Acids and AlkalisCaustic Agents

Acids and Alkalis

Corrosives - denotes an acidic substance Caustics - denotes an alkaline substance Federal Hazardous Substance Act of 1967 Cause tissue injury by a chemical reaction - accept

(base) or donate (acid) a proton. Severity of tissue injury is determined by:

• the substances pH or pKa,

• concentration,

• duration of contact and

• volume of contact.

Acids and Alkalis Ingestion is an extremely common event, accounts

229,500 alkali drain cleaners and acidic toilet bowl cleaners

are responsible for most fatalities 10% of caustic ingestions result in severe injury

requiring treatment between 1-2% result in stricture formation 80% of ingestions are in children > 5 years most adult ingestions are intentional

Acids Mechanism of action - denature proteins

• coagulative necrosis• cell morphology not grossly altered, destruction of

enzymatic proteins• acid burns cause formation of tough leathery eschar

or coagulum (which sloughs in 3-4 days)• little to no systemic absorption• stomach is most commonly involved organ

Acids, cont.

Management - any ingestion constitutes a medical emergency

skin or eye contact - • flush with copious amounts of water. remove

contact lens and jewelry• wash skin with mild soap• do not apply topical ointments, creams, or

dressings

Acids, cont. Ingestion

• serious solid ingestions are rare as the particles usually stick to the oropharynx, but liquid exposures can be severe

• burning is so severe patient probably can not swallow

• do not give carbonated beverages• do not give water, water + acid explosive release of

steam - exothermic reaction• do not induce vomiting• maintain airway

Acids, cont.

Clinical concerns:• perforation may occur after the third to

fourth day as eschar sloughs• gastric outlet obstruction may develop over a

2-4 week period• upper GIT hemorrhage

Acids, cont.

Common acid containing sources• toilet bowl cleaners• automotive batteries• rust removal porducts• metal cleaning products• drain cleaning products

Acids, cont.

Boric acid - H3BO3• weak bacteriostatic agent• used as an insecticide for roaches (roach motels)• do not apply to open wounds• toxic to the kidneys• can cause a severe dermatitis - boiled lobster rash -

seen on palmar and plantar surfaces and buttocks

Acids, cont.

Carbolic acid - phenol• one of the oldest disinfectants known• used as a deodorizer - Lysol• absorbed through intact skin

Signs - nausea, diaphoresis, CNS stimulation, hypotension, renal failure

Treatment - demulcents, activated charcoal

Alkalis

More common cause of toxicity than acids Most common alkaline agents causing toxicity

• Ammonia• Sodium hydroxide• both of these are found in household cleaners and

drain cleaners

Most cases are in children under the age of five years

Alkalis, cont. Mechanism of action

• tissue injury causes by liquefactive necrosis (saponification of fats and solubilization of proteins)

• cell death occurs from emulsification and disruption of cell membranes

• OH ion reacts with tissue collagen causing it to swell and shorten

• most severe injured tissues are the squamous epithelial cells of the oropharynx and esophagus (the most commonly involved organ)

• alkali burns to the skin are yellow, soapy and soft

Acids, cont.

Clinical concerns• tissue edema - leading to possible airway

obstruction• erythema• ulceration • necrosis of tissues with possible stricture

formation (depends on depth of burn)• perforation can occur

Alkalis, cont.

Management of toxicity• eye and skin contamination - flush with copious

amounts of water• ingestion - any ingestion constitutes a medical

emergency• do not induce vomiting• give demulcents (milk, water or egg whites)

Alkalis, cont. Common base containing sources

• drain cleaning products• ammonia - containing products• over cleaning products• swimming pool cleaning products• automatic dishwasher detergent• hair relaxers• clinitest tablets• bleaches• cement

Alkalis, cont.

Disc batteries• usually pass through GIT in 48 hours• can become lodged

• pressure necrosis

• leak out potassium or sodium hydroxide

Soaps - most are non toxic• have emetic action so vomiting is spontaneous• automatic dishwashing soap - highly corrosive

Alkalis, cont. Ammonia - NH3 - at room temp is a highly H2O

soluble, colorless, irritant gas with a pungent odor. 1993 anhydrous ammonia was the 3rd most produced

chemical in the US farmers use 1/3 for fertilizer and animal feed A component of may household cleaning products -

glass cleaners, toilet bowl cleaners, metal polishes, etc.) highly alkaline and corrosive

• household ammonia - not as corrosive

Alkalis, cont. Most common mechanism is exposure to anhydrous

ammonia - liquid or gas• NH3 + H2O ------ NH4OH

• this reaction is exothermic - causes significant thermal injury

Ammonium hydroxide also causes severe alkaline burns 1998, US PCC reported 6,000 cases, 95% accidental,

13% resulted in moderate to severe outcomes Ingestion of household solutions is usually accidental

and occurs in young children, adult ingestions are usually suicide attempts

Alkalis, cont. Typical household ammonia

• contain 3-10% ammonia hydroxide• pH less than 12.5 - caustic burns usually only seen

with pH’s >12.5 so household products do not typically lead to significant burns

• patients present with oropharyngeal and epigastric pain

• may cause aspiration pneumonitis• kids may bite smelling salts - 20% ammonia - can

cause esophageal burns and mild respiratory symptoms

Alkalies, cont.

Bleach - sodium hypochlorite - NaOCl• taste terrible and spontaneously vomited• never mix bleach with acid or alkaline cleaning

agents - release of chlorine gas• good to apply topically for any bites

Hydrocarbons

Hydrocarbons Organic compounds containing H and C Derived from plants or from petroleum

distillates 3 basic types

• aliphatic• aromatic• halogenated

Petroleum distillates - produced from fractional distillation of crude petroleum

Terpenes - distillates of pinewood

Hydrocarbons, cont. Examples of petroleum distillates

• kerosene• gasoline• mineral spirits• naphtha• mineral seal oil• diesel oil• fuel oil

Hydrocarbons, cont. Characteristics surface tension - cohesiveness of molecules

on the surface of a liquid volatility - tendency of a liquid to change into

a gas or vapor viscosity - resistance of a substance to flow

over a surface, directly relates to the aspiration hazard

• low verses high viscosity

Hydrocarbons, cont. Mechanism of Toxicity 64, 634 cases of HC exposure in 1994, as reported by

the American Association of Poison Control Centers 24% required hospital treatment more than 1/2 of all exposures occur in children under

the age of 6 years most exposures are accidental 22 people died in 1994

Hydrocarbons, cont.Mechanism of toxicity, cont. major threat is danger of aspiration pneumonitis vomiting increases the risk of aspiration when aspirated, petroleum distillates :

• inhibit surfactant - causing alveolar collapse and resultant hypoxemia

• cause bronchospasm and capillary damage• cause hemorrhagic bronchitis• cause pulmonary edema

Hydrocarbons, cont.

Mechanism of toxicity, cont. Systemic toxicity can occur after oral

ingestion• CNS depression, GIT irritation, liver and

kidney damage, cardiovascular toxicity

Hydrocarbons, cont. Characteristics of poisoning, 3 organ systems

usually involved: Pulmonary, GI & CNS Signs and symptoms of pulmonary involvement

• coughing, gasping and choking• smell of gasoline to the breath• rales and wheezing upon auscultation• hemoptysis and pulmonary edema

Hydrocarbons, cont. Signs and symptoms of GIT involvement

• irritation of oropharynx• nausea and vomiting• abdominal pain

Signs and symptoms of CNS involvement• cerebral hypoxemia• lethargy• somnolence• coma or seizures

Hydrocarbons, cont. Management of poisoning To induce vomiting or not to induce

vomiting Do not induce vomiting in patients who

have ingested low viscosity petroleum distillate hydrocarbons ingestion as it increases the risk of aspiration pneumonitis

Do Maintain airway and support respiration

Hydrocarbons, cont.

Do induce vomiting in patients who have ingested:• halogenated hydrocarbons• insecticides• turpentine• aromatic hydrocarbons• or ones which contain of heavy metals - must

protect airway (endotracheal intubation)

Hydrocarbons, cont. Terpenes include pine oil, turpentine, and camphor pine oil - product of pine trees (Pine Sol) turpentine is a distillate from pine trees camphor - distillate of the camphor tree Have lower volatility and higher viscosity

therefore less of a risk of aspiration than the petroleum distillates

Hydrocarbons, cont. Mechanism of Action of Turpentine and Pine oil Systemic toxicity results in GIT irritation and

CNS depression• see nausea, vomiting, diarrhea, weakness,

somnolence, stupor and coma

Treatment:• GI tract decontamination - induce vomiting• maintain airway• transport

Hydrocarbons, cont. Camphor

• uses - OTC preparations such as local anesthetics, chest cold inhalants, etc.

• basically no therapeutic value, but still used• problem occurs if it is ingested• can cause CNS excitation and seizures, mechanism

of action is unknown• causes irritation of upper airway and mucous

membranes• Treatment - supportive care

Toxic Gases

Carbon Monoxide

The most common form of poisoning From 1979 to 1988, 56,000 people died from CO Colorless, odorless, nonirritating gas Produced by incomplete combustion of carbon

containing compounds Combines with Hb to form carboxyhemoglobin CO-Hb will not transport O2 T 1/2 of CO-Hb is 5-6 hours in room air, 90 min in

pure O2 at 1 atm, 23 min in O2 at 3 atm

Carbon monoxide, cont.

Sources:• propane powered engines• natural gas appliances - space heaters • automobile exhaust• gas log fireplaces• kerosene heaters• hibachi grills• portable generators

Carbon monoxide, cont.Mechanism of action: Competes with O2 for active sites on Hb (220x

the affinity for Hb as O2) Interference with cellular respiration at the

mitochondria level, binds to cytochrome oxidase Induces smooth muscle relaxation Hypoxemia, tissue hypoxia, no cyanosis, CO-

Hb is cherry red in color

Carbon monoxide, cont.

Diagnosis based on patient presentation and a good history

Signs and symptoms vary widely Signs depend on % CO-Hb levels in the blood Presence of cherry red blood is pathognomonic

Carbon monoxide, cont.Clinical grading of CO poisoning Mild

• headache, nausea, dizziness, vomiting, flu like symptoms

Moderate• confusion, slow thinking, shortness of breath, blurred

vision, tachycardia, tachypnea, ataxia, weakness Severe

• chest pain, palpitations, severe drowsiness, disorientation, hypotension, syncope, myocardial ischemia, pulmonary edema

Carbon monoxide, cont.

Exposure during pregnancy can be teratogenic Chronic low level exposure can cause:

• tiredness• lethargy• irritability• visual impairment• increased incidence of heart disease on

atherosclerosis

Carbon monoxide, cont.

Management of Toxicity: The antidote for CO poisoning is 100%

oxygen hyperbaric chambers should be used

more frequently than they currently are in the treatment of CO poisoning

Hydrogen sulfide poisoning

Highly toxic, malodorous, intensely irritating gas Sources:

• decaying organic materials

• natural gas

• volcanic gas

• petroleum

• sulfur deposits

• sulfur springs

Most exposures are occupational

Hydrogen sulfide, cont.

Mechanism of action: inhibits mitochondrial cytochrome oxidase paralyzes the electron transport system inhibits cellular utilization of O2 metabolic acidosis secondary to anaerobic

metabolism plenty of O2 in the bloodstream, cells can not

utilize it, so no hypoxemia but tissue hypoxia

Hydrogen sulfide, cont.

Mechanism of action, cont.: more potent cytochrome oxidase inhibitor than

cyanide rapidly absorbed through the inhalation route metabolized by the liver and excreted through the

kidneys cause of death is respiratory paralysis due to toxic

effects of H2S on respiratory centers in the brain

Hydrogen sulfide, cont.Concentration (ppm) Clinical effect 0.02 odor threshold 100-150 nose/eye irritation,

olfactory nerve paralysis 250-500 sore throat, cough,

keratoconjunctivits, chest tightness, pulmonary edema 500-1000 headache, disorientation,

loss of reasoning, coma, convulsions

>1000 death

Hydrogen sulfide, cont.Treatment: rescuer protection basic life support give O2, hyperbaric oxygenation is beneficial nitrates are antidotal by inducing Meth-Hb -

providing a large available source of ferric-heme which has a greater affinity for H2S than does cytochrome oxidase, sequestering sulfide ions freeing cytochrome oxidase

Cyanide Hydrocyanic acid, Prussic acid In 1994 only 360 cases of cyanide poisoning

(300 were unintentional, 9 patients died) Sources:

• electroplating, jewelry and metal cleaners• photographic processing• fumigant rodenticide• criminal tampering with OTC capsules• Amygdalin - pits of peaches, cherries, apricots,

apples, plums• laetrile

Cyanide, cont.

Mechanism of action: causes tissue hypoxia by binding with ferric iron of

mitochondrial cytochrome oxidase, thus inhibiting the functioning of the electron transport chain and the cells ability to utilize O2 in oxidative phosphorylation

substantial decrease in ATP production see a shift to anaerobic metabolism increased lactic acid production - metabolic acidosis

Cyanide, cont.

Clinical presentation: tissue hypoxia, especially of the heart and brain

(plenty of O2 in the bloodstream, cells can not utilize what is there)

signs depend upon route and dose inhalation of cyanide gas usually produces rapid death delayed onset after exposure to Amygdalin

Cyanide, cont.

Clinical presentations, cont. Patients who do not experience sudden collapse you will

see anxiety, hyperventilation, CNS stimulation, tachycardia, palpitations

Late signs of poisoning include nausea, vomiting, hypotension, generalized seizures, coma, apnea, a variety of cardiac dysrhythmias

Smell of bitter almonds to the breath Absence of cyanosis

Cyanide, cont.

Treatment: amyl nitrate - to induce Meth-Hb (same

as with H2S) give O2

Heavy Metal Toxicity

Mechanism of Action

Most common route of exposure is oral • secondary is inhalation of fumes

Toxicity is expressed biologically because of their ability to bind to one or more ligands of biologic enzyme systems which then inactivates the enzyme system

One of the few poisons that we have a chemical antidote for:

Chelating Agents Chemical antidotes - chemically inactivate

the poison Compete with enzyme systems for the metals Reverse the metals toxic effects Enhance the excretion of the metal The chelate formed is a stable compound Chelates are water soluble Chelates are excreted by the kidneys

Chelating Agents, cont.

How effective these chelating agents are depends upon:

1) the affinity of the chelator for the metal 2) distribution of the chelator to the parts of the

body where the metal is 3) ability of the chelator to mobilize the metal

from the body once the chelate is formed

Chelating Agents, cont.

Properties of the ideal chelating agent: 1) greater affinity for the metal than for ligands of

tissues 2) high water solubility 3) can penetrate into tissues 4) resistant to metabolic degradation by the body 5) forms a tight stable bond with the metal which

is non toxic to the body

Chelating Agents, cont.

Properties of the ideal chelating agent, cont. 6) be readily excreted unchanged 7) low affinity for calcium 8) minimal inherent toxicity 9) be absorbed readily when given orally

Chelating Agents, cont.

No drug has a single effect, drugs are two edged swords.

Examples of a chelating agent:• calcium disodium EDTA - can cause renal

problems, fever, dermatitis, used to treat lead toxicity

Heavy Metals

Lead toxicity

Sources - used in the past in medicines (sugar of lead), insecticides, pesticides, gasoline (tetraethyl lead), batteries, paints, manufacturing, automobile exhaust.

The fall of the Roman empire was due to the fact they used lead for pipes to carry water and for drinking goblets and utensils.

Lead Toxicity, cont.

Clinical features, plumbism:

Acute intoxication: not common colic metallic taste to mouth vomiting, diarrhea or constipation increased thirst hemolysis, hemoglobinuria oliguria paresis and paresthesias

Lead Toxicity, cont.

Chronic lead intoxication - much more common

Burtonian line - dark gray bluish black line on the gingival margin (H2S + Pb = PbS)

Basophilic stippling (clumping of RNA) Anemia Colic, diarrhea, vomiting Skeletal muscle weakness Increase uric acid in blood Headache, confusion, insomnia Lead palsy (wrist drop and foot drop)

Lead Toxicity, cont.

Patient management: Acute intoxication - induce vomiting,

give cathartics, give proteins to delay absorption (milk, egg whites), chelating agents

Chronic toxicity - give chelating agents

Iron Toxicity Seen mostly in children, 40, 000 exposures/yr. Toxic doses:

• 20-60 mg/kg of elemental iron is potentially toxic• 60-120 mg/kg is toxic but not usually fatal• > 120 mg/kg is potentially fatal

Only 10% of ingested iron is absorbed Most iron tablets contain 10-30% elemental

iron by weight

Iron Toxicity, cont. Sources - dietary supplements

Clinical features: toxicity develops when serum iron levels exceed the iron

binding capacity of transferrin in the blood body is poorly equipped to handle excessive amounts of

iron - can eliminate only very small amounts/day free iron damages tissues by direct corrosive effects, free

iron is a potent vasodilators, directly injures blood vessels, causes hepatocellualr death, coagulation disturbances, and metabolic acidosis

Iron Toxicity, cont.Clinical presentation of acute toxicity- 4 Stages Stage I - 30 min. to 6 hrs. post ingestion

Acute GI corrosive effects of iron, nausea,

abdominal pain, vomiting, and diarrhea,

hematemesis, hematochezia and melena.

Most patients with mild to moderate toxicity do not progress beyond this phase.

Stage II - 6-24 hours post ingestionsometimes called the latent or quiescent period

transient resolution of patient’s GI signs

Iron Toxicity, cont. Stage III - 12-48 hours post ingestion

recurrence of GI hemorrhage, hematemesis, melena and bowel perforation may be

seen

acute circulatory shock, metabolic acidosis,respiratory distress syndrome

death is common is this stage

Stage IV - 4-6 weeks post ingestiongastric outlet obstruction or pyloric stenosis

as a result of gastric scarring, vomiting

Iron Toxicity, cont.

Chronic toxicity: pigmented hepatic cirrhosis, diabetes mellitus,

hyperpigmentation of the skin, hemosiderosis hemochromatosis

Treatment: induce vomiting activated charcoal is of no value transport chelators

Mercury Toxicity Sources: Hg (Gr. - hydrargyros - water silver) drugs (antisyphilitic agents, diuretics, cathartics,

topical salves), batteries, paint, shell fish, neon lamps, thermometers, industry (“mad as a hatter”), BP cuffs, wood preservatives, vaccines

dental amalgam fillings (50% mercury, 35% silver, 13% tin, 2% copper with a trace of zinc)

Mercury Toxicity, cont.

Exists in nature in 3 major forms:• organic (methyl mercury)• inorganic • elemental

Mechanism of Action:• Forms covalent bonds with sulfide groups

disrupting many important cellular functions

Mercury Toxicity, cont.

Elemental mercury - quicksilver liquid at room temperature vaporizes easily at room temperature lung is major target organ due to inhalation of

volatilized fumes lipid soluble and passes rapidly into blood

stream see acute pulmonary symptoms, fever, chills,

dyspnea, lethargy, confusion, vomiting

Mercury Toxicity, cont.

Elemental mercury - quicksilver, cont. Chronic exposure - tremors, gingivitis,

insomnia, shyness, memory loss, anorexia, depression

ingestion is usually no problem - poor absorption from GIT

Mercury Toxicity, cont.

Inorganic mercury - mercurial salts route of exposure - oral source - disc batteries, mercurous chloride,

vaccines (0.01% thimerosal) clinical signs associated with the caustic effects signs and symptoms - pain, vomiting,

hematemesis, renal failure

Mercury Toxicity, cont.Organic mercury: source - contaminated food products, methyl

mercury contaminated seafood in the 1950’s in Japan killed over 1000 people (Minamata Bay)

elevated levels found in blood stream of mothers and infants - source? (tuna)

major signs and symptoms are neurological, visual field constriction, ataxia, paresthesia, hearing loss, muscle tremors, and even death

Mercury Toxicity, cont.

Diagnosis is based on: patient history and clinical signs urinary levels of mercury (values greater

than 20-25 ug/L is abnormal)

Treatment: acute therapy - same as any poison chronic - chelation therapy (BAL)

Arsenic Toxicity Commonly found throughout the earth’s

crust, contaminates well water used in manufacture of herbicides and

pesticides and computer chips tasteless and resembles sugar has been used as a therapeutic agent and as

a poison for more than 2000 years most exposures are accidental and deaths

are very rare

Arsenic Toxicity, cont.Mechanism of action: Inhibition of sulfhydryl group-containing

cellular enzymes and the replacement of phosphate molecules in “high energy” compounds

Trivalent arsenic is a carcinogen (lung and skin cancer) and is the most toxic form

Toxic dose ranges from 1 mg to 10 grams Can be recovered from the hair, nails and skin

Arsenic Toxicity, cont.

Clinical presentation: Acute exposure

• burning of the mouth and throat, nausea, vomiting, profuse diarrhea (rice water stool), garlic like odor to breath, increased capillary permeability, shock, renal damage

Arsenic Toxicity, cont.Chronic toxicity: skin pigmentation changes, palmar and plantar

hyperkeratosis anorexia, GI symptoms anemia (see pale patient with areas of increased

pigmentation and hyperemia - “Milk and Roses” complexion)

Mee’s lines (white transverse bands in the nails) metallic taste to the mouth gangrene of the feet (“blackfoot disease”) encephalopathy

Arsenic Toxicity, cont.

Diagnosis: Urine sample provide the most reliable

diagnostic testing, >200ug/L are abnormal• use of hair or nails is generally not useful in

evaluating individual patients

Treatment: supportive care and chelation therapy

Natural Chelators

Chlorella (from algae) is a natural immune stimulant and has a high affinity for heavy metals (it contains sulfur bound amino acids and acts as a natural chelator)

Garlic and cilantro (Chinese parsley) aid in the removal of heavy metals