Exam 4 Flashcards
Metalloids
elements that share some of the properties of metals and non-metals
Ex: Arsenic
T/F Arsenic is a metal
F: it is a metalloid
Class A / Hard Metals
highly stable and preferentially bind anions with O as electron donors
Class B/ Soft Metals
metals that have a pronounced preference for Sulfur primarily and nitrogen. Bind strongly with Selenium
Intermediate Metals
metals that have ligand binding characteristics
intermediate to soft and hard metals but still readily bind with Sulfur
Mercury (Hg) is a Class B metal meaning it
binds sulfur (thiols) in biological systems
Cadminium (Cd) is a Class b metal meaning it
binds sulfur (thiols) in biological systems
Intermediate metals such as Arsenic (As) and Lead (Pb) have a strong preference to binding_______
sulfur (thiols)
Thiol groups
present in cysteine, tripeptide glutathione, and cysteine residues of enzymes and proteins- playing a role in active sites, directly involved in catalysis
Molecular targets of Class B and intermediate elements
What metals bind oxygen readily
Class A Metals
What is the target of Class B and intermediate elements?
thiol groups
Metallothionein
metal binding proteins present in the animal cells that function to detoxify metals to some extent
If too prevalent, metals overwhelm antioxidant defenses, resulting in oxidative stress
so they have a large number of thiols, can sequester heavy metals and prevent oxidation of critical protein or non-protein thiols
Metallothionein knock out mice will have…
increased susceptibility to heavy metals
General detoxification of metals involves:
preventing inappropriate binding of non-essential metals with sensitive sites
What is the source of Mercury in the environment
emissions via mining, coal combustion, and volcanic eruptions
Elemental mercury vapor can travel up to a year or more in the atmosphere
Metallic form of Mercury (Hg)
Hg0 - “quick silver” lipid soluble
not absorbed well in the GI
readily absorbed as vapor in the lungs
Neurotoxicant
Oxidized to Hg(II)-inorganic form in the blood then accumulates in the kidneys
Inorganic form of Mercury (Hg)
Hg(II), HgS, HgCl2
more readily absorbed in the GI than metallic HG
Oral route causes damage to the GI and kidneys
Highest concentration will be found in kidneys
Organic form of Mercury (Hg)
MeHg
highly bioavailable- 90 to 95% is absorbed in the GI
Crosses the blood brain barrier
Potent neurotoxicant especially for the developing fetus
What form of Mercury is able to cross the BBB and a potent neurotoxicant for the developing fetus?
Organic form
Methylmercury
binds with cysteine to form Cysteine-MeHg
functionally resembles methionine
Allows crossing into the blood brain barrier via molecular mimicry
also bioaccumulating in environment and biomagnifies food webs
How does Methylmercury bioaccumulate in the environment
Elemental Hg oxidized to inorganic in atmosphere
Removed inroanic Hg via dry or wet depsoition
Inorganic Hg converted by bacteria to MeHg mainly in aquatic environments
What are the clinical signs of mercury poisoning
Ataxia
Salivation
Blindness
Tremor
Convulsions
GI disturbance (inorganic)
Kidney damage (inorganic and elemental)
What forms of mercury cause kidney damage
Elemental and Inorganic
What form of mercury causes gi disturbance
inorganic
How do you treat mercury poisoning
In acute exposure of inorganic Hg- egg white, charcoal followed by Dimercaptosuccinic acid (DMSA or Succimer)
MeHg often futile by time of clinical signs
Is Hg poisoning in domestic animals common?
No but occurs when accidental consumption of obsolute products containing Hg i.e barometer or sled dogs eating fish with MeHg (more bioavailable than inorganic or elemental Hg which cause liver and kidney toxicosis)
Cadmium (Cd)
soft, silver white metal that is present as cadmium oxide, cadmium chloride or cadmium sulfate
used in batteries, semiconductors, solar cells, plastic stabilizers
enters environment from coal combustion, mining activities, zinc smelting, and the use of rock phosphate and sewage sludge as fertilizers
can be increased in soils when using
plants bioaccumulate
cigarette burning
What is a likely exposure to Cadmium in cattle?
cattle grazing on sewage sludge-treated pastures
T/F Cadmium can cause feline hypertension
True
What metal can an animal be exposed to through inhaling cigarette smoke?
Cadmium
What dietary deficiency can increase uptake of Cadmium?
Calcium deficiency
Cadmium mechanism of action
bind to plasma proteins (thiols) and RBC (anemia) and is distributed to the liver and kidney
may replace copper and zinc at binding sites, inducing a copper deficiency
can cause oxidative stress
Clinical signs of Cadmium toxicity
aggression
anxiety
GI disturbance
Mild anemia
How do you treat Cadmium toxicity?
Minimize/reduce exposure
EDTA, British anti-Lewisite (BAL or dimercaprol) or DMSA/Succimer generally not proven effective
At the molecular level, thiol groups are often the targets of arsenic, lead, cadmium, and mercury. Which element in the thiol group is the specific target of these metals?
sulfur
Above a threshold concentration, metals can overwhelm cellular antioxidant defenses resulting in ________ stress.
oxidative
Tobacco plants are known to concentrate the metal _______ in their tissues, which is liberated as an oxide during cigarette smoking.
cadmium
About 30% of the amino acid residues in metallothionein are _____
which allows this ubiquitous protein to bind as many as _______ cadmium atoms.
cysteine, 7
A cow was accidentally exposed to an arsenic-based pesticide resulting in diarrhea and ataxia. What is the best course of action?
Treat with IV fluids to counteract dehydration and sodium thiosulfate to chelate arsenic
Why shouldnt you use British anti-Lewisite (BAL or dimercaprol) in treating Cadmium toxicity?
it can increase nephrotoxicity
Arsenic
a metalloid that is often classified as a metal
found in both the inorganic and organic forms
Binds to sulfur in cells
Toxicity varies with the form (arsenite- As3+) more toxic than Arsenate As5+ and inroganic forms are more toxic than inorganic forms
Is inorganic or organic form of Arsenic more toxic?
Inorganic
What is the order toxicity levels of different Arsenic forms?
Inorganic As3+ > Inorganic As5+> Organic Arsenic 3+ > Organic Arsenic 5+
Is Arsenic3+ or 5+ more toxic?
Arsenic 3+
What are some sources of Arsenic
Insecticides (PbAsO4, As2O3, Paris Green)
Immiticide (heartworm)
Herbicides
Treated wood, CuCrAsO4
Water
What is the mechanism of action of Arsenite (As3+)
it binds with lipoic acid (the cofactor in the TCA cycle) thus effecting energy metabolism
What is the mechanism of action of Arsenate (As5+)
it uncouples oxidative phosphorylation because it competes with phosphate during conversion of ADP to ATP.
What are the target tissues of arsenic poisoning?
Tissues with high oxidative energy use (actively dividing cells)
such as the intestinal epithelium, liver, kidney, spleen, and epidermis
What are the clinical signs of arsenic poisoning?
sudden death*, abdominal pain/colic, vomiting, staggering gait, ataxia, watery diarrhea, dehydration, respiratory distress
How do you treat Arsenic poisoning?
-Minimize/reduce exposure
-GI detox
-IV fluids**
-Dimercaprol (BAL)
-DMSA/Succimer
What are some sources of lead toxicity
-Batteries
-Weights (curtains,fishing)
-Pb based paints
-Pb shot
-Pastures near Pb smelters
-Leaded gas
What metal poisoning is the most common?
Lead poisoning
What is the most important source of lead poisoning in North American cattle?
lead-acid batteries found on agricultural pasture land
Lead poisoning
main entry route is GI, organic Pb is more bioavailable than inorganic salts or metallic Pb
What nutritional deficiency leads to increased lead aborption
calcium deficiency
What species are most commonly reported with lead intoxication
Cattle and dogs
Clinical signs of Pb poisoning
blindness
aggression
head pressing
circling
roaring
anorexia
anemia
tonic-clonic epileptic seizures
How do you treat lead poisoning?
Remove Pb objects from GI tract
Ca-EDTA
DMSA/Succimer
What from of chromium is a recognized carcinogen?
Hexavalent chromium (CrVI/Cr6+) - lung cancer and dermatitis
Chromium toxicity
exist in six valence states, 6 is most carcinogenic and associated with increased risk of lung cancer and dermatitis. 3 is little concern for toxicity
Essential trace element that functions in a number of metabolic processes. cofactor for associated with potentiating the activity of insulin
Acute: inflammation and GI damage, kidney and liver damage
Chronic: GI and dermatitis
Signs of Chromium toxicity
Acute toxicosis: inflammation and damage to the GI, kidney damage, liver damage
Chronic toxicosis: gastroenteritis and dermatitis
How does copper toxicity typically occur
over supplementation because it is ubiquitous in the diet (ex: liver and whole grains, mineral, infeed, injection, or palm kernel extract)
COMMD1 mutation
an inherited metabolic defect resulting in impaired biliary copper excretion, common in Bedlington Terriers
What is a result of accumulation of copper in the liver
Chronic hepatitis progressing to cirrhosis. Symptomatic >2000ug/g
Anorexia, Lethargy, Vomiting, and Weight loss
What dog breeds are susceptible to copper poisoning due to genetic defects of copper deposition leading to chronic hepatopathy?
American cocker spaniels
Bedlington Terriers (COMMD1 mutations)
Doberman Pinschers-ATP7A and 7B mutations
Keeshonds
Labrador Retrievers- ATP7B polymorphism and RETN mutations
Skye terriers- defect in biliary copper transport
West Highland White Terriers
Mechanism of Copper Toxicity
when copper levels are too high, free copper ions exist in the cell and undergo redox reactions leading to damage to membranes, proteins, and nucleic acids through reactive oxygen species
Signs of copper associated chronic hepatitis in dogs
signs may lag behind severe accumulation
initial signs: salivation, vomiting, nausea
advanced: PU/PD, icterus and diarrhea, and ascites
What farm animal is most susceptible to copper poisoning
sheep
(sheep>goats>cows>pigs)
HOw can plants like Senecia, ragworts, and groundsels lead to copper release and hemolysis
they have alkaloids that cause liver damage and lead to copper release from the damaged liver leading to elevated blood levels and hemolysis
What are the clinical signs of copper poisoning in small ruminants?
weakness, panting, and dull attitude
pale mucous membranes
yellow discolaration (icterus)
dark brown or red colored urine
abortion
death
mobilized copper from liver will show up in kidneys
How do you treat copper toxicosis in dogs
-feed a low copper diet, avoid organ meets
-use oral chelating agents to enhance urinary elimination of copper (ex: D-penicilllamine and Trientine Hydrochloride)
follow up:
-liver enzymes monitored every 6 months
-consider liver biopsy to assess liver copper levels
-addition of elemental zinc as a dietary supplement to reudce copper absorption
What effect does adding zinc to the diet have on copper levels?
it decreases copper absorption, as it increases metallothionein within enterocytes. It preferentially binds copper ions due to increased affinity. This then leads to increased excretion of dietary copper in the feces
How do you treat ruminants with copper toxicosis?
unsuccessful following hemolytic crisis but:
-fluid therapy and potential blood transfusion
-Ammonium or sodium molybdate and sodium thiosulfate should be used daily as a drench for up to 3 weeks in affected animals as well as any other animals on the same diet
-Ammonium tetrathiomolybdate
-Increase molybdenum in the diet to 5ppm
-Supplement zinc in the diet to 100ppm
What might you want to supplement in copper toxicity?
Zinc and also molybdenum+sulfur (ruminants)
What does molybdenum and sulfur do to ruminant copper levels
It decreases copper availability as it forms thiomolybdate in the rumen and forms an insoluble complex with copper
Predominant molybdenum poisoning is associated with:
-Secondary copper deficiency (due to its interactions with copper and sulfur)
-Also excess intake of plants with Mo and soils/mining
What is the reason for delayed molybdenum absorption in ruminants
due to the formation of thiomolybdates in the rumen
What is a result of molybdenum toxicity in monogastrics?
absorbed and formed thiomolybdate that bind copper and copper dependent enzymes to make it unavailable/inactivated
are ruminants or monogastrics more sensitive to molybdenum
ruminants
Clinical signs of molybdenum toxicity in sheep and cattle
-Feed withdrawl
-Lethargy
-Weakness
-Hind limb ataxia progressing to front limbs and recumbency
Pathology: Hydropic degeneration/necrosis of liver and proximal and distal renal tubules
General rule that ruminants might succumb to molybdenosis
1) when MO intake is greater than 20 ppm in the diet
2) Low Cu:Mo ration (<2:1)
3) High dietary sulfur with normal Cu and Mo
teart scours
soil or plants with unusually high Mo”teart”
teart scours- diarrhea from Molybdenum rich soil
How do you treat molybdenum toxicity
with copper supplementation, not too much or youll get copper toxicosis
What is the optimal copper:molybendum ratio
6:1
Uses of iron
1) Hb: binds O2
2) Myoglobin: binds O2 in muscle
3) P450 enzymes: critical role in metabolism
4) Electron transport proteins in mitochondria-energy formation
Why is iron so tightly regulated and controlled within living systems
because it is very active in reduction and oxidation reactions, can readily for hydroxyl radicals that damage nucleic acids, proteins, and lipids
What is iron’s mechanism of action
it is good at gaining and losing electrons. in an undirected fasion a hydroxyl radical can form which damages proteins, nucleic acids, and lipids
How might iron toxicity occur?
Ingestion of iron containing vitamins (dogs)
Excess amount of iron supplements (cattle, horse, pigs)
Molluscicides containing iron phosphate or iron EDTA
What are the clinical signs of iron toxicity
Necrosis of GI cells
Fluid loss
Cardiotoxicity
How do you treat iron toxicity?
1) Limit absorption (GI decontamination). remove bezoars if sticky vitamin pills
2) Enhance urinary elimination (chelating agents- deforoxamine must be given IV via slow drip)
3) Symptomatic and supportive care
What is one of the least toxic of the essential elements?
Manganese
What is the primary effect of Manganese Toxicosis
neurological- disruption of proteins involved in oxidative phosphorylation in the brain as well as mitochondrials calcium flux and sequestation
Oxidative stress and generation of ROS
Reduced appetite, anemia, abdominal discomfort, abortions and cystic ovaries, neurological syndrome of gait disorders in dogs indicative of injury to the extrapyramidal motor system in the brain
How do you treat Manganese toxicosis
-remove from any further exposure, gi decontamination if pills consumed
-Chelation therapy- EDTA increases urinary excretion
-Antioxidant therapy (Vitamin E, N-acetylcysteine)
-Supportive and Symptomatic care
How does zinc toxicity typically occur?
absorbed in the GI by a carrier-mediated mechanism
Stomach acid provided for rapid release of zinc from ingested metallic objects (Pennies, galvanized steels, and nuts/bolts, ointments for sunburn or diaper rash)
What is Zinc’s mechanism of action
unknown but plays a role in regulation of cell death and protection as well as interactions with other metals such as copper
Toxicity at high levels=oxidative stress
What are the clinical signs of zinc toxicity in dogs and cats
vomiting, diarrhea, red urine, icterus, liver failure, kidney failure, and anemia
some degree of hemolytic with erythrocytic regenerative response, renal damage with meaturia, urinary casts and proteinuria
Who is the most susceptible to zinc toxicity?
foals- nonpainful joint enlargement for 7-21 days that progresses to a reluctance to rise, stiff gait and increased joint fluid
How do you treat zinc toxicity?
-Antacids (zinc mobilized due to acidity in stomach)
-Proton pump inhibitor
-Removal of the zinc eluting foreign body
Supportive care: IV fluids, Blood transfusion, Sucralfate for GI bleeding, CBC and serum chemistries- monitor liver and kidney function
Why is chelation therapy in zinc toxicity
controversial
can facilitate zinc absorption from the stomach if foreign bodies are still present and eluting zinc
once the foreign body is removed, chelation therapy may increase renal elimination (chelator of choice for zinc is Ca-EDTA)
What does botulinum toxin block
acetylcholine release in the presynaptic neuron resulting in flaccid paralysis through SNAP-25, cleaving synaptobrevin, and syntaxin
What three ways can can botulism occur
1) ingestion of preformed toxin (improper ensiled feed, rotten vegatation in shallow waters, homemade foods improperly canned/preserved/fermented)
2) ingestion of spores
3) Contamination of wounds with spores
What species are reportedly less sensitive to botulism
Swine, dogs, and cats
What is the classical clinical sign of botulism
progressive flaccid paralysis (ascending lower motor neuron paresis with paraympathetic signs)
-weakness and ataxia that is more pronounced when forced to move
-difficulty with prehension and swallowing
Death due to respiratory paralysis
How to you diagnose botulinum
Serum, GI contentents and feedstuff can be analyzed for preformed toxin
Riminal fluids
Botulinum toxin tested via mouse bioassay
ELISA but only specific for one toxin type
How do you treat botulinum toxin
-Remove contaminated feedstuff
-Treatment of affected animals may include antitoxin therapy
-Antitoxin, penicillin, and debridement of woounds
-Symptomatic and supportive care
Tetanospamin
neurotoxin produced by Clostridium tetani that blocks release of inhibitory neurotransmitter, particularly glycine
Tetanus mechanism of action
prevents release of inhibitory neurotransmitters, particularly glycine, from neurons in the CNS, resulting in uncontrolled muscle contractions
*Add more
Clinical signs of tetanus
generalized musculoskeletal stiffness
elevated third eyelid
Sardonic grin (carnivores)
Locked jaw
Recumbency and inability to rise
Convulsions may occur
Death from marked contraction of the muscles of respiration
What can cause Shaker Foal Syndrome
foals with tremors from botulinum toxin
How does cyanobacteria intoxications occur?
ingestion of water with excessive growth of cyanobacteria producing anatoxin and hepatotoxin nodularin
Nodularin
a hepatotoxin produced by cyanobacteria
Anatoxin
a: toxin of cyanobacteria that causes the depolarization of nicotinic membranes and can lead to respiratory paralysis
a(s): inhibits AChase in the peripheral nervous system
Cantharidin
a toxin spread by blister beetles
acantholysis and vesicle formation leading to ulcers or erosion where the compound contacts a mucosal surface
may act by inhibiting protein phosphatase
How does cantharidin toxicosis typically occur
in alfalfa feef. release when beetles are crushed contaminating the hay. compound is colorless, odorless, and very stable
Envenomation
the injection of a poisonous material by sting, spine, bite, or other similar means
What species is most likely to be bitten by snakes/lizards
dogs, due to their inquisitive nature
The majority of bites of companion animals are from what animal?
Pit vipers (crotalidae)
Where are coral snakes (Elipidae) located
Arizona (Arizona coral snake)
Texas/Louisana (Texas Coral snake)
Florida and surrounding states (Eastern coral snake)
T/F North American coral snake bites are less common than pit vipers due to their shy, aggressive and nocturnal behaviors
T
How is venom delivered by coral snakes
they have short, fixed non hinged front fangs that are partially membrane covered. The membrane is pushed back and the venom duct empties at the base of the fang, bathing the fang in venom
Even when bitten, 60% do not result in venom delivery.
T/F the size of the coral snake does not correlate to the amount of venom it has
F
What is the mechanism of action of coral snake venoms?
-Neurotoxic with local tissue rxn/pain at site
Several neurotoxins involved that act as non-depolarizing neuromuscular blocking agents. Curare like syndrome
CNS depression, muscle paralysis and vasomotor instability
severe anemia from hemolysis in dogs
What are the clinical signs of coral snake envenomation
Dogs: Acute CNS depression, emesis, excessive salivation, quadriplegia with decreased spinal reflexes in all limbs and respiratory paraylsis. may have IV hemolysis, anemia, hemoglobinuria and RBC alteration
Cats: Acute ascending flaccid quadriplegia, CNS depression, and reduced nocperception. Anisocoria, spinal reflexes absent in all four limbs, hypothermia, and loss of cutaneous trunci reflex have been documented
How do you treat coral snake envenomation
use of compression bandage around and over the bite site
signs may be delayed by 12 hours so hospitalize for minimum of 24 hours
Antivenin (discontinued)
Respons to respiratory collapse, dysphagia, and aspiration pneumonia via ventillary support
What venom causes neurologic and curare-like involving paralysis
Coral snake venom
Coral Snake Envenomation
Rare due to their lifestyle and low likelihood of venom delivery
Dogs are mostly recipients
Neurologic and curare like involving paralysis
Delayed onset and long lasting
Supportive care tx
Good prognosis with early medical intervention
Major complication is aspiration pneumonia which worsens the prognosis
Crotalidae
Pit vipers like Crotalus (rattlesnakes), sisturus (pygmy rattlesnakes and massasauga), Agkistrodon (water moccasins, cottonmouths, and copperheads)
Where are pit vipers found
Every state in US except Hawaii, Maine, and Alaska
99% of all snakebites to animals in north america are by
Pit vipers (Crotalidae)
How is pit viper venom delivered
rotating the retractable front fangs downward and stabbing forward
muscle contraction of the venom glands force venom through the hollow fangs into the victim
25% of bites are dry (often defensive bites)
Pit viper species venom toxicity levels
RattleSnakes > Water moccasin > Copperhead
Pit viper venom mechanism of action
primarily to immobilize prey and digest its tissues
mixture of enzymatic and nonenzymatic proteins. min of 10 enzymes.
nonenzymatic fractions are hte killing fraction and are 50X more potent than crude venom
What are the three venom types of North American rattle snakes
1) Classic diamonback rattlesnake venom- causes marked tissue destruction, coagulopathy, and hypotension
2) Mojave A rattle snake venom: virtually no tissue destruction or coagulation defect but it induces severe neurotoxicosis
3) Intergrade found in multiple species- contains both neurotoxins and classic venom components
What are the effects of classic diamondback rattlesnake venom
causes marked tissue destruction, coagulopathy, and hypotension
What are the effects of Mojave A rattlesnake venom
virtually no tissue destruction or coagulation defects but it induces severe neurotoxicosis
Pit viper clinical signs
1) initially marked regional swelling - ecchymosis and petechiation may be evident
2) Delayed onset of clinical signs for several hours
3) Progressive swelling that is progressive for up to 36 hours after envenomation
4) Tachycardia, shallow repsiration, lethargy, nausea, obtundation, muscle fasciculations, increased salivation, and enlarged regional lymph nodes
Where are dogs typically bitten by pit vipers
on the head or front legs
usually a defensive strike
seek humans right after bite thus presented early
Where are cats typically bitten in the torso
usually an offensive strike in reaction to playing with snake
presents late due to hiding after being bitten
Where are horses typically bitten by snake
on the nose leading to marked tissue necrosis
Where are cattle typically bitten by snake
on the muzzle or tongue leading to tissue necrosis and secondary infection
What is elevated and can serve as an indicator of pit viper envenomation
Early high levels of creatine phosphokinase
(marker of tissue/muscle damage)
What should be monitored during suspected pit viper envenomation
Coagulation parameters (aPTT, prothrombin time, fibringogen, fibrin split products, and platelet counts)
Why should you do a urinalysis for suspected pit viper envenomation?
to examine signs of hematuria or rhabdomyolysis
What RBC shape is seen with pit viper envenomation
Echinocytes
What causes the echinocytes sen with pit viper envenomation
venom phospholipases that alter the membrane structure of erythrocytes
How do you treat pit viper envenomation?
-Keep victim calm
-Monitor severity with severity score
-IV crystalloid fuid to combat hypovolemic crisis (hypovolemic crisis leads to cardiovascular collapse)
-Broad-spectrum antibiotics in species susceptible to clostridial infections
-Diphenhydramine aids in calming fractious or painful animals and is a pretreatment against possible allergic reactions to antivenin
Antivenin
only proven treatment of pit viper venom
IV administration
stops progression of swelling, reverses coagulopathy, reverses thrombocytopenia, and improves muscle strength in patients with weakness and paralysis
not associated with clinical outcome
Does the rattlesnake vaccine work?
it does enhance recovery but is not preventative against rattlesnake venom
What is the prognosis of pit viper envenomation
With early medical intervention, most snakebitten dogs an cats survive
Large animals often survive initial venom effect but are at risk of death from secondary tissue damage and infection
Heloderma
venomous lizards of north and central america
-Gila Monster
-Mexican Beaded Lizard
How does lizard envenomation occur?
Do not inject venom
venom is released from two venom glands on the lower jaw and onto the gum, and then flows up the grooved teeth into the wound via capillary action
Degree of envenomation is directly related to the duration of the bite
victim often presented for vet care with the lizard still attached
Lizard venom mechanism of action
Mixture of biologically active proteins (no neurotoxins and generally do not affect coagulation)
Kallikrein- releases bradykinins inducing pain and hypotension
Arginine Ester Hydrolase - hydrolyzes amino acid esters
Phospholipase A2- greater than 50% homologous to bee venom
Hyaluronidase- spreading factor breaks down connective tissue
Gilatoxin- kallikrein
Helothermine- disrupts Ca2+ release from SR by binding to ryanodine receptor
Helospectin- vasodilatory peptide
Lizard venom contains many biologically active proteins, Kallikrein being one of them. What does this result in?
releases bradykinins inducing pain and hypotension
What are the clinical signs of lizard envenomation
extreme pain at bite site
Edema around wound
Hypotension and tachycardia
Feline-tachypnea, tachycardia, and vomiting from pain
Regional muscle fasciculations
Rare: tissue necrosis and secondary infection, particularly if tooth fragments embedded in wound
How do you treat lizard envenomation
pry the lizard off still attached
hospitalize and monitor the victim for progression of the envenomation syndrome
No specific antivenin available
Treatment- largely supportive
IV fluids for hypotension
Narcotics or fentanyl drip for pain control
-irrigate would with lidocaine and probe for broken lizard teeth
Broad spectrum antibiotics to combat secondary infection
What is the single largest predictor of lizard envenomation?
the duration of the bite
the longer the bite, the more venom is delivered
How is spider venom delivered?
stored in the cephalothorax venom glands and delivered via fangs (chelicerae)
T/F coral snake venom is rapidly cleared from the body
F
The primary toxic response observed following envenomation from a Coral Snake is:
neurotoxicity
The onset of clinical signs resulting from a possible Coral Snake envenomation may be delayed by
__________
and thus the patient should be hospitalized for a minimum of
__________
in order to determine if a significant envenomation has or has not occurred.
12; 24
T/F All pit viper venoms are made up of the same constituents.
F
Which of the following statements is FALSE regarding treatment of pit viper envenomation in a dog?
A) IV crystalloid therapy is indicated to combat hypovolemic crisis
B) Most dogs survive pit viper envenomation with early medical intervention
C) A rattlesnake vaccine has been developed, but current evidence does not support the broad use of this product
D) Antivenin treatment (CroFabTM) helps stop progression of symptoms and leads to a more rapid recovery
E) Antivenin treatment (CroFabTM) substantially increases the likelihood of survival
Antivenin treatment (CroFabTM) substantially increases the likelihood of survival
Which of the following statements is TRUE regarding envenomation from a poisonous lizard such as a Gila Monster?
A) Death from Gila Monster envenomation in companion animals is common
B) Venom is injected deep into tissues via enlarged, retractable fangs
C) The elusive nature of Gila Monsters coupled to the quick strike of the envenomation leads to these bites being difficult to identify
D) Venom is for defensive purposes and results in extreme pain at the bite site
D) Venom is for defensive purposes and results in extreme pain at the bite site
Causes a “curare-like” syndrome
coral snake
Efficient venom delivery via hollow fangs
pit vipers
Primary purpose of venom is defensive and to cause pain
gila monster
Treatment of this snake bite often requires ventilatory support for an extended time
coral snake venom
Marked regional swelling is often initial sign of envenomation
pit viper
Teeth often break off in the wound requiring careful debridement
gila monster
Most spider envenomations only cause__________
local swelling and pain
-anaphylaxis and other allergic reactions to venom components are possible
Cats are very sensitive to the effects of this venom
Widow spiders
Toxicity involves formation of a Bull’s Eye lesion
Recluse spiders
Paralysis can occur following the bite of as few as one of these organisms with heavily infested animals succumbing quickly
Ticks (ixodes)
Single envenomations rarely cause more than transient pain at the site but anaphylactoid reactions are possible
Hymenoptera
These spider species native to the United States are not capable of delivering serious envenomation and thus are effectively innocuous
Tarantula
Poisoning from these animals is referred to as tegenarism and can generate a wound that takes years to properly heal
Hobo spiders
Which of the following statements are TRUE regarding treatment for Black Widow envenomation in animals?
A) An antivenin (LycovacTM) is available, relatively cheap and effective and should be considered
B) An antivenin (LycovacTM) is available but is expensive, ineffective and should not be considered
C) Treatment of symptoms (pain & muscle rigidity) should not be considered
D) Treatment of symptoms (pain & muscle rigidity) should be considered
E) Treatment should only include irrigation and debridement of the bite site
A) An antivenin (LycovacTM) is available, relatively cheap and effective and should be considered
D) Treatment of symptoms (pain & muscle rigidity) should be considered
Which of the following statements are FALSE regarding “Tick Toxin” toxicity and/or treatment?
A) The toxin has not been isolated and exact mechanism of action is not known
B) Treatment should include beta-blockers and diazepam
C) Treatment should include removing ticks, potentially via the use of topical insecticides, and providing supportive care
D) Primary toxicity is ascending ataxia progressing to paresis and flaccid paralysis
E) Removing ticks following presentation of clinical signs is not indicated due to toxin already being delivered
B) Treatment should include beta-blockers and diazepam
E) Removing ticks following presentation of clinical signs is not indicated due to toxin already being delivered
Which of the following statements is/are TRUE with regards to our current understanding of envenomation from a scorpion in companion animals?
A) Evidence is lacking that scorpion stings are a serious medical issue
B) Cats are hypersensitive to scorpion stings
C) Death from a scorpion sting is nearly assured
D) Indicated treatment would be wound care and analgesics
A) Evidence is lacking that scorpion stings are a serious medical issue
D) Indicated treatment would be wound care and analgesics
A client brings a new kitten into your clinic for a “new baby” check up and tells you that they have heard that cats are ultra sensitive to spider bites and that tarantulas are especially toxic to cats. They then explain that they have a pet tarantula and are worried about an interaction between the kitten and the tarantula. What would be the best advice to give this client based on our current knowledge regarding cats and tarantula envenomation?
A) Cats are known tarantula hunters so it should be fun to watch
B) North American Tarantulas are relatively harmless but more exotic species from South America, Africa and Australia can be dangerous
C) Cats are immune to all known spider venoms
D) Have the spider de-fanged
B) North American Tarantulas are relatively harmless but more exotic species from South America, Africa and Australia can be dangerous
Are the female or male Widow Spiders (Latrodectus) more dangerous?
Females
The males are too short to inflict and envenomating bite to humans or other mammals
What is the mechanism of Widow spider venom?
Complex mixture of 6 neuroactive and proteolytic proteins
a-latrotoxin: principle toxin for mammals- causes large release and depletion of acetylcholine and norepinephrine at postganglionic sympathetic synapses
Alpha-Latrotoxin
Widow venom- principle toxin for mammals- causes large release and depletion of acetylcholine and norepinephrine at postganglionic sympathetic synapses
causes lactrodectism
Lactrodectism
a syndrome caused by a-latrotoxin of Widow Spiders
taken up by lympathics and enters the bloodstream
short lived localized pain and generalized pain, mild to moderate hypertension and tachycardia
signs may resolve
caused by a large release and then depletion of ACh and norepinephrine at the postganglionic sympathetic synapses
What species is very sensitive to widow venom?
Cats- paralysis occurs early in course
hypersalivation, restlessness, vomiting, and diarrhea are common
muscle tremors, cramping, ataxia, and inability to stand may precede an atonic paralysis
Cheyne-Stokes respiratory pattern prior to death
How should you treat widow spider envenomation?
Largely symptomatic
-Opioids to control pain
-Diazepam and Methocarbamol to control muscle rigidity
-Calcium gluconate, which used to be used for treatment, is no longer recommended due to it being less effacious than opioids and muscle relxants
Equine-origin antivenin (Lycovac) is available and effective (Cheap, long shelf life, rare delayed allergic reactions)
Lycovac-equine-origin antivenin
Latrodectus (Widow spider) antivenin that is available and effective
relatively cheap, long shelf life, delayed allergic reactions are rare
suggested activity in felines
What is the mechanism of action of the Recluse Spider venom?
1) Necrotizing enzymes (Hyaluronidase, Esterases, Alkaline phosphatases)
2) Sphingomyelinase D- phospholipase that binds to cell membranes and induces migration and activation of neutrophils to site of envenomation
3) Inactivates serum hemolytic complement
-Intravascular coagulation, occlusion of small capillaries, tissue necrosis, systemic depletion of clotting factors (VII, IX, XI, and XII)
What spider venom causes Thrombocytopenia, reticulocyte absence, hemolysis, anemia, hemorrhage, and bulls eye lesion
Recluse spider venom
Bull’s Eye Venom
a vesicle that my form and be replaced by black scab in response to a recluse spider venom
Healing is slow and may ulcerate and leave a large scab
How do you treat Brown Recluse Venom?
1) Necrotic lesions via chemical debridement with Burrows solution of H2O2 and bandaging,
2) Pruritus with diphenhydramine
3) Antibiotics if infection is evident
4) Pain via analgesics (NSAID for minor, opioids for severe)
5) Dapsone- inhibits neutrophil migration and may limit the severity of the necrotic lesion
6) antivenins have been developed and shown to be effective if given within 4h of envenomation
Why might you give Dapsone
It inhibits neutrophil migration and may limit the severity of the necrotic lesion of a Brown Recluse Venom
Are male or female Hobo spiders more venomous?
Male
Tegenerism
caused by hobo spider envenomation
initial bite is relatively painless but erythema will occur. 15-35 hours later the area will rupture with serious discharge from the wound
treat via supportive and symptomatic.
wound may require 3 years to heal if in fatty tissue
same lesion and tx as Brown recluse spider envenomations
Rubustoxin
neurotoxin in funnel web spiders (Atrax and Hadronyche) binds to the pre-synaptic neuron and both inbiti CNS mediated neurotransmitter release while increasing spontaenous release neurotransmitters
Both the ANS and skeletal muscles
Is male or female funnel web spider venom worse
Male (6x more potent than female)
What species are relatively resistant to funnel web venom
Dogs and Cats
Humans and primates are very sensitive
T/F Tarantulas that live in the US are not capable of delivering serious envenomation
T
Venom of tarantulas of South America, Africa, and Australia
contain a neurotoxin and potentially a necrotoxin and hemolytic toxin
following envenomation, muscle spasms, edema, hemoglobinuria, jaundice, and circulatory shock may develop
Selenocosmia and Phlogiellus
Telson
a barbed appendage of scorpions that houses two venom glands that exit via a stinger at the end of the telson
What is the only scorpion in the US that is capable of delivering a life-threatening sting?
The Arizona Bark scorpion
Centruroides sculpturatus
What is the mechanism of action of the alpha and beta scorpion toxins
they block the voltage sensitive sodium and potassium channels in nerves
What venom blocks the voltage sensitive sodium and potassium channels in the nerves?
Scorpion venom
What species is very susceptible to scorpion stings with 100% fatality reported?
ferrets
Scorpion venom toxicity
-Instant sharp pain at the site of envenomation
-Localized edema and pruritus are common
-Regional lymph nodes may enlarge and potentially an allergic reaction characterized by swelling of the eyelids, tongue, and vomiting
-Systemically: numbness of face, myalgia, tachycardia or bradycardia, respiratory depression, and seizures
How do you treat scorpion envenomation
Analgesics and wound care
Systemic signs should be treated symptomatically
No FDA approved antivenins
little evidence on dog and cat exposure
Is eating a scorpion a concern regarding toxicity?
it is not an issue because the protein toxin that blocks the voltage sensitive sodium and potassium channels gets degraded
The exact mechanism of tick paralysis is not known, however what is the suspected mechanism of action
interferes with the synthesis and/or release of ACh at the neuromuscular junction resulting in lower motor neuron paresis and paralysis
What genera of tick cause lower motor neuron paresis and paralysis, similar to botulinum toxin
Ixodes
T/F Tick paralysis requires many ticks to be present to induce the lower motor neuron paresis and paralysis
F- can occur as fews as one tick and heavily infested animals may succumb quickly
What are the clinical signs of tick paralysis
-Ascending ataxia that progresses to paresis and flaccid paralysis
-Early in intoxication, animals remain bright, alert, and able to eat and drink if properly supported
Eventually paralysis of respiratory muscle leads to respiratory failure a death
How might tick paralysis result in death?
paralysis of the respiratory muscles leading to respiratory failure
How do you treat tick paralysis
1) Remove ticks
2) Supportive care, especially respiratory support until the recovery occurs
good prognosis if ticks are removed before bulbar paralysis
Australia- polyclonal dog antiserum to treat
Forcipules
fangs of centupedes that are connected to venomous glands directly under the head
include a serotonin, cytolysin, hemolysin, and vesicating agent
What do millipedes do instead of biting
they can emit irritating and foul smelling secretions from the repugnatorial glands
irritating to mucosal surfaces, particularly the eyes
use corticosteroids to decrease inflammation
How do you treat the secretions released by the repugnatorial glands of the millipede?
corticosteroids to decrease inflammation
T/F Centipede envenomation leads to systemic toxicosis
F- it generally only causes local irritation and potentially necrosis
may require analgesics
Hymenoptera
bees, wasps, and hornets that secret venom from specialized cells in the acid gland and transported to the venom sac
Which hymenoptera can sting multiple times
wasps and hornets,
honeybees cannot because their stinger apparatus is pulled
What are the components of honeybee venoms?
mixture of proteins, peptides, and small organic molecules
-Phospholipases and hyaluronidases account for majority of allergic reactions
-Mellitin is membrane disruptive that increases damage caused by phospholipases and triggers the release of histamine and serotonin
Apamin (neurotoxin that blocks Ca2+ activated K+ channels and is associated with transient peripheral nerve effects)
Apamin
a neurotoxin in honeybee venom that blocks calcium activated K+ channels and is associated with transient peripheral nerve effects
Mellitin
a membrane disruptive compound in honeybee venom that increases the damage caused by phospholipases and triggers the release of histamine and serotonin
What is in the venom of vespid wasps
peptides, enzymes, and amines designed to trigger pain
kinins. serotonin, histamine, tyramine, catecholamines, acetylcholine can contribute to pain and local vasoactivity
several constituents can act as allergens and trigger reactions
What is seen with Hymenoptera Venom toxicity
Local rxns- swollen, edematous and erythematous plaques at the orgin site
Systemic effects from multiple stings: prostration, convulsions, CNS depression, shock, hyperthermia, bloody diarrhea, bloody vomiting, leukocytosis, IV hemolysis, renal/hepatic toxicity
Classic anaphylactoid response to bee and vespid venoms - also can cause immune mediated hemolytic anemia secondary to bee envenomation
How to do treat hymenoptera envenomation
Remove stinger if remains
Cold compresses to relieve pain and swelling
Monitor for anaphylactic rxns (EPI if anaphylaxis is suspected)
True systemic toxicity: aggressive IV fluid therapy, corticosteorids, antihistamines, oxygen for dyspnea, and diazepam as needed for convulsions
monitor renal and hepatic function
Venom with alkaloids that cause dermal necrosis when injected into the skin. Can have cytotoxic, hemolytic, fungicidal, insecticidal, and bactericidal properties
Ant venom
How does ant venom toxicity typically occur
in animals that cant move away from the colony (ie neonatal, juvenile, or disabled)
What are the clinical effects of ant venom toxicity
Intense pain at the site of the sting
develop erythematous pruritic papules that generally resolve within 24 hours
no reports of anaphylaxis
multiple stings may result in systemic signs similar to those of multiple bee/wasp stings
What do you suspect with a dog experiencing intense pain and developed erythematous pruritic papules that generally resolve within 24 hours
Ant venom toxicity
How might you treat ant venom toxicity (multiple envenomations) resulting in severe systemic rxns or anaphylaxis
-IV fluids
-Corticosteroids
-Supportive care
What causes limber neck syndrome in avians
Botulism
What causes shaker foal syndrome in horses
Botulism
What is an anaerobic, gram positive spore forming rod that is commonly found in soils, causing flaccid paralysis
Clostridium botulinum
What cleaves neuronal proteins (SNAP-25) involved in acetylcholine release
Botulinum toxin
What cleaves neuronal synaptobrevin thus inhibiting the release of inhibitory neurotransmitters
Tetanus toxin
A cyanobacterial derived toxin that inhibits serine/threonine phosphatases type 1 and 2
microcystin
inhibits acetylcholinesterase in the peripheral nervous system
Anatoxin -a(s)
Vesicanct causing damage to mucosal surfaces
Cantharidin
Setae cause damage to the submucosa of the alimentary canal leading to bacteria in the circulatory system, fetus, and placenta
Eastern Tent Caterpillars
Structurally related to bufodienolides but kill reptiles via and unknown mechanism
Lucibufagins
Inhibit Sodium-Potassium ATPase
Bufodienolides
Which of the following is/are NOT a mechanism by which botulism infection can occur?
A) Contamination of wounds with spores
B) Transdermal absorption of toxin
C) Ingestion of spores
D) Ingestion of preformed toxin
B) Transdermal absorption of toxin
Which of the following are clinical signs associated with tetanus toxin?
A) Convulsions
B) Neutropenia
C) Locked jaw
D) Jaundice
E) Flaccid paralysis
A) Convulsions
C) Locked jaw
Toxins found in cyanobacteria can cause which of the following toxicities?
Hepatoxicity
Neurotoxicity
Cardiotoxicity
Ototoxicity
Myelotoxicity
Hepatoxicity
Neurotoxicity
Contamination of alfalfa with cantharidin is due to ___________ __________ being crushed into the alfalfa during baling.
Blister beetles
Mare reproductive loss syndrome (MRLS) was identified as an abortigenic disease associated with the consumption of what?
Eastern Tent Caterpillars
The bufodienolides found in toad secretions belong to what class of compounds?
Cardiac glycosides
Toxicity is due to estrogenic activity
Zearalenone
A nephrotoxin primarily affecting chickens
Oosporein
Poor metabolism in pigs accounts for their relative sensitivity to vomitotoxin
Trichothecenes
Primary effect is renal toxicosis and ruminants are immune due to detoxification by rumen microbes
Ochratoxin A
Disease syndrome is staggers and more significant symptoms are triggered by activity and excitement
Tremorgenic Mycotoxins
CNS toxin found in blue cheeses and other moldy cheeses
Roquefortine
Primary effect is vasoconstriction resulting in multiple toxicoses including cutaneous and gangrenous lesions of the tail and extremities in livestock
Ergot
Reactive metabolites cause hepatic toxicosis
Aflatoxin
Block Sphingolipid biosynthesis with primary toxicoses including porcine pulmonary edema and equine leukoencephalomalacia
Fumonisins
Active metabolite is a parasympathomimetic causing the stimulation of exocrine and endocrine glands and excessive salivation
Slaframine
Does Botulinum toxin result in flaccid or rigid paralysis
flaccid paralysis through blocking the release of acetylcholine vesicles (cleaving SNAP-25)
What three mechanisms can Botulism occur via
1) ingestion of preformed toxin
2) Ingestion of spores
3) Contamination of wounds with spores
Shaker Foal Syndrome
toxico-infectious botulism occuring when foals ingest spores, resulting in an overgrowth of the organism within the GI tract resulting in flaccid paralysis
foals develop tremors
What species are less sensitive to botulism?
Swine, dogs, and cats
What are the clinical signs of Botulinum toxin?
1) progressive flaccid paralysis- weakness and ataxia, more pronounced when animal is excited or forced to move (Lower motor neuron paresis with parasympathetic signs)
2) Difficulty with prehension and swallowing- ileus, constipation, or ruminal atony
*Death via respiratory paralysis
How can you diagnose Botulinum
1) Serum, GI contents, ruminal fluids, and feedstuff for preformed toxin
2) Mouse bioassay for botulinum toxin
3) ELISA but only specific for one toxin type
How do you treat Botulinum toxin?
initial treatment to remove contaminated feedstuffs
antitoxin therapy or penicillin
debridement of wounds
Symptomatic and supportive care
Is Botulinum prognosis good or poor?
guarded to poor with animals with clinical signs
How can you prevent Botulinum toxicoses
-Vaccination against C.botulinum toxins with toxoid
Proper ensiling of poultry litter
Examine feed for evidence of decaying carcasses
rodent control program to reduce the number of mice or rats in stored feeds
proper disposal of any dead animals (deep burial)
Cytolysin (tetanolysin)
produced by Clostridium tetani. induced pore formation in a variety of cells to aid in the replication of the tetanus organism locally at the wound site
What is the mechanism of action of tetanus toxin?
prevents the release of inhibitory neurotransmitters (glycine) from neurons in the CNS, resulting in uncontrolled muscle contractions
also cleaves VAMP (synaptobrevin) interupting the translocation and exocytosis of neurotransmitters from inhibitory neurons at the spinal cord
What species are more susceptible to tetanus?
Horses and ruminants due to differences in gangliosides on the neurons and thus entry of the toxin into the neurons
Have persistent spores that are ubiquitois in the feces and soil in areas where animals are raised
Tetanus spores
Clinical signs of tetanus toxin
-Generalized musculoskeletal stiffness
-Nictiating membrane often elevated
-Sardonic grin in carnivores
-Sawhorse stance
-Locked jaw
-Progression to recumbancy and inability to rise
-Convulsions and death from marked contraction of respiratory muscles
What toxicoses might you see the sardonic grin in carnivores
Tetanus toxin
How can you diagnose Tetanus toxicity?
-Finding C. tetani in culture of wound
How should you treat Tetanus toxicosis
-Antbiotic therapy with penicillin
-antitoxin therapy
-clean would
-Move animals to dark, quiet area to minimize convulsions induced by external stimuli- tranquilizers to control convulsions?
What is a possible complication upon administering tetanus antitoxin in horses
Theiler’s Disease (Serum Hepatitis)
Theiler’s Disease
Serum Hepatitis that can occur when administering the tetanus antitoxin in horses
How does cyanobacteria intoxications typically occur?
ingestion of water with excessive growth of blue-green algae
species that produce anatoxin a(s) and microcystis sp. that produce hepatoxin microsystin and Nodularia that produce hepatotoxin nodularin
Microcystin and Nodularin are______
hepatotoxin produced by cyanobacteria
inhibit serine/threonine phosphatases type 1 and 2
directly cytotoxic leading to apoptosis to mammalian cells
Anatoxin-a causes _______________, while anatoxin-a(s)___________
depolarization of nicotinic membranes rapidly, leading to respiratory paralysis
inhibits acetylcholinesterase in the peripheral nervous system
What increases the risk of cyanobacterial toxins
Warm weather with increased nutrients in the water (late summer/early fall)
rapid growth by increased nitrogen and phosphoris in the water- runoff from fertilized fields
What 4 factors enhance cyanobacterial growth
1) Warm weather
2) Increased nitrogen and phosphorus in water
3) Increased wind concentrates it at the shoreline
4) Runoff from fertilized fields
How do the clinical signs of anatoxin-a differ from anatoxin a(s)
anatoxin-a: respiratory distress and convulsion. Death from respiratory paralysis, quick onset, death can occur within 30min (depolarizing nicotinic receptors)
anatoxin-a(s): signs consistent with the inhibition of AchE. Increased salivation, urination, lacrimation, defecation as well as tremors, dyspnea, and convulsions. Death from respiratory arrest can occur within 1 hour
What are the clinical signs of animals that ingest microcystin or nodularin
Hepatic toxic via inhibiting serine/threonine phoshphates type 1 and 2- liver toxicity within 1-4 hours including lethargy, vomiting, diarrhea, GI atony, weakness, and pale mucous membranes
What is the treatment of cyanobacteria ingestion
no antifotes
decontamination- emesis, activated charcoal, cathartic
aggressive hepatoxocity treatment w fluids, corticosteroids
Neurotoxicity- aggressive respiratory support and seizure control as needed
How can you treat anatoxin-a(s) toxicosis
Atropine, just like for other AChE inhibitors
What is the prognosis of cyanobacteria intoxication
poor to grave if exhibited clinical signs
Precention is limiting animal exposure to water containing the algae
Canthardiasis
a disease that is caused through the ingestion of a blister beetle. Cantharidin is a vesicant that causes irritation characterized by acantholysis an vesicle formation leading to ulcers or erosions where the compound contacts the mucosal surface
Where are blister beetles found
feed principally on lush alfalfa fields. Some swarm in large numbers
Large numbers are baled into hay
Cantharidin is released when beetles are crushed contaminating the hay. The compound is odorless, and very stable
T/F Cantharidin compound released once beetles are crushed are easy to detect in alfalfa bails
it is odorless, colorless, and very stable
What is the mechanism of cantharidin toxicosis
unknown by may act by inhibiting protein phosphatase 2A resulting as a vesicant and causing irritation characterized by acantholysis
What dictates the clinical signs of cantharidin toxicosis
the dosage
-Range from depression and discomfort to severe coli
Colic signs: restlessness, depression, sweating, congested mucous membranes, increased HR, increased respiratory rate. Gastric lesion horses may submerge muzzles or play in water
fever, pollakiuria, salivation, stiff gain, and blood tinged urine
What can lead to gross lesions throughout the urinary and GI tract, most commonly the terminal portion of the esophagus, stomach, and intestines with classic lesions of areas of ulceration or erosion
cantharidin toxicosis
How can you confirm cantharidin toxicosis?
with urine or intestinal contents being the preferred diagnostic specimens for analytical analysis
How should you treat Cantharidin Toxicosis
focus on enhanced fecal and urinary elimination, correcting dehydration, managing serum calcium and magnesium, and controlling pain
supportive care may be needed for 3-10 days depending on severity
-Mineral oil to hasten movement through the GI tract
Analgesics may not work but a-2 adrenergic agonist may be required in horses
fluid therapy and enhance urinary elimination
What should you absolutely NOT use in the treatment of Cantharidin
Acepromazine - potentiation of shock
How do you prevent Cantharidin toxicosis
-inspect hay an use bales to make inspecting easier
cut hay early before bloom stage, first cut and late cutting often escape contamination because they are produce prior to and after peak beetle activity
Scout field before and during harvest to disperse swarms before harvesting the alfalfa
Is the prognosis of Cantharidin toxicosis good or bad
poor prognosis
What causes Mare Reproductive Loss Syndrome (MRLS)
Abortigenic disease by Eastern Tent Caterpillars
setae (hair) imbed into submucosa of alimentary tract creating microgranulomatous lesions that allow streptococci, actinobacilli, and potentially entercocci to invade the circulatory system
Bacteria establish infections in tissues where immune surveillance of mare is reduced such as the fetus and the placenta
What is the effect of lucibufagins
they are structurally related to the cardiotoxic bufodienolides of toads and cardenlides of plants
(Cardiotoxic)
Lizards are especially susceptible to them
Not much is known on treatment
What do secretions from toad glands have
-Epinephrine
-Serotonin
-Ergosterol
-Bufodienolides (bufogenins)- cardiac glycosides that cause arrhythmia
Do Toxic toads or Rattlesnakes kill more arizona dogs
Toxic toads
What is the mechanism of action of budodienolides
Cardiac glycosides
bind to and inhibit sodium-potassium ATPase in a manner that is similar to the other cardiac glycosides such as digoxin and digitoxin
Leads to an increased extracellular concentration of K with concomitant increased intracellular Na+. This leads to an influx of calcium into the cytosol via the Na+ Ca++ exchange
Change alters resting membrane potential of excitable cells resulting in depressed electrical conduction
What does toad toxicity result in
Hypersalivation, vomiting, and anxiety
Neurological abnormalities like convuslions, ataxia, nystagmus, stupor, or coma
as seen with the inhibition of Na/K ATPase and depressed electrical conduction
How do you treat toad toxicosis
Decontamination- rise w copious amounts of water unless animal is seizing
Diazepam if seizing
Bradycardia- Atropine
Tachycardia- beta antagonists
Hyperkalemia- insulin, glucose, an sodium bicarbonate
Digoxin-specific fab fragment used successfully in mice and in humans
Is toad prognosis good or bad
generally good with early decontamination and appropriate symptomatic therapy
What is designated as X disease
Aflatoxicosis
What fungus is associated with Aflatoxins
Aspergillus species like flavus, parasiticus and nomius
What kind of plants are aflatoxins typically found on
crops with substantive energy content such as corn, peanuts, cottonseed, and rice
How do Aflatoxins cause toxicosis
they are metabolized to reactive metabolites like aflatoxin epoxide that react with DNA RNA and proteins leading to organ function disruption, carcinogenesis, immunosuppression, mutagenesis, and teratogenesis
common w hepatocellular damage
Aflatoxin clinical signs
Liver disease
Chronic- reduced weight gain, roughed hair coat, anemia, janudice, anorexia, and depression
Dogs will develop GI disturbance with occasional hemorrhage and ascites
How do you treat aflatoxicosis
-get off feed
-no antidote or specific treatment
-oxytetracycleine to reduce hepatic damage and mortality
-Activated charcoal
Assess liver function as a response and predict prgnosis
How do you control aflatoxin
Insect control to decrease fungal invasion
Mold retarants such as propionic acid
Ammoniation of feeds such as corn and cottonseed
Na Ca aluminosilicate is an adbsorbent that binds aflatoxin
What causes porcine mycotoxin nephropathy
citrinin and ochratoxin
What produces ochratoxins and citrinin
some Aspergillus and penicillium species which are found in contaminated grains, soybeans, white beans, peanuts, brazil nuts, surface of hams, red pepper, black pepper, coffee, and decaying vegetation and soil
Does the fungal mass correlate to the amounts of ochratoxins/citrinin
NO
What species are immune to ochratoxins/citrinin
Ruminants as the rumen microbes cleave it to a nontoxic form
What is ochratoxin’s mechanism?
1) inhibition of phenylalanine metabolizing enzymes
2) Promotion of lipid peroxidation
3) Inhibition of mitochondrial ATP production
Reduces protein and mRNA pools in the kidney cells
Renal gluconeogenesis and phosphoenolpyruvate carboxykinase is inhibited in rats and swine
Immunosuppression may be related to inhibition of peripheral B and T lymphocyte proliferation
Carcinogenic in lab animal suppression of NK cell activity
How does acute toxicosis of ochratoxins differ from chronic exposure
Acute (high dose): gastroenteritis, diarrhea, emesis, tenesmus, depression, anorexia, and dehydration
Chronic: slower onset of kidney disease. Water intake and urination frequency is increased
What reduces the amount of ochratoxin toxicosis in the feed
Ammoniation
Ascorbic acid of feed in egg producing hens
or feed the contaminated feed to ruminants
What fungal species produce Ergot
Claviceps pupurea fungal bodies on rye
What is the cause of summer slump in cattle
Ergotism
What causes adverse effects on reproduction and lactation in horses- clinically indistinguishable from Fescue Foot
Ergot
Ergot replaces the __________ of the grass seed or cereal grain during mycelia infection
ovary
What is Ergot’s mechanism of action
agonist and antagonist activity at tryptaminergic, dopaminergic and alpha-adrenergic receptors
-Serotonin (5-HT)
-Dopamine
-Norepinephrien
ex: vasodilation via D1 antagonist
and Dopaminergic agonst at D2 receptors causing inhibition of prolactin secretion
Vasoconstriction via agonist activity varies depending on vascular bed
You see a cow with 1) cutaneous and gangrenous lesions on the tail and extremeties 2) hyperthermia 3) Reproductive failure and is convulsive. What do you suspect?
Ergot toxicity
Name the four forms of Ergot toxicosis
1) Cutaneous and gangrenous lesions on the tail and extremities (assoc. w subacute or chronic ingestion, cold temperatures enhance the clinical effects
2) Hyperthermia and production loss- reduces feed intake and milk production
3) Reproductive failure- hyperthermia- induced embryonic loss, agalactia, small weak foals, stillborns in pregnant horses, prolactin secretion causes loss of CL and abortion in dogs and rodents
4) Convulsive or nervous form- caused by acute ingestion of a large dose of sclerotia
How do you treat Ergot toxicity
-Remove source of ergot from animals diet
hyperthermic effect in cattle will abate in 1-2 weeks
euthanize animals with gangrenous extremities (poor recovery)
Dopamine antagonist domperidone for uterine/agalactia mare
Screen to prevent
Trichothecenes
a mycotoxin that poisons animals when contaminated feedstuffs are consumed
produced by Fusarium fungi
associated with excessive rain/high humidity
pigs are more susceptible (due to poor vomitoxin metabolism)
confusion on clinical signs - refusal to eat, vomiting at higher doses.
Chickens might be tolerant but some mouth lesions and refusal to eat
Fusarium fungi produces_________
Trichthecene and
Zearalenone
Zearalenone
a resorcyclic acid lactone produced by Fusariam fungi and absorptive enzymes produced at low temperatures so it is an issue in temperate zones
Corn is the primary substrate
Stable in the environment
Toxin levels are not associated with the amount of mold
Is the amount of Fusariam mold associated with the amount of Zearalenone toxicity levels?
No
what is Zearalenone’s mechanism
weak estrogen and binds to receptors for estradiol-17B. cause thymic atrophy, macrophage activation, and inhibit mitogen-stimulated lymphocyte proliferation
Can Zearalenone be in milk
yes but «<1%
you notice an animal with hyperestrogenism, hyperemia, and swelling of the vulva, mammary glands, and uterus as well as ovarian atrophy. Elevated progesterone with decreased prolactin and LH hormones. What is the likely cause
Zearalenone
How can Zearalenone be fatal
it virtually isnt unless morbidity sequelae lead to complications
How do you treat Zearalenone?
-Remove contaminated feed
-Tx external genitalia physical damage
-Give PGF2a to correct anestrus due to retained corpora lutea
-Good prognosis with estrogenic signs that usually disappear within a week
-Prevention involves adequate drying of harvested crop to prevent further toxin production
What can cause porcine pulmonary edema
Fumonisins
What can cause equine leukoencephalomalacia (ELEM)
Fumonisins
Fusarium verticilloides produces_________
Fumonisins
Fumonisins have only been detected on what feed?
Corn
What fumonisin compounds are the most relevant?
B1 and B2
Fumonisins
mycotoxin in corn by Fusarium verticolloides
causes ELEM and porcine pulmonary edema
corn specific inhibit sphinganine and sphingosine N-acyltransferase- inhibiting sphingolipid
acute onset of signs
What is the mechanism of Fumonisins
inhibit sphinganine and sphingosine N-acetyltransferase
causes porcine pulomary edema as phingosine mediated inhibition of myocardial L-type calcium channels, decreases cardiac contractility, resulting in left sided heart failire and pulmonary edema
causes ELEM- cardiac dysfunction leads to leukoencephalomalacia in horse
How do Fumonisins lead to porcine pulmonary edema
inhibit sphinganine and sphingosine N-acetyltransferase leading to sphingosine mediated inhibition of myocardial L-type calcium channels, decreases cardiac contractility, resulting in left sided heart failire and pulmonary edema
Porcine Pulmonary Edema Fumonisin toxicosis
Signs develop 3-6 days after exposure
Dyspnea
open mouth breating, tachypnea, cyanosis, inactivity and sudden death
due to sphingosine mediated inhibition of myocardial L-type calcium channels, decreases cardiac contractility, resulting in left sided heart failure and pulmonary edema
Equine Leukoencephalomalacia
caused by fumonisin
both neurotoxic and hepatic syndome
hepatic: icterus, mucous membrane petechiae, and swelling of lips or muzzle
Neurotoxic syndrome incluses frenzy, aimless circling, head pressing, paresis, ataxia, apparent blindness, depression and hyperexcitability
How should you treat Fumonisin toxicosis
No treatments
-Dilute corn to have lower concentrations or feed to less sensitive species like ruminants and poultry
What causes staggers
Tremorgenic Mycotoxins
-Sclerotia or endophye fungi growing on grasses that the animals consume
via Reduced GABA and glutamate levels
and vasoconstriction of the cerebrum leading to cerebral anoxia
Tremorgenic Mycotoxins
Causes Staggers - presynamptic motor release and prolonged depolarization leading to reduced CNS GABA levels and Reduced CNS glutamate levels
Vasoconstriction in the cerebrum leading to cerebral anoxia
Minimal excitement triggers more significant symptoms like tremor, stiffness, ataxia, hypermetria, and seizure, opisthotonus
What exacerbates the symptoms of tremorgenic mycotoxins?
minimal excitement- when forced to run, animals have exaggerated flexure of the forelegs and incoordination causing them to fall
then revert to signs of resting animal (minimal fine tremors)
What are tremorgenic mycotoxins mechanism of action
presynamptic motor release and prolonged depolarization leading to reduced CNS GABA levels and Reduced CNS glutamate levels
Vasoconstriction in the cerebrum leading to cerebral anoxia
How do you treat/prevent tremorgenic mycotoxins
-Replace contaminated forage and keep animals in a quiet,secure place until they recover
-Medication enhance glycine in the CNS
-deny animal access to endophyte-infested grass and planting only endophyte free grass seed
Good prognosis with high morbidity but low mortality
Do tremorgenic mycotoxin toxicosis have a good prognosis?
Yes
What causes Slobber syndrome
Slaframine, an alkaloid synthesized from lysine by the fungus Rhizoctonia legumicola, which infects plants and causes Black Patch disease of clovers
disease of red clover and other forage legumes caused by the fungus Rhizoctonia leguminicola
Black Patch Disease on clovers- causes slobber syndrome by Slaframine
Can Slaframine cross the BBB
unlikely
How does slaframine act
it is metabolized to a hetoimine metabolite that acts a a parasympathomimetic agent to stimulate the exocrine and endocrine glands
What effect does atropine have on slaframine toxicity
it can block activity by pre-administration but does not reverse response once initiated
reversal is unlikely but can reduce severity of signs
Does slaframine have an effect on cardiovasclar function/blood pressure?
Not at dosages stimultory to exocrine glands. except possibly in dogs
How do you treat slaframine toxicity?
-Atropine (before clinical signs) , reversal is unlikely
-antihistamines relief clinical signs
-early removal from offending forage leads to rapid resolition of the problem with few if any aftereffects
What is special about slaframine in dogs
cardiovascular effects
What is Fescue toxicosis associated with
Fescue foot: indistinguishable from dry gangrene of extremities
Summer Slump: decreased feed intake, weight gain, milk production, and impaired reproduction
Fat necrosis: Presence of necrotic fat in the abdominal and pelvic cavities
What are the effects of slaframine toxicity
aside from hypersalivation
higher doses with longer exposure times are dehydration and cholinergic stimulation that can lead to decreased milk production, intestinal disturbances, and possibly abortions
death is rare
Oosporein
a mycotoxin that is nephrotoxic
no treatment
avoid storing feedstuffs in moist environment
Patulin
produced by numerous filamentous fungi
cytotoxic agent whose activity to linked to rapid reaction with thiol and amine groups
-inhibits protein synthesis, depleted GSH, induces oxidative stress
-impaires mitochondrial function
no antidote. treatment is symptomatic and supportive
Prevention of exposure is best method to control
What is Patulin’s mechanism
cytotoxic agent whose activity to linked to rapid reaction with thiol and amine groups
-inhibits protein synthesis, depleted GSH, induces oxidative stress
Melamine/Cyanuric acid
used in the manufacture of plastics, adhesives, cleaners and yellow dyes. thought to be originally nontoxic
added to pet food to fraudulently increase apparent protein content because protein is often estimated based on mitrogen content (67% content)
when formed togher forms a crystalline lattice under acidic conditions leading to renal toxicosis and renal failure
In what conditions does melamine form a crystalline lattice with cyanuric acid
acidic conditions
How can melamine by itself lead to renal toxicosis and failure
enteric bacterial enzymes can convert melamine to cyanuric acid
How does melamine form uroliths
it forms a lattice with uric acid resulting in insoluble forms.
Water intake plays a role in treating as with removing melamine and alkalizing the diet
What are the clinical signs of melamine toxicity
Clinical signs: vomiting, inappetance, polyuria, polydipsia, lethargy
Urine: USG<1.035, elevated BUN, elevated creatinine, hyperkalemia and hyperphosphatemia, circular green-brown crystals present
Postmortem findings: bilateral renogealy, uremia, tubular necrosis
How do you treat melamine toxicosis
fluid therapy, supportive care, urine alkalization (sodium bicarbonate, potassium citrate)
older animals and those with pre-existing conditions were less likely to survive
What are ionophores
compounds that form lipid soluble dynamically reversible complexes with cations and facilitate specific ion transport across biologic membranes
1) Neutral ionophores- highly toxic due to forming charged complexes that perturb membrane and action potentials
2) Carboxylic ionophores- form zwitterionic complexes with cations and promote electrically neutral cation exchange diffusion
highly toxic due to forming charged complexes that perturb membrane and action potentials
Neutral ionophores
form zwitterionic complexes with cations and promote electrically neutral cation exchange diffusion
Carboxylic ionophores-
5 uses of ionophores
1) Reduction of coccidial oocyst discharge in ruminants
2) Prevention of acute bovine pulmonary edema and emphysema
3) Decreased incidence of bloat
4) Prevention of ruminal lactic acidosis
5) Amelioration of ketosis in lactating dairy cows
How to ionophore toxic exposures occur
1) ingestion by non-target species (Feed-mixing errors, ingredient contamination, labeled feed to inappropriate species)
2) Excessive dietary concentration in intended species
What is the mechanism of action of ionophores
transport of ions across biologic membranes leading to net cellular imbalance- sodium, potassium, calcium, and hydrongen
Loss of ATP production in mitochondria
-uncoupling of OX/Phos
-loss of mitochondrial integrity
How do clinical signs occur in ionophores
cellular and subcellular ion imbalances causing deficits in the function of excitable tissues: neurlogic, musculoskeletal, cardiac or smooth muscle.
What species have more neuromuscular effects to ionophores
pigs, dogs, and cats
How do you treat ionophore toxicity
no specific antidote
-GI decontamination- emesis, activated charcoal, cathartic
-Vitamin E or Selenium to minimize secondary oxidative damage (little benefit in cattle and pigs)
Supportive care (Fluids for hydration and preventing renal casting of myoglobin)
Keep quiet, good nutrition and husbandry support
What is the prognosis of ionophore toxicity
Myocardial damage: guarded to poor
Horses: breeding or foaling may be life-threatening
Limited feed efficiency and weight gain in food producing animals
Dogs- may recover over weeks or months but heart damage may still be a concern
How do you prevent ionophore toxicity
only use in species for which they are formulated
store ionophore premixes or concentration
carefully calculate and mix feed formulations
Gossypol
produced in cotton plants
absorption is inversely proportional to amount of dietary iron and supplementation with ferrous sulfate
ruminants more susceptible
accumulates in tissues
hepatic metabolism
multiple cellular porcesses but has anti-fertility activity by inhibiting sperm mitochondria and suppressing P4 and E2
What influences gossypol’s absorption
Iron and ferrous sulfate
inversely proportional
inactivates free gossypol in cattle
Are ruminants or monogastrics more resistant to gossypol
ruminants, binds to proteins in rumen
What can result in thumping (labored breathing) with chronic exposure
gossypol
What are the effects of gossypol
Degeneration and necrosis in myocardium- fluid accumulation
Liver toxicity
Reproductive effects (male infertility- decreased spermatogenesis; female reproduction of decreased elvels of eastradiol 17-b)
What can result in polioencephalomalacia (PEM)
sulfide when its overproduced by ruminal microflora
Do Ruminants need sulfur in their diet
no microbial synthesis of protein and vitamins
-sufficient energy
-inorganic nitrogen
-inorganic sulfut
Source of gossypol toxicosis
cottonseed meal
Source of sulfide toxicosis
high sulfate diet
Source of 4-Methylimidazole toxicosis
ammoniation of feed
Source of Ammonia toxicosis
Urea
Melamine is relatively non-toxic when consumed. However, when present with cyanuric acid it can form a ____________ under acidic conditions?
Crystalline Lattice
The primary toxicosis of ionophore exposure in cattle is?
cardiac
Which of the following clinical signs/toxicoses can be observed with gossypol poisoning?
Male infertility
Neuronal degeneration
Liver toxicity
Myocardium degeneration
Male infertility
Liver toxicity
Myocardium degeneration
The primary toxicity observed with sulfur toxicosis in ruminants is:
Polioencephalomalacia (PEM)
Ammoniation of feed can lead to the formation of pyrimidines and imidazoles. This occurs more frequently when this process is utilized with which of the following?
Alfalfa hay (good quality)
The use of nonprotein nitrogen (NPN) supplemented feed in ruminants can lead to toxicosis when levels of NPN are too high leading to the ruminal production and accumulation of:
Ammonia (NH3)
Which of the following feed additives is/are susceptible to “mixing errors” leading to toxicosis.
Ionophores
Sulfur
NPN
What is the sulfur toxicosis mechanism of action
inhibition of the e- transport chain by sulfide will lead to a decrease in ATP
Oxidation in the mitochondria of sulfide to silfite can also lead to direct damage from sulfite radicals as well as inhibition of enzymes involved in the TCA
high energy emands of neurons make these tissue more susceptbilbe to damage
What factors influence sulfur toxicity
-Dose of sulfur
-Rate of dietary change
-Dietary form of sulfur
-Age of animals
-Dietary factors apart from sulfur
-Ambient temperature
How can you diagnose sulfur toxicosis
Pathologic concentrations of sulfide gas are transient and will dissipate by the time clinical signs are apparent.
-Retrospective dietary analysis
-Measurements of sulfide in clinically normal hermdmates
-PEM outbreaks, H2S concentration in 4/6 clinically normal pen mates were >2000ppm, a level that can precede development
Excess sulfur intake can contribute to __________ deficiency
copper
How do you treat PEM
-Supportive care- corticosteroids for cerebral edema and oral fluids and nutrients
-Removal of source of sulfur
-Roughage for animals on high concentrate diets
How do you prevent sulfur toxicosis
1) Reduce dietary sulfure to <0.40% or preferably <30%
2) Assess total sulfur intake before using ammonium sulfate for urinary acidification- ammonium chloride may be a safer option
3) Gradual adaptation to a high sulfure diet
Why does ammoniated feed occur
it substantially improves the nutrient characteristics of roughages by
-Increasing digestibility
-Increasing intake
-Increasing crude protein content
-Allowing storage of higher moisture roughage by inhibiting mold development
Bovine bonkers/hysteria/ammoniated feed syndrome
names to describe the hyperexcitability syndrome seen in cattle after ingesting ammoniated feedstuffs.
pyridines and imidazoles formed by the Maillard Rxn in toxic hay, occurs more frequent in higher quality forages, with more reducing sugar content are ammoniated
4-methylimidazole
a potent convulsant that causes hyperexcitability as a result of the Maillard Reaction
when ammonation occurs at temperatures >70C
How do you treat feed ammoniation toxicosis
=Remove ammoniated feed
-Acepromazine and Thaiamine Hydrochloride
-Milking out cows with affected calves
good prognosis in adults when managed
nursing lambs and claves have guarded prognosis
Should you ammoniate poor or high quality roughage
poor quality
Nonprotein nitrogen
the most common source is urea although other NPN sources have been used
mixed into feeds
liquid supplements mixed into molasses are popular
exposure may also be through consumminh ammonium or urea-containing fertilizers
What happens to NPN in the rumen
Excess NPN increases Ammonia (NH3)
Ruminal pH increases
Increased NH3 transit to the liver where it is converted to Urea (urea cycle)
Excess ammonia enters the systemic circulation leading to toxicosis
What is ammonia mechanism of action
in blood transits to brain. then incorporated into transamination reactions
a-ketoglutarate i depleted- intermediate in TCA
Gluamate is depleted- required for GABA
Are very young calves or older cows more susceptible to ammonia
older cows
very young cows lack the ruminal flora
What are the risk factors of NPN
-A lack of acclimation of an individual to urea
-Anything that increases the alkalinity of rumen
-Rations that are high in roughage and low in carbohydratr
-Animals that are in poor body condition
-Poorly mixed rations
-Unrestricted access to palatable supplements
What are the clinical signs of NPN toxicosis
-Rapid development between 20min - 4 hours
Terminal convulsion and death (2hr cattle, 4 hr sheep, 3-12 hours sheep)
uneasiness, muscle and skin tremors, dyspnea, tachypnea, frequent urination and defecation, stiffening of front legs, prostration
colic, rumen atony, bloat, regurg, cardiac arrythmias, cyanosis
How do you diagnose NPN
Analysis for ammonia nitrogen in rumen fluid, CNS fluid, vitreous fluid, blood, serum/plasma
Normal <0.5mg/dL
toxicosis - 1 mg/dL
Death 3-6 mg/dL
Analysis of feed for NPN content
How do you treat NPN toxicosis
-often impossible w rapid progression
infusing rumen with 5% acetic acid
cold water
rumenotomy to replace rumen contents with hay slurry
Does NPN toxicosis have good or poor prognosis
poor, highly fatal.
but survivors have no sequelae and recover 12-24 hours
How do you prevent NPN toxicosis
-Client education on NPN induced ammonia toxicosis
Careful formulation and feeding (NPN<3% of concentrate)
Slowly acclimate animals to increased NPN in diet
Acclimation is lost if animals stop eating the NPN for 1-3 days
