carbonic acid lowers the pH this decreases the ration between cHCO3- and cdCO2 to 20:1, which decrease the blood pH

hypoventilation

laboratory findings in compensation for metabolic alkalosis

ctCO2 increased PCO2 increased pH normal

primary cdCO2 excess expressed as an increase in PCO2 (hypercapnia) inability of a person to exhale CO2 through the lungs (hypoventilation) causes an increase of PCO2 thereby increasing the concentration of dissolved carbon dioxide which forms the carbonic acid in the blood decreasing the 20:1 ratio between cHCO3- and cdCO2 hence the low blood pH

respiratory acidosis

acid-base disorder: chronic obstructive pulmonary disease, such as chronic bronchitis and emphysema

respiratory acidosis

acid-base disorder: ingestion of narcotics and barbiturates

respiratory acidosis

acid-base disorder: severe infections of the central nervous system such as meningitis

respiratory acidosis

laboratory findings in respiratory acidosis

ctCO2 normal PCO2 increased pH decreased

renal compensatory mechanism in respiratory acidosis: the kidneys ___ sodium-hydrogen exchange, ammonia formation and the bicarbonate retention the increased bicarbonate concentration aids the return of the 20:1, which ___ the blood pH

increase raises

laboratory findings in renal compensation for respiratory acidosis

ctCO2 increased PCO2 increased pH normal

primary cdCO2 deficit expressed as decrease in PCO2 results from an accelerated rate or depth of respiration, or a combination of both excessive exhalation of carbon dioxide reduces the PCO2 causing a decrease in the concentration of dissolved CO2, which forms less carbonic acid in the blood this increase the 20:1 ratio between cHO3- and cdCO2, which increases the blood pH may be caused by hypoxia, anxiety, nervousness, excessive crying, pulmonary embolism, pneumonia, congestive heart failure, salicylate overdose and so on

respiratory alkalosis

laboratory findings in respiratory alkalosis

ctCO2 normal PCO2 decreased pH increased

renal compensatory mechanism corrects respiratory alkalosis by ___

excreting bicarbonate

laboratory findings in renal compensation for respiratory alkalosis

ctCO2 decreased PCO2 decreased pH normal

three factors control oxygen transport

PO2 free diffusion of oxygen across the alveolar membrane affinity of hemoglobin for oxygen

oxygen saturation of hemoglobin under normal circumstances

95%

when the PO2 is ____, greater than ___ of hemoglobin binds to oxygen

>110mmHg 98%

causes of hypoxemia

decreased pulmonary diffusion decreased alveolar spaces due to resection or compression poor ventilation/perfusion

chemical compounds secreted into the blood that affect target tissues generally at a site distant from original production

hormones

three classes of homones

steroids proteins amines

synthesized by adrenal glands, gonads and placenta from cholesterol as needed, not stored, lipid-soluble need a carrier protein to circulate in the blood

steroid hormones

MOA: free hormone is transported across cell membrane to interact with intracellular receptor; complex binds to chromatin, producing mRNA; mRNA initiates production of proteins that carry out the function attributed to the specific hormone

steroid hormones

synthesized by anterior pituitary, placenta, pancreas and parathyroid glands synthesized, the stored in the cell as secretory granules until needed do not need carrier proteins to enter blood; water soluble

protein hormone

cortisol aldosterone testosterone estrogen progesterone

steroid hormones

follicle-stimulating hormone luteinizing hormone thyroid-stimulating hormones human chorionic gonadotropin insulin glucagon parathyroid hormone growth hormones prolactin

protein hormones

MOA: interact with a cell membrane receptor, activating a second messenger system and then cellular action

protein hormones

class of hormone: regulated through negative feedback by another hormone

steroid hormones

class of hormone: regulated through change in analyte concentration in serum and negative feedback by another hormone

protein hormones

synthesized by thyroid and adrenal glands from amino acids some require a carrier protein

amino hormones

epinephrine norepinephrine thyroxine triiodothyronine

amino hormones

MOA: epinephrine and norepinephrine do not bind to carrier proteins and interact with the receptor site on the cell membrane while thyroxine and triiodothyronine circulate bound to carrier proteins, with the tree hormone being transported across the cell membrane to interact with the intracellular receptor

amino hormones

class of hormones: regulated by nerve stimulation, another hormone and negative feedback

amino hormones

stimulates secretion of adenocorticotropic hormone

corticotropin-releasing hormone

stimulates secretion of follicle-stimulating hormone and luteinizing hormone

gonadotropin-releasing hormone

stimulates secretion of growth hormone

growth hormone-releasing hormone

stimulates secretion of thyroid-stimulating hormone and prolactin

thyrotropin-releasing hormone

inhibits prolactin release

dopamine

inhibits secretion of TSH and GH

somatostatin

supraoptic and paraventricular nuclei of the hypothalamus produce ___ and ___, which are being stored in ___

ADH (vasopressin) oxytocin posterior pituitary

hormones produced by the anterior pituitary gland

ACTH LH FSH TSH GH prolactin

stimulates synthesis of cortisol

ACTH

exhibit diurnal variation, with highest levels in the morning and lowest levels in the late afternoon to early evening

ACTH cortisol

stimulates the release of growth hormone (somatotropin) from the anterior pituitary

growth hormone releasing hormone

inhibits the release of growth hormone (somatotropin) from the anterior pituitary

somatostatin

direct effect on metabolism in numerous tissues: antagonistic effect to insulin in relationship to glucose metabolism, stimulates gluconeogenesis in the liver, stimulates lipolysis and promotes protein syntehsis

growth hormone

reference range for growth hormone

2-5ng/ml

generally caused by a growth hormone-secreting pituitary hormone enlarged feet, hand, facial bones, impaired glucose tolerance, hypertension

acromegaly

causes of decreased levels of growth hormone in adults

pituitary adenomas or irradiation

causes of decreased levels of growth hormone in children

familial tumor: craniopharyngioma

secreted by pituitary lactotroph cells and released upon stimulation from TRH initiates and maintains lactation, effects reproduction through ovarian and testicular steroidogenesis, affects the immune system

prolactin

inhibits release of prolactin

dopamine

reference range for prolactin in male

3.0-14.7ng/ml

reference range for prolactin in female

3.8-23.0ng/ml

causes of increased prolactin levels

pituitary adenomas trauma inflammation chronic renal failure side effect of tricyclic antidepressant, phenothiazines, reserpine

hyperprolactinemia causes ___

hypogonadism

cause of decreased prolactin levels

panhypopituitarism

hormones released by posterior pituitary, but they are synthesized in the hypothalamus, where they form secretory granules for transport down the nerve axons to the posterior pituitary for storage

ADH (vasopressin) oxytocin

controls water homeostasis by affecting the permeability of the collecting tubules of the kidney and enhancing water resorption, which makes the urine more concentrated and the blood more dilute raises blood pressure by stimulating musculature of arterioles and capillaries; affects uterine contraction; and, promotes intestinal muscle contraction

ADH

regulatory effect on secretion of ADH

osmolarity of plasma

uncontrolled secretion of ADH without any stimulus for such release ADH is released even though the blood volume is normal or increased and plasma osmolality is low caused by ectopic tumor production of ADH as in small cell carcinoma of the lung, central nervous system disease, pulmonary diseases or as a side effect of administration of certain drugs

syndrome of inappropriate ADH secretion

decreased ADH level (hypofunction)

diabetes insipidus polydipsia

release is stimulated by the uterine stretch receptors, which in turn stimulates uterine contraction during the childbirth action of suckling stimulates tactile receptors that promote the secretion of oxytocin which causes ejection of breast milk

oxytocin

adrenal glands: produce steroid hormone

adrenal cortex

three layers of the adrenal cortex

zona glomerulosa zona fasciculata zona reticularis

outermost layer, secrete mineralocorticoids, with aldosterone being the major hormone

zona glomerulosa

second layer, secretes glucocorticoids, with cortisol being the major hormone

zona fasciculata

third layer, secretes sex hormones, principally the androgens

zona reticularis

adrenal glands: produce amine hormone inner portion of the gland

adrenal medulla

hormones secreted by the adrenal medulla

catecholamines

steroid hormones released by the adrenal glands that regulate salt balance

mineralcorticoids

steroid hormones released by the adrenal glands that assist in carbohydrate metabolism

glucocorticoids

steroid hormones released by the adrenal glands required for sexual function

androgens

controls the retention of sodium, chloride, and water, excretion of potassium and hydrogen ion, and therefore the amount of fluid in the body

aldosterone

controls the aldosterone production

renin-angiotensin system of the kidney

protein that acts on angiotensinogen to produce angiotensin I, which is acted on by the angiotensin-converting enzyme to catalyze the formation of angiotensin II

renin

stimulates the secretion of aldosterone and is a potent vasoconstriction

angiotensin II

what part of the kidney detects low serum sodium or pressure changes in the blood perfusing the kidney, hence producing renin upon detecting a decreased blood pressure or blood volume

juxtaglomerular apparatus

reference range for aldosterone in adults supine

3-16ng/dl

reference range for aldosterone in adults upright

7-30ng/dl

causes of primary hyperaldosteronism

adrenal disease (Conn syndrome) aldosterone-secreting adrenal carcinoma or hyperplasia of the adrenal cortex

causes of secondary hyperaldosteronism

renin-angiotensin system disorder due to excess production of renin malignant hypertension renin-secreting renal tumor

atrophy of the adrenal glands with depressed production of aldosterone and the glucorticoids pigmentation of the skin, muscle weakness, weight loss, decreased blood pressure, nausea and diarrhea

Addison disease

causes decreased secretion of aldosterone and cortisol, increased ACTH, increased beta-MSH, decreased blood glucose, decreased sodium and chloride, increased potassium

hypoadrenalism

what is deficient in Addison disease

21-hydroxylase enzyme

has anti-insulin effects on carbohydrates that result in increased glucose levels: increased gluconeogenesis increased lipolysis increased protein catabolism decreased protein synthesis decreased antibody formation suppressed inflammatory response

cortisol

hypothalamus secretes corticotropin-releasing hormone and the anterior pituitary secretes ___, which controls cortisol production via a feedback loop

adrenocorticotropic hormone

reference range for cortisol at 8am

5-23 microgram/dl

reference range for cortisol at 4pm

3-16 microgram/dl

causes of primary hypercortisolism

adrenal adenoma or carcinoma exogenous administration of cortisol Cushing syndrome

increased serum cortisol cortisol lacks diurnal variation hyperglycemia when adrenal gland secretes excess cortisol, the ACTH will be decreased weight gain in the face (moon facie) and abdomen, buffalo hump back, thinning of skin, easy bruising, hypertension, muscle wasting, decreased immune response

Cushing syndrome

causes of hypocortisolism

atrophy of adrenal autoimmune disease tuberculosis prolonged high-dosage cortisol therapy

catecholamines synthesized from ___ by ___ of the adrenal medulla, brain and sympathetic neurons

tyrosine chromaffin cells

what hormones are considered cathecholamines

epinephrine norepinephrine dopamine

mobilizes energy stores by converting glycogen to glucose, which allows the voluntary muscles to have greater work output, released in response to low blood pressure, hypoxia, cold exposure, muscle exertion and pain

epinephrine

functions as neurotransmitter affecting the vascular smooth muscle and heart, released primarily by the postganglionic sympathetic nerves

norepinephrine

functions as neurotransmitter in the brain affecting the vascular system

dopamine

final end product of epinephrine and norepinephrine metabolism

vanillylmandelic acid

tumor of the adrenal medulla usually benign causes increased levels of epi and norepi

phenochromocytoma

test methodology: for quantifying plasma epinephrine and norepinephrine

fluorometric methods

test methodology: used for quantifying VMA

colorimetric/spectrophotometric method

malignant tumor of the adrenal medulla that occurs in children produces epinephrine and norepinephrine along with dopamine characterized by increase in HVA and VMA urinary excretion

neuroblastoma

end product of dopamine metabolism

homovanillic acid

stimulates the growth of the ovarian follicles and increases the plasma estrogen level secreted by anterior pituitary under the control of gonadotropin-releasing hormone

FSH

stimulates the production of progesterone, provides hormonal trigger to cause ovulation and release of eggs from the ovary secreted by anterior pituitary under the control of gonadotropin-releasing hormone

secreted by the ovarian follicles and by the placenta in pregnancy promotes development and maintains the female reproductive system including the uterus, fallopian tubes and vagina development and maintenance of secondary female sex characteristics

estrogen

three primary estrogens

estradiol-17beta estrone estradiol

principal estrogen synthesized by the ovary

estradiol

secreted by the ovarian follicles, mainly corpus luteum following ovulation and by the placenta in pregnancy

progesterone

first half of the menstrual cycle, ___ promotes growth of ovarian follicles and an increase in ___ (low in 7 days of cycle)

FSH estrogen

___ peaks at midcycle, causing a decrease in __ but promoting the ___ surge

estrogen FSH LH

___ triggers ovulation, which is followed by a decrease in ___ and ___ levels

LH estrogen LH

after ovulation, the follicle becomes ___, which produces ___ and ___

corpus luteum estrogen progesterone

lack of fertilization causes the corpus luteum to degenerate along with decrease in the ___ and ___ levels ___ falls to the initial low level of the follicular phase about 24 hours prior to the onset of menstruation

estrogen progesterone progesterone

menstrual cycle: characterized by estrogen stimulating growth of the uterine lining, progesterone levels are low

follicular phase

menstrual cycle: characterized by progesterone promoting endometrium tissues accept the fertilized ovum

luteal phase

useful to confirm ovulation

progesterone

caused by precocious puberty, ovarian tumor, hypothalamic tumor, adrenal tumors may be difficult to determine infertility and irregular menses postmenopausal bleeding

hyperestrinism

genetic defect in females where there is partial or complete loss of one of the two X chromosomes, resulting in nonfunctional ovaries

Turner syndrome

prevents menstrual cycle from occuring

hyperprogesteronemia

causes infertility and abortion of fetus

hypoprogesteronemia

main source of estrogen synthesis during pregnancy, making primarily estradiol

placenta

placenta requires a precursor compound that can only be made by the fetal adrenal glands, ____, hydroxylated form of DHFAS

16alpha-dehydroepiandrosteronesulfate

what are being measured in triple test, which is used to estimate the risk of Down syndrome

alpha1-fetoprotein (AFP) unconjugated estriol (uE3) human chorionic gonadotropin (hCG)

pattern suggestive of increased risk of the baby having Down syndrome

dec AFP dec uE3 inc hCG interpretation utilizes multiples of median definitive testing

definitive testing for down syndrome

amniocentesis chromosome analysis

what test is included in the quad test aside from the triple test

inhibin A

polypeptide hormone, produced by the fetoplacental unit and inhibits production of FSH decreased in Down syndrome

inhibin A

hormones synthesized and secreted by placenta

estrogen progesterone hCG human placental lactogen

prolongs the viability of the corpus luteum, which synthesizes progesterone and estrogen in early pregnancy until the placenta can assume the function highest in the first trimester used to detect pregnancy

hCG

pathologic causes of increased hCG

hydatidiform mole choriocarcinoma pre-eclamptic toxemia

pathologic causes of decreased hCG

threatened abortion ectopic pregnancy

functions with hCG to produce estrogen and progesterone during pregnancy rises throughout gestation and reaches its highest level near term reflects the integrity of placental function

human placental lactogen

decreased HPL is suggestive of what conditions

placental malfunction potential fetal distress

in male, the anterior pituitary gland secretes FSH, which stimulates ___

spermatogenesis

in male, anterior pituitary secretes ___, which stimulates the production of testosterone

principal male sex hormone and is secreted by the testes promotes development and maintains the male reproductive system responsible for development and maintenance of secondary male sex characteristics

testosterone

caused by an enzyme defect of 21-hydroxylase, which prevents cortisol production and results in accumulation of cortisol precursors including 17-OHP characterized by increased blood levels of 17-OHP and ACTH, and decreased cortisol

congenital adrenal hyperplasia

in adult males, this causes impotence and loss of secondary sex characteristics occurs. in prepubertal males, delayed puberty results

hypoandrogenemia

male possesses an increase X chromosome (XXY) characteristics include tall with long extremities, small testes, gynecomastia, infertility, low IQ

Klinefelter syndrome

located in trachea-larynx area, composed of two lobes that consist of two types of cells

thyroid gland

single layer of epithelial cells arranged spherically to create a follicle make and secrete thyroid hormones, which are stored in lumina of follicle

follicular cells

secrete calcitonin, which is involved with calcium regulation

parafollicular cells

aid in regulation of several metabolic functions, including rate of oxygen consumption and heat production, growth, sexual maturity and protein and carbohydrate metabolism

thyroid hormones (T4, T3, rT3)

released by hypothalamus and stimulates anterior pituitary to secrete thyroid-stimulating hormone

thyrotrophin-releasing hormone

polypeptide hormone that originates in the anterior pituitary gland regulates synthesis and release of the thyroid hormones

TSH

regulate secretion of TSH

TRH somatostatin free T3 free T4

regulation of TSH secretion: functions as an inhibitory factor

somatostatin

regulation of TSH secretion: stimulate hypothalamus to secrete somatostatin

FT3 FT4

protein carriers of thyroid hormones in the blood

thyroxine-binding globulin (TBG) thyroxine-binding prealbumin thyroxine-binding albumin

principal carrier protein of thyroid hormones

TBG

T3 or T4: which is more metabolically potent in the tissues

classified as thyrotropin-receptor antibodies they bind to TSH receptor sites and activate thyroid epithelial cells

thyroid-stimulating immunoglobulins (TSI)

causes tissue destruction, and analysis is generally directed to the measurement of anti-thyroid peroxidase antibodies detected in Hashimoto's thyroiditis

thyroid microsomal antibodies (TMAbs)

characterized by enlarged thyroid gland, impaired speech and memory, fatigue, weight gain, personality changes, cold intolerance, increased serum cholesterol, LDL

hypothyroidism

in primary hypothyroidism, total T3, T4, FT3 and FT4 are ___, and TSH is ___

decreased increased

advanced form of hypothyroidism

myxedema

if untreated in first 3 months of life, irreversible neurological and mental deficiency occurs, newborn screening is required

congenital hypothyroidism/cretinism

most common cause of primary hypothyroidism chronic autoimmune thyroiditis TgAb present

Hashimoto's disease

serum levels of the following in primary hypothyroidism: ___ TT3 ___ TT4 ___ FT4 ___ TSH

dec dec dec inc

serum levels of the following in secondary hypothyroidism: ___ TT3 ___ TT4 ___ FT3 ___ FT4

dec dec dec dec

serum levels of the following in primary hyperthyroidism: ___ TT3 ___ TT4 ___ FT3 ___ FT4

inc inc inc dec

serum levels of the following in secondary hyperthyroidism: ___ TT3 ___ TT4 ___ FT3 ___ FT4

inc inc inc inc

serum levels of the following in primary increase TBG: ___ TT3 ___ TT4 ___ FT3 ___ FT4

inc inc N N

serum levels of the following in primary decrease TBG: ___ TT3 ___ TT4 ___ FT3 ___ FT4

dec dec N N

characterized by weight and muscle loss, fatigue, heat intolerance, nervousness, exophthalmos

hyperthyroidism

increased serum levels of thyroid hormones

thyrotoxicosis

life-threatening complication of uncontrolled thyrotoxicosis

thyroid storm

most common autoimmune disorder with TRAb and TSI present

Graves disease

normal functioning thyroid gland in the presence of abnormal concentration of thyroxine-binding globulin primary increase in the concentration of TBG is seen in conditions such as pregnancy and estrogen therapy, manifesting as increase in TT4, but the individual has normal levels of FT4 and TSH due to the negative feedback regulation to the anterior pituitary being intact

euthyroid

when the serum concentration of TBG is increased, thyroid hormone binding ratio (THBR) is _____

decreased

located bilaterally on or near the thyroid gland capsule

parathyroid glands

parathyroid glands are composed of:

chief cells oxyphil cells

synthesize, store, and secrete parathyroid hormone

chief cells

aids in the regulation of calcium and phosphate having direct action on bone and kidney, and indirect action on the intestines through vitamin D increases serum Ca level by increasing Ca resorption from bone, increasing Ca reabsorption in the renal tubules and increasing intestinal absorption of Ca by stimulating production of vitamin D

PTH

in kidneys, PTH increases Ca reabsorption in the ___ and decreases reabsorption of ___ in the ___, resulting in ___

distal tubules phosphate proximal tubules phosphaturia

in intestines, PTH promotes absorption of calcium and phosphate by stimulating increased production of ___

1,25(OH)2D

reference range for PTH

15-65pg/ml

causes of primary hyperparathyroidism

parathyroid adenoma parathyroid carcinoma or hyperplasia

causes of secondary hyperparathyroidism

vitamin D deficiency chronic renal failure

causes of hypoparathyroidism

osteomalacia autoimmune disease inborn error of metabolism unintentional removal of parathyroid hormone during surgery

secreted by the stomach in response to the vagus and food entering the stomach stimulates secretion of gastric HCl and pancreatic enzymes

gastrin

acidification of what causes a decrease in gastrin enzymes

antrum (stomach)

elevated gastrin level, accompanied by gastric hyperacidity, caused by gastrinomas, duodenal or pancreatic endocrine tumors that secrete gastrin

Zollinger-Ellison syndrome

synthesized from tryptophan and secreted by the enterochromaffin cells in the gastrointestinal tract smooth muscle stimulant and vasoconstrictor that is transported by platelets

serotonin

liver metabolizes serotonin to ____

5-hydroxylindole acetic acid

organ that has both endocrine and exocrine functions

pancreas

endocrine functions of pancreas

insulin glucagon gastrin somatostatin

exocrine function

digestive enzymes

secretion of the digestive fluid by the pancreas is regulated by what nerve and endocrine hormones

vagus cholecystokinin secretin

synthesized in the islets of Langerhans by the beta cells and secreted into the blood when the blood glucose is elevated promoting glycogenesis and lipogenesis while inhibiting glycogenolysis

insulin

inhibitors of insulin

epinephrine norepinephrine

cause of hyperinsulinemia

insulinoma

synthesized in the islets of Langerhans by the alpha cells and secreted into the blood when the blood glucose level is low increases blood glucose by promoting glycogenolysis in the liver and gluconeogenesis secretion is promoted by exercise, stress, and amino acids

glucagon

inhibits the secretion of glucagon

insulin

entails the analysis, interpretation, and evaluation of drug concentration in serum, plasma or whole blood samples employed to establish maximum benefits with minimal toxic effects for drugs whose correlation with dosage, effect or toxicity is not clear

therapeutic drug monitoring

drug concentration that produces benefits

therapeutic range

all drugs absorbed from the GI tract must go through the liver before entering the general circulation

first pass metabolism

acidic drugs primarily bind to ___

albumin

basic drugs primarily bind to ___

alpha-1-acid-glycoprotein

cardiac glycoside used to threat congestive heart failure

digoxin

digoxin inhibits membrane ___ causing decrease in intracellular ___ and increase in intracellular ____ in cardiac myocytes, which improves ___

Na-K-ATP K Ca contraction of cardiac muscle

therapeutic range for digoxin

0.8-2.0ng/ml

anti-arrhythmic drug used to treat ventricular arrhythmia and prevent ventricular fibrillation oral administration is contraindicated

lidocaine

therapeutic range for lidocaine

1.5-4.0microgram/ml

anti-arrhythmic drug used to treat cardiac arrhythmia may be administered orally as the sulfate or gluconate form sample collection is performed 1 hour following the last ingested dose for trough determination because of its slow absorption rate

quinidine

therapeutic range for quinidine

2-5microgram/ml

anti-arrhythmic drug used to treat cardiac arrhythmia metabolized to NAPA, which exhibits a similar physiological effect as the parent drug peak plasma levels occur approximately 1 hour after ingestion

procainamide

therapeutic range for procainamide

4-8micrograms/ml

used to treat infections caused by gram negative bacteria include gentamicin, tobramycin, kanamycin and amikacin administered IV or IM because GI absorption is poor

aminoglycoside

aminoglycoside is associated with these conditions

nephrotoxicity ototoxicity

used to treat infections caused by gram positive bacteria administered by IV due to poor GI absorption

vancomycin

vancomycin may be associated with these conditions

nephrotoxicity ototoxicity red man syndrome

erythematic flushing of extremities

red man sydnrome

slow acting barbiturate used to control seizures MOA: increases the amount of time chloride channels are open, consequently depressing the central nervous system. This action occurs by acting on GABA-A receptor subunits. chloride ion gates open and stay open, allowing a steady flow of these ions into neuronal cells, which hyperpolarizes the cell membrane, increasing the action potential threshold administered orally with a peak plasma level occurring 10 hours following ingestion characterized by slow absorption and a long half life toxicity effects: drowsiness, depression, fatigue, altered mental ability

phenobarbital

inactive form of phenobarbital and this isoform is administered when rapid absorption is indicated quickly converted to phenobarbital

primidone

therapeutic range

15-40 microgram/ml

used to control seizure and to keep the brain from swelling and injuring tissue during brain traumas MOA: a first-generation anti-convulsant drug that is effective in the treatment of generalized tonic-clonic seizures, complex partial seizures, and status epilepticus without significantly impairing neurological function 90-95% protein bound in the circulation toxicity is characterized by seizures

phenytoin

therapeutic range of phenytoin

total serum level: 10-20microgram/ml free serum level: 1-2microgram/ml

IM injectable proform of the drug

fosphenytoin

antiseizure meds several MOA: inhibition of voltage-gated sodium channels, inhibition of gamma-aminobutyric acid (GABA) transaminase, enhancement of GABA synthesis, inhibition of HDACs, modulation of calcium channels administered orally, 93% protein bound in the circulation, and metabolized by the liver for elimination

valproic acid

therapeutic range of valproic acid

50-100microgram/ml

antiseizure meds MOA: enhancement of sodium channel inactivation by reducing high-frequency repetitive firing of action potentials and action on synaptic transmission administered orally 70-80% protein bound in the circulation, and metabolized by the liver for elimination

carbamazepine

therapeutic range of carbamazepine

4-12 microgram/ml

anti-psychotic drugs MOA: modifies sodium transport in nerve and muscle cells, alters the metabolism of neurotransmitters, specifically catecholamines and serotonin, may alter intracellular signaling via second messenger systems by inhibition of inositol monophosphate which, in turn, affects neurotransmission through the phosphatidylinositol secondary messenger system; decreases protein kinase C activity, which alters genomic expression associated with neurotransmission; appears to increase cytoprotective proteins and possibly activates neurogenesis and increases gray matter volume administered orally, does not bind to plasma proteins in the circulation, peak plasma levels occur 2-4 hours after oral ingestion and filtered by the kidney for elimination

lithium

therapeutic range of lithium

1.0-1.2mmol/L

anti-psychotic meds used in cases of depression, insomnia, extreme apathy and loss of libido MOA: inhibiting serotonin and norepinephrine reuptake within the presynaptic terminals, resulting in elevated concentrations of these neurotransmitters within the synaptic cleft; act as competitive antagonists on postsynaptic cholinergic (alpha-1 and alpha-2), muscarinic, and histamine receptors (H1) administered orally, but GI absorption is slow, peak concentration occurring 2-12 hours after ingestion

TCA

drugs included in TCAs

amitriptyline imipramine doxepine

used to treat asthma and other COPD MOA: relaxes the smooth muscles located in the bronchial airways and pulmonary blood vessels administered orally, with elimination dependent on it being metabolized by the liver and filtered by the kidney

theophylline

therapeutic range of theophylline

10-20microgram/ml

used to suppress transplant rejections and graft-vs-host disease MOA: inhibition of the production of cytokines involved in the regulation of T-cell activation by inhibiting the transcription of interleukin 2

cyclosporine

used to suppress transplant rejections and GVHD MOA: bonds to an immunophilin, FK506 binding protein (FKBP). This complex inhibits calcineurin phosphatase. The drug inhibits calcium-dependent events, such as interleukin-2 gene transcription, nitric oxide synthase activation, cell degranulation, and apoptosis.

tacrolimus

therapeutic range of tacrolimus

10-15ng/ml

used to suppress transplant rejections and GVHD MOA: forms an immunosuppressive complex with intracellular protein, FKBP12. This complex blocks the activation of the cell-cycle-specific kinase, TOR. The downstream events that follow the inactivation of TOR result in the blockage of cell-cycle progression at the juncture of G1 and S phase.

sirolimus

therapeutic range of sirolimus

4-12ng/ml

used to destroy neoplastic cells by inhibiting the synthesis of DNA in all cells, its action is based on the principle that neoplastic cells contain a greater amount of DNA because of their rapid rate of division as compared to normal cells

methotrexate

refers to the administration of this drug to offset the effect of methotrexate in an attempt to prevent cytotoxicity of normal cells

leucovorin rescue

study of poisonous substances

toxicology

amount of damage done to an organism when the substance is administered at less than lethal dose

toxic response

one-time exposure of short duration to an agent that immediately causes a toxic response

acute toxicity

multiple exposures for extended time periods to an agent at a dosage that will not cause an acute response

chronic toxicity

performed first and usually of a qualitative nature; may lack specificity

screening test

usually quantitative with good specificity and sensitivity

confirmatory test

type of alcohol chronic exposure is associated with toxic hepatitis and cirrhosis

ethanol

type of alcohol ingestion is related to severe acidosis, blindness and even death due to conversion to formaldehyde, which is metabolized to formic acid

methanol

type of alcohol in which ingestion produces severe acute symptoms, similar to ethanol intoxication that persists for a long period of time because it is metabolized to acetone, which has a long half life

isopropanol

type of alcohol found in anti-freeze, ingestion produces severe metabolic acidosis and renal tubular damage

ethylene glycol

reference method for analysis of ethanol as this can differentiate among various types of alcohol and quantify

gas-liquid chromatography

toxic because it binds very tightly to hemoglobin and does not allow oxygen to attach to the hemoglobin causes hypoxia in brain and heart

carbon monoxide

super toxic substance with exposure occurring through various routes, including oral ingestion, inhalation or transdermal absorption used in insecticide and rodenticide products binds to heme iron and mitochondrial cytochrome oxidase

cyanide

binds to thiol groups in proteins, ionized arsenic excreted in urine specimens: blood and urine used to assess short-term exposure; hair and fingernails used to assess long-term exposure

arsenic

binds to proteins and it inhibits many enzymes, inhibits synthesis, this alteration results in the formation and accumulation of zinc protoporphyrin causes basophilic stippling of RBCs and increased urinary excretion of aminolevulinic acid

lead

binds to proteins and inhibits many enzymes believed to interfere with DNA transcription and protein synthesis including protein synthesis in the developing brain, with destruction of endoplasmic reticulum and disappearance of ribosomes

mercury

analysis of pesticides, which contain organosphosphate and carbamate insecticides which inhibit acetylcholinesterase

erythrocyte acetylcholinesterase serum pseudocholinesterase

used as analgesic, anti-pyretic and anti-inflammatory causes mixed acid-base imbalance seen as metabolic acidosis and respiratory alkalosis, ketone body formation, excess formation ferric nitrate method with colored product read spectrophotometrically

salicylate

used as analgesic inhibitor of the synthesis of prostaglandins (PGs)

acetaminophen

other name for vitamin A

retinol

other name for vitamin B1

thiamine

other name for vitamin B2

riboflavin

other name for vitamin B3

niacin

other name for vitamin B5

pantothenic acid

other name for vitamin B6

pyridoxine

other name for vitamin B9

folic acid

other name for vitamin B12

cyanocobalamin

other name for vitamin C

ascorbic acid

other name for vitamin D

cholecalciferol

other name for vitamin E

tocopherol

other name for vitamin K

phylloquinones

vitamin A deficiency

night blindness

vitamin B1 deficiency

beriberi wernicke-korsakoff syndrome

vitamin B2 deficiency

cheilosis angular stomatitis glossitis

vitamin B3 deficiency

pellagra

vitamin B5 deficiency

paresthesia

vitamin B6 deficiency

seborrheic dermatitis

vitamin B9 deficiency

megaloblastic anemia

vitamin B12 deficiency

neurologic abnormalities

vitamin C deficiency

scurvy

vitamin D deficiency

rickets osteomalacia

vitamin E deficiency

mild hemolytic anemia red cell fragility

vitamin K deficiency

bleeding hemorrhage

standard hazard identification symbols: blue quadrant

health hazard

standard hazard identification symbols: yellow quadrant

reactivity/stability hazard

standard hazard identification symbols: red quadrant

flammable hazard

standard hazard identification symbols: white quadrant

other special information

class of fire: cloth

class of fire: combustible/reactive metals

class of fire: operating electrical equipment

class of fire: wood

class of fire: flammable liquids and gases

class of fire: paper

extinguisher being used to put out class A fire

pressurized water dry chemicals

extinguisher being used to put out class B fire

dry chemicals carbon dioxide

extinguisher being used to put out class C fire

dry chemicals carbon monoxide halon

extinguisher being used to put out class D fire

leave to professional fire fighters