Cell Quiz Review - Dr Magranndrmagrann.com/MLT/ChemPPT Flashcards Unit 3.docx · Web viewHormones...

Chem PPT Flashcards, Unit 3

What is the function of electrolytes? Run maintenance of water homeostasis, maintenance in acid-base balance and muscle functions as well as serves as cofactors for enzymes.

What is the major cation of extracellular fluid? Sodium (Na+)What does Sodium determine in the extracellular fluid?

The osmolality.

When is sodium excreted in the urine? When serum sodium exceeds 110-130 mmol/L

What happens when serum levels are below 110 mmol/L?

All the sodium in the glomerular filtrate is virtually reabsorbed in the proximal and distal tubules, a process that is influenced by aldosterone.

Sodium specimens consist of…?And should be stored at…?

Serum, plasma and urine specimens and may be stored at 4°C or may be frozen. Lipemic samples need to be ultracentrifuged.

What are the methods of measuring sodium? Atomic Absorption Spectrophotometry (AAS),Sodium Ion selective electrode (ISE), and Spectrophotometry.

What is the major intercellular cation? Potassium (K+)How are high concentrations of potassium maintained?

Na+K+ adenosine triphosphate (ATP) pump which is fueled by oxidative energy and continually transports K+ into the cell against a concentration gradient.

Does potassium exhibit a renal threshold? No, however it is excreted into the urine even in K-depleted states.

What are some of the functions of potassium? Regulation of neuromuscular excitability (both hypo- and hyperkalemia can cause muscle weakness) and contraction of the heat and cardiac rhythm (decrease K+ increases cardiac excitability and often leads to arrhythmia. High K+ slows the heart rate).

How does potassium affect acid-base status? In hypokalemic states, sodium and H+ ions move into the cell to replace K+. The H+ concentration is therefore decreased in the ECF=alkalemia (reverse is true of hyperkalemia).

What should the concentration of K+ be? In plasma and whole blood the concentration is 0.1-0.7 mmol/L lower than those in serum.

How does the release of K+ affect values? As few as 0.5% K+ of RBCs will increase K+ values by 0.5 mmol/L. An increase of K+ of 0.6% has been estimated for every 10 mg/L of plasma hemoglobin (Hb) caused by hemolysis.

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What causes glycolysis to be inhibited and the energy-dependent Na+, K+-ATPase will not maintain the Na+/K+ gradient?

When a whole blood specimen is maintained at 4°C versus 25°C before separation.

What does a K+ leakage from erythrocytes and other cells cause?

It causes an increase in plasma K+.

What causes falsely decreased K+ value? When an un-separated sample is stored at 37°C because glycolysis occurs and K+ shifts intracellularly. Leukocytosis will initially cause falsely decreased K+ concentration at room temp.

What are reliable determinations recommended for K+?

Collect blood with heparin, maintain near 25°C and separate the plasma within minutes by high-speed centrifugation without cooling.

What can falsely increase K+ concentration? Skeletal muscle activity as a result of repeated clenching of fist and application of the tourniquet.

What are methods for the determination of sodium and potassium?

Ion selective electrodes (ISE) and spectrophotometric methods.

What is the major anion of the extracellular fluid?

Chloride (CI-)

What is the function of chloride? Maintains the water distribution, osmotic pressure, and anion-cation balance in the ECF.

Where is chloride absorbed? In the intestinal tract and is excreted by kidneys.

What specimens contain chloride? Serum, plasma, urine and sweat.How is chloride affected by hemolysis, change in posture or stasis, and tourniquet use?

It is not affected.

Methods for chloride determination? Coulometric-amperometric titration of chloride (cotlove chloridometer technique) and ion selective electrode methods.

Measurement of sweat chloride (sweat testing)? Cystic fibrosis, the most common lethal genetic disorder of Caucasian population characterized by increased sweat chloride concentration.

Sweat testing and newborn screening… Are performed in conjunction, with a positive screening test are referred to as a quantitative sweat chloride test.

What phases are done for sweat testing? Sweat stimulation by pilocarpine electrophoresis, collection of sweat, qualitative or quantitative analysis of sweat, sodium or conductivity.

What is an abnormal infant sweat testing result? ≥60 mmol/L = indicative of CFBicarbonate is another name for: Total carbon dioxideTrue or False: Plasma or serum can be used to measure bicarb?

True

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True or False: Sample must be centrifuged in an open tube?

False, be must be unopened

True or False: Ambient air contains far more CO2 than plasma?

False

If CO2 is allowed to escape from the sample into air, ___to___ mmol/L will be lost per hour.

4 - 5

Two ways of measuring total CO2 are acidification and ____

Alkalinization

Acidification is a(n) ___ electrode based method?

Indirect

Define osmometry: a technique for measuring the concentration of solute particles that contribute to the osmotic pressure of a solution.

Define osmotic pressure: the pressure required to stop osmosis through a semipermeable membrane between a solution and pure solvent.

Define osmosis: process by which molecules of a solvent tend to pass through a semipermeable membrane from a less concentrated solution into a more concentrated one.

Name 4 colligative properties of solutions: 1. Increased osmotic pressure2. Lowered vapor pressure3. Increased boiling point4. Decreased freezing point

Colligative properties of solutions are all directly related to:

total number of solute particles per mass of solvent.

The term osmolality expresses: concentrations relative to mass of the solvent.The term osmolarity expresses: concentrations per volume of solution.Plasma and urine osmolality is useful in the assessment of:

Electrolyte and acid-base disorders

The 4 major osmotic substances in normal plasma are:

Na+ / Cl- / glucose / urea

The Henderson-Hasselbalch equation defines pH as:

The negative log of the H+ activity

The Henderson-Hasselbalch equation is widely used to calculate the ___ point of proteins.

isoelectric

Total O2 content (cdO2) is: the sum of the concentrations of hemoglobin-bound O2 (oxyhemoglobin) and of dissolved O2 (cdO2).

Oxyhemoglobin (O2Hb) is defined as: erythrocyte hemoglobin with O2 reversibly bound to Fe2+ of its heme group.

Define the following terms:pO2 =pCO2 =ctCO2 =HCO3 =cdCO2 =

pO2=partial oxygen pressure.pCO2=partial carbon dioxide pressure.ctCO2=total concentration of carbon dioxide.HCO3=bicarbonate.cdCO2=concentration of dissolved carbon dioxide.

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What specimen is used for blood gas analysis? Whole blood.What is the only clinical reason for an arterial draw?

PO2 value

PO2 is generally 60 mm Hg ___ in venous blood.

Lower

PCO2 is 2-8 mm Hg ___ in venous blood. HigherArterial and venous specimens for blood gas analysis are best collected:

anaerobically with lyophilized heparin using glass syringes

Lyophilized heparin is preferred to liquid heparin because:

liquid heparin dilutes the sample, and the effect is greatest when the syringe is not completely filled

3 effects of exposing blood gas samples to the air:

Increase in pO2, increase in pH, decrease in pCO2

The pCO2 in blood is much ___ than the pCO2 in the air.

greater

On exposure of blood to the air, the total CO2 and the pCO2 both ___

decrease

On exposure of blood to the air pO2 __ increasesIn blood gas samples, clots are ___ unacceptableIn blood gas samples, air bubbles cause (increase or decrease) in total CO2, pCO2, pH, pO2.

Decrease, decrease, increase, increase.

What are the reasons for the following changes in pCO2, pH and pO2 in a sealed specimen left at room temperature for 2 hours:

Increase in pCO2 as a result of continued metabolism, decrease in pH due to increased production of carbonic acid and lactic acid during glycolysis, decrease in pO2 because O2 is consumed during prolonged standing.

Arterialized capillary blood is an acceptable alternative to arterial blood but it has to be:

freely flowing cutaneous blood.

The first drop is discarded and the subsequent free forming drops should be taken up in a:

capillary collection tube containing lyophilized heparin

Transport and analysis of specimen should be within ___ of collection.

30

Because electrodes are not stable over long periods of time, frequent calibration of ___, ___ and ___ is required:Proper maintenance includes:

pH, PCO2, and PO2

-meticulous care.-adherence to the manufacturer's procedures.-control of the equipment.-proper collection and handling of specimens.-the frequency with which maintenance should be maintenance = volume of analysis performed.

Good quality assurance includes: -proper maintenance of the instrument.-use of control materials.-verification of electrode linearity.-checking of barometer accuracy.-accurate measurement of temperature.

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External quality assurance (proficiency testing) mandated by:

CLIA'88

A hormone is: a chemical substance produced in the body by an organ, cells of an organ, or scattered cells that has a specific regulatory effect on the activity of an organ or organs.

Hormones are produced at one site in the body and exert their action(s):

at distant sites through what is called the endocrine system.

Paracine action is: action of certain hormones that exert their effect locally on nearby cells.

Autocrine action is: action of certain hormones that exert their effects on the cells of origin.

Adrenocorticotropic hormone (ACTH), insulin, parathyroid hormone (PTH) are examples of ___ or ___ hormones

Polypeptide or Protein

This class of hormone is soluble in: Water/bloodThis class of hormone has a half-life of ___ to ___.

≤10 to 30 minutes

This class of hormone initiates response by: Binding to cell membrane receptors and exciting the second messenger system.

Cortisol and estrogen are 2 examples of _____ hormones.

Steroid

Steroid hormones are hydrophobic and water insoluble.

True

Steroid hormones circulate in plasma, reversibly bound to transport proteins with only a small fraction free or unbound and available to exert physiological action.

True

What is the half-life of steroid hormones? 30-90 minutesHow do steroid hormones enter the cell? Passive diffusionWhat are 2 examples of amino acid-related hormones?

Thyroxine and catecholamines

Amino acid-related hormones are water soluble. TrueAmino acid-related hormones interact with membrane associated receptors and use a second messenger system.

True

Amino acid-related hormones circulate in plasma bound to ______ or _______

Proteins, free

Estrogen and androgen are examples of ______ hormones.

Gonadal

What is the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes?

Homeostasis

In response to a glucose load, _____ is released from the ______.

Insulin, pancreas

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What is responsible for regulating the dispersal of glucose into cells for the metabolism necessary to produce energy?

Insulin

What are the counter regulatory hormones that regulate glucose concentration?

Glucagon, cortisol, epinephrine, growth hotmone and incretins

What are some examples of incretins? GLP-1 and GIPWhat is GLP-1? Glucagon-like peptide 1What is GIP? Gastic inhibitory pepideWhat is CaSR? Calcium-sensing receptorThe CaSR on the parathyroid gland recognizes the circulating level of ionized calcium and regulates the synthesis and secretion of ____.

PTH

What is PTH? Parathyroid hormonePTH enhances renal tubular reabsorption of ? CalciumPTH catalyzes the synthesis of renal hormone _____ to increase intestinal absorption of calcium.

Calcitrol

The metabolism of water and electrolytes is regulated by _____, _______, and ______.

Aldosterone, renin, vasopressin

Where is aldosterone produced? Adrenal glandWhere is renin produced? KidneyWhere is vasopressin produced? Posterior pituitary glandWhat is the posterior pituitary gland called? neurohypophysisVasopressin is an _______ hormone. AntidiureticWhat is the role of hormone receptors? The unique or specific action of a hormone on

its target tissue is a function of the interaction between the hormone and its receptor

What are the two types of hormone receptors? Cell surface receptorsIntercellular receptors

What is a large superfamily of membrane receptors whose intracellular effects are mediated by G proteins?

G-protein-coupled receptors (GPCR)

What are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell?

Guanine-nucleotide-binding proteins (G proteins)

What are characterized by a hormone binding domain, DNA-binding domain and an amino terminal variable domain?

Intracellular receptors

Measurement of hormones -Bioassay Techniques-Receptor-Based Assay-Immunoassay Techniques-Instrumental Techniques -Mass Spectrometry (coupled with gas and liquid chromatography) -Matrix Assisted Laser Desorption/Ionization (MALDI)

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What is a monoamine, an organic compound that has a catechol(benzene with two hydroxyl side groups) and a side-chain amine?

Catecholamine (CA)

Where is Catecholamines produced? Catecholamines are produced mainly by the chromaffin cells of the adrenal medulla and the postganglionic fibers of the sympathetic nervous system

Which Catecholamines acts as a neurotransmitter in the central nervous system, is largely produced in neuronal cell bodies in two areas of the brainstem: the substantia nigra and the ventral tegmental area?

Dopamine

Where does Catecholamines derived from? Amino acid tyrosineIncluded among catecholamines are: epinephrine (adrenaline), norepinephrine

(noradrenaline) and dopamine; all of which are produced from phenylalanine and tyrosine

Fight-or-flight response Release of the hormones epinephrine and norepinephrine

Epinephrine (adrenaline) functions as a hormone released by the

Adrenal medulla

What is a monoamine neurotransmitter, biochemically derived from tryptophan?

Serotonin or 5-hydroxytryptamine (5-HT)

Where does Serotonin primarily found? Gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans

How many percent of the human body's total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements?

Approximately 90%

When platelets bind to a clot, they release? SerotoninOnce released by the platelets, serotonin serves as a ______ and helps regulate homeostasis and blood clotting.

Vasoconstrictor

Serotonin also serves as a ______ for some type of cells, possibly giving it a roll in wound healing.

Growth factor

What is serotonin mainly metabolized into? 5-HIAA (hydroxyindoleacetic acid)5-HIAA (hydroxyindoleacetic acid) is exerted by?

The kidneys

Phenylethylamines with hydroxyl groups on positions three and four of the benzene ring and on ethylamine sidechain on position one are called.

Catecholamines

Serotonin, norepinephrine,dopamine, and epinephrine are all types of?

Catecholamines

This catecholamine is acted upon by the pineal Serotonin

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gland to produce melatonin.Tyrosine is converted to 3,4-dihydroxyphenylalanine (L-dopa) by the enzyme...

tyrosine hydroxylase

Conversion of L-dopa to ____is catalyzed by aromatic-L-amino acid decarboxylase

dopamine

Dopamine formed is further converted to _______by dopamine β-hydroxylase

norepinephrine

further conversion of norepinephrine to _______is through the presence of phenylethanolamine and N-methyltransferase in the adrenal medullary chromaffin cells

epinephrine

_____is converted to 5-hydroxytryptophan by the enzyme _______.

Tryptophan, tryptophan hydroxylase

Conversion of 5-hydroxytryptophan to ____is catalyzed by aromatic-L-amino acid decarboxylase

Serotonin

______is synthesize from ______in the pineal gland by the serotonin-N-acetyltransferase and by the hydroxyindole-O-methyltransferase

Melatonin, serotonin

Monoamines include… Epinephrine, norepinephrine, serotonin, & dopamine

How are monoamines stored Monoamines are stored in secretory granules in equilibrium with the surrounding cytoplasm

How are monoamines released Monoamines are released from secretory vesicles into the extracellular space through the process of exocytosis

The process of releasing monoamines is stimulated by?

an influx of calcium and acetylcholine

In which nervous system does the presence of monoamine oxidase (MAO) lead to the conversion of norepinephrine to 3,4-dihydroxy-phenylglycol (DHPG)? Parasympathetic or Sympathetic

Sympathetic nervous system.

DHPG is then metabolized by cathechol-O-methyltransferase (COMT) in the extraneuronal tissues to

3-methoxy-4-hydroxyphenylglycol (MHPG).

What is the primary end product of epinephrine and norepinephrine metabolism?

Vanillylmandelic acid (VMA)

Where is vanillylmandelic acid produced? LiverWhat is the enzyme required for conversion of MHPG to VMA

Alcohol dehydrogenase

What is the product of serotonin deamination? 5-hydroxyindoleacetic acid (5-HIAA)What is the major urinary excretion product of serotonin metabolism?

5-hydroxyindoleacetic acid (5-HIAA)

Which system does norepinephrine regulate? The sympathetic nervous system and overall

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state of attention and vigilanceWhich processes are influenced by dopamine? 1) Reward seeking behavior

2) Initiation and maintenance of movement3) Processing of sensory signals4) Regulation of hormonal release.

Which processes are regulated by serotonin? 1) Memory2) learning3) feeding behavior4) sleep patterns5) thermoregulation6) pain modulation7) cardiovascular function8) Regulation of pituitary hormones.

How does the sympathetic nervous system operate?

It operates below the level of consciousness in controlling the physiological function of many organs and tissues of the body.

What does the sympathetic nervous system regulate?

It regulates cardiovascular function in response to postural, exertional, thermal and mental stress

What happens when the sympathetic nervous system is activated?

Activation increases heart rate, constricts peripheral blood vessels, dilates skeletal arterioles, and elevates blood pressure.

Which system is characterized by the presence of numerous catecholamine storage granules?

Adrenal Medullary system

These turn brown when exposed to what? 1) Potassium bichromate solution2) Ammoniacal silver nitrate3) Osmium tetroxide

What does this color change indicate? Oxidation and polymerization of epinephrine and norepinephrine.

What are these cells/granules called? Chromaffin cells/chromaffin granulesAdrenal Medullary system secretes what? EpinephrineWhat processes are stimulated by the release of epinephrine?

1) Lipolysis2) Ketogenesis3) Thermogenesis4) Glycolysis

How does epinephrine raise glucose concentrations?

Stimulates glycogenesis and gluconeogenesis

What other function does epinephrine affect? Pulmonary function causing the dilation of airways

What is dopamine? A neurotransmitter produced in sympathetic nerves and the adrenal medulla

In the kidneys, what does dopamine regulate? Sodium excretionWhere else are dopamine metabolites produced? In the GI tractWhat is the major urinary dopamine metabolite? Homovanillic acid (HVA)What is the Enteric nervous system (ENS)? An independent and integrated system of

neurons and supporting cells located in the

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gastrointestinal tract, gallbladder and pancreasThe ENS is composed of what two networks? 1) Myenteric plexus

2) Submucous plexus.How is the ENS connected to the CNS? It is connected by intrinsic sympathetic and

parasympathetic motor neurons and by spinal and vagal sensory neurons.

What are examples neuroendocrine tumors that produce catecholamine?

1) Pheochromocytomas2) Paragangliomas3) Neuroblastomas

What are serotonin producing tumors? Carcinoid tumorsPheochromocytomas occur within what gland? Adrenal glandParagangliomas occur outside what gland that is commonly referred to as extra adrenal pheochomocytoma’s?

Adrenal gland

Hypertension, headaches, palpitations, diaphoresis, pallor, nausea, attacks of anxiety and generalized weakness are all symptoms of what referring to the adrenal gland?

Pheochromocytoma and Paragangliomas

Patients with higher risk for pheochromocytoma include those with a_____ predisposition to the tumor and finding of an ______ ______ during a routine abdominal imagine procedure.

hereditary

adrenal mass

In terms of pheochromocytoma and paraganglioma, this type of diagnosis are based on evidence of excess production of catecholamines by measurements id metanephrines in urine or plasma.

Biochemical Diagnosis

Presence of most pheochromocytomas are __% benign of adrenal tumors and ___% of extra-adrenal tumors are malignant.

15%

35%This is a neoplasm that id derived from primordial neural crest cell of the sympathetic nervous system.

Nueroblastoma

Neuroblastoma causes sporadic ______cancer, common malignancies in the first year of life

pediatric

Mutations of neuroblastomas activate in the ______ kinase domaine of the anapestic lymphoma kinase oncogene account for most cases of heredity

tyrosine

Neuroblastomas have Variable biological behavior but most are ____?

aggressive

____ and ____ are most widely used for diagnosis of neuroblastoma.

HVA and VMA

Diagnosis of neuroblastoma is diagnosed catecholamine

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mainly on measurements of_______ metabolites.Gastroenteropancreatic neuroendocrine and carcinoid tumors are tumors from the ____________ cells.

enterochromaffin

Gastroenteropancreatic neuroendocrine and carcinoid tumors are most common in the _____ or lungs, _____ or jejunum, _____ and rectum.

bronchusileumrectum

Gastroenteropancreatic neuroendocrine and carcinoid tumors usually appear in ____ (pediatrics, older adults)

older adults

These tumors are characterized by large quantities of serotonin.

Carcinoid tumors

In carcinoid tumors, ______ is converted to serotonin and is stored in circulatory granules and in platelets.

5-HTP

What type of test result elevations are seen in wide ranges of serotonin rich foods or medication?

False-positive

What type of false result can be caused by alcohol and other drugs?

False-positive

Neuroendocrine tumors derive from enterochromaffin cells of the respiratory tracts and _______. Bowel obstruction and abdominal pain are presented.

gastrointestinal

Biochemical diagnosis of carcinoids depends mainly on measurements serotonin, serotonin metabolites (____), and the serotonin precursor (____) in urine, plasma, whole blood and platelets.

(5-HIAA)

(5-HTP)

What type of false result are a common problem resulting from dietary influences.

False-positive

For catecholamines and their metabolites, serotonin and its metabolites and urinary or plasma metanephrines are determined by laboratory what type of methods?

Analytical methods

What kind of anticoagulant should be used for whole blood measurement of serotonin?

EDTA, gently mixed and placed on ice and transferred to a storage tube

Aliquots of blood is removed to count what? PlateletsHow are blood serotonin samples stored? Frozen at -20C within 2 hours after collectionPlatelet rich plasma is prepared from whole blood using what speed on the centrifuge?

Low-speed

Why should platelet rich plasma be prepared within 1 hour after collection and be placed on ice?

To prevent lowering of serotonin concentration

Plasma and platelets should be stored at what -20C

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temperated?Plasma and platelets are analyzed within how many weeks after collection?

1-2 weeks

How are 24-hour urine samples for serotonin and 5-HIAA collected?

In 2 L brown polypropylene bottles each containing 250 mg of sodium metabisulfite and EDTA as preservatives

What pH lever are urine samples acidified to? pH 4What is used to acidify urine samples before freezing?

Acetic acid

True or False?Urine samples don’t have to be refrigerated during collection.

False. Urine specimens should be refrigerated during collection.

How do drugs affect monoamine systems? By Inhibiting monoamine reuptakeGive an example of a drug from the above question.

Tricyclic anti-depressants

Drugs that affect monoamine systems are the major reason of false-positive results for the measurements of what?

Norepinephrine and normetanephrine

What kind of dietary food sources should you avoid 3-4 days before and during urine collection?

Dietary sources of 5-hydroxyindole such as walnuts, avocado, bananas, eggplants, pineapples, plums, and tomatoes.

True or False?Metanephrines and methoxytyramine are present in plasma and urine

True

How is urinary and plasma fractionated metanephrines measured?

By LC-MS/MS

What kind of preparation step is taken for measurement of urinary and plasma fractionated metanephrines?

An ion exchange chromatography

What detection methods are used for plasma catecholamines?

LC-EC

What is LC-EC? Liquid chromatography with electrochemical detection

What does VMA stand for? Vanillylmandelic AcidWhat does HVA stand for? Homovanillic AcidWhat is the major end product of epinephrine and norepinephrine metabolism?

VMA

HVA is the major end product of the metabolism of what?

Dopamine

Urinary VMA and HVA are used for the diagnosis of what?

Neuroblastoma

What methods are used to detect VMA and HVA?

Gas or liquid chromatography and LC-MS/MS

What does 5-HIAA stand for? 5-hydroxyindoleacetic acidSerotonin and 5-HIAA are measured in what? Whole blood, platelet rich plasma, or patelet

pellets

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What can serotonin and 5-HIAA identify? Tumors deficient in aromatic amino acid decarboxylase

What is used to measure serotonin and 5-HIAA?

Liquid chromatography with fluorometric or electrochemical detection, HPLC

Fill in the blank:Water soluble vitamins are retained (less/more) and excreted (less/more) in the urine

Less; more

Water soluble vitamins can function as what? Give 2 examples

Coenzymes; B-complex group vitamins and Vitamin C

True or False?Fat soluble vitamins are soluble in organic solvents

True

Fat soluble vitamins are absorbed, transported, and stored for (shorter/longer) periods of time

Longer

Give 4 examples of fat soluble vitamins Vitamins A, D, E, KWhat are sources of vitamin A? Eggs, meat, and dairyWhat are sources of beta-carotene? Green leafy vegetables, and vibrant colored

fruits and vegetables.Retinol is principally stored as what? of retinyl esters (palmitate) and includes

dietary carotenoids such as α-carotene, β-carotene, and β-cryptoxanthin

Where is retinol obtained? from liver, other organ meats, fish oils, full cream milk, butter and fortified margarines.

Provitamin A carotenoids are obtained from what?

yellow or orange pigment fruits and green leafy vegetables

What is a major function of vitamin A? Good visionWhat are other functions? include its role in reproduction, growth,

embryonic development and immune function.

What else does it provides protection against? cancer by blocking tumor promotion, inhibiting proliferation, inducing apoptosis and inducing differentiation

Deficiency of Vitamin A causes? Night blindness (nyctalopia), Xerophthalmia, Keratomalacia, Dryness /roughness of the skin, papular eruptions and follicular hyperkeratosis

What is the laboratory assessment? Measurement of RBP (retinol binding protein) and transthyretin (thyroxine-binding prealbumin) by nephelometry

What is the chemical assessment? Carr-Price and Neeld-Pearson methodsWhat are sources of vitamin D? Cheese, margarine, butter, fortified milk,

healthy cereal, fatty fishWhen does the body make vitamin D? When exposed to sunlightWhat is vitamin D’s main circulating form? 25 hydroxyvitamin D [25(OH)D],What is its biologically more active form? 1, 25 dihydroxyvitamin D [1,25 (OH)2D],What is vitamin D3? the parent compound of the naturally

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occurring family and is produced in the skin from 7 dehydrocholesterol on exposure to the UV B portion of sunlight

What is vitamin D2? the parent compound of the other vitamin D family, manufactured by irradiation of ergosterol produced by yeast

What are ways Vitamin D may be acquired? by exposure of skin to sunlight or ingestion of foods containing vitamin D, primarily fish liver oils, fatty fish, egg yolks and liver

Vitamin D2 and vitamin D3 are metabolized to what?

25(OH)D2 and 25(OH)D3, respectively, in the liver by vitamin D-25-hydroxylase.

Metabolites are further metabolized by? in the kidneys and also in the placenta of pregnant women by 25(OH)-D-1α-hydroxylase.

What is the biologically most active form of vitamin D

? is 1,25 (OH)2D

What is the main circulating form of vitamin D? 25(OH)D.How vitamin D plays in control of calcium levels?

Hypercalcemia reduces 25(OH)-D-1α-hydroxylase activity and production of 1,25(OH)D.Hypocalcemia increases the synthesis of 1,25 (OH)2D by increasing 25(OH)-D-1α-hydroxylase activity

How vitamin D plays in control of phosphate? Hyperphosphatemia reduces 25(OH)-D-1α-hydroxylase activity and production of 1,25(OH)D.Hypophosphatemia increases the synthesis of 1,25 (OH)2D by increasing 25(OH)-D-1α-hydroxylase activity

Where are calcium and phosphate concentrations in serum that are maintained by the actions of 1,25(OH)2D?

intestine, bone, kidney, and parathyroid.

How does 1,25 (OH)2D act? 1,25 (OH)2D reduces 25(OH)-D-1α-hydroxylase activity and production of 1,25(OH)D.It also induces 25(OH)D-24-hydroxylase, an enzyme producing 24,25-dihydroxyvitamin D (24,25 [OH]2D), which is the most prevalent dihydroxylated vitamin D form in serum. The activity of this enzyme may reduce the formation of biologically active 1,25(OH)2D.

How does1,25(OH)2D act on intestine ? 1,25(OH)2D stimulates calcium absorptionHow does 1,25(OH)2D act on bones? 1,25(OH)2D increases bone resorption and

increases the circulating concentration of bone

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alkaline phosphatase (BALP), and the non-collagenous bone protein osteocalcin (OC)

How does 1,25(OH)2D act on kidney? 1,25(OH)2D inhibits its own synthesis and stimulates its metabolism

How does 1,25(OH)2D act on parathyroid? 1,25(OH)2D acts directly to inhibit the synthesis and secretion of PTH

What does measurement of 25(OH)D use? Useful in evaluating hypocalcemia, vitamin D status, and bone disease

What does measurement of 1,25(OH)2D use? Useful in detecting in adequate or excessive hormone production in the evaluation of hypercalcemia, hypercalciuria, hypocalcemia and bone and mineral disorders

What are measurements of vitamin D metabolites?

1. Competitive Protein Binding Assay (CPBA)2. Immunoassay3. UV absorbance after separation by High Performance Liquid Chromatography (HPLC)4. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

What is the nutrition term for the group of vitamin E?

These are tocopherols and tocotriennols.

How are tocopherols and tocotriennols found? principal sources of dietary vitamin E are oils and fats, particularly with germ oil and sunflower oil, grains and nuts

What is the major form of vitamin D in many plant seeds?

γ-tocopherol

Where isVitamin E absorbed in the human body?

Vitamin E is absorbed from the small intestines in the presence of bile

How vitamin E is secreted? It is secreted in chylomicron particles which are then transported to the peripheral tissue, mainly adipose tissue, with the aid of lipoprotein lipase (LPL)The liver takes up the chylomicrons where the α-tocopherol is incorporated into VLDL

How isVitamin E excreted? Vitamin E is excreted via the bile and in the urine as tocopheronic acid and its β-glucuronide conjugate

What is Vitamin E necessary for? Vitamin E is necessary for neurological and reproductive functions, protection of red cells from hemolysis, prevention of retinopathy in premature infants and inhibition of free-radical chain reactions of lipid peroxidation.

What is Vitamin E? Vitamin E is an antioxidant that acts as a scavenger for molecular oxygen and free radicals and has a role in cellular respiration

What are the risks of deficiency of vitamin E? Deficiency of vitamin E are generally

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observed in premature and low birth weight infants

Excess of vitamin E? It is primarily due to dietary supplementation and may cause deficiency of fat soluble vitamins D and K by competitive absorption.

What is the method of choice to quantify tocopherols in serum?

High performance liquid chromatography (HPLC)

What is Phylloquinones (Vitamin K1 type)? Synthesize in plantsWhat is Menaquinones (Vitamin K2 type) Bacterial originHow does vitamin K get destroyed? It Got destroyed by alkaline solution and

reducing agents and are sensitive to ultraviolet light

What are the Dietary sources of phylloquinones?

Dietary sources of phylloquinones are green vegetables, margarines and plant oils.

What are the Dietary sources of menaquinones? Dietary sources of menaquinones our cheese, eggs and milk products

Where is vitamin K absorbed from? Vitamin K is absorbed from the small intestines in the presence of bile, bound to chylomicrons.

Where do the traces of urinary metabolites of vitamins of K-1 and K2 appear in?

Only traces of urinary metabolites of vitamins K-1 and K2 appear in urine

What does vitamin K promote? What is vitamin K required for?

Vitamin K promotes clotting of the blood and is required for the conversion of several clotting factors and prothrombin.

What is the risk factor of vitamin K? Risk of vitamin K deficiency is increased in fat malabsorption states such as bile duct obstruction, cystic fibrosis, chronic pancreatitis and liver disease. Risk is also increased by the use of drugs that interfere with vitamin K metabolism such as coumarin anticoagulants (warfarin) and some antibiotics (cephalosporin).

What are the labrotory assessments for vitamin K?

Laboratory Assessment includes:Prothrombin time (PT) determinationdirect measurement of plasma phylloquinone by High Performance Liquid Chromatography (HPLC)

What do the Dietary sources of vitamin B1 include?

Dietary sources include unrefined cereal grains, breakfast cereals and enriched flour.

Where does absorption of Vitamin B1 Occur? Absorption occurs primarily in the proximal small intestines.

Where is vitamin B1 Stored? About half of the body stores are found in skeletal muscles, with much of the remainder in the heart, liver, kidneys and nervous tissue including the brain which contains most of the triphosphate.

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What is the function of Thiamine in Vitamin B1?

Thiamine functions to form the coenzyme thiamine pyrophosphate (TPP), which is required for the essential decarboxylation reactions catalyzed by the pyruvate and 2-oxoglutarate complexes.

What are the two general reactions of Thiamine in Vitamin B1?

The two general reactions are:1. Oxidative decarboxylation of 2-oxo acids catalyzed by dehydrogenase complexes2. Formation of 2-ketols (ketoses) as catalyzed by transketolase

What is thiamine necessary for? Thiamine is necessary for the metabolism of carbohydrates, fats and alcohol.

What does the deficiency results to? What are the symptoms?

Deficiency results to beriberi, involving the nervous and cardiovascular systems. Symptoms include mental confusion, anorexia, muscular weakness, ataxia, peripheral paralysis, opthalmoplegia, edema (wet beriberi), muscle wasting (dry beriberi), tachycardia and an enlarged heart.

What is the deficiency in thiamine due to? Deficiency of thiamine is due to:1. Inadequate intake caused by diets largely dependent on milled, non-enriched grains2. Ingestion of raw fish containing microbial thiaminases3. Chronic alcoholism4. Those receiving total parenteral nutrition (TPN) without adequate thiamine supplementation5. Elderly patients taking diuretics6. Patients undergoing long-term renal dialysis

What is the labrotory assessment for vitamin B1?

Laboratory Assessment:Measurement of transketolase

• Brin procedureDirect measurement of circulating thiamine in plasma, erythrocytes or whole blood using High Performance Liquid Chromatography (HPLC)

What is an essential component of Riboflavin? (Vitamin B2)

Is an essential component of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), coenzymes that are involved in many redox reactions.

What do the dietary sources include in Vitamin B2

Dietary sources include liver, kidney, heart and milk.

What is Vitamin B2 absorbed in? It is primarily absorbed in the proximal small intestines in the presence of bile, tightly

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bound to immunoglobulins.Does vitamin B2 trace in urine? Because little storage of riboflavin occurs,

urinary excretion reflects dietary intake.What are signs of riboflavin deficiency? Deficiency of riboflavin is characterized by

sore throat, hyperemia, edema of the pharyngeal and oral mucous membranes, cheilosis, angular stomatitis, glossitis (magenta tongue), seborrheic dermatitis and normochromic, normocytic anemia.

What are the 4 laboratory assessment for riboflavin?

Laboratory Assessment:1. Determination of urine riboflavin excretion2. A functional assay using the activation coefficient of stimulation of the enzyme glutathione reductase by FAD3. Direct measurement of riboflavin or its metabolites in plasma or erythrocytes4. HPLC combined with fluorometric detection is the method of choice

What are the 3 natural forms of vitamin B6? Three natural forms of vitamin B6:- pyridoxine [pyridoxol] (PM)- pyridoxamine (PM)- pyridoxal (PL)

All three are converted to pyridoxal phosphate, which is required for synthesis, catabolism and inter-conversion of amino acids

What are the dietary sources of Vitamin B6? Dietary sources include meat, poultry and fish, used certain seeds, bran, bananas and fortified ready-to-eat cereals.

What is the major coenzyme of vitamin B6? The major coenzyme (PLP pyridoxal-5’-phosphate) used by the PLP dependent enzymes that are involved in amino acid metabolism.

What is the main catabolite excreted in urine from vitamin B6?

The main catabolite excreted in urine is 4-pyridoxic acid (4-PA)

What are the steps for laboratory assessment for vitamin B6?

Laboratory Assessments :1.Measurement of PLP (pyridoxal-5’-phosphate) in plasma or red cells2. Measurement of its metabolite, 4-pyridoxic acid (4-PA) in urine or plasma3. Measurement of the activity and activation coefficient of red cell aminotransferases (aspartate and alanine)4. Tryptophan load metabolite excretion tests5. High Performance Liquid Chromatography (HPLC) with fluorescence detection

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What are some characteristics of vitamin B12? A water-soluble hematopoetic vitamin that is required for the maturation of erythrocytes.

- Cyanocobalamin is a stable compound that forms dark red, needlelike crystals.

- It is the reference compound used to calibrate serum cobalamin methods

- The predominant physiological form in serum is methylcobalamin, whereas that in cytosols is adenosylcobalamin.

Cyanocobalamin is gradually destroyed on exposure to light

What are the dietary sources of Vitamin B12? Dietary sources are meat and meat products, dairy products, fish and shellfish and fortified ready-to-eat cereals.

Where is vitamin B12 secreted? It is continually secreted in the bile, but most is reabsorb and available for metabolic functions.

Where will excess vitamin B12 be excreted? If circulating vitamin B12 concentrations exceed the binding capacity of the blood, the excess will be excreted in the urine.

Where is the greatest loss of vitamin B12 occurring?

In most circumstances, the greatest looses of vitamin B12 occur through the feces.

What is vitamin B12 deficiency associated with?

Deficiency of vitamin B12 is associated with megaloblastic anemia and neuropathy.The most common cause of vitamin B12 deficiency is pernicious anemia.

What are the hematological effects of vitamin B12 deficiency?

The hematological effects of vitamin B12 deficiency are indistinguishable from those of folate deficiency. The classic morphological changes in the blood are hypersegmentation of neutrophils, macrocytosis, anemia, leukopenia and thrombocytopenia with megaloblastic changes in bone morrow accompanying peripheral blood changes.

What is the laboratory assessment of vitamin B12 ?

Laboratory Assessment:Indirect tests include:

1. Assays for urinary and serum concentrations of methylmalonic acid2. Assays for plasma homocysteine3. The deoxyuridine suppression test4. Vitamin B12 absorption tests

Direct tests include:1. Microbiological Competitive Protein Binding (CPB)2. Immunoassay

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What are the characteristics of Vitamin C? - Serves as a reducing agent in several important hydroxylation reactions in the body

- One of the most effective water-soluble antioxidants in biological fluids

- Dietary sources include citrus fruits, berries, melons, tomatoes, green peppers, broccoli,

- Brussels sprouts and leafy green vegetables.

The gastrointestinal absorption is regulated by a combination of sodium dependent active transport at low concentrations, and simple diffusion at high concentrations.

What are Laboratory assessment for VITAMIN C- ASCORBIC ACID?

1. Direct measurement of plasma, urine, or tissue concentrations of ascorbic acid or total vitamin C.2. Measurement using ascorbate oxidase enzyme3. High Performance Liquid Chromatography (HPLC) methods

What are good sources of biotin? Liver, kidney, pancreas, eggs, yeast and milk.What characteristic Biotin has? Biotin in the diet is largely protein bound and

digested by gastrointestinal enzymes.What is the principal biochemical function of Biotin or Vitamin H?

To serve as a cofactor for carboxylation reactions.

In what disorders Biotin deficiency may be seen?

TPN (total parenteral nutrition) without biotin supplementation and in patients with a genetic deficiency of biotinidase.

What test organism is used in microbiological assay for Vitamin H?

Lactobacillus plantarum

What is considered to be a better indicator of biotin status?

Urinary excretion of biotin and 3-hydroxyisovaleric acid

What is the function of Folate and folic acid? functions as coenzymes in the processing of one carbon units

Folate and Folic acid are derived from ……….. and the principal form is ……………...

pteroic acid, 5-methyltetrahydrofolate

What are food source for Folic acid? Liver, spinach, and other dark green leafy vegetables, legumes such as kidney and Lima beans and orange juice.

What causes deficiency of folate? Absence of intestinal microorganisms, poor intestinal absorption, insufficient dietary intake (chronic alcoholism), and excessive demands is in pregnancy, liver disease and malignancies, administration of anti-folate

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drugs and anticonvulsant therapy leading to increase folate requirements.

What is the major clinical manifestation of folate deficiency?

Megaloblastic anemia (characterized by large, abnormally nucleated erythrocytes in the bone morrow)

What are laboratory assessment for folic acid? Measurement of folate concentration using C room erythrocyte or whole blood the specimenCPB (Competitive Protein Binding) assays

What the term Niacin refer to? 1. Nicotinic acid (pyridine-3-carboxylic acid)2. it's amide niacinamide (nicotinamide)3. Derivatives that show the same biological activity as nicotinamide

What are sources of Niacin? Yeast, lean meats, liver, poultry, milk, canned salmon and several leafy green vegetables, corn and wheat.

What is the main circulating form of Niacin in the plasma after absorption or release from hydrolyzed liver NAD?

Nicotinamide

In what form Excess niacin is excreted in liver? N-methylnicotinamide (NMN)Name the Vitamin that is essential for the coenzymes NAD and NADP?

Niacin

What is the function of Nicotinic acid, when used as a pharmaceutical agent?

It has important anti-atherogenic properties. It effectively lowers triglycerides, raises HDL cholesterol, and shifts LDL particles to a less atherogenic phenotype.

What disease is result of Niacin deficiency? Pellagra is the classic deficiency disease associated with niacin and tryptophan

What is characterization of pellagra? Chronic wasting disease presentation associated with dermatitis, dementia and diarrhea.

What are laboratory assessments for NIACIN and NIACINAMIDE?

Urinary measurement of N'-methylnicotinamide and N'-methyl-2-pyridone-5-carboxamide using HPLC.

What Vitamin is a component of Coenzyme A? Pantothenic acidWhat is the most common commercial synthetic form of pantothenic acid?

Calcium salt

What are the source of Pantothenic acid? It is widely distributed in foods, mostly within Co-A containing compounds like animal sources, legumes, whole-grain cereals, egg yolk, kidney, liver and yeast.

What is the function of Pantothenic acid? It is required for the metabolism of fat, protein, and carbohydrate via the citric acid cycle.

What are Pantothenic Acids two major metabolic roles?

It is part of coenzyme A and is a prosthetic group of the acyl-carrier protein, ACP.

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What methods are used in determining the whole blood or urine concentrations of Pantothenic Acid?

By microbiological assay, radio immunoassay, gas chromatography, gas chromatography mass spectrometry and a stable isotope dilution assay.

What are trace elements? Inorganic molecules found in human and animal tissues in milligrams per kilogram amounts or less.

What are referred to as trace and ultratrace elements?

Those present in body fluids (µg/dL) and in tissues (mg/kg) are referred to as trace elements, and those of found at ng/dLor µg/kg as “ultratrace elements.”

What type of specimens are tested for trace elemeants?

Specimens commonly submitted include whole blood, plasma, serum, or anybody fluid or tissue.

What types of contamination should be avoided?

Contamination from environmental pollution, cosmetics, shampoos must always be avoided.

Is it proper procedure to remove white cells and platelets from blood before testing for trace elements?

No, separation of white cells and platelets in whole blood before trace element analysis is subject to serious problems of contamination.

Which variables may affect trace element determination?

Variables that can affect trace element determination include age, sex, ethnic origin, time of sampling in relation to food intake, time of day, history of medication and tobacco usage.

Is knowledge of any acute phase reactions required before testing for trace elements?

Yes, knowledge of the extent of any acute phase reaction is required.

Is there a possibility of contamination wich containers made of rubber, cork, or colored plastics?

Yes, avoid contamination with sample containers made up of rubber, cork and colored plastics.

What type of tube should be used when testing trace elements in blood plasma?

For blood plasma, plastic tubes with lithium heparin as an anticoagulant are suitable for most analyses.

What type of tube should be used when testing trace elements in blood serum?

For blood serum, plain glass containers have been used.

What type of tube should be used when testing ultratrace metals (Mn,Cr)?

For the ultratrace metals (Mn, Cr), special arrangements have to be made to collect blood via plastic cannulae or siliconized steel needles, and then the sample is placed into acid washed containers.

How are containers cleaned? It is a good practice to run dilute acid blanks through all containers and collection systems to ensure that all batches remain as free from contamination as possible.

What type of tube should be used when testing trace elements in urine?

For 24 urine collection, polyethylene bottles with glacial acetic acid should be used as a

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preservative.What methodologies are used to test for trace elements?

1. Spectrophotometry2. Atomic Absorption Spectrophotometry (AAS)3. Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES)4. Inductively Coupled Plasma Mass Spectrometry (ICP-MS)5. Accelerator Mass Spectrometry (AMS)6. X-ray based techniques

What are speciation methods? Involve techniques to separate the chemical complexes of individual elements present in any particular medium. They are regarded as crucial for an understanding of the absorption, utilization, function of elements and problems of excess and potential toxicity.

What occurs naturally in various crystal materials?

Chromium

How is Chromium used of and disposed? It is a transitional element with many industrial uses and is discharged into the environment as industrial waste.

What are some good sources of chromium? Good sources of chromium include processed meats, whole-grain products, green beans, broccoli and some spices

What does Chromium do after ingestion? After absorption, chromium binds to plasma transferrin with an affinity similar to that of iron.

What physiological effect does Chromium have?

It functions to enhance the response of insulin receptors and potentiates kinase activity to normalize glucose and insulin levels.

What does a deficiency in Chromium lead to? Poor chromium nutritional status plays a role in impaired glucose tolerance, diabetes and cardiovascular disease.

Does Hexavalent Chromium have any toxic effects?

Hexavalent chromium is a recognized carcinogen, and industrial exposure to fumes and dusts containing this metal is associated with increased incidence of lung cancer, dermatitis and skin ulcers.

What type of specimen should be used when testing directly for chromium?

Blood plasma or urine should be used.

What vitamin is cobalt an essential integral part of?

Vitamin B12

What can hip prostheses and increased exposure to cobalt lead to?

High mean urinary cobalt concentrations

What are some dietary sources of copper? Organ meats, shellfish, nuts, whole grain cereals, and cocoa containing products

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How is absorbed copper transported to the liver?

Bound to albumin in portal blood

What happens to absorbed copper in the liver? It is incorporated by hepatocytes into cuproenzymes and then exported in peripheral blood mainly as ceruloplasmin to tissue and organs.

What is the function of copper? It functions for energy production, connective tissue formation, iron metabolism, norepinephrine and serotonin metabolism, synthesis of melanin, antioxidant functions, and regulation of gene expression and intercellular copper handling.

What does DMO stand for? Dopamine mono-oxygenaseWhat does DMO require as a cofactor for the conversion of dopamine to norepinephrine?

Copper

What is tyrosinase? A copper containing enzyme that is present in melanocytes and catalyzes the synthesis of melanin.

What diseases is copper deficiency associated with in infants?

Menkes disease, Wilson disease, malabsorption syndromes, cardiovascular disease, anemia, and neuropathy

How is laboratory assessment of copper toxicity done?

By determination of plasma copper and ceruloplasmin levels

What element is the most widely used of the pharmacologically beneficial trace elements?

Fluoride

Where are fluoride ions absorbed? The stomach and the small intestinesHow is excess fluoride excreted? In the urineHow does toxicity occur in children? By the mottling of enamel in the erupting

teeth of children, possibly caused by ingestion of fluoride containing toothpaste.

What sort of exposure to fluoride has resulted in sever bone abnormalities in adults?

Occupational exposure to inhaled fluoride dust among cryolite workers during aluminum refining

How is fluoride level determined in drinking water and urine?

Direct determination using fluoride specific electrode is performed.

What is manganese bound to when present in biological systems?

Protein in the 2+ or 3+ valence state

What functions does manganese serve in the body?

Formation of connective and bony tissue, growth and reproductive functions, and carbohydrate and lipid metabolism.

What are some dietary sources of copper? include whole-grain foods, nuts, leafy vegetables, soy products and tea

What sort of enzyme activator does manganese act as?

Non-specific

What can deficiency in manganese result in? Impaired growth and reproductive function, skeletal abnormalities, impaired glucose

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tolerance and impaired cholesterol synthesis.How is manganese assessed in the laboratory? By measurement of nonhemolyzed whole

blood manganese using plastic cannulae for phlebotomy.

What do molybdenum enzymes facilitate? Important carbon, nitrogen, and sulfur cycles.What are some dietary sources of molybdenum? Peas, lentils and beans, grains and nuts.What is the essential need for molybdenum based on?

Its incorporation into metalloenzymes

How is molybdenum level assessed in the laboratory?

By measuring urate or sulfite in the urine as a means of confirming molybdenum cofactor disorders or possible molybdenum deficiency.

What element is a constituent of the enzyme glutathione peroxidase?

glutathione peroxidase

What is glutathione peroxidase believed to be closely associated with?

Vitamin E and its function

What do the most important biologically active compounds contain?

Selenocysteine

What is selenocysteine Amino acid in which selenium is substituted for sulfur in cysteine.

What are some dietary sources of selenium? Wheat and other cereal productsWhat is seleniums major route of excretion? Urinary outputWhat does urinary output of selenium reflect? Recent dietary intake of seleniumWhat are some selenium dependent diseases associated with selenium deficiency?

Keshan disease, and Kashin-Beck disease, and also associated with thyroid function, immune function, reproductive disorders, mood disorders, inflammatory conditions, cancer chemoprevention and viral virulence.

How is selenium measured? Carbon furnace atomic absorption spectroscopy (CFAAS) is widely used to measure plasma and/or serum selenium.

What is the major selenium containing plasma protein?

selenoprotein P

How is selenoprotein P determined? By immunological methodsHow can long-term dietary selenium intake be measured?

Hair and nail selenium analysis

Next to iron, what is the most abundant trace element in the body?

Zinc

What is it usually bound to in zinc rich foods like red meat and fish?

Proteins

What is impaired in wound healing for people with zinc deficiency?

Wound Healing

What is the function of zinc in sperm? Maintain vitality and sperm motilityWhich factors help absorption of zinc in breast milk? Picolinate and citrateWhat are the clinical effects of ingestion of a zinc contaminated diet?

Abdominal pain, diarrhea, nausea, vomiting.

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Why are plasma zinc determination preferred over zinc serum samples?

Because of possible zinc contamination fromerythrocytes platelets and leukocytes duringclotting and centrifugation.

What are good sources of boron? Fruits, leafy vegetables, nuts and legumes.How is boron absorbed and secreted? It is sufficiently absorbed as boric acid and is

efficiently excreted in the urine.What is inductively coupled plasma- atomic emission spectrophotometry (ICP-AES) and an ICP time-of-flight mass spectrometer (TOF-MS) developed for?

Investigation of boron neutron capture in cancer therapy.

What is silicon primarily used for in the body? Structural Identity.How is the laboratory assessment for silicon done?

By determination of healthy fasting plasma concentration of silicon.

How is vanadium found in neutral solutions? Metavanadate (V3)How is vanadium helpful in treating diabetes? By reducing the requirement for insulin by

activating the cellular response without the presence of insulin.

How is plasma and urine concentrations are usually measured?

GF-AAS or ICP-AES

What is hemoglobin and what is it responsible for?

Hemoglobin is the oxygen-carrying pigment of the erythrocytes. It is for transportation of O2 from lungs to the body tissues, as well as CO2 from peripheral tissues to the lungs.

Where is hemoglobin formed? Hemoglobin is formed by the developing erythrocyte in the bone marrow.

What composes hemoglobin? composed of two types of globins organized into four subunits

How does the heme bind with the globin portion of hemoglobin?

The heme chelates with the globin portion.

How is hemoglobin classified? Hemoglobins are classified into different types, depending on the combination of the two sets of globin units

What are the most common types of globin units in adult humans?

α-globins and β-globins

What is a prosthetic group? A prosthetic group is any tightly-bound non-protein entity,that is essential for the structural and functional integrity of the protein.

What is the prosthetic group of hemoglobin? The heme group.What composes the heme group? Porphyrin ring, which is formed by the

combination of four heterocyclic rings called pyrroles with an Fe2+ ion in the center of the ring bound to the nitrogen of the pyrroles.

What is the function of the function of the iron ion in hemoglobin?

It is this central iron which provides the reversible binding to oxygen and carbon dioxide molecules

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What is Hemoglobin? • Is the oxygen-carrying pigment of the erythrocytes that is formed by the developing erythrocyte in the bone marrow.

• It is mainly responsible for the transportation of oxygen from lungs to the body tissues, as well as carbon dioxide from peripheral tissues to the lungs.

Each hemoglobin molecule is composed of two types of globins organized into four subunits

What is oxyhemoglobin or carbaminohemoglobin?

The heme is bound to an oxygen molecule or carbon dioxide molecule.

What is deoxyhemoglobin? When the heme groups of hemoglobin molecule are not bound by any molecule.

What is oxyhemoglobin? Is the bright red color of blood?What is carboxyhemoglobin? When hemoglobin binds with carbon

monoxide, compromising the oxygen-carrying ability of Hb.

What is methemoglobin? Is the formed as a result of a change in oxidation state of the iron atom in heme from the normal ferrous state (2+) to ferric (3+) state, resulting in decreased oxygen-carrying ability.

What is the cause of methemoglobinemia? Is caused by the presence of nitrate in well water.

What is Sulfhemoglobin? Is commonly resulting from exposure to certain drugs, is formed when one or more oxygen atoms in the porphyrin rings of heme is replace by sulfur. Removal of the source of the chemical leads to restoration of normal Hb.

What is the adduct Hbs? Are formed by the attachment of molecule to the globin chins most commonly at the N-terminal amino acid, but may also occur anywhere along the globin chain.

Where do you see carbamylated Hb? In patients with end-stage renal disease, is formed by the attachment of urea.

How is glycated, glycosylated Hb if form? Is form by the attachment of glucose to the N-terminus of the Beta globin chain, It (HbA1c) is clinically important in diagnosis and monitoring of glycemic control in patients with diabetes mellitus

What is fetal Hb (HbF) Is the main oxygen transport protein in the human fetus during the last seven months of

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development in the uterus and persists in the newborn until roughly 6 months old.

What is the Function of HbF? Fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream.

1.What are the disease or disorders that related to Hemoglobin?

Thalassemia’s and Hemoglobinopathies

What is Thalassemia’s? Insufficient globin chain production.What is hemoglobinopathies? Are structural hemoglobin variants arising

from mutations in the globin genes and resulting in disruptions in the normal amino acid sequence in one or more of the globin chains of hemoglobin.

What are the etiology of Thalassemias? Are identified according to the globin chains in which there is a production deficiency:α-thalassemia arise from defective α-globin chain productionβ-thalassemia arise from defective β-globin chain productionδβ-thalassemia arise from deficiencies in production of both δ- and β-globin chains.

What are the etiology of Thalassemias? Are also classified by the extent of reduction in globin chain production and resultant anemia:Single gene deletion = Silent α-thalassemia ( ααTwo gene deletion = α-thalassemia trait or α-thalassemia minor (αα/- or α-/α-)Three gene deletion resulting in HbH diseaseFour gene deletion commonly called Hb Bart’s hydrops fetalis

What are the classifications of B-Thalassemia? β°-Thalassemia (β-Thalassemia Major) Sometimes called Cooley’s anemiaΒ+-Thalassemia (β-Thalassemia Intermediate)β-Thalassemia (β-Thalassemia Minor) Sometimes called β-thalassemia trait

What is the Hereditary Persistence of Fetal Hemoglobin (HPFH)

Used to describe a group of genetic conditions in which the concentration of HbF is increased above the reference interval with reduction β-globin synthesis and a compensatory increase in γ-globin synthesis.

What is Hemoglobinopathy? Is a kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule.

What is Hemoglobinopaties? Are inherited single-gene disorders; in most

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cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease.

What is the Cyanmethemoglobin? The oxidation of the Fe2+ of hemoglobin to the Fe3+ of methemoglobin by ferrycyanide, with methemoglobin then converted into stable cyanmethemoglobin by the addition of potassium cyanide (KCN).

What is the Analytical Methodology for Hb Determination of Cyanmethemoglobin?

Absorbance is measured at 540 nm and is used to calculate the concentration of hemoglobin.Based upon the oxidation of the Fe2+ of hemoglobin to the Fe3+ of methemoglobin by ferrycyanide, with methemoglobin then converted into stable cyanmethemoglobin by the addition of potassium cyanide (KCN).

What method is used for hemoglobin determination?

Completed Blood Count

What is the completed blood count method? It is a test that evaluates the cells that circulate in blood; also known as full blood count (FBC), full blood exam (FBE), or blood panel.

What is FBC? It consists of counts of cells such as RBCs (erythrocytes), WBCs (leukocytes), and platelets

What is FBE? A measure of hemoglobin; Estimates of the volume of red cells; and an estimation of white blood cells subtype (differential counting for neutrophils, lymphocytes, basophils, eosinophils, and monocytes).

What is the other method of hemoglobin determination?

Electrophoresis; Using agarose gel and a pH 9.2 barbital buffer

What type of statins are used in hemoglobin determination?

Stains would include Ponceau S (reddish staining), or preferably Amido black (dark blue to black staining)

How does the hemoglobin behave on agarose gel?

Cannot accurately quantify HbA2, and co-migration of many hemoglobin variants is observed

What is the advantage of using HPLC in hemoglobin determination?

HPLC (High Performance Liquid Chromatography); Uses a column packed with cation exchange resin to quantify HbA2 and HbF

What is the advantage of HPLC over electrophoresis on hemoglobin?

Advantages over electrophoresis:superior resolution of hemoglobin variantsrapid assay timeaccurate quantification of hemoglobin

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fractions, including HbA2 and HbFHow does the Capillary Electrophoresis being used in hemoglobin determination essay?

Separation in an alkaline buffer using high voltages is based on (1) charge differences, (2) electrolyte pH, and (3) electro-osmotic flow.

What is the use of Electrospray Mass Spectrometry in hemoglobin variation?

Has become the method of choice for the characterization of hemoglobin variants and hemoglobin adducts since it immediately establishes:(1) whether the variant is an α or β-chain variant;(2) the location and identity of the amino acid residue substitution;(3) the quantity of variants present.

What is the used of DNA analysis for hemoglobin:

Diagnose and characterize α-thalassemiaInvestigate potentially life-threatening disorders of hemoglobin synthesis in the fetusCharacterize the β-thalassemia genotypeDistinguish between conditions that have similar clinical and laboratory presentations but are due to different genetic conditions

What is the HbS Solubility Test? Tests for specific hemoglobin variants; The most common type of abnormal hemoglobin and the basis of sickle cell trait and sickle cell anemia

When does the hemoglobin S produce visible turbidity?

HbS when oxygenated, is insoluble in concentrated phosphate buffer and produces visible turbidity, unlike the other hemoglobins (A, F, C, E and D)

List the substances used for determination of hemoglobin S in the sample?

1) Using a reducing substance, sodium hydrosulfite (Na2S2O4, sodium dithionate);

2) Used to deoxygenate the hemoglobin and saponin to lyse the RBCs;

How is HbS indicated in the sample? HbS is indicated by increased turbidity in the sample.

What are the False-positive test results of HbS Solubility?

False-positive results are found in samples with Heinz bodies;

• High concentrations of monoclonal protein or cold agglutinins.

How are the False-negative results of HbS obtained on samples?

False-negative results are obtained on anemic patients or on samples with hematocrit less than 15%.

What is the HbH test? Tests for specific hemoglobin variants;It is a beta 4 (β4) insoluble tetramer moderate

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to severe form of α-thalassemia characterized by pronounced microcytic hypochromic hemolytic anemia.

What are the charactistic of variant hemoglobins on HbH test?

It punctuate inclusions, usually described as looking like "golf balls", are found in the RBCs of a peripheral blood smear that has been stained with new methylene blue or brilliant cresyl blue at 37°C.

How to detect unstable hemoglobins? an increase in turbidity or complete precipitation in the blood sample was treated with heat at 55°C to 60°C or with isopropanol is used to detect the presence of unstable hemoglobins which precipitate in 3 to 4 minutes under this conditions.

What is Iron? metal at the active site of many important redox enzymes dealing with cellular respiration and oxidation and reduction in plants and animal

What is the importance of Iron in oxygen transport?

forms complexes with molecular oxygen in hemoglobin and myoglobin; these two compounds are common oxygen transport proteins in vertebrates

Where is iron distributed into? - Hemoglobin- storage iron (ferritin and hemosiderin)- myoglobin- A labie iron pool- other tissue iron- transport iron (transferrin and

apotransferrin)What is/are stored iron form(s)? - ferritin

- hemosiderin.What is/are transport iron form? apotransferin.

What is apotransferin/Fe3+

comple called?Transferrin

What is the regulator of iron absorption? Hepcidin , A peptide hormone produced by the liver, is the central regulator of iron absorptionChildren dietary deficiency because milk has low iron content and iron requirements for growth and development are high.adults, iron deficiency is almost always the result of chronic blood loss or childbearing.

What are common conditions decrease serum iron concentration?

patients with iron deficiency anemia and with chronic inflammatory disorders, such as (1) acute infection, (2) immunization, and (3) myocardial infarction.

What other conditions decrease serum iron - blood donation

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concentration? - hemorrhage- menstruation.

Measurement of iron deficiency includes - Serum iron determination- Iron binding capacity- Serum ferritin- Stainable iron in the bone marrow- Erythrocyte protoporphyrin- Circulating transferrin receptor and

reticulocyte hemoglobin- DNA analyses

What is IRON OVERLOAD? Hemochromatosis and types of anemia associated with ineffective erythropoiesis.

What is the best term used to describe iron overload at tissue level?

- Hemosiderosis- siderosis

In what condition, serum iron levels will be elevated?

- patients with aplastic anemia- children with acute iron poisoning- after oral or parenteral iron use- acute liver injury- The use of hormonal contraceptive

What are the analytical methods for iron determination?

- Colorimetric method- Transferrin Saturation %- TIBC = UIBC + serum iron- Serum transferrin (g/L) = 0.007 x

TIBC (ug/dL)What are the Methods for the determination of the serum Ferritin?

- Immunoradiometric assay- Enzyme-linked Immunosorbent assay

(ELISA)- Immunochemiluminescence assays- Immunofluorometric methods

What’s conditions known to affect serum iron concentration, TIBC and transferrin ssturarion %?

- Diurnal variation- Menstrual cycle- Pregnancy- Ingestion of iron- Oral contraceptives- Iron dextran injections- Hepatitis- Acute inflammation- Iron deficiency- Iron overload

What is Bilirubin? Bilirubin is the orange yellow pigment derived mainly from aging red blood cells that are destroyed in the reticuloendothelial cells of the liver, spleen and bone morrow.

Where is Bilirubin extracted and metabolized? In the liver.Where is Bilirubin excreted? In bile and in the urine.What is Bilirubin the end product of? Hemoglobin metabolism.

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BilirubinMetabolism

-

Continuation of BilirubinMetabolism

Bilirubin (B1)

Attaches to albumin

Liver UDP-glucoronyl transferase (uridine diphosphate)

Bilirubin monoglucoronide

-Continuation of BilirubinMetabolism

Bilirubin monoglucoronide UDP-glucoronyl transferase

(uridine diphosphate)

Bilirubin diglucoronide (B2)

Bile

Intestines

Continuation of BilirubinMetabolism

Intestines (normal flora)

Urobilinogen

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Bilirubin Metabolis

mHemoglobin heme (iron porphyrin)

heme oxygenase

Biliverdin

biliverdin reductase

Bilirubin (B1)


Oxidation Unchanged

Stercobilinogen

Urobilins

(stool) Stercobilin (stool)

Continuation of BilirubinMetabolism Reabsorb by the

enterohepatic circulation(Enterohepatic cycle)

Urobilin (urine)

What are other names of Bilirubin 1? 1) Unconjugated bilirubin2) Water insoluble / Non-polar bilirubin3) Indirect reacting bilirubin4) Hemobilirubin5) Free bilirubin / Unbound bilirubin6) Prehepatic bilirubin

What are other names of Bilirubin 2? !) Conjugated bilirubin2) Water soluble / Polar bilirubin3) Direct reacting bilirubin4) Cholebilirubin / cholestatic bilirubin5) One-minute bilirubin / Prompt bilirubin6) Post hepatic bilirubin7) Obstructive bilirubin8) Regurgitative bilirubin

What are some clinical significance of Bilirubin?

Jaundice or hyperbilirubinemia

How does someone with Jaundice or hyperbilirubinemia looks like?

They have yellow discoloration or pigmentation of the skin, sclera and mucous membranes.

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What is another name for this? Also called IcterusWhen does hyperbilirubinemi~a becomes clinically evident?

When serum bilirubin levels exceed 2.5 mg/dL (normal 0.3-1.0 mg/dL)

What are some classifications of Jaundice? 1) Increased serum unconjugated bilirubin.2) Result of excessive bilirubin presented to the liver.

The classifications of Jaundice are also seen in? 1) HDN (hemolytic disease of the newborn)2) Malaria3) Extensive hematoma4) Hemolytic transfusion reaction

Post- Hepatic jaundice increased ____ bilirubin High levers of unconjugatedKernicterus refers to ? The yellow staining caused by bilirubinKernicterus is commoly seen in ? NewbornsIf levels of bilirubin are very high the substance will move out of the blood and collect in

Brain tissue

What are some of the symtoms of kernicterus? Yellow of the eyesExcess bilirubin in the blood

Treatment of kernicterus ? Light therapyExchange transfusions

Jaundice types? Pre-hepatic (hemolytic)Hepatic (hepatocellular)

Post-hepatic (obstructive)Hemolytic anemia can cause ____ Jaundice Pre-hepaticTrue or false failure of bile to flow to the intestines due to an obstruction in the biliary tree

True

Where has post hepatic seen in ? CholedocholelithiasisBiliary atresiaParasitism

Caused of hepatic jaundice ? By increase of both unconjugated and conjugated bilirubin levels

Clinical examples of intrahepatic jaundice cause by genetic errors in bilirubin metabolism

Gilberts syndrome, dubin –johnson and rotor syndronme

Prehepatic jaundice caused by hemolysis Autoimmune abnormal HbIntrahepatic jaundice caused by infection? Hep A,B,CClinical examof intrahepatic jaundice seen in neonates

Physiologic

What is lucey driscoll syndrome ? Familial form of unconjugated hyperbilirubinemia caused by circulating inhibitor of bilirubin conjugation

How long does hyperbilirubinemia lasts? 2 to 3 week’s of lifeDifference between type 1 and type 11 criger najjar syndrome ?

Type 11 is less severe with a response to phenobarbital p450 inducer

What are the two inherited disorders in which bilirubin is conjugated ?

Dubin Johnson syndrome, rotor syndrome

What is the origin of Physiologic Neonatal Hepatic

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Jaundice?Deficiency of which enzyme leads to Physiologic Neonatal Jaundice (Physiological Jaundice of the Newborn)?

uridine diphosphate glucuronyl transferase (not fully developed)

What are the factors contributing to physiological jaundice?

- Increased bilirubin load in the newborn-Decrease conjugation of bilirubin resulting from relative lack of UDPGT enzyme-Exposure of breast-feeding infants to pregnanediol, nonesterified fatty acids, and other inhibitors of bilirubin conjugation

How is the physiological jaundice of the newborn is treated?

It is treated with phototherapy; the infant is exposed to light of approximately 450nm that disrupts intramolecular hydrogen bonds in the bilirubin molecule and yields photoisomers that are water-soluble and thus are excreted in the bile.

How bilirubin is measured in body fluids? 1. Spectrophotometric (Diazo - Chemical, Direc Spectrophotometric, Enzymatic, and Transcutaneous) methods2. Chromatographic methods

Which substance acts as coupling accelerator in Evelyn and Malloy?

Methanol

Which substance acts as coupling accelerator in Doumas and colleagues?

Sodium Benzoate

Van den Bergh and Muller method. Involves the coupling of bilirubin with diazotized sulfanilic acid (Ehrlich diazo reagent)

Total Bilirubin method. Serum is added to an aqueous solution of caffeine and sodium benzoate, and after 10 minute incubation at room temperature alkaline tartrate is added.

Direct Bilirubin method. Bilirubin monoconjugates and di-conjugates (mainly glucuronides) and δ- bilirubin, because they are water-soluble, react with the diazo reagents in the absence of accelerator.

What s ditaurobilirubin? It is a water-soluble synthetic material, is used by instrument manufacturers for calibrating direct bilirubin methods; it is also present in materials used for quality control and for proficiency testing.

Application of High-Performance Liquid Chromatography (HPLC)

It is used for rapid separation and quantification of 4 main bilirubin fractions: (1) α-unconjugated bilirubin; (2) β-bilirubin monoglucuronide; (3) γ-bilirubin diglucuronide; and (4) δ-bilirubin

Enzymatic methods for bilirubin determination. At the pH near 8 and in the presence of

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sodium cholate and sodium dodecylsulfate, on four bilirubin fractions are oxidized to purple and finally colorless products.The decrease in absorbance at 425 or 460nm is proportional to the concentration of total bilirubin

Which form of bilirubin is excreted in urine and its presence indicates conjugated hyperbilirubinemia.?

Conjugated Bilrubin (B2)

What is Porphyrins? Porphyrins are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α-carbon atoms via methene bridges.

What is the parent porphyrin? The parent porphyrin is porphinWhat are the functions of porphyrins? Porphyrins are essential for the function of

hemoglobin — a protein in red blood cells that links to porphyrin, binds iron, and carries oxygen to different organs and tissue.

What does ALA stands for? Aminolevulinic acid

What does PBGstands for? PorphobilinogenWhich are the precursors of porphyrin? Aminolevulinic acid (ALA) and

Porphobilinogen (PBG)Solubility of porphyrin precursors. porphyrin precursors that are highly water

soluble.Which is the major component of hemoglobin? Heme is a major component of hemoglobin,Which tissue organ made Heme? Heme is made mainly in the bone marrow and

liver through the production of porphyrin and linkage with iron.

What is the main function of Heme? The protein in red blood cells that carries oxygen from the lungs to all parts of your body.

Which are the enzymes used for the Heme biosynthesis?

5-Aminolevulinate Synthase, ALAS5-Aminolevulinic Acid Dehydratase, ALADHydroxymethylbilane Synthase, HMBSUroporphyrinogen-III Synthase, UROSUroporphyrinogen Decarboxylase, URODCoproporphyrinogen Oxidase, CPOXProtoporphyrinogen Oxidase, PPOXFerrochelatase, FECH

What are functions of Heme?Heme containing proteins participate in a variety of redox reactions:-Oxygen transport (by hemoglobin in the blood) and storage (by myoglobin in muscle)-Mitochondrial respiration-Enzymatic destruction of peroxides (by

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catalase and peroxidase)-Drug metabolism-Desaturation of fatty acids-Tryptophan metabolism (by tryptophan oxygenase

Which are the Precursors Excretion of Heme in urine?

Aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrinogen, and coproporphyrinogen III are excreted in urine

Which are the Precursors Excretion of Heme in feces?

Protoporphyrin, protoporphyrinogen and coproporphyrinogen-I are excreted in feces

What is the Porphyria? Porphyria refers to a group of disorders that result from a buildup of natural chemicals that produce porphyrin in the body.

Which organs are affected by the Porphyria? Porphyria mainly affects your nervous system, skin and other organs. The signs and symptoms of porphyria can vary, depending on the specific type and severity.

Types of porphyria. -porphyria — acute, which mainly affects the nervous system,- nonacute or cutaneous, which mainly affects the skin.

Types of Acute pophyrias. Acute porphyrias include forms of the disease that typically cause nervous system symptoms, which appear quickly and can be life-threatening.Acute intermittent porphyria (AIP)Variegate porphyria (VP)Hereditary coproporphyria (HCP)

Which are the factors cause acute porphyrias? The most important precipitating factors are (1) drugs, (2) alcohol, especially binge drinking, (3) the menstrual cycle, (4) calorie restriction, (5) infection, and (6) stress.

Which are the drugs cause acute porphyrias? Drugs known to provoke acute attacks include (1) barbiturates, (2) sulfonamides, (3) progestogens, and (4) many anticonvulsants.

Which are the Possible signs and symptoms of acute porphyria?

-Severe abdominal pain-Swelling of the abdomen (abdominal distention)-Pain in your chest, legs or back-Constipation or diarrhea-Vomiting-Insomnia-Heartbeat (palpitations)

The following symptoms of High blood pressure, Anxiety or restlessness, Seizures, Mental changes, such as confusion,

ACUTE PORPHYRIA

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hallucinations, disorientation or paranoia, Breathing problems, Muscle pain, tingling, numbness, weakness or paralysis, Red or brown urine are associated with what?What type of porphyria(s) include forms of the disease that cause skin symptoms as a result of oversensitivity to sunlight, but does don't usually affect the nervous system?

Cutaneous or nonacute porphyrias

What type of porphyria have attacks that last for several days, with some forms, signs and symptoms that may start during infancy or childhood?

CUTANEOUS PORPHYRIAS

What are the two categories of nonacute or cutaneous porphyrias?

1) Bullous skin lesions: Porphyria Cutanea Tarda (PCT) Congenital Erythropoietic Porphyria (CEP)2) Acute photosensitivity: Erythropoietic protoporphyria (EPP) X-linked dominant protoporphyria (XLDPP)

Name 1 type of symptom of CUTANEOUS PORPHYRIAS As a result of sun exposure.

Sensitivity to the sun and sometimes artificial light, causing burning pain

Sudden painful skin redness (erythema) and swelling (edema); blisters that take weeks to heal

Itching, fragile skin Scars or skin color changes from

healing blisters Increased hair growth Red or brown urine

Exposure to various toxins such as lead can cause what effects?

Increases the urinary ALA and coproporphyrin-III excretion and cause accumulation of zinc protoporphyrin (ZPP) in erythrocytes.

The definitive test is used for lead toxicity and measures what?

Measurement of blood lead and ZPP measurements

Secondary coproporphyrinuria is also caused by what?

Toxic effects of alcohol, arsenic, other heavy metals and various drugs.

What is Hereditary tyrosinemia type I? Succinylacetone, which accumulates in this disease, has a structural resemblance to ALA and therefore a competitive inhibitor of ALAD. Patients suffer neurological crisis very similar to attacks of acute porphyria.

What is going on physiological during Renal disorders?

Impaired glomerular function reduces the clearance of water-soluble porphyrins normal excreted in the urine

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Hepatobiliary disorders cause what? Urinary excretion of coproporphyrin-I is increased in Dubin-Johnson syndrome, Rotor syndrome and in Gilbert's disease.

Give an example a Hematological disorders 1)In iron deficiency anemia, zinc acts as an alternative substrate for ferrochelatase (FECH, also known as heme synthase), leading to increased ZPP.2)Increased red cell protoporphyrin (mostly ZPP) may also occur in sideroblastic, megaloblastic and hemolytic anemia

Dietary, bacterial, and gastrointestinal bleeding factors cause what?

Porphyrins may also come directly from the diet additional protoporphyrin and other dicarboxylic porphyrins may be formed by the action of gut flora on heme-containing proteins derived from the diet or by gastrointestinal hemorrhage.

What is Pseudoporphyria? Patients with PCT likely skin lesions with no accumulation of porphyrin's demonstrated

There are 8 different Laboratory Diagnosis for Porphyria, name 1.

1.Urinary porphobilinogen (PBG) determination2.Fecal and Urine Porphyrin determination3.High Performance Liquid Chromatography (HPLC)4.Fluorescence Emission Spectroscopy5.Erythrocyte/Whole blood Porphyrin measurement6.Analysis of Plasma Porphyrins7.Enzyme measurements8.DNA analysis

All samples for porphyrin assay must be protected from what?

light

Urinary concentrations decrease by up to percentage if exposed to light for 24 hours

50%

Porphyrins and PBG are best analyzed in fresh, early-morning (10 to 20 mL) specimens collected without preservative. They are stable in urine in the dark at 4°C for up to how many hours and for at least a month at -20°C.

48 hours

Specimens for ALA should be properly refrigerated. Urine specimens can be stored at 4°C in the dark for at least ? weeks without significant loss of ALA, and frozen specimens are stable for weeks.

2 weeks

PBG is more stable around pH ?, ALA is more stable around pH ? , although more acidic

PBG pH of 8 to 9ALA pH of 3 to 4

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environments greatly reduced ALA stability.How many grams wet weight of feces is adequate for porphyrin measurements stable for many months at what temperature?

5 to 10 and -20°C

EDTA whole blood shows no loss of protoporphyrin for how many days at room temperature? and for at least eight weeks at 4°C in the dark

8 days

EDTA whole blood shows no loss of protoporphyrin for how many weeks being refrigerated in the dark?

8 weeks

All samples received from patients with suspected bullous porphyria are treated as what and why?

"High risk" because the frequency of infection with hepatotrophic viruses, particularly HCV, is increased in PCT

What are 4 methods that are used for searching for metabolites of Porphobilinogen (PBG)?

Watson-Schwartz and Hoesch methods High performance liquid chromatography

(HPLC) Ion Exchange ChromatographyTandem Mass Spectrometry

What color does Watson-Schwartz and Hoesch methods stain Porphobilinogen?

• Rose-red or Magenta

How is 5-Aminolevulinic acid (ALA) usually converted into an Ehrlich-reacting pyrrole?

By condensation with a reagent such as• acetylacetone, after separation from PBG.

What is this method known as? Mauzerall and Granick methodWhat does the spectrophotometric scanning of acidified of porphyrins in urine or fecal extracts for the presence of?

Soret band

Name 3 other methods that are used to look for porphyrin in Urine and Feces.

Fluorometric methods Paper and Thin Layer Chromatography Reversed-phase High Performance Liquid

Chromatography (HPLC)What is the current method of choice for looking for porphyrin in Urine and Feces?

a. Reversed-phase High Performance Liquid Chromatography (HPLC)

What are the 3 methods used to look for blood porphyrins?

Piomelli method Blake et al method Spectrofluorometric method

What are the 2 methods used to look for plasma porphyrins?

Fluorescence Emission SpectroscopyHPLC

Enzyme measurements are? Rarely required, but useful for family studies and for identification of subtypes.

DNA analysis is? Identification of mutation from family member with definite diagnosis.

DNA analysis is used to? Screen of relatives for mutationWhat is Therapeutic Drug Monitoring/Management (TDM)?

A process used to measure blood drug levels so that the most effective dosage is maintained and toxicity prevented.

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Therapeutic Drug Monitoring/Management (TDM) is a multidisciplinary science of individualization of what?

Drug dosages

What does Therapeutic Drug Monitoring/Management (TDM) do to synthesize clinical information and laboratory testing results?

To facilitate selection of the optimal drug and dose for each patient

Therapeutic drug monitoring allows assessment of what?

Therapeutic compliance and efficacy Detection of drug interactions Drug-induced toxicity

What does therapeutic drug monitoring indicate?

How much of the drug has been absorbed, distributed, metabolized, and eliminated.

What is pharmacogenomics? The study of the inherited variations in genes that dictate drug response and the way these can be used to predict individual responses to a drug, using a genome-wide approach.

What is pharmacodynamics (PD)? The study of the physiological response to drugs which encompasses the interaction of drugs with target sites, and the biochemical and physiological consequences that lead to therapeutic or adverse effect

What is another statement used for pharmacodynamics?

“What the drug does to the body?”

The pharmacologically active substance produces an effect on a living organism or in a biochemical system is known as?

Mechanism of action

What is the site of action? The location (organ or specific cell type) of the target molecules upon which a drug acts

Most drugs exert their effects by binding to a protein target such as?

Enzyme or a transporter

Many drugs have increasing effects with ____ dose.

Increasing

Explain some of a therapeutic drug’s mechanism of action

Therapeutic drugs mechanism of action include:Therapeutic Range:•Represents the relationship between minimum effective concentration (MEC) and minimum toxic concentration (MTC).Trough concentration:•The lowest concentration achieved just before the next dosePeak concentration:•The highest concentration achieved within the dosing cycle.

What is a Drug biologic half-life or terminal The time it takes for a drug to lose half of its

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half-life? pharmacologic, physiologic, or radiologic activity.This means that it takes 4 to 5 times the half-life for a drug's serum concentration to reach steady state after regular dosing is started, stopped, or the dose changed.

What is xenobiotics? A chemical compound that is foreign to a living organism

Define Pharmacokinetics (PK) Pharmacokinetics (PK) is Øthe mathematical description of the physiological disposition of xenobiotics or endogenous chemicals,“what the body does to a drug”

What is ADME ? The processes of Absorption, Distribution, Metabolism, and Elimination included in the activity or fate of drugs in the body over a period of time. These processes are affected by factors specific to the individual receiving the drug including disease state, co-medication, age and sex.

How can pharmacokinetic absorption be describe?

Oral dosing requires the drug to pass from the GIT into the vascular system through a process known as absorption.To be absorbed, the drug has to be dissociated (called liberation) then must cross through cell membranes by passive diffusion.

What is the most direct route of administering a drug?

Intravenous (IV) delivery

What is a drug’s bioavailability? Bioavailability is the amount of drug absorbed relative to the quantity given.Bioavailability is affected by first-pass metabolism (intestines and liver) which will reduce the quantity of drug to reach the systemic circulation.

How does a drug distribution work? Drugs undergo distribution once in the bloodstream, and spreads throughout the systemic circulation and into various tissues.

What does distribution of a drug depends on? The distribution of a drug to a particular site depends on (1) molecular size, (2) degree of ionization, (3) lipid solubility, (4) extent of protein binding and (5) body composition. Drugs that distribute extensively into tissues tend to be lipophilic, as this facilitates passage through cell membranes.

What are some of the plasma protein drugs bind to?

Albumin, globulins, and lipoproteins.

Which protein do acidic or basic drugs bind to? Acidic drugs associate primarily with albumin

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Basic drugs preferentially bind globulins and lipoproteins

What is a Pharmacokinetic drug metabolism? It is the biotransformation of a compound, whether endogenous or exogenous.Drug metabolism is typically the result of enzymatic activity, found in the liver, GIT and kidneys.

What is elimination? The final removal of drugs from the bodyWhat are the steps in elimination? Most common routes are excretion into urine

or stool. Drugs are eliminated into breast milk, sweat and hair.Clearance can be measured directly and renal elimination can be estimated by using the glomerular filtration rate.In practice, urine is rarely used for TDM purposes

List some of the clinical utility of Therapeutic Drug Monitoring/Management (TDM)

TDM can be used to assess compliance, address physiological or pathological changes, and maintain optimal dosing for each individual patient.It is also useful in the management of many conditions requiring long-term pharmacological therapy like hyperlipidemia and hypertension.TDM can also guide initial selection and dosing of a drug.Routine TDM is also helpful for detecting and managing alterations in drug dispositions within an individual.

What is a major asset of consistent use of TDM?

The potential to detect noncompliance

What are some concerns in Therapeutic Drug Monitoring (TDM)?

The need for accurate, reproducible methods

Requirement for quality assurance and proficiency testing programs

Necessity for establishing target rangesWhat does GC-MS stand for? Gas Chromatography-Mass SpectrometryWhat does LC-MS/MS stand for? Liquid Chromatography-Mass

Spectrometry/Mass SpectrometryWhat does HPLC-UV stand for? High Performance Liquid Chromatography-

UltravioletName 6 traditional antiepileptics? Benzodiazepines

Carbamazepine Ethosuximide Phenobarbital and Primidone Phenytoin and Fosphenytoin Valproic acid

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What are the effects of Benzodiazepines? sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties.

Benzodiazepines work by? Enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor.

What are 2 kinds of benzodiazepines? Diazapam (Valium) and ClonazepamCarbamazepine toxicity is associated if levels exceed?

15 mg/L

What is the mode of action of Carbamazepine and what are its effects?

Modulates the synaptic sodium channel, which acts to reduce central synaptic transmission, aiding in control of abnormal neuronal excitability

Ethosuximide (Zarontin) is used for the treatment of?

Absence seizures characterized by brief loss of consciousness.

How does Ethosuximide take effect in the body?

It reduces the flow of calcium through T-type calcium channels in the synapse and slows the rate of this seizure inducing pulses.

Phenobarbital (Luminal) and Primidone (Mysoline) affect the body in what manner?

By reducing synaptic transmission through action on the GABAA receptor, resulting in decreased neuronal excitability.

Phenytoin (Diphenylhydantoin, Dilantin) and Fosphenytoin (Cerebyx) are used in the treatment of?

Used in the treatment of all but absent seizures

What is the mode of action and the effects of phenytoin and fosphenytoin?

They interfere with sodium channel activity by prolonging inactivation, which reduces synaptic transmission and assist in control of abnormal neuronal excitability.

Valproic acid (Depakote) is most commonly used for treatment of?

absence seizures

What is the mode of action and the effects of Valproic acid?

It inhibits the enzyme GABA transaminase, resulting in increased concentrations of GABA and overall inhibition of neuronal activity in the brain.

Hepatic toxicity and acute toxic encephalopathy have been associated with what concentration of valproic acid?

Concentrations greater than 100 mg/L

Name 6 contemporary antiepileptics: Gabapentin Lamotrigine Levetiracetam Oxcarbazepine Topiramate Zonisamide

Which contemporary antiepileptic promotes the release of GABA but does not interact directly with the GABA receptor?

Gabapentin (Neurontin)

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What is Lamotrigine and how does it affect the body?

A broad spectrum antiepileptic drug that acts through multiple mechanism including blocking sodium and calcium channels and reducing glutamate release

Name the broad spectrum antiepileptic that acts through synaptic vesicle protein SV2A, which is involved in the release of neurotransmitters from presynaptic terminals?

Levetiracetam (Keppra)

What antiepileptic drug is metabolized to monohydroxycarbamazepine (MHC), the metabolites responsible for the therapeutic effect?

Oxcarbazepine (Trileptal)

Which broad spectrum antiepileptic drug that has sodium and calcium channel blocking activity, potentiates the activity of GABA, and inhibits glutamate release?

Topiramate (Topomax)

What is Zonisamide (Zonegran)? Is a sodium and calcium channel blocker and considered a broad spectrum antiepileptic

Antifungal or Antibacterial agents?1) Aminoglycosides2) Triazoles3) Vancomycin4) Amikacin5) Gentamicin6) Tobramycin

1) Antibacterial2) Antifungal3) Antibacterial4) Antibacterial5) Antibacterial6) Antibacterial

How does bacterial susceptibility to antibiotics being measured?

Bacterial susceptibility to antibiotics is commonly measured in terms of the minimum inhibitory concentration (MIC), the concentration of drug sufficient to inhibit growth of an organism.

What is minimum inhibitory concentration mean?

The concentration of drug sufficient to inhibit growth of an organism.

Gentamicin is an example of Aminoglycosides which inhibits what?

They inhibit protein synthesis to kill aerobic, gram-negative bacteria

What do you call a glycopeptide antibiotic with activity against antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA)?

Vancomycin (Vancocin)

What most common pathogen species are being inhibited by antifungal agents?

The most common pathogens are species of Candida yeast or Aspergillus molds

Voriconazole (Vfend) and Posaconazole ( Noxafil) are examples of what type of antifungal agent?

Triazole

__________ is an antifungal agent that has a broad-spectrum compounds that kills by inhibiting synthesis of the major fungal sterol,

Posaconazole ( Noxafil)

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ergosterol.What do you call a chemotherapeutic drug that inhibits the growth of malignant cells by alkylating DNA?

Busulfan

What antitumor agent can also minimize the risk of secondary tumor development and growth retardation in children when compared with irradiation?

Busulfan

What anti-neoplastic s or anti-cancer drugs is being used in the management of acute lymphoblastic leukemia, choriocarcinoma, elated trophoblastic tumor, and in maintenance of remission in leukemia and treatment of severe psoriasis?

Methotrexate

_____________ inhibits DNA synthesis and competitively inhibits the enzyme dihydrofolate reductase.

Methotrexate

What are arrhythmias? Arrhythmias are disturbances in normal cardiac sinus rhythm and are sometimes associated with substantial morbidity and mortality.

What is the most common serious arrhythmia? Atrial fibrillationMany antiarrhythmic drugs exert their action by regulation of what cation channels?

Na+, K+ or Ca2+

What cardioactive drug is obtained from Digitalis plants such as the foxglove, it is a cardiac glycoside used in the treatment of arrhythmias and heart failure?

Digoxin (Lanoxin)

What does Digoxin (Lanoxin) do to your heart rate?

It acts by slowing heart rate, increases the strength and velocity of cardiac contraction and regulate the nervous (sympathetic) and endocrine (renin-angiotensin) system.

What cardioactive drug is particularly prescribed in cases of congestive heart failure?

Digoxin (Lanoxin)

Identify to which immunosuppressant they belong to:1) Cyclosporine2) Tacrolimus3) Mycophenolate Mofetil4) Sirolimus5) Everolimus

1) Calcineurin inhibitor2) Calcineurin inhibitor3) IMPDH inhibitor4) mTOR inhibitor5) mTOR inhibitor

What do you call the drugs capable of suppressing immune responses used to treat autoimmune diseases, allergies, multiple myeloma, other cancers and chronic nephritis, and most important, to prevent rejection in

Immunosuppressant drugs

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organ or bone marrow transplantation?_________is important in optimizing immunosuppressant therapy because of possible serious consequences of under dosing or overdosing.

TDM (Therapeutic drug monitoring)

What prevents drug-related toxicity and is used to evaluate compliance?

TDM (Therapeutic drug monitoring)

Cyclosporine is a immunosuppressant derived from bacterial sources. True or False

False; it comes from Fungus

Cyclosporine is a fat______ cyclical peptide that______ the activation of T lymphocytes via a multifaceted mechanism.A soluble, blocksB insoluble, enablesC neutral, inhibitsD rich, starts

A

Tacrolimus has two names. Identify them.A. PrografB. FK506C. BGM109TLM1

A and B

Cellcept arrests T-cell proliferation by the suppression of guanine nucleotide production when IMPDH is inhibited by MPA. True or FalseA. TrueB. FalseT

A

Opioids can be monitored in urine to detect compliance, diversion, and use of non-perscribed opioids?A. TrueFalse

A.

Codeine is a fully synthetic opioid. True or False?A. TrueFalse

B

Which one of these choices is a nueraleptic agent?A. LithiumB. Classical AntipsychoticsC. A and BNone of the above

C

Toxicology is most specifically a branch of ___ PharmacologyToxicology is concerned with the study of Living organisms

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adverse effects of chemicals on ___.There are 9 different procedures for detection of drugs. Name as many as you can:

Spot test, determination of anion gap, electrocardiogram, determination of Osmol gap, immunoassay, planar chromatography, gas chromatography, high performance liquid chromatography, point of care devices

Spot tests are qualitative or quantitative? qualitativeDo Spot tests suggest or prove: SuggestName two examples of spot tests for salicylate: Ferric chloride test, Trinder testWhat is the formula used to identify increased anion gap?

AG = [Na+] - [Cl- + HCO3-]

What is the reference interval for anion gap determination?

8 to 16 mmol/L

What are the common causes of anion gap? MUDPILES mnemonicWhat is the MUDPILES mnemonic? Methanol

UremiaDiabetic ketoacidosisParaldehydeIron, inhalants, isoniazid, ibuprofenLactic acidosisEthylene glycol, ethanol ketoacidosisSalicylates, starvation ketoacidosis, sympathomimetics

Name the causes of persistent anion gap. Continued absorption of exogenous acidsFormation of acidic metabolitesCellular ischemia with worsening lactic acidosis

Correct interpretation of results facilitates: Laboratory testingDiagnosis of poisoningManagement

What is one of the screening procedure for detection of drugs

Electrocardiogram (ECG)

What are the formulas to determine Osmol Gap?

OSMc (mOsm/kg) = 2Na (mmol/L) + glucose (mg/dL)/18 + urea (mg/dL)/2.8OSMc (mOsm/kg) = 2Na (mmol/L) + glucose (mmol/L) + urea (mmol/L)

What are the formulas to determine Osmol Gap?

OSMc (mOsm/kg) = 1.86 Na (mmol/L) + glucose (mg/dL)/18 + urea (mg/dL)/2.8 + 9OSMc (mOsm/kg) = 1.86 Na (mmol/L) + glucose (mmol/L) + urea (mmol/L)+ 9

How do you determine the Osmol Gap OSMg = OSMm – OSMcDifference between Actual osmolality (measured) and the calculated osmolality

What is the method of choice for initial screening of most drugs of abuse

Immunoassay

True or False True

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Immunoassay tests for drugs of abuse are capable of semiquantitative results.Planar Chromatography is also referred to as.. Thin layer chromatographySpecimens for planar chromatography to determine drugs of abuse include?

Urine, serum, gastric contents.

What is the specimen of choice for planar chromatography and why?

Urine, because most drugs and drug metabolites are present in urine in relatively high concentrations.

What is one type of screening procedure for the detection of drugs?

Gas Chromatography

What else is gas chromatography known as? Gas liquid chromatography (GLC, GC)Why is gas chromatography used in drug screening?

It is rapid, and capable of resolving broad-spectrum of drugs

It is widely used for what two kinds of drug analysis?

Qualitative and quantitative

How does gas chromatography analyze specimens? What are some parts of the procedure?

It uses capillary column, flame ionization and alkali flame ionization for analysis

What procedure achieves the greatest accuracy in drug screening?

Gas chromatography coupled to a mass spectrometer (GC-MS)

What procedure is used for comprehensive drug screening in biological fluids?

High-Performance liquid chromatography (HPLC)

What are some advantages HPLC has over gas chromatography?

1) It can analyze polar compounds without derivatization

It can analyze thermally labile drugsThe incorporation of a diode array detector has what effect?

It greatly increases the discriminatory power of this technique

What are some advantages of Point-of-care devices?

1) Easy to use2) durable3) portable4) rapid

may be adjusted to detect one or many drugsWhat body fluids are used in these types of point of car devices?

Urine and Saliva

Carbon monoxide (CO) are agents that cause ____ _____.

Cellular Hypoxia

You are considered legally intoxicated at 0.08% if you consume what?

Alcohol

Bought over the counter and can cause hepatic and renal toxicity with overdose.

Non-prescription Analgesics

Acetylcholine is what type of agent CholinergicAny drug that is repeatedly and deliberately used in a way other than prescribed or socially sanctioned is considered what?

Drug Abuse

DFSA is abbreviation for? Drug Facilitated Sexual Assault

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What does CO stand for? Carbon MonoxideHow can CO be described? Colorless, odorless, and tastelessWhat is CO the product of? Incomplete combustion of carbonaceous

materialCO will combine readily to what? Heme Fe2+ of hemoglobinWhat is the produce when CO binds with Heme Fe2+?

Carboxyhemoglobin

True or FalseThe binding affinity of hemoglobin for CO is about 250 times weaker than that for oxygen

False. The binding affinity for hemoglobin and CO is 250 times greater than that for oxygen

What will CO compete with for hemoglobin? OxygenCO will decrease what content? Blood oxygen content and oxygen’s

availability to tissueWhat is the treatment for the above situation? Remove individual from contaminated area

and administer oxygenHow can CO be measured in the blood? Gas chromatography and spectrophotometryWhich method of measurement for CO is described:Accurate, precise, and considered to be the reference procedure

Gas chromatography

Which method of measurement for CO is described:Fast, convenient, accurate, precise

Spectrophotometry

What will Cyanide bind to? Heme iron in the cytochrome within mitochondria and cross biological membranes

What are symptoms of rapid onset of hypoxia? Flushing, headaches, tachypnea, dizziness, and respiratory depression

What is tachypnea? Abnormal rapid breathingWhat can respiratory depression lead to? Coma, seizures, complete heart block, and

deathWhat is the treatment for cyanide? Hydroxycobalamin, or the cyanide antidote kitHow is methemoglobin formed? When the heme iron in hemoglobin (Fe2+) is

oxidized to the Fe3+ stateDoes methemoglobin bind to oxygen? noWhat is the enzyme responsible for maintaining hemoglobin iron in the reduced state?

nicotinamide adenine dinucleotide (NADH)-methemoglobin reductase

Where is the deficiency of the enzyme is seen?

in congenital methemoglobinemia

Acquired toxic methemoglobinemia may be caused by what?

various drugs and chemicals.

A normal pO2 in a cyanotic patient indicates what?

is a significant indication of the possible presence of methemoglobinemia.

Specific therapy for toxic methemoglobinemia involves what?

the administration of methylene blue.

Methemoglobinemia is measured in taking automated multi-wavelength measurements

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blood manually or by using what automated method?

with a co-oximeter.

Where should keep Methemoglobin-forming Agent?

Since methemoglobin is not stable at room temperature, specimens should be kept on ice or refrigerated but not frozen (freezing results in an increase in methemoglobin concentration).

What is toxic that most widely used and often abused chemical substances?

Ethanol is one of several alcohols that is toxic and medically important.

Where do the actions of ethanol involve? Central nervous system (CNS) depressant

How is the blood alcohol concentration that is allowed by DMV?

You are considered legally intoxicated at a BAC of 0.08% (80 mg/dL)

How long is take for BAC level to release alcohol?

It can take up to 6 hours for BAC level to drop from a 0.08 to a 0.00

Where does Ethanol metobolize? Ethanol is metabolism by the liver alcohol dehydrogenase to acetaldehyde, which is subsequently oxidized to acetic acid by aldehyde dehydrogenase

What is the side effect of Ethanol? Ethanol is a teratogen and alcohol consumption during pregnancy can result in the birth of a baby with fetal alcohol spectrum disorder (FASD) which may include physical, mental, behavioral and learning disabilities with lifelong implications.

How can we analyze Ethanol In blood? Blood analysis: serum, plasma, or whole blood• Higher concentrations in serum than in blood• Venipuncture site should be cleansed with an alcohol-free disinfectant (aqueous benzalkonium chloride)• Specimens should be capped to avoid evaporative loss.Blood may be stored, when properly sealed, for 14 days at room temperature or at 4°C, with or without preservative.

How can we analyze Ethanol In blood? • Blood analysis: serum, plasma, or whole blood

• For longer storage or for non-sterile postmortem specimens, sodium fluoride should be used as a preservative to

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prevent a decrease or occasionally an increase (via fermentation) in ethanol concentration.

To measure ethanol in serum/plasma, the enzymatic assay is the method of choice (alcohol dehydrogenase)

What ratio is breath alcohol analysis based on? Evidential breath alcohol measurements are based on the ratio of 2100:1 (blood/breath)

What is the deprivation period for breath alcohol analysis?

Before breath alcohol analysis, a deprivation period of at least 15 minutes is recommended to allow for clearance for any residual alcohol that may be present in the mouth from very recent drinking, use of alcohol-containing mouthwash, or vomiting of alcohol-rich gastric fluid.

What safeguard is there to ensure against mouth alcohol contamination?

Duplicate tests, performed 3 to 10 minutes apart, typically must agree within 20 mg/dL (0.02%) as an additional safeguard against mouth alcohol contamination.

What is the use of urinalysis in ethanol analysis?

Detection of alcohol in urine represents ingestion of alcohol within the previous 8 to 12 hours.

What are some analysis of Ethyl Glucuronide (EtG) and Ethylsulfate (EtS)?

- Minor metabolites of ethanol- Ethyl glucuronide (EtG) may be

detected as long as 80 hours after ethanol consumption and is found even when small amounts of alcohol are consumed.

Used as a marker of recent ethanol intake due to its long urinary elimination time and its specificity for ethanol exposure.

Where methanol is used? Commercial solvent for products such as deicers and windshield washer fluids.

Name the agent that cause cellular hypoxia and it is metabolized by liver alcohol dehydrogenase to formaldehyde?

methanol

Formaldehyde is subsequently oxidized to …………….by aldehyde dehydrogenase.

Formic acid

Methanol causes what type of disorders? acidosis, optic neuropathy, resulting in blindness, or death if not treated promptly

Between ethanol and methanol which one oxidized slower?

methanol

What are the mainstay of therapy for methanol toxicity?

Administration of ethanol or fomepizole as a competitive alcohol dehyrogenase inhibitorAdministration of either folate/folinic acidDialysis

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What percentage of aqueous isopropanol is rubbing alcohol?

70% aqueous solution of isopropanol = rubbing alcohol

What is isopropanol metabolized to? By which enzyme?

Isopropanol metabolized by alcohol dehydrogenase to acetone, which is eliminated much more slowly.

Does isopropanol have the same CNS depressant action as ethanol?

It has about twice the CNS depressant action as ethanol.

Does Acetone have CNS depressant activity? Yes

What is Ethylene Glycol commercially known as?

Antifreeze

Are the effects of Ethylene Glycol harmless? Relatively harmless initially, but metabolites like oxalic acid and glycolic acid can be lethal

What metabolite would be measured after ingesting Ethylene Glycol?

Determination of ethylene glycol and glycolic acid provides useful clinical and confirmatory analytical information in cases of ethylene glycol ingestion

What is the treatment for accidental ingestion of Ethylene Glycol?

Treatment: Administration of ethanol or fomepizole as a competitive alcohol dehydrogenase inhibitor dialysis and dialysis

What is Flame Ionization Gas Chromatography? It is the most common method used to detect and quantify volatile alcohols in biological samples. It distinguishes types of alcohol and measure concentrations as low as 10 mg/dL (0.01%)

How are samples prepared for Flame Ionization Gas Chromatography?

They are prepared by direct injection and headspace analysis.

Is a prescription required for acetaminophen? NoWhat type of drug is acetaminophen? AntipyreticWhat can overdose of acetaminophen cause? Hepatic and renal toxicityWhat is the treatment for acetaminophen overdose?

Administration of N-acetylcysteine (NAC)

What does Rumack-Matthew nomogram do? relates serum acetaminophen concentration and time after acute ingestion to the probability of hepatic necrosis

What are other screening methods for acetaminophen?

Spectrophotometry and immunoassays

In the Rumack-Matthew Nomogram what hour increments are used on the x-axis?

The x-axis are in 4 hour increments.

What does the Rumack-Matthew line indicate in the Nomogram?

Any values (concentration) above the line may indicate hepatic damage.

What is the treatment line in the Rumack-Matthew Nomogram?

The treatment line is 25% less than the rumack matthew line, which is the threshold for acetaminophen toxicity.

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What is the common name for Acetylsalicylic acid?

Aspirin

What is Acetylsalicylic acid used for? Analgesic, antipyretic, antiinflammatory

What does Acetylsalicylic acid enhance and inhibit?

Acetylsalicylic acid enhances anaerobic glycolysis but inhibit the Krebs cycle and transaminase enzymes.

How does one treat Acetylsalicylic acid toxicity?

Acetylsalicylic acid toxicity is treated by decreasing further absorption, increasing elimination, and correcting acid-baseand electrolyte disturbances.

What can be used to treat Acetylsalicylic acid? Activated charcoal (prevents absorption)

Alkaline diuresis (elimination) NaHCO3 (alleviates metabolic

acidosis)What is Trinder Tests? Spot Tests, HPLC, fluorescent polarization

immunoassay, salicylate hydroxylase-mediated photometry, gas and liquid chromatography methods.

What is Tricyclic Antidepressants? • Represent a class of drugs frequently prescribed for the treatment of depression

• Therapeutic mechanism is the blockade of neuronal reuptake of serotonin and/or norepinephrine

• Measured by chromatographic methods or by immunoassay

What is the use of Antipsychotic Drugs? Generally used for psychiatric and other disorders

What is the effect of Antipsychotic Drugs? Principal manifestation involve the CNS and cardiovascular system

What methods are used to measure the concentration of Antipsychotic Drugs?

Measured by chromatographic methods or by immunoassay

What is the use of Antihistamines? Used to treat allergies and aid sleepDoes Antihistamines available over the counter? Many available over the counterWhat is Histamine role in the body? Histamine is released from mast cells and

plays an important physiological role in immediate hypersensitivity and allergic response

What is the function of Histamine? Histamine functions as a neurotransmitter in the CNS and stimulates gastric acid secretion.

What methods are used to determine Histamine concentration?

Spectrographic methods: GC-MS/MS, LC-MS/MS

What are the characteristics of Antimuscarinic Synonymous with anticholinergic, inhibiting

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Agents? the action of acetylcholine, a neurotransmitter in the parasympathetic nervous system.

What is the best use of Antimuscarinic drugs? Antimuscarinic drugs relax smooth muscle, decrease the secretion of saliva, sweat, and digestive juice, and dilate the pupil of the eye.

How does the Antimuscarinic agent go inside the body?

May be eaten or ingested in tea

Is there any treatment involved for Antimuscarinic?

Treatment: based on clinical presentation

What is Acetylcholine? an essential neurotransmitter that affects parasympathetic synapses (autonomic and CNS), sympathetic preganglionic synapses, and the neuromuscular junction

How do agents Related to the Cholinergic Toxidrome act?

by producing uncontrolled acetylcholine transmission through inactivation of cholinesterase enzymes or direct stimulation of acetylcholine receptors

What is duration of acetylcholine action is controlled by?

- Acetylcholinesterase butyrylcholinesterase / pseudocholinesterase

Where is Acetylcholinesterase found? - in red blood cells- nervous tissue- skeletal muscle.

Where is Butyrylcholinesterase found? Butyrylcholinesterase is found in plasma, liver, heart, pancreas and brain.

What is Organophosphate poisoning results from?

from exposure to organophosphates (OPs), which cause the inhibition of acetylcholinesterase (AChE), leading to the accumulation of acetylcholine (ACh) in the body

What is most commonly Organophosphate poisoning?

results from exposure to insecticides or nerve agents

How does Organophosphates work? Organophosphates inhibit AChE, causing OP poisoning by phosphorylating the serine hydroxyl residue on AChE, which inactivates AChE.

What is the purpose of AChE? It’s critical for nerve function, so the irreversible blockage of this enzyme, that causes acetylcholine accumulation, results in muscle overstimulation.

What does diagnosis of organophosphate and carbamate toxicity depend on?

Mainly on exposure history, physical presentation, clinical suspicion, and laboratory support.

What is the treatment for organophosphates and carbamate?

Administration of atropine, pralidoxime.

Measurement of organophosphates and carbamate?

Spectrophotometric measurement of acetylcholinesterase and butyrylcholinesterase

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activity. GC-MS and GC-MS/MS of urine for organophosphate and carbamate metabolites?

What are drugs of abuse? Any drug that is repeatedly and deliberately used in a way other than prescribed or socially sanctioned.

What are the drugs of abuse? 1. Tricyclic antidepressants2. Benzodiazepines3. Barbiturates4. Methadone5. Methylenedioxymethamphetamine (MDMA)6. Methylenedioxyethylamphetamine (MDEA)7. Oxycodone8. Amphetamines9. Cocaine10. Marijuana11. Opiates12. Phencyclidine

What are the drugs mentioned above collectively known as?

SAMHSA (Substance Abuse and Mental Health Services Administration) or NIDA (National Institute on Drug Abuse).

Under which department do the SAMHSA drug tests are required?

Department of Transportation.

What are Barbiturates? They are drugs that act as central nervous system depressants, with wide spectrum of effects, from mild sedation to total anesthesia.

Barbiturates are also effective as? As analgesics, anxiolytics, hypnotics, and anticonvulsants.

What is one of the problems that you face when taking Barbiturates?

They have addiction potential, both physical and psychological

Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – for example, in the treatment of anxiety and insomnia – mainly because?

Because benzodiazepines are significantly less dangerous in overdose as there is no specific antidote for barbiturate overdose.

In what cases are Barbiturates still being used? Barbiturates are still used in general anesthesia, for epilepsy, for the treatment of acute migraines and cluster headaches.

What are some of the barbiturates confirmatory test ?

Gc with flame Ionization detection, Nitrogen phosphorus detection,mass spectrometry MS detectioncapillary electro

What are the immunoassay techniques ? Screening testWhat is the main action of barbiturates ? Suppression of cns sedative-hypnotic drugsWhat are some main uses of barbiturates? Induce anesthesia, treat seizures, decreased

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intracranial pressure, enthanasiaAre barbiturates acids or bases? Weak or strong?

Weak acids

What are the active duration time of long acting ?

2-6 days48-52

Which class of of drugs sometimes called benzos are a class of psychoactive drugs that enhanced effect of the neutransmitter gamma-aminobutyric?

Benzodiazepines

If used alone, do benzodiazepines commonly cause fatal cns depression ?

No but at high doses will cause hyponosis and stupor

True or false the prototype benzodiazepines are diazepam nordiazepam (n-desmethyldiazepam)

True

Uses of benzodiazepine. useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures.

Classification of Benzodiazepines. They are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.

Confirmatory tests of Benzodiazepines -extraction procedures by Liquid-Liquid extraction or Solid-Phase extraction, analysis of urine specimens by GC-MS, LC with UV detection, LC-MS and LC-MS/MS.

Where is the Cannabinoids derived from? Cnnabinoids found in the marijuana plant Cannabis sativa

What are the effects of Cannabinoids? Psychotropic effects are euphoria, distorted perception, relaxation and a feeling of well-being.

Which is the primary psychoactive component of Cannabinoids?

Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive component

Cannabinoids measure by which specimen? Delta-9-tetrahydrocannabinol (THC), which is measured in urine.

which methods used to measure Cannabinoids? presumptive positive result using immunoassay method should be confirmed by quantitative GC-MS/MS or LC-MS/MS

Where is the Opiates derived from? Opiates found naturally in the opium poppy plant Papaver somniferum.

Which Form of Opiates is better In medical? In a medical context the term usually indicates medications that are artificially made rather than extracted from opium.

What are primarily used in medicine for the Opioids

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treatment of pain?sedation, respiratory depression, constipation, and a strong sense of euphoria are side effects of what?

opioids

Opioid ? can develop with ongoing administration, leading to a withdrawal syndrome with abrupt discontinuation.

dependence

Opios can cause death in overdose from what? respiratory depression.Opioids work by binding to opioid receptors, which are found principally iwhere? These receptors mediate both the psychoactive and the somatic effects of opioids

the central and peripheral nervous system and the gastrointestinal tract.

Although the term opiate is often used as a synonym for opioid, the term opiate is properly limited to the natural alkaloids found in the resin of the___?___ while opioid refers to synthetic substances

Papaver somniferum (opium poppy),

Natural Opium Alkaloidsare Phenanthrenes which include what?

MorphineCodeineThebaine

Natural Opium Benzylisoquinolines are what? Papaverine Noscapine

Poppy seeds (Papaver somniferum) are a type of natural _____?___

Opium

Semisynthetic Opiates are what? Heroin Hydrocodone Hydromorphone Oxycodone Oxymorphone

Name the 5 Fully Synthetic Opioids. Fentanyl Meperidine Methadone PropoxypheneTramadol

Name the 3 antagonist to Opioids. Buprenorphine NaloxoneNaltrexone

What method of choice is used for urine screening?

Immunoassay

What are the 3 Confirmatory test used for Opioids

Gas chromatography mass spectrometry (GC-MS)

Liquid chromatography mass spectrometry (LC-MS)

Liquid chromatography Tandem Mass Spectrometry (LC-MS/MS)

Sympathomimetic drugs are stimulant Effects of agonists of the sympathetic nervous

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compounds which mimic the what effects? system such as the catecholamines.

Give some examples of catecholamines. epinephrine (adrenaline)norepinephrine (noradrenaline)dopamine

Sympathomimetic drugs are used to treat what? Cardiac arrest, low blood pressure, or even delay premature labor, among other things.

List some drugs considered to have a high potential of abuse

Amphetamine, Methamphetamine,Ephedrine, Pseudoephedrine, Phenylpropanolamine

What is Amphetamine and Methamphetamine primary action?

To increase dopamine, serotonin, norepinephrine (extracellular monoamine neurotransmitters); Also increase blood pressure, heart rate, body temperature and motor activity, relaxed bronchial muscle and depress the appetite.

What is the main system Amphetamine and Methamphetamine affect?

Central and peripheral nervous system.

Where do Ephedrine and Pseudoephedrine naturally occurs?

In plants of Ephedra genus

What kind of receptor is Ephedrine? Ephedrine is both an α- and β- adrenergic receptor agonist

Explain the mechanism of Ephedrine It enhances the release of norepinephrine from sympathetic neurons and is considered a mixed-acting sympathomimetic drug causing hypertension, tremors, myocardial infarction, seizures and stroke.

How is Pseudoephedrine primarily used? As a decongestant because of its vasoconstrictive properties (alpha adrenergic action), and as a precursor for the illicit synthesis of methamphetamine.

Name a psychoactive drug of the phenethylamine and amphetamine chemical classes which is used as a stimulant, decongestant, and anorectic agent.

Phenylpropanolamine (PPA)

Phenylpropanolamine (PPA) is a metabolite of? Ephedrine and pseudoephedrinePPA is commonly used in prescription and over-the-counter for?

cough and cold preparations.

Designer Amphetamines are also known as? “club drugs” or “designer drugs”

Short-term effects of designer amphetamines include:

euphoria, energy, desire for social interaction, distortion of visual and auditory sensation

Long-term effects of designer amphetamines include:

Serotonin syndrome Hepatotoxicity Neurotoxicity Psychopathology

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AbuseWhat psychostimulant used to treat attention deficit hyperactivity disorder and narcolepsy?

Methylphenidate (Ritalin)

What drugs has clinical effects similar to those of amphetamines


Because of stimulant and purported aphrodisiac properties, increasingly subject to diversion and abuse, what drugs is this?


What do you call a drug that is chemically alkaloid methylbenzoylecgonine found in Erythroxylum coca

Cocaine

A kind of drug used for local anesthesia and vasoconstriction in nasal surgery, and to dilate pupils in ophthalmology?

Cocaine

What is this form of cocaine that is administered by nasal insufflation or snorting?

hydrochloride salt (powder)

What is this form of cocaine that is heated and its vapors inhaled?

freebase known as crack cocaine

What drug is a potent CNS stimulant that elicits a state of increased alertness and euphoria (same as amphetamine but of shorter duration)?

Cocaine

What analyte of choice in screening for cocaine use?

Benzoylecgonine (BE)

What is the initial screening method by choice for cocaine use?

Initial screening is by immunoassay detectionGC-MS is the confirmatory method of choice

LSD is structurally similar to________.A. MelatoninB. ADHC. SerotoninD. Epinepherin

C

LSD causes several psychological effects. These include:A. perceptual distortions of colorB. depersonalizationC. loss of body imageD. All of the above

D

LSD is made from bacteria. True or False.A. TrueB. False

B

Current ways of use for LSD include:A. Postage StampsB. Gel CapsC. TabletsD. All the above

D

Current detection methods for LSD as an analyte include:

D

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A. GC-MS/MSB. LC-MS/MSC. LC-MSD. All of the AboveCan drugs facilitate sexual assault?Yes or NoA. YesB. No

A

Current drugs that DFSA(defined as the use of alcohol, drugs, and/or chemical agents to incapacitate an individual can facilitate sexual assault) include:A. AlcoholB. BenzodiazepineC.Chloral hydrateD. All of the above

D

All or most athletes are required to undergo drug screening. The procedure is defined as:

A. Drug screeningB. In competition testingC. PrescreeningD. Out of competition testing

D

Drug abuse can be detected using several samples taken from patients.Choose the answer you think is correct.A. Blood, Plasma, SerumB. Meconium, Hair, SweatC. Oral Secretions(Saliva)D. All of the above

D

Heavy metal poisoning is ___ the accumulation of heavy metals, in toxic amounts, in the soft tissues of the body

Symptoms and physical findings associated with heavy metal poisoning

vary according to the metal accumulated

Name 5 heavy metals, essential to body function in very small amounts. But, if these metals accumulate in the body in concentrations sufficient to cause poisoning, then serious damage may occur

zinc, copper, chromium, iron and manganese

The heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmiumHeavy metal poisoning may occur as a result of (6 ways).

industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints

What is AA-F? Atomic absorption spectrometry with flameWhat is AA-ETA? Atomic absorption spectrometry with

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electrothermal atomization furnaceWhat is ICP-ES? Inductively coupled plasma emission

spectrometryWhat is ICP-MS? Inductively coupled plasma mass

spectrometryWhat is LC-ICP/MS? High performance liquid chromatography

inductively coupled mass spectrometryPatients with renal failure are candidates for what?

Aluminum toxicity

Aluminum avidly binds to proteins such as? TransferrinAluminum has been implicated in which disease?

Alzheimer's Disease

What accumulates in blood if not filtered by kidney?

Aluminum

Aluminum is neurotoxic, targeting the central nervous system, which can lead to?

Serious immunological and neurodegenerative disorders

The primary side-effect or "wake-up call" that indicates aluminum has intoxicated the brain is a very serious condition called?

HYPERSENSITIVITY

Symptoms of aluminum hypersensitivity include:

-Heightened sensitivity to light or darkness.-Abnormal sensitivity to hot and cold temperatures.-An aversion to noise, touch, movement, odors, etc.-Unexplained feelings of apprehension or uneasiness.-Feelings of inferiority, embarrassment or shame.-Feelings of irritability, agitation or annoyance.-Those who are easily frightened or alarmed sometimes become overly disturbed and provoked, displaying irrational outbursts of anger, road rage, and bad temper

What metal can cause the following symptoms, becoming easily frightened or alarmed sometimes become overly disturbed and provoked, displaying irrational outbursts of anger, road rage, and bad temper

Aluminum hypersensitivity

What are the sensory symptoms caused by hypersensitivity to aluminum?

Overly sensitive to all of the five senses.-Heightened sensitivity to light or darkness.-Sensitivity to hot and cold.-Aversion to noise, touch, odors, movements.

What are the emotional symptoms caused by hypersensitivity to aluminum?

Emotional variance of all types of negative emotions.-Unexplained feelings of apprehension, dread,

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uneasiness-feelings of shame, embarrassment, and inferiority-irritability annoyance and and agitation-these feelings can become violent.

What are some industries were exposure to aluminum can happen?

1) Mining industry2) Factory work3) Welding

agricultureWhat is another source of aluminum exposure? Aluminum vapors are ingested every time the

nose catches cigarette smoke wafting by.What foods can lead to aluminum exposure? 1) Baking powder

2) Self-rising flour3) Salt4) Baby formula5) Coffee creamers6) Baked and processed foods

Coloring and caking agentsWhat drugs are sources of aluminum exposure? 1) Antacids

2) Analgesic3) Anti-diarrheals

Additives such as magnesium stearateWhat vaccines are sources of aluminum exposure?

1) Hepatitis A and B2) Hib3) DTap4) Pneumococcal vaccine

Gardasil (HPV) and othersWhat cosmetics and personal care products are sources of aluminum exposure?

1) Antiperspirants2) Deodorants3) Lotions4) Sunscreens

shampoosWhat are some other sources of aluminum exposure?

Aluminum products including1) foil2) cans3) juice pouches4) tins5) water bottles

Red meats cooked in aluminum foil showed an increase in aluminum by 89 to ___ percent.

378

Poultry is increased by 76 to ____ percent when cooked in aluminum foil.

214

Aluminum levels increase with ___ (longer/higher) cooking temperatures and longer cooking times.

higher

How can Antimony toxicity occur? Through occupational exposure or during

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therapyWhat can occupational exposure cause? Respiratory irritation, pneumoconiosis,

antimony spots on skin, and gastrointestinal symptoms

True or False?Antimony trioxide is possibly carcinogenic to humans

True

What can antimony be used for therapeutically? Treatment of leishmaniasis and schistosomiasis

What is the major toxic side-effect of antimonials as a result of therapy?

Cardiotoxicity and pancreatitis

Where are the above side-effects mostly seen in?

HIV and visceral leishmaniasis co-infections

How/where can antimony be measured in? Urine, feces, and bloodArsenic is a heavy metal. It exists in compounds that may be organic or inorganic. Which form is toxic?

It is highly toxic in its inorganic form.

Why is arsenic toxic? on many cell enzymes, which affect metabolism and DNA repair

What is an effective antidote? British anti-lewisite (BAL), The active agent in BAL is dimercaprol, a sulfhydryl-reducing agent.

What is the one of the most widely known toxic metal?

It is Arsenic (As)

What are the most common routes of exposure to arsenic?

Ingestion and inhalation are the most common routes of exposure to arsenic, and they are the routes that most commonly lead to illness

Where are major sources of inhaled arsenic may come from?

Major sources of inhaled arsenic may come from air emissions from burning of fossil fuels that contain arsenic, cotton gins, glass manufacturing operations, pesticide manufacturing facilities, smelters, and tobacco smoke

Where is arsenic found? Meat, fish, and poultry account for 80% of dietary arsenic intake. Fish, bivalve shellfish, and algae also contain arsenic in the form of arsenobetaine and arsenocholine, sometimes referred to as "fish arsenic."

What is shown to have high levels of inorganic Arsenic?

Recent studies have shown one form of seaweed, hijiki, to contain high levels of inorganic arsenic

What is the effect of Beryllium poisoning? Beryllium poisoning is illness resulting from the toxic effect of beryllium in its elemental form or in various chemical compounds

What is the toxicity of Beryllium? The toxicity of beryllium depends upon the duration, intensity and frequency of exposure

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(features of dose), as well as the form of beryllium and the route of exposure (i.e. inhalation, dermal, ingestion).

What are some uses of Beryllium in everyday life?

It has been used in electronics, ceramics, research and development labs, aircraft, and the atomic energy and defense industry

What is Chronic berylliosis? It is a pulmonary and systemic granulomatous disease

What is the cause of Chronic berylliosis? Exposure to beryllium.What is the form of Acute beryllium disease? Chemical pneumonitis.Is the quantification of Beryllium in serum or urine useful in making the diagnosis?

No, air analysis (TLV threshold limit value), is the preferred method of exposure evaluation.

Nam specific metal which is Byproduct of zinc and lead smelting?

Cadmium (Cd)

What does breathing the fumes of Cd vapors lead to?

Nasal epithelial deterioration and pulmonary congestion resembling chronic emphysema.

What is a common source of chronic exposure? Spray painting of organic base paints without the use of protective breathing apparatus

Auto repair mechanics represent a workgroup that has significant opportunity for exposure to -

Cadmium (Cd)

What does exposure to Cadmium cause? Cd toxicity present with renal dysfunction with proteinuria. Chronic exposure causes accumulated renal damage.

What is a side effect of tobacco smoke? Moderately increased blood CadmiumAt what concentration would you observe acute toxicity by Cadmium?

If blood concentration exceeds 50 ng/mL

By what methods would you be able to quantify Cadmium?

Cadmium is usually quantified by atomic absorption spectrometry, but it also has been accurately quantified by ICP-MS

Occupational exposure to which element is considered hazardous?

Chromium

Which work industries use Chromium? Used in the manufacture of stainless steel, chrome plating, tanning of leather, as a dye for printing and textile manufacture, as a cleaning solution, as an anticorrosive agent in cooling systems, and in metallic orthopedic implants.

What is the toxic form of Cr? Toxic form of Cr is Cr6+.Which would be the best method of analyzing Chromium?

ICP MS is the preferred technology for quantification of chromium in body fluids

What is an essential cofactor for vitamin B12? Cobalt.

What are symptoms of acute Cobalt exposure? Cardiomyopathy and Renal Failure.

What kind of sample is usually used to Urine.

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determine excessive exposure of cobalt?

Where is cobalt usually found? They are found in metal alloys that are hard and resistant to corrosion.

How is cobalt quantified in biological tissues? It is quantified by atomic absorption spectrometry or by ICP-MS.

What is Copper (Cu)? • Found in common pesticides, marine antifouling paints, and wood preservatives

• Ingestion of copper produces gastrointestinal symptoms, hemolytic anemia, hepatitis with jaundice, and renal damage.

Deficiency in Copper cause what Disease? The classical presentation of Cu toxicosis is represented by the genetic disease of Cu accumulation known as Wilson's disease. This disease is typified by hepatocellular damage (increased transferases) and/or changes in mood and behavior caused by accumulation of Cu in central neurons.

What is the specimen of choice for diagnosis Wilson Disease?

Evaluation of serum and urine copper concentration is useful in diagnosing Wilson's disease.

Where does Copper circulate in the body? Since copper circulating in blood is bound to ceruloplasmin and ceruloplasmin formation is decreased in Wilson's disease, serum copper concentration is less than the reference interval for serum, and urinary copper concentrations are increased.

What is Gadolinium (Gd)? A chemical element found in image contrast agents used during Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) procedures.

What is the name of an agent involved in nephrogenic systemic fibrosis?

Gadolinium based contrast agent (GBCA) is thought to be involved in nephrogenic systemic fibrosis.

When will be the most consistent risk factor in GBCA?

Exposure to GBCA during a condition of low glomerular filtration rate appears to be the most consistent risk factor.

How is GBCA excreted? Because GBCA is excreted by the kidney, exposure is prolonged in patients with renal insufficiency.

How Lead (Pb) has been found in the environment?

Commonly found in the environment that is an acute and chronic toxin.

Where is Lead (Pb) commonly found? Common in paints, ceramics, leaded gasoline in automobiles and in soil.

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How does a person exposure to Lead? Exposure to Pb is through ingestion, inhalation or dermal --contact.

What is the main reason of measuring blood Pb?

The definitive test for lead toxicity is measurement of blood Pb

What is the Pb concentration in adults to be considered of significant exposure?

WHO has defined blood Pb concentrations >30 µg/dL in adults as indicative of significant exposure

What is the Lead concentrations required chelation therapy

Is >60 µg/dL

What is analysis of Lead routinely performed by?

ICP MS, electrothermal atomic absorption spectrometry, or anodic stripping voltammetry

What is the specimen of choice for lead analysis?

EDTA blood

What are other methods can be used in urine quantification?

Urinalysis

What is Manganese? Ubiquitous in environment used as a binding agent in red bricks, An anti-corrosive in most steel alloys, a cleaning agent for glassware, and a common pigment in paints and glazes.

How can you get toxicity from Manganese? Toxicity comes as a result of exposure from dust from mining, ore crushing, machining of alloys, manufacture or destruction of bricks.

What can accumulation of Manganese in the brain cause?

Manganism (Parkinson-like neurodegenerative disorder).

What can be tested for indication of Manganese in the body?

Blood and urine concentrations are good indicators of exposure.

What is Mercury commonly known as? QuicksilverWhat was Mercury formerly named as? HydrargyrumWhat is Mercury? A heavy, silvery d-block element, mercury is

the only metallic element that is liquid at standard conditions for temperature and pressure.

What is Mercury used in? Mercury is used in thermometers, barometers, manometers, sphygmomanometers, float valves, mercury switches, mercury relays, fluorescent lamps.

What is Mercury replaced by? Replaced by alcohol- or galinstan-filled glass thermometers and thermistor- or infrared-based electronic instruments.

What are some applications for use of mercury? Clinical scientific research application dataWhat is mercury used for as an almalgam material?

Dental restoration

What is the name of a medical condition caused by exposure to mercury?

Hydrargyria

Toxic effects of Mercury Includes damage to the brain, kidneys and lungs. Mercury poisoning can result in several

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diseases, including acrodynia (pink disease), Hunter-Russell syndrome, and Minamata disease.

Symptoms of Mercury. It includes sensory impairment (vision, hearing, speech), disturbed sensation and a lack of coordination. The type and degree of symptoms exhibited depend upon the individual toxin, the dose, and the method and duration of exposure.

What is the used of Nickel (Ni)? Used in the production of metal alloys, Ni-based rechargeable batteries, and as a catalyst in the hydrogenation of oils

What happened when Nickle exposed to air? Patients exposed to Ni carbonyl exhibit rapid onset of pulmonary congestion and inability to oxygenate hemoglobin, followed by development of lesions of the lung, liver, kidney, adrenal glands and spleen.

Uses Platinum (Pt) in chemotherapy. Pt-containing anti-neoplastic agents, cisplatin and carboplatin are used in chemotherapy-Cause nephrotoxicity-Can induce neutropenia-Can induce renal failure if administered with nephrotoxic antibiotics

Platinum (Pt) measured by Which methods? Measured by AA-ETA and ICP-MSSelenium is a Essential element that may play a role in mitigating biological damage caused by what?

oxidative damage.

Selenium is a cofactor required to maintain what type of activity?

glutathione peroxidase

What type of muscle is the most susceptible to selenium deficiency ?

Cardiac (cardiomyopathy)

Name one type of Symptom caused by Se poisoning

hair loss, muscle cramps, nausea, vomiting, diarrhea, joint pain, fatigue, fingernail changes and blistering skin

Selenium deficiency is also related to what? total parenteral nutritionWhat is the most abundant element in earth's environment (26% of earth's crust)

silicon

Silicon toxic forms include what? asbestos and silicone

Inhalation of asbestos containing dust leads to the position of asbestos fibers in the pulmonary alveoli causing asbestosis with the presence of what?

asbestos bodies

Diagnosis of silicon toxicity can be made by chest radiograph and presence in sputum and

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what type of tests? lung biopsyHow does dangerous exposure to asbestos occur?

When materials containing the fibers are disturbed.

What is asbestosis? Fibers accumulate in the lungs’ narrow branches, inflamming, and scarring airways.

What does asbestosis cause? Chronic cough and chest painWhat are pleural plaques? The needle-shapes fibers may also migrate

into the pleural lining. Pleura becomes inflamed, plaques builds up and may restrict breathing.

What significantly increases lung cancer? SmokingWhat is the Silver analysis limited to? Silver analysis is limited to monitoring of

burn patients treated with silver sulfadiazine, and monitoring of patients treated with silver-containing nasal decongestants.

What is argyria? graying of the skinWhen is argyria produced? Argyria is produced when Silver (Ag) is

deposited in many organs including the sub- epithelium of the skin and mucous membranes

Which toxic metal is a byproduct of lead smelting, coal combustion, and cement manufacture?

Thallium (Tl)

Which toxic metal is formerly used in rodent poisons?

Thallium (Tl)

Thallium is absorbed by____(1)____, , ___(2)____and ___(3)____

1) ingestion2) inhalation3) skin contact

What are the effects of exposure to high doses of thallium?

hair loss, peripheral neuropathy and seizures, and renal failure

What toxic metal is the 9th most abundant element in the earth's crust?

Titanium

If ingested, titanium is rapidly excreted where? urine and stoolTrue or FalseTitanium dust is irritating and almost completely fibrogenic.

False(nonirritating and almost completely nonfibrogenic)

Where does titanium-containing alloys being used?

in artificial joints, prosthetic devices, and implants

What allows osseointegration? Titanium dioxideTrue or FalseConcerning titanium, serum concentrations are used to monitor prosthesis degradation.

True

Vanadium is not a recognized occupational hazard. True or FalseA. TrueB. False

A

Vanadium is a byproduct of refining, D

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Specifically:A. IronB. TitaniumC. UraniumD. All of the AboveA clinically significant reaction of Vanadium by the human body includes:A. Green tongueB. Runny NoseC. Green blood at venipunctureD. Discoloration of Nails

A

A patient sample has a flag for Vanadium, a clinically significant toxin. What are the possible causes for the elevated serum concentrations present?A. Compromised renal function and

dialysisB. Joint replacementC. Prosthesis degradationD. All of the above

D

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