Toxicology Flashcards
(218 cards)
1
Q
Study of poisons and xenobiotics
A
TOXICOLOGY
2
Q
substances that can cause harmful effects upon exposure
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Poisons
3
Q
substances that are not normally found or produced by the body
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Xenobiotics
4
Q
4 MAJOR INTERRELATED DISCIPLINES OF TOXICOLOGY
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Mechanistic Toxicology
Descriptive Toxicology
Forensic Toxicology
Clinical Toxicology
5
Q
Dose-Response Mechanism
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Mechanistic Toxicology
6
Q
Dose of toxin that will result in harmful effects
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Dose-Response Mechanism
7
Q
Determines the dose of toxin that will result in harmful effects
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Mechanistic Toxicology
8
Q
Provides a basis for rational therapy design from the known harmful dose
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Mechanistic Toxicology
9
Q
Development of laboratory tests to assess the degree of exposure in individuals
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Mechanistic Toxicology
10
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involves risk assessment of toxins
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Descriptive Toxicology
11
Q
Performed by FDA and part of pre-clinical studies of novel drugs
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Risk assessment
12
Q
Assesses toxic, lethal, and effective dose
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Risk assessment (Descriptive Toxicology)
13
Q
Uses result from animal experiments to predict what level of exposure will cause harm in humans
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Descriptive Toxicology
14
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Medical & legal consequence of toxin exposure; performed in autopsy
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Forensic Toxicology
15
Q
Establishes & validates analytical performance of tests methods used to generate evidence in legal situations
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Forensic Toxicology
16
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Study of interrelationship between toxin exposure and disease states (toxic effect)
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Clinical Toxicology
17
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Emphasis on diagnostic testing and therapeutic intervention (antidote to toxins)
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Clinical Toxicology
18
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ROUTES OF TOXIN EXPOSURE
A
Ingestion – most often in clinical setting
Inhalation
Transdermal absorption
19
Q
how is toxin absorbed in GI tract
A
Passive diffusion
*not requiring transport protein
20
Q
substances readily diffusible across cell membranes along GI
A
Hydrophobic (non-polar) subs.
21
Q
substances that cannot passively diffuse across cell membranes (require transporters)
A
Ionized subs.
22
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absorbed in the stomach; proteinated by gastric juices → became non-ionized → readily absorbed by stomach
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Weak acids
23
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absorbed in the intestine (neutral to slightly alkaline pH)
A
Weak bases
24
Q
some toxins that are not absorbed by GI produce these local effects given that they are toxic to that site
A
diarrhea
malabsorption
GI bleeding
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Factors that influence toxin absorption
Rate of Dissolution
GI mobility
Resistance to degradation
Interaction with other substances in GI
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Effect in absorption rate when there is imbalance in mobility such as low bowel movement, diarrhea
Less/decreased toxin absorption
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T/F
Some toxins are resistant to degradation = remains intact in GI (may or may not be absorbed by the GI)
T
28
Effect in absorption rate when toxins interact with other GI substances
Decreased rate of absorption
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single, short-term exposure to toxic substance
Acute toxicity
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repeated exposure for extended period of time
Chronic toxicity
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dose that would predict to produce a toxic response in 50% of the population
TD50 (toxic dose)
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dose that would predict death in 50% of the population
LD50 (lethal dose)
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dose predicted to be effective or have a therapeutic benefit in 50% of the population; used in therapeutic drugs that may cause adverse effects
ED50 (effective dose)
34
Rapid, simple, qualitative procedure intended to detect the presence of specific substance
Screening test
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test that has good sensitivity, lack specificity
Screening test
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Quantitative tests; specific for a single substance or class
Confirmatory test
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Example of Confirmatory tests for toxic agent analysis
TLC (Thin Layer Chromatography), GC (Gas Chromatography)
ICP-MS/AA (Inductively Coupled Plasma – Mass Spectrometry/Atomic Absorption)
GC-MS (Gas Chromatography-Mass Spectrometry)
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test used for inorganic substance
ICP-MS/AA (Inductively Coupled Plasma – Mass Spectrometry/Atomic Absorption)
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test used for organic substance
GC-MS (Gas Chromatography-Mass Spectrometry)
40
reference method for toxic agents analysis
GC-MS (Gas Chromatography-Mass Spectrometry)
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Common CNS depressant
Alcohol
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effect of LOW dose exposure to alcohol
Confusion
Euphoria
Disorientation
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effect of HIGH dose exposure to alcohol
Unconsciousness
Paralysis
Death
44
Sample used for alcohol det.
Whole Blood
Serum
Plasma
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Methods used for alcohol det.
Enzymatic method
Gas Chromatography
Osmometry methods (Osmolal Gap)
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test that uses alcohol dehydrogenase (ADH)
Enzymatic method
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Reference method for ethanol det.; may quantitate methanol and isopropanol
Gas Chromatography
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Computed method; NOT ethanol specific (may increase in other conditions)
Osmometry methods (Osmolal Gap)
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formula of Osmometry methods (Osmolal Gap)
Osmolal Gap = MEASURED osmolality - CALCULATED osmolality
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serum ethanol if there is ↑ 10 mOsm/Kg
60 mg/dL serum ethanol
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Most common toxicant & substance of abuse (US)
Ethanol (Grain Alcohol)
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aka ethanol
Grain Alcohol
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Depresses CNS; ↑ heart rate and BP
Ethanol (Grain Alcohol)
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a Vasopressin inhibitor (↑ urine output leading to diuresis)
Ethanol (Grain Alcohol)
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Effects of ethanol intoxication
blurred vision
incoordination
slurred speech and coma
“hangover symptoms”
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FATAL DOSE of ethanol
300-400 mL (pure alc.) in <1 hr
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TOXIC BLOOD LVL of ethanol
>400 mg/dL
>500 mg/dL: requires hemodialysis to filter all alcohol
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ANTIDOTE for ethanol intoxication
Diazepam
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method for ethanol det.
Gas Chromatography
Enzymatic (ADH) method
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T/F
Serum and plasma have lower ethanol conc. than whole blood
F
Serum and plasma have HIGHER ethanol conc. than whole blood (ethanol is uniformly distributed in body water such as serum or plasma)
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conditions that causes false INCREASED ethanol
Use of alcohol antiseptic during venipuncture
Failure to use fluoride tubes
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Tube necessary for blood collection during ethanol det.
Fluoride tubes (prevent glycolysis and bacterial fermentation as they produce alc. (byproduct)
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aka methanol
Wood Alcohol
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Most commonly used solvent
Methanol (Wood Alcohol)
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Homemade liquor contaminant
Methanol (Wood Alcohol)
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Methanol (Wood Alcohol) metabolites
formaldehyde
formic acid
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Methanol (Wood Alcohol) metabolite that causes intoxication
Formic acid
68
T/F
Ethanol has more severe intoxication than methanol
F
METHANOL has more severe than ethanol
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Effects of methanol intoxication
metabolic acidosis
pancreatic necrosis
ocular toxicity (frank blindness)
70
toxins that can cause ocular toxicity (frank blindness)
Methanol (Wood Alcohol)
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FATAL DOSE of methanol
60-250 mL
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TOXIC BLOOD LVL of methanol
>50 mg/dL
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ANTIDOTE for methanol intoxication
Sodium Bicarbonate
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Commonly available alcohol
Isopropanol (Rubbing Alcohol)
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aka Isopropanol
Rubbing Alcohol
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Isopropanol (Rubbing Alcohol) metabolite
acetone
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enzyme that converts isopropanol to its metabolite
hepatic ADH
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has longer halflife in the body compared to ethanol metabolite
acetone
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has similar to ethanol toxicity but has a longer intoxication due to its metabolite having a longer half life
Isopropanol (Rubbing Alcohol)
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FATAL DOSE of Isopropanol
250 mL
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ANTIDOTE for Isopropanol intoxication
Active charcoal
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aka Ethylene Glycol
1,2-ethanediol
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Component of hydraulic fluid and anti-freeze
Ethylene Glycol (1,2-ethanediol)
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Accidentally ingested by children due to its sweet taste
Ethylene Glycol (1,2-ethanediol)
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Ethylene Glycol (1,2-ethanediol) metabolites that can cause severe metabolic acidosis
oxalic acid
glycolic acid
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Effects of Ethylene Glycol intoxication
severe metabolic acidosis
Ingestion (↑levels): Calcium oxalate crystals
deposition in renal tubules → kidney damage
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Blood ethanol level if there is no obvious impairment
0.01-0.05%
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Blood ethanol level if there is mild euphoria, decrease inhibitions, some impairment of motor skills
0.03-0.12%
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Blood ethanol level if there is decrease inhibitions, loss of critical judgment, memory impairment, diminished reaction time
0.09-0.25%
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Blood ethanol level if there is decrease inhibitions
0.03-0.25%
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Blood ethanol level if there is mental confusion, dizziness, strongly impaired motor skills (staggering, slurred speech)
0.18-0.30%
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Blood ethanol level if there is inability to stand or walk, vomiting, impaired consciousness
0.27-0.40%
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Blood ethanol level indicating coma and possible death
0.36-0.50%
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Produced by incomplete combustion of carbon-containing substances
Carbon monoxide (CO)
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Colorless, odorless and tasteless gas that is rapidly absorbed into the blood
Carbon monoxide (CO)
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Carbon monoxide (CO) has _____X more affinity to Hb than O2
200–225x
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caustic agents of carbon monoxide (CO)
household products
occupational settings
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formed when CO is bound to Hb
Carboxyhemoglobin
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Leads to hypoxia since O2 is not bound to Hb → affects heart and brain
Carboxyhemoglobin formation due to CO
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one of the indication is cherry-red colored blood
Carboxyhemoglobin formation
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routes of exposure to CO
Aspiration
Ingestion
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CO intoxication if exposed through aspiration
pulmonary edema and shock
can lead to death
103
CO intoxication if exposed through ingestion
esophageal lesions and GIT lesions (perforation)
CAN LEAD TO:
hematemesis (vomiting of blood)
abdominal pain & shock (if there is chronic blood loss)
metabolic acidosis/alkalosis
104
T/F
Carboxyhemoglobinemia Symptoms depends on the carboxyghemoglobin formed
T
105
COHb (%) typical in nonsmoker
0.5
106
COHb (%) seen in smokers
5-15
107
COHb (%) having shortness of breath with vigorous exercise
10
108
COHb (%) having shortness of breath with moderate exercise
20
109
COHb (%) having severe headache, fatigue, impairment of judgment
30
110
COHb (%) having confusion, fainting on exertion
40-50
111
COHb (%) when there is unconsciousness, respiratory failure, death with continuous exposure
60-70
112
COHb (%) that is immediately FATAL
80
113
CoHb Tx
100% O2 therapy
114
ANTIDOTE for CO
Dilution (of substance)
115
METHODS for CO det.
Spot Plate Test
Differential Spectrophotometry
Gas Chromatography
116
How is spot plate test for CO det. performed?
5mL aqueous whole blood (1/20) + 5mL of 40% NaOH
Aqueous whole blood: prepared by diluting blood with water (1 part of blood per 20 parts volume of solution)
Add 5mL of 40% NaOH
Pink color solution = >20% COHb
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Indication if there is >20% COHb in Spot Plate Test
Pink colored solution
118
Principle: Different forms of Hgb present with different spectral absorbency curves (6 diff. wavelengths)
Differential Spectrophotometry
119
Most commonly used method and basis of automated systems for CO det.
Differential Spectrophotometry
120
Principle: utilizes thermal conductivity by releasing carbon monoxide using potassium
ferricyanide
Gas Chromatography
121
an accurate and precise method (Ref. method) for CO
Gas Chromatography
122
Supertoxic substance
Cyanide
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Cyanide may exist as
solid or gas
124
odor of the gas form of cyanide
Bitter almond odor
125
One of the most common suicidal agents (in the form of silver cleaners)
Cyanide
126
Used in many industrial processes
Cyanide
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Insecticides and rodenticides component
Cyanide
128
Produced by pyrolysis of some plastics
Cyanide
129
Routes of exposure to cyanide
Inhalation
Ingestion
Transdermal absorption
130
route of exposure when one may be exposed to both cyanide and CO
smoke inhalation
131
blood component where cyanide may bind
heme iron
mitochondrial cytochrome oxidase
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intoxication if Cyanide + heme iron
Hb can no longer bind O2 leading to hypoxia and anemia
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intoxication if Cyanide + mitochondrial cytochrome oxidase
Inhibits mitochondrial cytochrome oxidase → increases cellular oxygen tension and venous partial O2 pressure
134
METHODS for cyanide det.
Ion-selective electrode
Photometric assay (two-well microdiffusion separation)
Urinary thiocyanate concentration
135
most commonly used methods for cyanide det.
Ion-selective electrode
Photometric assay (two-well microdiffusion separation)
136
test used in exposure to very low levels of cyanide
Urinary thiocyanate concentration
137
Some METALS AND METALLOIDS assessed in toxicology
Arsenic
Cadmium
Lead
Mercury
Pesticides
138
A metalloid that exists as a bound to or as a primary constituent of many organic or inorganic compounds
Arsenic
139
Binds to thiol groups in protein due to high affinity
Arsenic
140
Common homicidal & suicidal agent
Arsenic
141
Can cross the placenta
Arsenic
142
Arsenic intoxication
IV hemolysis
Hemoglobinemia
Nephrotoxicity
Multi-organ involvement
143
Indications of Arsenic intoxication
Garlic breath odor
Metallic taste
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SPECIMENS used if there is short-term Arsenic exposure
Blood
Urine
145
SPECIMENS used if there is long-term Arsenic exposure
Hairs
Nail
*As loves to bind to keratinized tissues
146
METHODS for As det.
Atomic Absorption Spectrophotometry (AAS)
Reinsch test
147
Utilized in electroplating and galvanizing
Cadmium
148
Found in paints and plastics
Cadmium
149
Binds to proteins and cellular constituents
Cadmium
150
Cadmium Intoxication
Nephrotoxic
o Tubular proteinuria
o Glucosuria
o Aminoaciduria
151
Spx for Cadmium det.
Urine
Whole blood
152
merhod for Cadmium det.
AAS
153
Paints & make-ups color enhancer
Lead
154
Found in gasoline & pipe plumbing
Lead
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Common water contaminant
Lead
156
Potent enzyme inhibitors
Lead
Mercury
157
Enzymes inhibited by lead
Delta-aminolevulinic acid (D-ALA) synthetase
Pyrimidine-5’-nucleotidase (P5’N)
Na-K ATPase
158
responsible for excess DNA removal in RBC nucleus
Pyrimidine-5’-nucleotidase (P5’N)
159
What will happen if Pyrimidine-5’-nucleotidase (P5’N) is inhibited by LEAD?
DNA accumulates inside the RBC causing basophilic stippling
160
Has high affinity to many macromolecular structures and distributed throughout the body; Present in all biologic system but has NO physiologic nor biochemical function
LEAD
161
has SLOW elimination through renal filtration
lead
162
reasons why lead has SLOW elimination through renal filtration
LOW Pb conc. in the blood
Pb combines with the bone matrix (hence, largest Pb conc. is in skeletal system): may persists up to 20 years
163
toxic dose of lead
>0.5 mg/day
164
fatal dose of lead
0.5 g
165
toxic blood lvl of lead
>70 ug/dL
166
Lead Intoxication
Anemia – Pb inhibits heme synthesis
Decreased RBC membrane integrity
Encephalopathy
Nephrosis
Anorexia
Peripheral neuropathy
Birth defects
Low IQ
Carcinogenesis
Renal damage
167
Indications of Lead intoxication
Basophilic stippling/ blueberry muffin-like RBC
Increased Urinary ALA
Free RBC protoporphyrin
168
sensitive indicator of Pb poisoning; due to inhibited P5’N
Basophilic stippling
169
this presence is due to Pb inhibiting multiple steps of heme synthesis
Free RBC protoporphyrin
170
Tx for lead intoxication
chelators
171
examples of chelators used for lead intoxication tx
EDTA
Dimercaptosuccinic acid (DMSA)
172
SPECIMENS used for Lead det.
Whole blood
Urine (recent Pb exposure)
Hair
173
spx used if there is RECENT lead exposure
urine
174
Methods for lead det.
1. Screening
a. Zinc Protoporphyrin test (Fluorometric test)
b. Aminolevulinic acid dehydratase (ALAD) test
2. In-vivo X-ray Fluorescence of Bone
3. AAS
4. ICP-MS
5. Anodic stippling voltammetry
175
sensitive method for Lead screening
Aminolevulinic acid dehydratase (ALAD) test
176
enzyme inhibited by mercury
Catecholamine-0-methyltransferase
177
Catecholamine metabolic enzyme (metabolizes epinephrine or norepinephrine)
Catecholamine-0-methyltransferase
178
unmetabolized catecholamines due to MERCURY presence may lead to
pheochromocytoma - tumor that autonomously produces catecholamines
179
reference value of mercury
<10 ug/dL
180
3 forms of mercury with different toxicity levels
elemental mercury
inorganic salts
component of organic compounds
181
value if there is significant exposure to Hg
>50 ug/dL (whole blood)
182
Hg intoxication mimics these disorders
adrenal gland disorders (due to inhibited catecholamine metabolism)
183
Indicators of Hg intoxication
Hypertension
Tachycardia
Sweating
*these are pheochromocytoma symptoms
184
spx for Hg det.
Whole Blood
24h Urine
185
methods for Hg det.
Reinsch test
AAS
Anodic Stippling Voltammetry
186
Hg liquid at RT
Elemental mercury
187
Ingested but may not show significant effects (not absorbed)
Elemental mercury
188
Inhalation is very rare and insignificant (due to low vapor pressure
Elemental mercury
189
Elemental mercury intoxication
Pink disease (acrodynia)
Erethism
190
continuous skin exfoliation upon exposure until skin turns pink caused by elemental mercury
Pink disease (acrodynia)
191
moderately toxic form of Hg
inorganic salts
192
Hg form that is partially absorbed by the GI tract
inorganic salts
193
this form of Hg not absorbed shows GI tract toxicity
Inorganic salts
194
Inorganic salts (Hg) intoxication
Nephrotoxic (glomerular proteinuria)
195
Alkyl mercury intoxication
congenital Minimata disease
196
a neurologic disorder resembling cerebral palsy
congenital Minimata disease
197
Most toxic form of Hg; rapidly absorbed
component of organic compounds
198
ex. of Hg component of organic compounds
methylmercury
199
Substances intentionally added to the environment to kill/harm undesirable life forms
Pesticides
200
Pesticides can be classified as either
insecticides or herbicides
201
Forms of insecticides
Organophosphate
Carbamates
Halogenated Hydrocarbons
202
most common form of insecticide
Organophosphate
203
responsible for 1/3 of all pesticide poisoning
Organophosphate
204
forms of insecticides that inhibits ACETYLCHOLINESTERASE
Organophosphate
Carbamates
205
Muscle cell stimulant; stimulant of some endocrine and exocrine glands
Acetylcholine
206
Metabolized by acetylcholinesterase
Acetylcholine
207
what is the effect of Organophosphate and Carbamates in inhibiting acetylcholine metabolism?
cause systemic effects (since acetylcholine stimulates several parts of the body)
208
Effects of low level exposure to pesticides
Salivation
Lacrimation
Involuntary urination & defecation
209
Effects of high level exposure to pesticides
* Bradycardia
* Muscular twitching
* Cramps
* Apathy
* Slurred speech
* Behavioral changes
* Death (due to respiratory failure)
210
spx used for pesticides det.
RBC for AIA
211
Used for INDIRECT measurement of organophosphate poisoning
Acetylcholinesterase Inhibition Assay (AIA)
212
T/F
direct organophosphate poisoning measurement is highly possible
F
Direct organophosphate poisoning measurement is highly IMPOSSIBLE because of its high affinity to proteins
213
Alternative & Screening test for pesticides
Serum Pseudocholinesterase Activity
214
a method used for pesticide det. that lacks sensitivity and specificity
Serum Pseudocholinesterase Activity
215
methods for pesticide det.
Acetylcholinesterase Inhibition Assay (AIA)
Serum Pseudocholinesterase Activity
216
other conditions where Serum Pseudocholinesterase Activity may be decreased?
acute infection, pulmonary embolism, hepatitis, cirrhosis
217
alcohols that can cause metabolic acidosis
methanol
ethylene glycol
218
nephrotoxic metals and metalloids
arsenic
cadmium
inorganic Hg
