Environmental/Toxicological Emergencies Flashcards
Antivenoms and Antitoxins definition
– neutralizing antibodies that are derived from a hyperimmunized donor.
– used to protect the body through the process of passive immunization
Tetanus antitoxin
– several equine tetanus antitoxin products available
– have been used off-label in dogs and cats
– Anaphylaxis is an anticipated adverse drug reaction to administered tetanus antitoxin
– intended for therapeutic use to enhance recovery rates in animals showing clinical signs of tetanus in combination of standard treatments
– Tetanus antitoxin binds and neutralizes any free toxin that is circulating in the bloodstream, but it is not effective against toxin that has already bound to nerve tissue.
Tick antitoxin
– Australian vector is Ixodes holocyclus
– vector in the United States is the Dermacentor tick
– syndrome is characterized by a rapidly progressive lower motor neuron neuropathy
– Treatment entails supportive therapy and removal of the tick
– Australia tick tx also includes tick antitoxin.
– antiserum is prepared from dogs that are hyperimmunized against the venom of I. holocyclus
Botulism antitoxin
– Dogs can become infected with Clostridium botulinum and acquire botulism caused by the type C and D exotoxins
– organism is an anaerobic Gram-positive spore-forming rod that produces a potent neurotoxin
– occurs when animals ingest preformed botulinum toxins in food or water or when clostridia spores germinate in anaerobic tissues within the body
– heptavalent antitoxin (BAT) made in horses for use in humans that is effective against type C toxin
– off-label use in dogs
Spider Envenomation
– black widow and brown recluse are the two most common and most serious spiders which can cause envenomation in dogs and cats
Black Widow vs Brown recluse
– Black widow venom is unique in that it causes no tissue trauma at the injection site; therefore, no pain occurs during the bite itself, making it hard to diagnose
– Black widow venom is a potent neurotoxin that initially stimulates secretion of neurotransmitters such as acetylcholine and norepinephrine, and then inhibits their reuptake
– brown recluse spiders is highly toxic to tissues by interfering with leukocytes and causing dermal necrosis.
– affects the coagulation system by clogging local capillaries and causing decreased tissue perfusion, thereby inciting necrosis
Black widow spider antivenom
– cats are very sensitive to black widow venom, whereas dogs are less sensitive to the neurotoxin
– clinical sign is severe pain, which rapidly follows an almost painless bite
– commercially available antivenom made for use in humans has been shown to be very effective in a cat
– specific venom-neutralizing globulins obtained from the blood serum of healthy horses immunized against the venom of black widow spiders
– Other supportive therapies include morphine, barbiturates, and glucocorticoids
Scorpion antivenom
– United States is the bark scorpion (Centruroides exilicauda)
– can cause systemic envenomation in humans, especially children, and in dogs and cats
– venom blocks voltage-gated potassium and sodium channels in nervous tissue
– systemic effects are serious and consist of nystagmus, paresthesia, referred pain, and myoclonus
– excessive salivation, tachycardia, fever, hypertension, and increased respiratory secretions
– Anascorp is made from the plasma of horses immunized with scorpion venom
Non‐Neurotoxic Snake Envenomation
– Crotalidae Crotalidae, commonly known as pit vipers or crotaline snakes
– Venom is 90% water and 10% enzymes and proteins, which function to immobilize the prey and digest its tissues
– local swelling, discharge, pain, hypotension, thrombocytopenia, petechiae and ecchymoses, coagulation abnormalities, cardiac arrhythmias, seizure activity, and obtundation or coma
rattlesnakes, copperheads (Agkistrodon spp.), and moccasins (Agkistrodon spp.)
Neurotoxic Snake Envenomation
– Mojave rattlesnake and coral snake.
– chemically similar to non‐depolarizing neuromuscular blocking agents and causes paralysis and central nervous system depression
– muscle fasciculations, spasms, paralysis, and respiratory failure
Pit viper antivenom
– limits the spread of swelling, reverses coagulopathy, and halts the progression of neuropathy
– does not reverse local tissue necrosis because of the immediate necrotoxic effect of the venom on the tissues
– Antivenom is optimally given within 4 hours after the snakebite, although it can still be effective up to 24 hours or longer after envenomation
AKA Crotalidae family
Coral snake antivenom
– IgG coral snake antivenom product
– coral snake antivenom is hard to procure because of the difficulty in finding enough coral snakes from which to extract venom
– US coral snakes: Micrurus fulvius, or eastern coral snake, and Micrurus tener, or Texas coral snake).
Common blood smear cytology finding after envenomation
echinocytosis (tiny sun) is a common cytological finding of red blood cells, characterized by an irregular shape and multiple blunt projections distorting the cell surface
– theorized to be caused by venom‐mediated ATP depletion, cation depletion (Na+ and K+), and phospholipase A2 (PLA2) activity
Methemoglobin (metHb)
– inactive form of Hb created when the iron molecule of Hb is oxidized to the ferric (Fe3+) state because of oxidative damage within RBC
– gives the red blood cell a darker brown color
– Oxidative injury occurs in cats due to their lack of glucuronide conjugation pathway
Causes of MetHb
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- acetaminophen ingestion,
- topical benzocaine products
- phenazopyridine (a urinary tract analgesic) ingestion
- nitrites
- nitrates
- skunk musk
metHb is often formed within minutes to hours of exposure
Which way does MetHb shift on the O2 dissociation curve?
– increases affinity for oxygen in the remaining ferrous moieties of the Hb molecule, decreasing the release of oxygen to the tissues and shifting the oxyhemoglobin dissociation curve to the left
CS of MetHb
– consistent with decreased oxygen carrying capacity, cellular hypoxia, and shock
– metHb level of 20% and include tachycardia, tachypnea, dyspnea, lethargy, anorexia, vomiting, weakness, ataxia, stupor, hypothermia, ptyalism, and convulsions in cats
– Chocolate brown mucous membranes
Substances that cause metHb production are likely to cause
Heinz Body production, and potentially hemolytic anemia, in the days after the exposure.
Diagnosis MetHb
– MetHb is apparent on blood sampling because the blood has a chocolate brown discoloration.
– blood contains elevated levels of metHb, it remains dark after exposing to air
– Comparing pulse oximeter oxygen saturation to arterial blood gas saturation (saturation gap)
Sulfhemoglobin
– most uncommon dyshemoglobin and may be caused by exposure to high levels of sulfur from drugs (sulphonamides such as sulfasalazines)
– formed when iron is oxidized from the ferrous (2+) to the ferric (3+) form by drugs or chemicals that contain sulfur
– sulfur atom irreversibly binds to the porphyrin ring of Hb
tx requires transfusion of new RBCs since it is irreversible
Which way does Sulfhemoglobin shift on the O2 dissociation curve?
–Sulfhemoglobin incapable of carrying oxygen, which prevents oxygen transport
– shifts the oxyhemoglobin dissociation curve to the right
Signs of Sulfhemoglobin
– cyanosis without clinical signs of respiratory distress
– occurs at levels of 0.5 g/dl of sulfhemoglobin
Treatment of Sulfhemoglobin
– no antidote, and since it is irreversible, it remains attached to the Hb for the life span of the red blood cell
Oxidation in the erythrocyte
– Erythrocytes are especially vulnerable to oxidative damage because they carry oxygen
– they are exposed to various chemicals in plasma, and have no nucleus or mitochondria.
– finite number of cell proteins rely on anaerobic respiration to generate energy and reducing agents
3
What do Oxidants continuously generated
- hydrogen peroxide (H2O2),
- superoxide free radicals (O2−),
- hydroxyl radicals (OH−)
Erythrocyte mechanisms to protect against oxidative damage
superoxide dismutase,
catalase,
glutathione peroxidase,
glutathione,
metHb reductase (also known as cytochrome b5 reductase or nicotinamide adenine dinucleotide diaphorase)
Phenacetin
component of over-the-counter drug formulations, is metabolized rapidly to acetaminophen and could result in toxicity in small animals
Metabolism of Acetaminophen
(1) It is conjugated to a sulfate compound by a phenol sulfotransferase,
(2) it is conjugated to a glucuronide compound by a uridine diphosphate-glucuronosyltransferase,
(3) it can be transformed and oxidized by the cytochrome P-450 system that converts it to the reactive intermediate, N-acetyl-P-benzoquinone-imine (NAPQI)
Cats trying to metabolize Acetaminophen
– Cats are limited in their ability to conjugate glucuronide because they lack a specific form of the enzyme glucuronyl transferase needed to conjugate acetaminophen
– cats are estimated to have one-tenth the capacity to eliminate acetaminophen compared with dogs
para-aminophenol (PAP)
what role does this have?
– additional metabolite of acetaminophen
– plays a role in erythrocyte oxidative damage
erythrocyte oxidative toxicity associated with acetaminophen
Lower levels of metHb reductase in dogs and cats relative to other species further increase potential for erythrocyte oxidative injury
Topical benzocaine toxicity
– Benzocaine sprays for laryngeal spasm in cats and over-the-counter creams for pruritus in dogs and cats have been associated with methemoglobinemia
– Metabolites of benzocaine are likely responsible for oxidative damage to Hb
– effects of HzBs associated with benzocaine toxicity are generally mild and rarely associated with hemolysis
Skunk Musk Toxicity
what does this form?
– toxic substances in skunk musk are thought to be thiols, which can react with oxyhemoglobin to form metHb, a thiyl radical, and H2O2
Nitrites and nitrates
– Exposure to these substances could occur in small animals that receive vasodilatory drugs that release nitric oxide, including nitroglycerin and sodium nitroprusside
– metHb is reduced by metHb reductase in red blood cells, but some evidence indicates that nitric oxide decreases metHb reductase activity
Treatment of CO toxicity
– Oxygen therapy is the mainstay of treatment for CO toxicity
– increasing the amount of oxygen in the blood decreases the half-life of CO as dissolved oxygen competes with CO for Hb binding
– CO is then displaced from Hb and exhaled through the lungs
MetHb treatment
– involves diuresis or medications that increase the rate of elimination or decrease the production of toxic metabolites
– Induction of vomiting followed by the administration of activated charcoal should be considered
– treatment with methylene blue should occur when methemoglobin exceeds 20-30%,
N-Acetylcysteine (NAC) for Acetaminophen toxicity
– preferred treatment for acetaminophen toxicity
– NAC augments the endogenous glutathione stores as it is hydrolyzed to cysteine (one of the components of GSH)
– increases the fraction of acetaminophen excreted as the sulfate conjugate
– NAC is most effective if administered within 12 hours of ingestion of acetaminophen
ascorbic acid (vitamin C) for MetHb treatment
– an antioxidant and can augment metHb conversion to Hb through nonenzymatic reduction
Cimetidine for MetHb treatment
– histamine-2 receptor antagonist, is theoretically useful in cases of acetaminophen toxicity because it inhibits the P-450 oxidation system in the liver, limiting the production of NAPQI
S-adenosylmethionine (SAMe) for MetHb Toxicity
– an essential metabolite that is vital to hepatocytes and has been reported to be hepatoprotective, have antioxidant properties, and decrease the osmotic fragility of erythrocytes
smoke inhalation injury
constellation of clinical signs secondary to
1. thermal injury,
1. particulate matter inhalation,
1. toxicant inhalation.
primary components of inhalation injury
- upper airway injury,
- lower airway injury,
- pulmonary parenchymal injury,
- systemic injury,
- systemic toxicity.
neurological signs from smoke inhalation
consequence of
impaired oxygen delivery,
mitochondrial dysfunction,
and direct neurological damage from systemic toxicity.
pathophysiology of smoke inhalation
inspiration of superheated particulate matter (soot)
– soot → carbonaceous particles cause direct damage via their high temperature.
– can carry large variety of toxins,
– facilitate the transport of toxins to the alveoli through the inhaled air.
Smoke inhalation
Upper airway injury
– direct thermal damage to the oral cavity, nasopharynx, nasal cavity, larynx, trachea and eventually the lower airways
– resulting in edema and inflammation of these tissues.
– soft tissue edema in the upper airway apparatus is the risk for airway obstruction
– usually peaks 24 hours postexposure
Smoke inhalation
Lower airway injury
– direct thermal injury of the lower airway is unusual
– injury typically secondary to chemical inhalation.
– inhalation of smoke containing chemical irritants incites the production of neuropeptides that leads to a severe inflammatory response by activating vagal nerve sensory fibers containing proinflammatory peptides, neurokinins, and calcitonin gene-related peptide.
– causes bronchoconstriction, pulmonary vasoconstriction, and airway fluid accumulation
What else occurs following burn and smoke inhalation injury?
Elevated levels of? what does this cause?
– elevated levels of nitric oxide
= impairing pulmonary hypoxic vasoconstriction, further exacerbating ventilation–perfusion mismatch and dead space ventilation.
Smoke inhalation
Pulmonary parenchymal injury
– classically delayed symptom
– Increased transvascular fluid efflux, lack of surfactant, and loss of hypoxic pulmonary vasoconstriction result in impaired oxygenation
– Atelectasis develops and fibrin deposition in airways is promoted by the procoagulant status and concurrent reduced antifibrinolytic activity
What plays a central role in the pathogenesis of smoke inhalation injury?
– activated neutrophils
– perpetuate the inflammatory injury to the pulmonary parenchyma
Systemic injury from Smoke inhalation
– volatile compounds present in smoke can cause disruption of the corneal tear film and consequently ocular irritation and direct corneal damage and ulceration as well as direct thermal injury.
– Left ventricular dysfunction → secondary to direct myocardial damage
– Sympathetic compensation is activated and leads to tachycardia and increased systemic vascular resistance, resulting in increased myocardial oxygen demand
– carbon monoxide (CO) further compromises oxygen carrying capacity and oxygen delivery and predisposes to development of arrhythmias, congestive heart failure, and systemic hypotension
Smoke inhalation
Hydrogen cyanide
– HC is a colorless gas → gaseous form of cyanide
– generated by the combustion of substances such as wool, silk, cotton, and paper as well as plastic and other polymers
–With Cyanide intoxication, the liver may not be capable of metabolizing the cyanide, particularly when large concentrations are present
Smoke inhalation
primary toxic effect of HC
– the level of the mitochondria, where it inhibits the electron transport chain, impairing cellular ATP production
– additional effects of HC toxicity include neurotoxicity, tachypnea through direct stimulation of chemoreceptors (aortic arch and carotid bodies), arrhythmias, and death.
Smoke inhalation
Half life of CO
CO has a half-life of 320 minutes in patients breathing room air;
– reduced to approximately 70 minutes when the patient is provided 100% oxygen at atmospheric pressure
Smoke inhalation Tx
– humidified supplemental oxygen therapy
– Oxygen therapy improves oxygen delivery and effectively decreases the half-life of CO
– prophylactic use of antimicrobial therapy is not indicated
– not reccomened to use corticosteriods
– inhaled β2-agonists may provide bronchodilation and antiinflammatory effects and promote alveolar fluid clearance.
Smoke Inhalation
Cyanide toxicity treatment
– Antidotes Amyl nitrate and sodium thiosulfate
– convert hemoglobin to methemoglobin and favor reduction of cyanide levels as it preferentially binds to methemoglobin.
– leads to reduced oxygen carrying capacity as a consequence of methemoglobin formation and should be reserved for only those patients highly suspected of cyanide toxicity
– Hydroxocobalamin (vitamin B12a) actively binds cyanide to form cyanocobalamin, which is directly excreted via the kidney
hallmark of heat stroke is
– severe central nervous system (CNS) disturbance
–associated with MODS
definition of heat stroke
form of “hyperthermia associated with a systemic inflammatory response leading to a syndrome of multiorgan dysfunction in which encephalopathy predominates.”
“the increase in ____ ____ temperature results in heat-associated illness”
core body
Thermal homeostasis
– balance between heat load (environmental heat and heat generated through metabolism and exercise) and heat-dissipating mechanisms controlled in hypothalamus
Body temperature increases when blank exceeds blank
Heat load
Heat dissapation
Heat dissipation may occur via:
x4
- convection, Bair hugger heat support, Hot shower
- conduction, Heating a pot on the stove
- radiation, Earth is heated by the Sun
- evaporation. Sweating, respiration
70% of heat loss in dogs and cats occurs by:
radiation and convection through the skin
Heat loss is facilitated by:
– increased cutaneous circulation as a result of increased cardiac output and sympathetically mediated peripheral
– involves a trade-off with blood supply to the viscera (intestines and kidneys)
Example of evaporation heat loss:
– via respiratory tract through panting
– predominant mechanism of heat loss when ambient temperature is equal to or greater than the body
– Respiratory evaporative heat loss may be diminished by humid climatic conditions, confinement in a closed space with poor ventilation, and obstructive upper respiratory tract abnormalities
Diminished radiational and convective heat loss can occur:
– from the skin may occur as a result of hypovolemia from any cause, poor cardiac output, obesity, extremely thick hair coat, or lack of acclimatization to heat
Increased body heat induces three protective mechanisms:
- thermoregulation
- acute-phase response,
- increased expression of intracellular heat shock proteins.
acute-phase response of heat stroke protective mechanisms
variety of proinflammatory and antiinflammatory cytokines.
1. Proinflammatory mediators induce leukocytosis,
2. promote synthesis of acute-phase proteins,
3. stimulate the hypothalamic-pituitary-adrenal axis,
4. activate endothelial cells and white blood cells.
– they are protective when the body is balance between the proinflammatory and antiinflammatory response systems
heat shock proteins protective mechanism
x3
– protect the cell and the body against further heat insults and prevent denaturation of intracellular proteins
– also help to regulate the baroreceptor response during heat stress,
– thus preventing hypotension and conferring cardiovascular protection
Heat stroke results from
failure of thermoregulation followed by an exaggerated acute-phase response and alteration of heat shock proteins
pathophysiologic sequence in heat stroke
what gets released?
initial production and release of interleukin-1 and interleukin-6 from the muscles into the circulation and increased systemic levels of endotoxin from the GI tract.
– results in the release of numerous proinflammatory and antiinflammatory cytokines as well as activation of coagulation and inhibition of fibrinolysis
causes of these neurologic abnormalities with heat stroke
– poor cerebral perfusion, direct thermal damage, cerebral edema, CNS hemorrhage, or metabolic abnormalities such as hypoglycemia or hepatoencephalopathy
Cooling measures for heat stroke
– tepid water and blowing fans over the body
– massage the muscles to maintain circulation
– External conduction cooling techniques include application of ice packs over major vessels (e.g., jugular veins), tap water immersion, ice water immersion, and use of cooling blankets
– room temperature intravenous fluids may be helpful.
Heat stroke
Risks of extreme cooling
– may result in vasoconstriction and paradoxical inhibition of body cooling
– and thus diminish heat dissipation overall.
Heat Stroke
Internal cooling conduction techniques include
– iced gastric lavage, iced peritoneal lavage, and cold water enemas, although the latter may interfere with rectal temperature monitoring
– risks of aspiration pnemonia, septic peritonitis
Effects of heat stroke on GIT
– Direct thermal damage and poor visceral perfusion and/or reperfusion may result in GI mucosal sloughing and ulceration
What clin path value is associated with a poor outcome with heat stroke?
– increasing number of NRBCs is associated with more severe injury and worse outcome
Definition of drowning
– process resulting in primary respiratory impairment from submersion or immersion in a liquid medium.
– Liquid is present at the victim’s airway, preventing respiration of air
Dry drowning
– cases in which liquid is not aspirated into the lungs
– often experience morbidity from laryngospasm
– which results in the same hypoxemic and hypercarbic state seen in those who have aspirated liquid
